阿帕替尼联合经肝动脉化疗栓塞术治疗老年中晚期原发性肝癌临床观察

目的观察阿帕替尼联合经肝动脉化疗栓塞术(TACE)治疗老年中晚期原发性肝癌(PLC)的效果与安全性。方法前瞻性入组我院2017年12月至2018年12月老年肝癌TNM分期ⅢA和ⅢB期的PLC病人152例,根据病人意愿分为2组,对照组81例采用TACE治疗,观察组71例采用TACE联合阿帕替尼治疗,病人均于治疗后3、6、9个月门诊CT复查。病人均随访至2019年5月或死亡,比较2组病人生存期和治疗期间不良反应发生率。结果观察组和对照组TACE术后3个月客观缓解率(ORR)分别为61.97%、56.79%,差异无统计学意义(P0.05)。观察组术后6、12个月ORR分别为59.15%、39.44%,均高于对照组的48.15%、11.11%,差异有统计学意义(P0.05)。观察组中位生存时间为17.09个月,对照组为12.65个月,2组生存曲线差异有统计学意义(χ~2=7.126,P=0.006)。观察组病理性血压升高、手足综合征、蛋白尿、腹泻发生率分别为60.56%、49.30%、33.80%、25.35%,均显著高于对照组(P0.05)。2组骨髓抑制、发热、疼痛、恶心呕吐发生率差异无统计学意义(P0.05)。结论阿帕替尼联合TACE治疗中晚期PLC可提高疗效,延长病人生存期,虽然一些不良反应发生率增加,但病人获益更大。     

阿帕替尼联合TACE对中晚期肝细胞癌患者优选治疗的临床研究

目的:研究中晚期肝细胞癌(HCC)患者分别接受肝动脉栓塞化疗术(TACE)联合阿帕替尼治疗和接受TACE联合安慰剂治疗的疗效和安全性。方法:48例中晚期HCC患者分为A、B两组,A组患者接受TACE和安慰剂治疗,B组接受TACE联合阿帕替尼治疗,分析比较两组患者3个月时甲胎蛋白(AFP)的变化和3,6,9,12个月时客观缓解率(ORR),并比较两组患者的中位病情无进展生存期(PFS)和不良反应的发生率。结果:治疗3月时两组患者AFP水平均较治疗前显著下降,差异具有统计学意义(P0. 05),但两组间比较差异无统计学意义(P 0. 05)。A组患者ORR在治疗3、6、9、12个月时分别为37. 5%、20. 83%、12. 5%、4. 17%; B组患者ORR在治疗3、6、9、12个月时分别为54. 55%、45. 45%、40. 91%、27. 27%。3和6个月时两组患者ORR比较,差异无统计学意义(P 0. 05),9和12个月时差异具有统计学意义(P 0. 05)。A组患者中位PFS为4个月,B组则为8. 5个月,两组比较,差异有统计学意义(P 0. 05)。与阿帕替尼相关的不良反应如高血压、手足综合症、蛋白尿等,B组的发生率高于A组,差异具有统计学意义(P 0. 05)。经过对症治疗后这些不良反应大多都能减轻。结论:对于中晚期HCC患者,长疗程的TACE联合阿帕替尼治疗比接受TACE联合安慰剂治疗能获得更高的ORR,并能延长中位PFS,且具有一定的安全性。     

经导管肝动脉化疗栓塞联合甲磺酸阿帕替尼在中晚期肝细胞癌中的应用

目的讨论经导管肝动脉化疗栓塞联合甲磺酸阿帕替尼治疗中晚期肝细胞癌(hepatocellular carcinoma,HCC)的临床疗效。方法选取2013年2月至2016年1月南方大学顺德医院收治的中晚期肝细胞癌患者114例为研究对象,采用随机数字表法分为3组,每组38例。其中A组患者仅使用经导管肝动脉化疗栓塞进行治疗,B组患者仅给予甲磺酸阿帕替尼治疗,C组患者给予经导管肝动脉化疗栓塞联合甲磺酸阿帕替尼治疗,对3组中晚期HCC患者的治疗效果进行分析。结果治疗前,3组HCC患者血清(vascular endothelial growth factor,VEGF)和(matrix metalloprotein 9,MMP-9)水平差异无统计学意义(P0.05);治疗后,C组患者VEGF、MMP-9水平显著低于A、B组(P0.05)。治疗6个月后,A组、B组和C组患者的生存率分别为34.12%、28.95%和60.52%,差异有统计学意义(χ~2=21.333,P0.001);治疗12个月后,A组、B组和C组的生存率分别为21.05%、15.79%和42.10%,差异有统计学意义(χ~2=7.600,P0.05)。A组、B组和C组的疾病控制率分别为23.68%、23.68%和50.00%,差异有统计学意义(χ~2=8.003,P=0.018)。3组HCC患者的不良反应发生率无显著差异(χ~2=1.416,P=0.493)。结论中晚期肝细胞癌患者采用经导管肝动脉化疗栓塞联合甲磺酸阿帕替尼治疗的临床效果显著,患者肿瘤进展得到有效抑制。     

TACE联合不同剂量阿帕替尼治疗中晚期肝癌的临床疗效及不良反应

目的 观察经肝动脉化疗栓塞(TACE)联合阿帕替尼治疗中晚期肝癌的临床效果及不良反应.方法 回顾性收集185例中晚期肝癌患者,分为TACE组(60例)和TACE+阿帕替尼组(125例,其中125 mg/d阿帕替尼组35例,250 mg/d阿帕替尼组69例,500 mg/d阿帕替尼组21例),比较两组治疗后客观缓解率(O...     

阿帕替尼联合肝动脉化疗栓塞术对原发性肝癌的肝功能、炎性细胞因子和细胞免疫功能的影响

[目的]探讨阿帕替尼联合肝动脉化疗栓塞术(TACE)对原发性肝癌的肝功能、炎性细胞因子和细胞免疫功能的影响。[方法]选取2018年1月～2019年12月住院的104例原发性肝癌患者为研究对象,所有患者均给予TACE治疗,依据是否服用阿帕替尼,分为TACE组(52例)和联合组(TACE+阿帕替尼组,52例)。观察2组患者的临床疗效、肝功能、炎性细胞因子和细胞免疫功能的影响。[结果]TACE组和联合组治疗后的总有效率分别为69.23%和48.08%,差异有统计学意义(P0.05))。2组患者治疗前,肝功能、炎性细胞因子、免疫指标、肿瘤相关血管生长因子比较差异无统计学意义(P0.05);治疗后,2组患者丙氨酸氨基转移酶、天门冬氨酸氨基转移酶、甲胎蛋白、甲胎蛋白异质体、肿瘤直径、IL-6、IL-10、肿瘤坏死因子-α、血管内皮细胞生长因子受体-2、转化生长因子-β1、CD8~+水平低于治疗前,CD3~+、CD4~+、CD4~+/CD8~+水平高于治疗前;且联合组的肝功能相关指标、炎性细胞因子、免疫指标、肿瘤相关血管生长因子改善情况显著优于TACE组;TACE组1年、2年生存率分别为73.08%和51.29%,低于联合组的90.38%和75.00%;TACE组不良反应发生率为19.23%,高于联合组的5.77%,差异有统计学意义(χ~2=4.308,P=0.38)。[结论]阿帕替尼联合TACE治疗原发性肝癌可改善肝细胞功能、免疫功能,有效缩小肿瘤直径,可减少复发概率,具有较高的有效率和安全性。     

阿帕替尼联合经肝动脉栓塞化疗治疗老年胃癌术后肝转移的临床疗效

目的探讨阿帕替尼联合经肝动脉栓塞化疗治疗老年胃癌术后肝转移的临床疗效。方法老年胃癌术后肝转移患者62例随机分成治疗组和对照组,每组31例。对照组给予单纯经导管肝动脉化疗栓塞(TACE)治疗,治疗组给予TACE联合阿帕替尼治疗。对比2组临床疗效、免疫功能指标变化情况、不良反应发生情况、术后生活质量及远期生存情况。结果两组治疗有效率比较差异无统计学意义(P0.05);治疗后,治疗组CD3~+、CD4~+、CD4~+/CD8~+均显著增高(P0.05),且治疗组明显高于对照组(P0.05);治疗组CD8~+较治疗前显著降低(P0.05),但组间差异不具有统计学意义(P0.05);2组白介素(IL)-2、肿瘤坏死因子(TNF)-α、干扰素(INF)-γ与治疗前相比均明显增高(P0.05),且治疗组明显高于对照组(P0.05);两组不良反应发生率比较差异无统计学意义(P0.05);治疗组1年生存率及3年生存率与对照组比较差异无统计学意义(P0.05)。结论阿帕替尼联合TACE治疗老年胃癌术后肝转移疗效显著,可明显提高机体免疫功能,有效降低不良反应发生率,安全性较高,并明显提高患者远期生存率。     

替吉奥联合经肝动脉化疗栓塞治疗中晚期肝细胞癌的疗效观察

目的对比观察经肝动脉栓塞化疗(TACE)单用或联合替吉奥治疗中晚期肝细胞癌(HCC)的疗效。方法将2009年8月-2010年10月本院收治的无法手术切除的中晚期HCC患者60例随机分为2组,每组30例。治疗组采用TACE联合替吉奥口服,对照组仅行TACE。观察2组的有效率、疾病控制率、生存率以及不良反应情况。计数资料采用χ2检验;生存分析运用Logrank检验。结果有效率:治疗组63.3%,对照组33.3%,差异有统计学意义(χ2=5.406,P=0.020);疾病控制率:治疗组86.7%,对照组43.3%,差异有统计学意义(χ2=12.308,P=0.000)。1年生存率:治疗组77.3%,对照组51.5%,差异有统计学意义(χ2=4.593,P=0.032);2年生存率:治疗组34.8%,对照组10.4%,差异有统计学意义(χ2=4.812,P=0.028)。治疗组、对照组不良反应轻微,主要是恶心呕吐、腹泻和骨髓抑制,为1、2级,对症治疗可缓解,两组比较差异无统计学意义(P0.05)。结论替吉奥联合TACE术对中晚期HCC有一定的治疗价值,值得进一步探讨。     

S-TACE联合阿帕替尼对中晚期原发性肝癌患者肿瘤血管因子、肝功能和预后的影响

目的探讨对中晚期原发性肝癌(HCC)患者采用超选择性肝动脉化疗栓塞术(S-TACE)联合阿帕替尼治疗的效果和安全性。方法将近年来的72例中晚期HCC患者分成两组,对照组采用S-TACE治疗,观察组采用S-TACE联合阿帕替尼治疗;观察两组的肿瘤血管炎症因子、肝功能的变化,治疗效果和安全性指标。结果治疗前,两组的VEGFR2、MMP-9和caspase-8等肿瘤血管因子指标水平,以及AFP-L3、ALT和LDH等肝功能指标水平比较,无统计学意义(P0.05);疗程结束后,观察组的肿瘤血管因子和肝功能指标水平均较对照组改善,有统计学意义(P0.05)。观察组的ORR和DCR高于对照组,MTTP和MOS大于对照组,有统计学意义(P0.05)。两组的栓塞后综合征比较无统计学意义(P0.05);观察组的药物不良反应高于对照组,有统计学意义(P0.05)。结论对中晚期HCC患者采用STACE联合阿帕替尼治疗,可抑制肿瘤血管再生,改善肝脏功能,提高临床获益率,安全性较高。     

阿帕替尼与替吉奥联合治疗晚期胃癌疗效分析及对相关细胞因子的影响

[目的]探讨阿帕替尼与替吉奥联合治疗晚期胃癌疗效分析及对相关细胞因子的影响。[方法]选取2014年1月~2016年1月我院门诊收治的30例一线治疗失败的晚期胃癌患者,按随机分组法将所有患者分为观察组和对照组,每组各15例。对照组采用替吉奥治疗,观察组采用阿帕替尼与替吉奥联合治疗。比较2组患者治疗有效率、血清肿瘤标志物水平、Th1和Th1类细胞因子水平、不良反应发生率及生存情况。[结果]观察组患者的有效率和疾病控制率(46.7%、80.0%)均显著高于对照组(33.3%、66.7%),差异有统计学意义(P0.05)。治疗后观察组患者血清CEA和CA199水平显著低于对照组(P0.05)。观察组IFN-γ和TNF-α水平显著高于对照组,而IL-4和IL-10显著低于对照组,差异有统计学意义(P0.05)。2组患者不良反应发生率差异无统计学意义(P0.05)。观察组患者的平均进展时(5.2±0.7)均显著低于对照组(7.1±1.3),平均生存期(9.3±2.5)均显著高于对照组(5.1±1.3),差异有统计学意义(P0.05)。[结论]阿帕替尼与替吉奥联合二线治疗晚期胃癌的疗效确切,可明显提高生存期,但不增加不良反应发生率,值得进一步研究。     

化疗联合阿帕替尼及调强放疗治疗老年中晚期宫颈癌患者临床效果观察

目的探讨化疗联合阿帕替尼及调强放疗治疗老年中晚期宫颈癌患者的临床效果及不良反应发生情况。方法选取2014年1月至2017年1月在我院诊治的老年中晚期宫颈癌患者86例为研究对象,采用随机数字法分为观察组与对照组,每组43例。对照组患者给予静脉化疗+阿帕替尼治疗,观察组患者在对照组患者治疗的基础上给予调强放疗。治疗28 d为1个周期,共治疗2个周期。比较两组患者的临床疗效;比较两组患者治疗前后的血清鳞状细胞癌相关抗原(SCC-Ag)、癌胚抗原(CEA)水平;比较两组患者的不良反应发生情况以及1年、3年生存率。结果疗程结束后,观察组患者的临床疗效明显优于对照组,差异有统计学意义(P0.05);两组患者的SCC-Ag、CEA水平均显著降低,观察组患者的水平显著低于对照组,差异有统计学意义(P0.05)。治疗期间,两组患者骨髓抑制、消化道反应、直肠炎发生情况比较,差异均无统计学意义(P0.05)。观察组患者的1年、3年生存率均显著高于对照组,差异有统计学意义(P0.05)。结论化疗联合阿帕替尼及调强放疗治疗老年中晚期宫颈癌患者,可显著提高疗效,有效控制病情进展,提高患者的1年、3年生存率,治疗安全性良好。     

The contribution of different organs and tissues of the rat to assimilation of glucose

Summary After intravenous injection of glucose, 750 mg/kg, together with a tracer dose of [U-¹⁴C] glucose, into fasted, adult white rats, the following percentages of the administered dose were found in whole organs and tissues: 1. after five minutes: skeletal muscle 30.3, skin 28.1, blood 13.1, adipose tissue 10.7, liver 8.9. 2. Forty minutes after injection the corresponding values were: 35.0, 11.1, 5.0, 4.6 and 9.4%. Expired ¹⁴CO₂ was negligible after five minutes: after 40 min it comprised 8% of the total dose administered. — After intragastric administration of 1500 mg/kg of glucose given with a tracer dose of [U-¹⁴C] glucose under the same experimental conditions, the alimentary tract contained, after 15, 90 and 180 min, 60.5, 14.8 and 8.4% respectively of the total ¹⁴C dose given. At these times the liver contained 2.9, 10.7 and 15.0%; skin contained 7.5, 7.1 and 5.4%; adipose tissue 2.0, 3.8 and 3.5%, and expired ¹⁴CO₂ 0.4, 11.8 and 31.3% respectively. Details of the uptake of ¹⁴C glucose by other organs and tissues are given, and a balance sheet for the injected material is attempted.

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Der Anteil verschiedener Organe und Gewebe der Ratte an der Glucoseassimilation

Zusammenfassung Nach i.v. Injektion von 750 mg Glucose/kg mit einer Sprüdosis U-¹⁴C-Glucose fanden sich bei fastenden, erwachsenen weißen Ratten folgende Prozentsätze der verabreichten Menge in Gesamt-Organen und -Geweben: 1. Nach 5 min: Skeletmuskel 30.3, Haut 28.1, Blut 13.1, Fettgewebe 10.7, Leber 8.9. 2. 40 min nach der Injektion lauteten die entsprechenden Werte: 35.0, 11.1, 5.0, 4.6, 9.4%. Nach 5 min ließen sich in der Ausatmungsluft nur Spuren von ¹⁴CO₂ nachweisen, nach 40 min lagen 8% der verabreichten Dosis in dieser Form vor. — Nach intragastrischer Zufuhr von 1500 mg Glucose/kg mit einer Spürdosis von U-¹⁴C-Glucose unter den gleichen Versuchsbedingungen enthielt der Verdauungstrakt nach 15, 90 und 180 min jeweils 60.5, 14.8 bzw. 8.4% der zugeführten Radioaktivität. In der Leber fanden sich zu diesen Zeiten 2.9, 10.7 und 15.0%, in der Haut 7.5, 7.1 und 5.4, im Fettgewebe 2.0, 3.8 und 3.5%. Die Ausatmungsluft enthielt 0.4, 11.8 und 31.3% als ¹⁴CO₂. Es folgen weitere Einzelheiten zur Aufnahme von Radioglucose durch andere Organe und Gewebe sowie der Versuch einer Bilanz für das injizierte Material.

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Contribution de différents organes et tissus du rat à l'assimilation du glucose

Résumé Après l'injection intraveineuse de glucose (750 mg/kg) en même temps qu'une dose traceuse de U-¹⁴C-glucose, à des rats blancs adultes à jeun, les pourcentages suivants de la dose administrée ont été retrouvés dans tous les organes et tissus: 1. après cinq minutes: muscle squelettique 30.3, peau 28.1, sang 13.1, tissu adipeux 10.7, foie 8.9. 2. Quarante minutes après l'injection, les valeurs correspondantes étaient les suivantes: 35.0, 11.1, 5.0, 4.6 et 9.4%. Le ¹⁴CO₂ dégagé était négligeable après 5 min: après 40 min il représentait 8% de la dose totale administrée.— Après l'administration intragastrique de 1500 mg/kg de glucose, donné en même temps qu'une dose traceuse de U-¹⁴C-glucose dans les mêmes conditions expérimentales, le tube digestif contenait au bout de 15, 90 et 180 min, 60.5, 14.8 et 8.4% respectivement de la dose totale de ¹⁴C administrée. A ces moments là le foie contenait respectivement 2.9, 10.7 et 15.0%; la peau contenait 7.5, 7.1 et 5.4%; le tissu adipeux 2.0, 3.8 et 3.5%, et le ¹⁴CO₂ dégagé était de 0.4, 11.8 et 31.3%. On donne des détails sur la captation du ¹⁴C-glucose par d'autres organes et tissus, et on essaye de dresser un bilan du produit injecté.

     

Age of onset and inheritance of diabetes: The importance of examining relatives

Summary Suggestions that diabetes of younger- and older-onset are inherited differently have been examined in a family study which compares the first-degree relatives of 735 diabetic patients with those of 514 control patients. Verbally reported histories from the propositi indicated an excess prevalence of known diabetes among the siblings of younger-onset diabetics; however, when the ostensibly normal, first-degree relatives were examined a high frequency of unsuspected glucose tolerance test abnormality was found. When the diabetes prevalence in relatives of diabetics was compared with that in relatives of controls (K ratio), a method at present widely used to determine the mode of inheritance, a number of problems arose suggesting that this means of genetic analysis may be misleading in diseases such as diabetes. It is concluded, for reasons which are discussed, that differences in prevalence ratios cannot be accepted as good evidence for different modes of inheritance of younger- and older-onset diabetes in man.

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Manifestationsalter und Vererbung des Diabetes: Die Wichtigkeit von Verwandten-Untersuchungen

Zusammenfassung Die Hypothese eines unterschiedlichen Vererbungsmodus für den Diabetes mit frühzeitiger Krankheitsmanifestation und den Diabetes mit späterem Krankheitsausbruch wurde auf Grund von Familienuntersuchungen geprüft. Blutsverwandte 1. Grades von 735 Diabetikern wurden mit einer entsprechenden Kontrollgruppe von 514 Personen verglichen. Bei den Blutsverwandten der Patienten mit früher Diabetesmanifestation ist aus den Krankheitsanamnesen und mündlichen Berichten eine größere Diabeteshäufigkeit zu ermitteln. Wenn indessen die scheinbar normalen Verwandten ersten Grades untersucht wurden, fand man eine große Anzahl vorher unbekannter Fälle von Glueosetoleranzstörung. Bei einem Vergleich der Diabeteshäufigkeit unter den Verwandten der Zuckerkranken und den Verwandten der Kontrollfälle (K Vergleichszahl) einer Methode, die z. Zt. oft zur Bestimmung des Vererbungsmodus benutzt wird, ergaben sich einige Probleme, die andeuten, daß diese Art Vererbungsanalysen bei Erkrankungen, wie dem Diabetes, irreführend sein können. Aus den Ergebnissen der Untersuchungen wird gefolgert, daß die zahlenmäßigen Unterschiede, die sich bei dieser Methode des Vergleichs ergeben, keinen Beweis für einen unterschiedlichen Vererbungsmodus des früher oder später sich manifestierenden Diabetes darstellen.

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Age de l'apparition du diabète et sa transmission héréditaire. Importance de l'examen des membres de la famille

Résumé La suggestion a été faite que le diabète commençant dans la première moitié de la vie est transmis d'une façon différente du diabète diagnostiqué plus tard.- Nous avons examiné cette hypothèse dans une étude qui compare les membres du premier degré des familles de 735 malades souffrant du diabète avec ceux des 514 sujets de contrôle. Les histoires familiales des malades, rapportées oralement, ont indiqué une prevalence excessive de diabète connu parmi les frères et les soeurs des diabétiques juvéniles. Toutefois, lorsque les membres —supposés normaux — furent examinés, une haute fréquence d'intolérance au glucose non-soupçonnée fut trouvée. Quand la prévalence de la maladie dans les familles des diabétiques fut comparée avec celle des sujets de contrôle (rapportK) — méthode souvent employée actuellement afin de déterminer le mode de transmission du diabète — nous nous sommes trouvés en face de certains problèmes qui sembleraient indiquer que cette méthode d'analyse génétique pourrait mener à certaines erreurs d'interprétation dans les maladies telles que le diabète. — Pour les raisons examinées, nous concluons que des différences dans les rapports de prévalence ne peuvent pas être acceptées comme preuves convaincantes d'un mode de transmission différent du diabète juvénile et du diabète d'apparition plus tardive.

     

Evaluation of mechanical strengths of three types of mini-implants in artificial bones

We investigates the effect of the anchor area on the mechanical strengths of infrazygomatic mini-implants. Thirty mini-implants were divided into three types based on the material and shape: Type A (titanium alloy, 2.0 × 12 mm), Type B (stainless steel, 2.0 × 12 mm), and Type C (titanium alloy, 2.0 × 11 mm).The mini-implants were inserted at 90° and 45° into the artificial bone to a depth of 7 mm, without predrilling. The mechanical strengths [insertion torque (IT), resonance frequency (RF), and removal torque (RT)] and the anchor area were measured. We hypothesized that no correlation exists among the mechanical forces of each brand. In the 90° tests, the IT, RF, and RT of Type C (8.5 N cm, 10.2 kHz, and 6.1 N cm, respectively) were significantly higher than those of Type A (5.0 N cm, 7.7 kHz, and 4.7 N cm, respectively). In the 45° test, the RFs of Type C (9.2 kHz) was significantly higher than those of Type A (7.0 kHz) and Type B (6.7 kHz). The anchor area of the mini-implants was in the order of Type C (706 mm²) > Type B (648 mm²) > Type A (621 mm²). Type C exhibited no significant correlation in intragroup comparisons, and the hypothesis was accepted. In the 90° and 45° tests, Type C exhibited the largest anchor area and the highest mechanical strengths (IT, RF, and RT) among the three types of mini-implants. The anchor area plays a crucial role in the mechanical strength of mini-implants.     

On the mode of transmission of hereditary diabetes

Summary Using the case records of 14000 diabetics followed up in the Antidiabetic Centre of Bucharest for 1–26 years, the authors have studied the problem of the mode of transmission of hereditary diabetes. The analysis, which takes into consideration four different aspects representing four stages of investigation, indicates a dominant transmission for diabetes. — 1.Consanguinity. In a group of 49 consanguine marriages, diabetes was found in 14 of 100 direct descendants. The probability of diabetes would have attained 24.6% if all had lived up to 80 years. This fact, to which we must add the late onset of diabetes in the offspring and the absence of a massive appearance of diabetes in siblings, raises doubts regarding the hypothesis of the recessive transmission of hereditary diabetes.- 2.Diabetic Couples. In 385 families in which both parents were diabetic there were 1,173 descendants; 326 of these suffered from diabetes (27.7%). The probability of diabetes calculated for a lifespan of 90 years for all the progeny would have been in the authors' material of 37.7%. This figure shows that the parents, who were diabetics of the hereditary type, could only have had heterozygotic genetic structures, pleading for the dominant transmission of hereditary diabetes mellitus. — 3.Diabetes in Multiple Successive Generations. In 113 of the 3,430 pedigrees studied, the disease could be noticed in 3 successive generations, which after the necessary corrections gives a proportion of 8.15%; in 4 pedigrees diabetes was found in 4 successive generations (1.19%). — 4.Anteposition presents a net statistical significance and upholds in the authors' opinion the dominant transmission of diabetes. — These findings (3 and 4) imply the dominant transmission of hereditary diabetes.

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Erbgang des genetisch bedingten Diabetes

Zusammenfassung Die Autoren untersuchten das Problem des Erbgangs des Diabetes an 14000 Personen, die in der Zentralstelle für Diabetes-Behandlung in Bukarest während 1 – 26 Jahren beobachtet wurden. Die Analyse berücksichtigt 4 verschiedene Aspekte, die 4 verschiedene Stadien der Untersuchungsreihe darstellen, und kommt zur Annahme einer dominanten Vererbung des Diabetes. — 1.Konsanguinität. In einer Gruppe von 49 Verwandtenehen wurde Diabetes nur bei 14 von 100 direkten Nachkommen gefunden. Die Wahrscheinlichkeit hätte 24.6% erreicht, wenn alle ein Alter von 80 Jahren erlebt hätten. Diese Tatsache, zu der wir den späten Beginn des Diabetes bei den Nachkommen und das Fehlen massiver Diabetes-Erscheinungen bei den Geschwistern zählen müssen, läßt die Annahme eines rezessiven Erbgangs für den ererbten Diabetes als fraglich erscheinen. — 2.Diabetische Ehepaare. In 385 Familien, in denen beide Eltern Diabetiker waren, fanden sich 1173 Nachkommen, von denen 326 (27.7%) an Diabetes litten. Die Wahrscheinlichkeit eines Diabetes bei der gesamten Nachkommenschaft unter der Annahme einer Lebenserwartung von 90 Jahren hätte im Material der Autoren bei 37.7% gelegen. Diese Zahl zeigt, daß diese Eltern mit erblichem Diabetes eine hétérozygote genetische Struktur aufwiesen und sprechen für einen dominanten Erbgang des ererbten Diabetes. — 3.Diabetes in mehreren aufeinanderfolgenden Generationen. In113 von 3430 untersuchten Stammbäumen konnte die Krankheit über 3 aufeinanderfolgende Generationen beobachtet werden, was nach den notwendigen Korrekturen einen Prozentsatz von 8.15 ergibt; in 4 Stammbäumen fand sich ein Diabetes in 4 aufeinanderfolgenden Generationen (1.19%). — 4. DieAnteposition läßt sich statistisch eindeutig nachweisen und spricht nach Ansicht der Autoren für eine dominante Vererbungsweise des Diabetes. Auch die unter 3. und 4. aufgeführten Befunde sprechen für einen dominanten Erbgang des erblichen Diabetes. Das unregelmäßige Auftreten der Erkrankung lenkte die Aufmerksamkeit der Verfasser auf die schützende Rolle eines Nicht-Träger-Allels der Heterozygoten und auf die Bedeutung von Umgebungseinflüssen bei der Auslösung der Erkrankung.

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Le mode de transmission du diabète héréditaire

Résumé Les auteurs ont étudié le problème du mode de transmission du diabète héréditaire sur 14000 diabétiques suivis au Centre Antidiabétique de Bucarest pendant 1–26 ans. L'analyse qui prend en considération 4 aspects différents représentant 4 stades de l'investigation, a conclu à la transmission dominante du diabète. — 1.Consanguinité. Dans un groupe de 49 mariages consanguins, le diabète a été trouvé chez 14 des 100 descendants directs. La probabilité du diabète aurait atteint 24.6%, si tous avaient vécu jusqu'à l'âge de 80 ans. Ce fait, auquel nous devons ajouter l'apparition tardive du diabète dans la descendance et l'absence d'apparition massive du diabète chez les frères et soeurs, soulève des doutes sur l'hypothèse de la transmission récessive du diabète héréditaire. — 2.Couples de diabétiques. Dans 385 familles chez lesquelles les deux parents étaient diabétiques, il y a 1173 descendants; 326 souffraient de diabète (27,7%). La probabilité du diabète calculée pour une durée de vie de 90 années pour toute la progéniture aurait été de 37.7% dans le matériel des auteurs. Ce chiffre indique que les parents, diabétiques de type héréditaire ne pouvaient avoir que des structures génétiques hétérozygotes, ce qui plaide en faveur de la transmission dominante du diabète sucré héréditaire. — 3.Diabète dans plusieurs générations successives. Pour 113 des 3430 arbres généalogiques étudiés, la maladie a pu être trouvée pendant 3 générations successives, ce qui donne, après les corrections nécessaires, une proportion de 8.15%; dans 4 arbres généalogiques le diabète a été trouvé dans 4 générations successives (1.19%). — 4.L'antéposition a une nette signification statistique et confirme, dans l'opinion des auteurs, la transmission dominante du diabète. -Ces résultats (3 et 4) peuvent être pris comme preuve de la transmission dominante du diabète héréditaire. — Lecaractère irrégulier de la maladie a attiré l'attention des auteurs sur le rôle protecteur de l'allèle non-porteuse des hétérozygotes et sur l'importance des facteurs environnants dans l'instauration de la maladie.

     

The force of contraction of isolated papillary muscle: A study of the interaction of its determining factors

This paper investigates the ways examples of three categories of experimental variables, changes in muscle length, variations in the rate and pattern of stimulation, and changes in the composition of the bathing medium, interact to determine the force of contraction—in particular the maximum rate of rise of force, $\text{F}\text{?}{}_{\mathrm{<mtext>max</mtext>}}$,—of isometric rabbit and cat papillary muscle. The shape of the ?_max-length relationship was unaltered by a change in calcium concentration or exposure to histamine; i.e. the effect of a given concentration was to multiply $\text{F}\text{?}{}_{\mathrm{<mtext>max</mtext>}}$ obtained at every muscle length by the same factor. The way changes in the bathing composition modified the rate dependency of contractile force, the ?_max-interval relationship, was also investigated. The effect of a change in calcium concentration or exposure of the muscle to one of a variety of inotropic agents (ouabain, histamine, norepinephrine or pentobarbital) was to modify the ?_max-interval relationship, in some instances radically. These results can be combined with the previous finding that a change of muscle length only scaled and did not modify the shape of the ?_max-interval relationship [2].The way $\text{F}\text{?}{}_{\mathrm{<mtext>max</mtext>}}$ depends on muscle length, rate and pattern of stimulation and composition of the bathing medium can thus be described as the product of two functions: one function, λ, dependent on muscle length but unaffected by a change in the pattern of stimulation or an inotropic agent; the other function, φ, dependent on the rate and pattern of stimulation. φ was found to depend on the composition of the bathing medium but to be unaltered by muscle length, i.e.F_max=kλphiv;(w) where k is a proportionality constant with dimensions of grams/second; λ and φ are dimensionless; ω denotes the concentration of calcium or of one of the inotropic drugs tested. In most instances, the function φ (ω) for each agent was distinctly different, perhaps characteristically so, from that of any of the other agents.     

Role of nitric oxide in relaxation of the longitudinal layer of rectal smooth muscle

PURPOSE: This study was designed to investigate the role of nitric oxide in neurogenic relaxation of the longitudinal layer of human rectal smooth muscle. METHODS: Tissue was obtained from the mid rectum of patients undergoing anterior resection for carcinoma. Adjacent strips of longitudinal muscle were dissected and mounted in organ baths for isometric tension recording. In preliminary experiments to determine the response of strips to cholinergic, adrenergic, and potential excitatory agonists, strips were superfused with standard Krebs solution (37±0.5°C; pH, 7.4±0.05). Investigation of inhibitory, nonadrenergic noncholinergic responses required the addition of 3×10⁻⁶ M histamine to induce reproducible and stable tension for five-minute “test” periods, during which electrical field stimulation (EFS) and additional drugs were applied. In these experiments, strips were superfused with Krebs solution that contained atropine sulfate (3×10⁻⁶ M) and guanethidine (3×10⁻⁶ M). RESULTS: The response to cholinergic and adrenergic agonists was typical of nonsphincter specialized gastrointestinal smooth muscle. EFS elicited frequency-dependent, neurogenic (tetrodotoxin-sensitive) relaxations of precontracted strips, which were reduced in dose-dependent fashion by addition ofNω-nitro-l-arginine and restored by addition of 3×10 ⁻⁴ M l-arginine but not by d-arginine. Addition of exogenous nitric oxide (sodium nitroprusside) mimicked the relaxant response induced by EFS. CONCLUSION: Smooth muscle from the longitudinal layer of human rectum receives an intrinsic inhibitory innervation mediated by nitric oxide. Supported and financed by the Medical Research Council, United Kingdom. John Stebbing is in receipt of a Medical Research Council Clinical Training Fellowship. Read at the meeting of The American Society of Colon and Rectal Surgeons, Seattle, Washington, June 9 to 14, 1996.     

Impact of a simulation-based training on the experience of the beginning of residency

IntroductionWe aimed to evaluate the impact of an immersive simulation session on the experience of the beginning of residency.MethodsThe interventional group consisted of newly recruited residents in 2019, who participated in the workshop presenting four emergency scenarios frequently encountered during night shifts; the control group comprised residents who had begun their internship in 2018, without having participated in the simulation workshop. The level of psychological stress and self-confidence were self-estimated in the simulation group before and immediately after the workshop. During the second semester of residency, stress, self-efficacy and anxiety were evaluated in both groups with the Perceived Stress Scale (PSS), General Self-efficacy Scale (GSES), and Generalized Anxiety Disorder-7 (GAD-7) scale.ResultsIn the second semester 2020, the PSS, GSES and GAD-7 were 20.71 ± 8.15 and 22.44 ± 5.68 (P = 0.40); 26.88 ± 6.30 and 27.11 ± 3.95 (P = 0.87); 6.94 ± 5.25 and 8.89 ± 4.78 (P = 0.22) for the simulation (n = 17, 89.5% of participation) and control (n = 9, 75%) groups, respectively. In the simulation group, the level of self-confidence had significantly improved from 1.82 ± 0.95 before the session to 2.29 ± 1.16 after the session (P = 0.05). Interestingly, this improvement in self-confidence was significantly correlated with GAD-7 (P = 0.014) and PSS (P = 0.05), and tended to be correlated with GSES (P = 0.09).ConclusionOur study showed a significant improvement in self-confidence between before and after the simulation session. Residents who experienced an improvement in self-confidence saw their stress and anxiety levels decrease during the second semester reevaluation, in favor of a prolonged benefit from the session.     

Plethora of transitions during breakup of liquid filaments

Thinning and breakup of liquid filaments are central to dripping of leaky faucets, inkjet drop formation, and raindrop fragmentation. As the filament radius decreases, curvature and capillary pressure, both inversely proportional to radius, increase and fluid is expelled with increasing velocity from the neck. As the neck radius vanishes, the governing equations become singular and the filament breaks. In slightly viscous liquids, thinning initially occurs in an inertial regime where inertial and capillary forces balance. By contrast, in highly viscous liquids, initial thinning occurs in a viscous regime where viscous and capillary forces balance. As the filament thins, viscous forces in the former case and inertial forces in the latter become important, and theory shows that the filament approaches breakup in the final inertial–viscous regime where all three forces balance. However, previous simulations and experiments reveal that transition from an initial to the final regime either occurs at a value of filament radius well below that predicted by theory or is not observed. Here, we perform new simulations and experiments, and show that a thinning filament unexpectedly passes through a number of intermediate transient regimes, thereby delaying onset of the inertial–viscous regime. The new findings have practical implications regarding formation of undesirable satellite droplets and also raise the question as to whether similar dynamical transitions arise in other free-surface flows such as coalescence that also exhibit singularities.Drop formation is ubiquitous in daily life, industry, and nature (1–3). The phenomenon is central to inkjet printing (4, 5), dripping from leaky faucets (6, 7), measurement of equilibrium and dynamic surface tension (8, 9), DNA arraying and printing of cells (10, 11), chemical separations and analysis (12, 13), production of particles and capsules (14, 15), printing of wires and transistors (16, 17), and mist formation in waterfalls and fragmentation of raindrops (18, 19). Fig. 1A shows an experimental setup for studying the dynamics of a drop of an incompressible Newtonian fluid of density ρ, viscosity μ, and surface tension σ forming from a tube of radius R (Fig. 1B and Drop Formation from a Tube and Filament Thinning). A salient feature of, and key to understanding, drop formation is the occurrence of a thin filament that connects an about-to-form primary drop to the rest of the fluid that is attached to the tube (Fig. 1 B and C). Thus, it often proves convenient to study filament thinning in the idealized setup depicted in Fig. 1D (Drop Formation from a Tube and Filament Thinning). As time t advances and the filament radius decreases, curvature and capillary pressure, both of which are at leading order inversely proportional to radius, increase and fluid is expelled with increasing velocity from the neck. At the instant t = t_b when the neck radius vanishes, a finite time singularity occurs and the filament breaks. When the filament breaks, one or more satellite droplets may also form. These satellites are typically much smaller than the primary drop (20) and almost always undesirable in applications (2).Open in a separate windowFig. 1.Methods used for studying and new phase diagram for capillary thinning and pinch-off. (A) Experimental setup used to capture images of the thinning neck of a drop forming from a nozzle. The images are then postprocessed to obtain the minimum neck radius as a function of the time remaining until breakup. (B) Snapshot of a drop forming from a tube that highlights the pinching zone in the vicinity of the pinch point. (C) Two series of images that focus on the pinching zones and depict the evolution in time of thinning filaments for drops of two fluids with different viscosities (i.e., different Oh). (D) Setup for simulating filament thinning and pinch-off: periodically perturbed jet (Left) and domain of axial length λ/2 used in simulations (Right). (E) Phase space showing trajectories taken by filaments of a slightly viscous (Oh < 1) and a highly viscous (Oh > 1) fluid. The large squares indicate the starting states at t = 0. The arrows along each trajectory show the direction of evolution.For Newtonian filaments, three theories have been developed to describe the dynamics in the vicinity of the pinch-off singularity (Scaling Theories of Pinch-Off). When viscous effects are weak, thinning and pinching occur in an inertial (I) regime (21–23) where inertial and capillary forces balance, and the minimum filament radius h_min (Fig. 1B) and the instantaneous Reynolds number Re(t) vary with dimensionless time τ to breakup ashminR∼τ2/3, Re(t)∼1Ohτ1/3,[1]where τ ≡ (t_b ? t)/t_I and tI≡ρR3/σ (Scaling Theories of Pinch-Off). For real liquids, the Ohnesorge number Oh=μ/ρRσ is not identically zero no matter how small the viscosity. Thus, for low-viscosity liquids, Oh ? 1 and Eq. 1 shows that regardless of how large the Reynolds number is initially, as τ → 0 and breakup is approached, Re(t) → 0. Therefore, the inertial regime cannot persist all of the way to breakup and can only describe the initial dynamics for low-viscosity fluids. Similarly, when viscous effects are dominant, thinning and pinching occur in a viscous (V) regime (24) where viscous and capillary forces balance, and h_min and Re(t) vary with τ ashminR∼τ, Re(t)∼1Oh2τ2β−1,[2]where τ ≡ (t_b ? t)/t_V, t_V ≡ μR/σ, and β = 0.175 (Scaling Theories of Pinch-Off). For real liquids, Oh cannot be infinite no matter how large the viscosity. Thus, for high-viscosity liquids, Oh ? 1 and Eq. 2 shows that regardless of how small the Reynolds number is initially, as τ → 0 and breakup is approached, Re(t) → ∞. Therefore, the V regime cannot persist all of the way to breakup and hence can only describe the initial dynamics even for high-viscosity fluids. Therefore, as the filament radius tends to zero, a transition occurs from either the I or the V regime to a final inertial–viscous (IV) regime in which all three forces, i.e., inertial, viscous, and capillary, balance and the instantaneous Reynolds number Re(t) ～ 1 (25). From Eqs. 1 and 2, the transition from the I to the IV regime and that from the V to IV regime can be calculated by setting Re(t) to be order one. Thus, transition from the I to the IV regime should occur when (2, 18)h_min/R ～ Oh², [3]and that from the V to the IV regime should occur when (2, 18)h_min/R ～ Oh^2/(2β?1).[4]However, whereas careful simulations and experiments have shown that the transition from the I to the IV regime does indeed occur, it has been found to take place for values of h_min that are about an order of magnitude smaller than that predicted from theory (Eq. 3) (26). Furthermore, the transition from the V to the IV regime has not yet been demonstrated to occur from simulation and an attempt for an experimental demonstration of the transition (27) was perhaps at too small a value of Oh (Oh = 0.49) to be conclusively in the V regime. In this paper, we demonstrate that in contrast with the conventional wisdom that the dynamics of capillary pinching should exhibit a transition from either the I to the IV regime or the V to the IV regime, the transition from either of the two initial regimes to the final IV regime is in fact more complex and, unexpectedly, can be delayed by the occurrence of a number of intermediate transient regimes as shown in Fig. 1E. The possibility of such complexity has been anticipated in part by Eggers (18) but no study has yet been carried out to explore the existence of these intermediate regimes or contemplate its implications in other free-surface flows exhibiting finite time singularities.In this work, the dynamics of filament thinning is studied both numerically and experimentally. Simulations are performed to track how sinusoidal perturbations on a liquid cylinder cause it to break, which have been successfully used in the past to study pinch-off and scaling for Newtonian (26, 28) as well as non-Newtonian fluids (29, 30) (Fig. 1D and Simulations). In the experiments, high-speed imaging and image analysis are used to measure the evolution in time of the minimum filament radius for liquids dripping from a tubular nozzle. Glycerol–water mixtures are used as working fluids to explore systems with different values of Oh.Fig. 2A shows the computed variation of h_min with τ for a slightly viscous liquid of Oh = 0.23. The simulations make plain that after sufficient time has passed so that the initial transients have decayed, the filament first thins in the I regime, where h_min ～ τ^2/3, as expected. According to conventional wisdom, the thinning dynamics is expected to transition from the I regime to the IV regime when h_min ～ Oh² = 0.053; thenceforward, the thinning is to follow IV scaling where h_min = 0.0304τ/Oh. However, the simulation results show that this transition is delayed and does not take place until h_min has fallen below a value that is about an order of magnitude smaller than that predicted by the theoretical estimate. Moreover, the simulations show unexpectedly that the dynamics switches over from the I to the IV regime only after passing through an intermediate V regime, where h_min = 0.0709τ/Oh. The existence of these regimes can be verified by plotting the local Reynolds number Re_local (Simulations) in the thinning filament in the vicinity of the pinch point as a function of h_min (Fig. 2B). Fig. 2B clearly shows that at early times when h_min ≈ 0.2, Re_local ? 1, confirming the existence of the I regime. However, when h_min has fallen to  ≈ 0.03, Re_local ? 1, which clearly demonstrates that the dynamics has entered the newly discovered intermediate V regime. Finally, as the filament asymptotically approaches breakup, i.e., for values of h_min ≈ 10^?3 or smaller, Re_local ～ 1, demonstrating that near the singularity, all three forces (viz., inertial, viscous, and capillary) balance each other and the dynamics lies in the IV regime. To confirm the correctness of these computationally made predictions, dripping experiments have been carried out with two liquids of Oh = 0.23 and Oh = 0.55. For the former, Fig. 2C shows the transition from the initial I regime to the intermediate V regime, with the latter regime lasting nearly over two decades in h_min. When Oh = 0.23, it is not possible to observe the transition from the V regime to the final IV regime because that transition occurs for neck radii smaller than a micrometer, which is the lower limit of length scales that can be imaged using visible light. The experimental results for Oh = 0.55 depicted in Fig. 2D, on the other hand, do show the transition to the final IV regime, albeit with an intermediate V regime of much shorter duration.Open in a separate windowFig. 2.Simulations and experiments demonstrating the existence of an intermediate viscous regime between the initial inertial regime and the final IV regime for slightly viscous fluids (Oh < 1). (A) Variation of minimum neck radius with time until breakup when Oh = 0.23 obtained from simulations. (B) Computed variation with minimum neck radius of the local Reynolds number in the neighborhood of the pinch point verifies the existence of all three regimes: Re_local ? 1 in the I regime, Re_local ? 1 in the V regime, and Re_local ～ 1 in the IV regime. (C) Experimental confirmation of the existence of an intermediate V regime when Oh = 0.23. The IV regime is not attained here because of optical limitations. (D) At a slightly higher value of Oh than that in C (Oh = 0.55), the V to IV transition is observed experimentally. (C and D, Insets) Same data as in the main figures are presented but use linear rather than logarithmic axes.Having demonstrated the existence of the intermediate V regime, we now turn our attention to understanding the reason for its occurrence, which is facilitated by examining flow fields within thinning filaments. To do so, we turn our attention to a filament of Oh = 0.07 which, as shown in Fig. 3A, clearly depicts the existence of all three scaling regimes. The instantaneous streamlines and pressure contours at three different times when the dynamics lies in each of these three regimes are shown in Fig. 3 B–D over 0 ≤ z ≤ λ/2 ≡ 4. At early times, the minimum in the filament radius is located at z = λ/2 ≡ 4, i.e., halfway between two swells, one located at z = 0 and the other at z = λ ≡ 8 (Fig. 3B). As the filament continues to thin, the fluid accelerates as it flows from the neck, where pressure is highest, toward the two swells, where pressure is lowest. On account of this effect, which is attributable to finite fluid inertia (20, 22), the filament begins to thin fastest at two locations that are located on either side of z = λ/2. Within the computational domain, this leads to a shift in the minimum radius from the end of the domain (z = 4) to its interior, i.e., z ≈ 1.95. As shown in Fig. 3C, the occurrence of this new minimum gives rise to a new stagnation zone in the interior of the domain in the vicinity of which the flow has slowed down considerably and even reversed. This shift in the location of h_min and the accompanying slowing down of the flow then takes the dynamics into the V regime. Although the new stagnation zone persists for some time, the filament does not break while in the V regime. The capillary pressure which continues to rise as the filament continues to thin accelerates fluid out of the thinning neck and causes inertia to become significant once again, thereby taking the filament into the IV regime. Hence, with the simulation and experimental results shown in Figs. 2 and ​and3,3, the thinning and breakup dynamics of slightly viscous filaments for which Oh < 1 are seen to exhibit I to V to IV scaling as τ → 0. Furthermore, these results at long last shed light on the reason for the delay in the transition to the final IV regime that had remained perplexing and unexplained for over a decade.Open in a separate windowFig. 3.Simulation results when Oh = 0.07 highlight the formation of a stagnation zone within the filament and help explain why the intermediate viscous regime exists. (A) Variation of minimum neck radius with time until breakup that shows occurrence of all three regimes and transition from I to IV regime through an intermediate V regime. (See below for the explanation of the arrow.) (B) Instantaneous streamlines and pressure contours within the thinning filament when the dynamics lies in the I regime. As shown in the figure, this I regime has a slender geometry (21) rather than a fully developed double-cone structure (23). The legend on the top right identifies contour values of the pressure. At this instant in time, the minimum neck radius is located at z = λ/2 = 4 and the fluid accelerates as it flows from the neck to the swell. (C) Instantaneous streamlines and pressure contours in the filament at a later time than in B where the acceleration of the fluid has resulted in shifting of the neck from the top end of the domain (z = 4) to a location between the two ends (0 < z < 4). The time and minimum filament radius when this shift commences is identified by the arrow in A. (Inset) A new stagnation zone has formed away from the two ends, resulting in a region of reversed flow and the slowing down of the flow in the vicinity of the new minimum in filament radius. (D) The stagnation zone persists but because of the large capillary pressures that develop as the neck continues to thin, fluid is once more accelerated as it flows away from the neck. Thus, inertial forces come into play again and compete with viscous and capillary forces in setting the final fate of the filament.Having clarified the heretofore inadequately understood thinning dynamics of slightly viscous fluids of Oh < 1, we next show that highly viscous fluids of Oh > 1 exhibit even more subtle behavior during capillary thinning. Fig. 4 shows results of simulations and experiments for a fluid of Oh = 1.81. As expected, both simulations (Fig. 4A) and experiments (Fig. 4B) reveal that the initial and final scaling regimes are the V and IV regimes. Conventional wisdom dictates that the transition from the V to the IV regime should occur when h_min ～ Oh^2/(2β?1) = 0.162, which is contradicted by both simulations and experiments. The simulations show (Fig. 4A), and experiments confirm (Fig. 4B), that there exists an intermediate I regime that follows the initial V regime. Local Reynolds number calculations near the pinch point from the simulations are yet even more revealing (Fig. 4C): they show the existence of an intermediate V regime that lies between the intermediate I and the final IV regime. Therefore, according to Fig. 4, the capillary thinning of highly viscous filaments for which Oh > 1 is seen to transition from V to I to V to IV regimes as τ → 0. Furthermore, it is worth noting that Fig. 4A depicts, to our knowledge, the first demonstration by simulation of the transition from an initial V regime to the final IV regime.Open in a separate windowFig. 4.Simulations and experiments demonstrating the existence of several intermediate regimes between the initial viscous regime and the final IV regime for a highly viscous fluid of Oh = 1.81. (A) Computations show that as the filament thins, the dynamics transitions from an initial V regime to the final IV regime through an intermediate I regime (but see C). (B) Experiments accord with the predictions from simulations and exhibit the same transition dynamics. (C) However, local Reynolds number calculations from the simulations reveal more information about the transitions. Whereas the initial V, intermediate I, and final IV regimes are confirmed from the computed variation of Re_local with h_min, this analysis also indicates the existence for a very short time of an intermediate V regime after the I regime.In conclusion, our analysis provides, to our knowledge, the first correct trajectories in the phase space of (h_min, Re_local) that are taken by filaments as they undergo capillary pinching. A particularly interesting finding is that the dynamics cannot reach the asymptotic universal IV regime directly from the I regime without passing through an intermediate transient V regime even though this latter regime may be very short-lived. The presence of the intermediate V regime indicates that even for a low-viscosity fluid, at some stage viscous force (along with capillary force) will dominate the dynamics during filament thinning and breakup. The existence of intermediate regimes has several practical implications as occurrence of slender threads that pinch symmetrically at their midpoints is associated with breakup of highly viscous filaments undergoing creeping flow, whereas occurrence of satellites is associated with inviscid fluids (20, 23, 24, 30). Therefore, the presence of the intermediate I regime makes plain that a visible satellite drop may form even during breakup of highly viscous filaments that reach the IV regime for values of h_min below the limit set by visible light. Additionally, the existence of multiple regime transitions before a filament enters the final IV regime helps explain why it has heretofore proven difficult to observe this regime during pinch-off of highly viscous filaments.The unexpected findings of this work raise a number of questions. Two issues that have not been addressed here are that the amount of time spent by filaments in each regime remains unclear and that similar transitions that may take place during capillary pinching of complex fluids (29, 30) remain unexplored. Moreover, it is well known that there are a number of other free-surface flows that exhibit finite time singularities. Chief among these is the coalescence singularity that arises when two drops are just allowed to touch and then merge into one (31). Whether transitions of the sort uncovered in this work exist in problems like coalescence are worthy topics for future study and may help explain why it took over a decade to uncover the true asymptotic regime of coalescence (31, 32).