The Pathogenesis of Idiopathic Hypercalciuria: Evidence for Renal Tubular Calcium Leak

A standard oral calcium loading test has been employed in agroup of idiopathic hypercalciuria (IH) subjects and in a groupof marginally hypercalcaemic subjects with primary hyperparathyroidism(PHPT) in whom the diagnosis was revealed by careful combinedmeasurements of serum ionized calclum and immuno-reactive parathyroidhormone (iPTH). Initial values for serum ionized calcium andcreatinine clearance were similar in IH and in a control groupof normal subjects, whereas iPTH levels were normal or low.Following oral loading, serum ionized calcium rose to similarlevels in both IH and control subjects, with no suggestion ofrelative hypercalcaemia due to a postulated intestinal hyperabsorptionin the IH group. A renal tubular calcium ‘leak’was however clearly evident in the IH group, in both the fastingand post-absorptive phase. In the marginally hypercalcaemic PHPT subjects on the otherhand, a relative postabsorptive hypercalcaemia was clearly apparent,as well as a gross renal tubular calcium leakage. Thus careful preliminary separation of masked PHPT from IH subjectsis an essential step before cvaluadon of response to oral calciumchallenge in stone-forming subjects. When this is done, no evidenceof a relative post-absorptive hypercalcaemia can be seen inthe residual IH group, and hypercalciuria appears to be ‘renal’rather than ‘absorptive’ in origin.     

Evidence for Secondary Hyperparathyroidism in Idiopathic Hypercalciuria

Circulating levels of immunoreactive parathyroid hormone (PTH) were measured in 40 patients with idiopathic hypercalciuria (IH) before and during reversal of hypercalciuria with thiazide, and in four normal subjects before and during induction of hypercalciuria with furosemide. 26 patients with IH had elevated serum PTH levels. The remaining patients had normal levels. Although the correlation was not complete, high PTH levels were generally found in patients who had more severe average urinary calcium losses. When initially elevated. PTH levels fell to normal or nearly normal values during periods of thiazide administration lasting up to 22 months. When initially normal, PTH levels were not altered by thiazide. Reversal of hyperparathyroidism by thiazide could not be ascribed to the induction of hypercalcemia, since serum calcium concentration failed to rise in a majority of patients. Renal hypercalciuria produced by furosemide administration elevated serum PTH to levels equivalent to those observed in patients with IH.The findings in this study help to distinguish between several current alternative views of IH and its relationship to hyperparathyroidism. Alimentary calcium hyperabsorption cannot be the major cause of IH with high PTH levels, because this mechanism could not elevate PTH. Idiopathic hypercalciuria cannot be a variety of primary hyperparathyroidism, as this disease is usually defined, because PTH levels are not elevated in all patients and, when high, are lowered by reversal of hypercalciuria. Primary renal loss of calcium could explain the variable occurrence of reversible hyperparathyroidism in IH, since renal hypercalciuria from furosemide elevates serum PTH in normal subjects. Consequently, a reasonable working hypothesis is that IH is often due to a primary renal defect of calcium handling that leads, by unknown pathways, to secondary hyperparathyroidism.     

Effects of Haemodialysis on Fractional Intestinal Absorption of Calcium in Uraemia

Fractional intestinal absorption of calcium was measured in 41 haemodialysed patients 4 hours after an oral dose of 47 Ca. Fractional intestinal calcium absorption was 40.3 ± 1.9% (SEM) when measured 10 to 12 hours after a haemodialysis session (dialysate calcium concentration: 1.75 mmol/litre). This value was significantly lower (p < 0.001) than that in 26 healthy controls (56.8 ± 1.8%) and higher (p < 0.05) than that of 3 5 patients with chronic renal failure treated conservatively (34.5 ± 2.1%). In 17 patients, fractional intestinal calcium absorption was measured just before and just after a dialysis session. Pre-dialysis fractional intestinal calcium absorption (33.7 ± 3.0%) was not significantly different from fractional intestinal calcium absorption in uraemic patients treated conservatively, while after dialysis fractional intestinal calcium absorption had increased significantly to 42.0 ± 2.6% (p < 0.001). It is suggested that the transient increase in fractional intestinal calcium absorption observed after dialysis could be related to dialysis induced volume depletion rather than to a vitamin D-dependent mechanism.     

Effect of Dietary Calcium and Age on Jejunal Calcium Absorption in Humans Studied by Intestinal Perfusion

Jejunal calcium absorption was measured from test solutions containing 1.0, 2.5, 5, and 10 mM calcium (as calcium gluconate). Absorption rates increased progressively as luminal calcium concentration was increased, although there was a tendency toward saturation of the absorptive process at the higher concentrations. Calcium absorption was higher in normal young adults than in normal subjects over age 60. In both groups a 300 mg calcium diet for 4-8 wk enhanced calcium absorption relative to absorption rates after 4-8 wk on a 2,000 mg calcium diet. This adaptation was more definite and dramatic in the young than in the old subjects. Indirect estimates suggest that adaptation to a low calcium diet and the higher absorption in young than old normal subjects are mediated by an increased V_max rather than a decreased K_m.     

Jejunal Absorption and Secretion of Calcium in Patients with Chronic Renal Disease on Hemodialysis

10 patients with chronic renal disease on hemodialysis and 8 normals were studied by constant jejunal perfusion of calcium gluconate solutions, using polyethylene glycol as a nonabsorbable marker. Results in normals indicated that calcium absorption from 1 and 5 mM calcium solutions is mainly active. Absorption from 5, 15, and 20 mM solutions was a linear function of luminal calcium concentration, suggesting that the active transport carrier is saturated when luminal calcium concentration is greater than 5 mM and indicating that the increment in absorption at higher luminal concentrations is mainly the result of passive absorption. With 1 mM calcium, normals absorbed calcium against a concentration gradient, whereas the patients secreted calcium. Absorption in the patients was much less than normal with 5, 15, and 20 mM luminal calcium concentrations; however, the slope of this linear (passive) portion of the curve was normal. Unidirectional calcium fluxes were measured with calcium-47. Flux out of the lumen was depressed 2.5-fold in the patients, but flux into the lumen was normal. Xylose, urea, and tritiated water were absorbed normally, indicating no generalized abnormality of jejunal transport in these patients. Endogenous calcium secretion, estimated by the amount of calcium added to a calcium-free solution, was normal in the dialysis patients. These results indicate that active calcium absorption is markedly depressed in patients with chronic renal disease who are receiving hemodialysis therapy. On the other hand, passive calcium movement and endogenous calcium secretions are normal.     

Intestinal Calcium Absorption and Serum Vitamin D Metabolites in Normal Subjects and Osteoporotic Patients: EFFECT OF AGE AND DIETARY CALCIUM

Intestinal calcium absorption assessed by a double-isotope method, decreased significantly with aging in 94 normal subjects (r = -0.22, P < 0.025). In 52 untreated patients with postmenopausal osteoporosis, calcium absorption was significantly lower than normal when either age or habitual calcium intake was used as a covariable (P < 0.001). Serum 25-hydroxyvitamin D (25-OH-D) and 1,25-dihydroxyvitamin D (1,25(OH)(2)D) were measured in 44 normal subjects and 27 osteoporotic patients. For all normals, calcium absorption and serum 1,25(OH)(2)D were positively correlated (r = 0.50, P < 0.001). In nonelderly normal subjects (ages 30-65 yr), dietary calcium intake correlated inversely with both calcium absorption (r = -0.39, P < 0.01) and with serum 1,25(OH)(2)D (r = -0.50, P < 0.01). Both osteoporotic patients and elderly normal subjects (ages 65-90 yr) differed from nonelderly normals in that these correlations were not present. In addition although serum 25-OH-D was normal, serum 1,25(OH)(2)D was significantly decreased in both osteoporotic patients and elderly normals (P < 0.001). In osteoporotic patients, calcium absorption increased significantly (P < 0.001) after 7 d administration of a small dose (0.4 mug/d) of synthetic 1,25(OH)(2)D(3). In osteoporotics mean serum immunoreactive parathyroid hormone was either normal (COOH-terminal assay) or low (NH(2)-terminal assay) relative to age-matched controls, and mean serum phosphate was increased.The data suggest that inadequate metabolism of 25-OH-D to 1,25(OH)(2)D contributes significantly to decreased calcium absorption and adaptation in both osteoporotics and elderly normal subjects. In patients with osteoporosis this abnormality could result from a decrease in factors that normally stimulate 1,25(OH)(2)D production, such as the decreased parathyroid hormone secretion and increased serum phosphate demonstrated in this group. In elderly subjects a primary abnormality in metabolism of 25-OH-D to 1,25(OH)(2)D, analagous to that seen in aging rats, cannot be excluded.     

Intestinal Calcium Absorption in Exogenous Hypercortisonism: ROLE OF 25-HYDROXYVITAMIN D AND CORTICOSTEROID DOSE

Pharmacologic doses of corticosteroids impair intestinal calcium absorption and contribute to negative calcium balance. However, the relationship between the impaired calcium absorption and a possible defect in the conversion of vitamin D to its physiologically active form, 1,25-dihydroxyvitamin D, is unknown. We compared fractional calcium absorption (double-isotope method, 100-mg carrier) and serum 25-hydroxyvitamin D (25-OH-D) (Haddad method) in 27 patients receiving pharmacologic doses of prednisone with 27 age-, sex-, and season-matched normal subjects. In patients receiving high daily doses of prednisone (15-100 mg/day), calcium absorption (P < 0.02) and serum 25-OH-D (P < 0.001) were decreased. However, in patients receiving low doses (8-10 mg/day) or high doses (30-100 mg) of prednisone on an alternate-day schedule, both of these parameters were normal. Calcium absorption in the patients treated with daily prednisone correlated inversely with the dose of corticosteroids (r = −0.52, P < 0.025) and, in all steroid-treated patients, correlated directly with serum 25-OH-D (r = 0.58, P < 0.01). In four patients who received high-dose corticosteroid therapy for an average of 4 wk, serum 25-OH-D decreased by 35.5% from pretreatment values. Administration of a physiologic or near-physiologic dose of synthetic 1,25-dihydroxyvitamin D₃ (0.4 μg daily for 7 days) to patients receiving high-dose corticosteroids led to an increase in calcium absorption in all patients. These results suggest that calcium malabsorption in the corticosteroid-treated patients is due to a dose-related abnormality of vitamin D metabolism and not to a direct effect of corticosteroids on depressing transmucosal intestinal absorption of calcium.     

特发性脊柱侧凸患者社会生活质量自我评价的调查

目的对特发性脊柱侧凸患者外科手术后社会生活质量问题进行调查研究。方法对本组54例接受脊柱侧凸矫正手术患者,30例(失访<2次)作为本次追踪调查的对象,其中男4例、女26例,年龄平均16岁,侧凸cobb角平均65°。参考美国脊柱侧凸研究会22项脊柱侧凸社会生活质量调查问卷,结合汉语的语言特点和青少年的接收能力编制成20项社会生活质量问卷调查表,进行术前、术后3个月、术后6个月、术后12个月社会生活质量问卷调查,并根据术后不同时间各项调查结果,进行统计分析(组间t检验)。结果术后3个月社会生活能力明显下降(P<0.0001),但6个月后恢复至术前水平;术后3个月疼痛程度明显加剧(P<0.01),但术后6个月、12个月与术后3个月比较明显减轻(P<0.01);术后3~12个月自我形象评价均比术前明显提高(P<0.0001);术前、术后3个月心理健康自我评价较低,无显著差异(P>0.05),术后6~12个月明显提高(P<0.01);术后3~12个月患者自我认可评分均处于较高水平,相互比较无显著性差异(P>0.05)。结论脊柱侧凸患者社会生活质量自我评价在术后1年内不同阶段发生了变化,提出对脊柱侧凸患者进行院内及短期院外健康教育、心理干预的重要性。     

影响特发性肺纤维化治疗和预后的常见合并症

特发性肺纤维化(idiopathic pulmonary fibrosis, IPF)是一种慢性进展性致纤维化性疾病, 预后极差。IPF以中老年男性多见, 容易出现多种临床合并症, 包括肺气肿、肺癌、心血管疾病等。存在合并症的IPF患者临床症状更多、预后更差。本文详细阐述影响特发性肺纤维化治疗和预后的常见合并症, 以期提高临床对于IPF合并症的认识和诊疗水平, 从而改善IPF患者的生活质量及预后。     

矫形鞋垫对青少年特发性脊柱侧弯患者脊柱畸形和步行的改善效果

目的 观察侧弯支具联合矫形鞋垫对青少年特发性脊柱侧弯(AIS)患者脊柱畸形和步行表现改善的效果.方法 2019年9月至2020年9月,门诊AIS患者42例随机分为支具组(n=21)和支具联合矫形鞋垫组(n=21).两组均每天佩戴支具22～23 h,矫正体操每天1次,每天30 min,共2个月.支具联合矫形鞋垫组在此基础...     

早期肠内营养对急性重症胰腺炎患者肠源性感染的影响研究

目的探究早期肠内营养对急性重症胰腺炎患者肠源性感染的影响。方法选取2013年1月~2014年1月在我院确诊为急性重症胰腺炎肠源性感染的患者100例作为研究对象,按照随机数字表法将患者分为对照组和观察组,每组50例患者,对照组采用肠外营养治疗,观察组采用肠内营养治疗,对两组的影响结果进行比较分析。结果两组患者治疗后除血清淀粉酶外,其他临床指标两组比较具有显著性差异(P0.05),观察组患者治疗后的不良反应的发生率(14.00%)明显低于对照组患者治疗后的不良反应发生率(40.00%),具有统计学意义(P0.05)。结论对急性重症胰腺炎患者肠源性感染的情况采用早期肠内营养治疗有很好的临床疗效,对患者临床指标的恢复有较好的作用,可以减少不良反应的发生率,为患者减轻痛苦有较好的临床价值,值得在临床中推广应用。     

低促性腺激素性性腺功能减退症患者胰岛功能评价

目的总结评价低促性腺激素性性腺功能减退症患者的胰岛功能。方法选取2009年11月-2010年9月期间我院收治的10例低促性腺激素性性腺功能减退症患者（IHH组）和10例正常体检者（对照组）为研究对象,分析比较性激素与胰岛功能之间的关系。结果 IHH组患者T、FSH、LH水平明显低于对照组,且差异具有统计学意义（P〈0.05）;IHH组空腹胰岛素、餐后2h胰岛素、HOMA-IR、HOMA-β等指标明显高于对照组,且差异具有统计学意义（P〈0.05）;性激素与胰岛功能呈负相关性。结论 IHH患者胰岛素水平高于正常人,且性激素越低者胰岛素水平越高。     

Abnormal Cardiac Innervation in Patients with Idiopathic Ventricular Fibrillation

BIFFI, M., et al .: Abnormal Cardiac Innervation in Patients with Idiopathic Ventricular Fibrillation. Idiopathic ventricular fibrillation (VF) is diagnosed in up to nearly 10% of survivors of out-of-hospital cardiac arrest. The arrhythmogenic substrate is unknown. This study examined the role of cardiac innervation as a possible contributor to this arrhythmia. Eight patients with idiopathic VF were compared with eight normal subjects (controls) by [¹²³] I metaiodobenzylguanidine SPECT (MIBG), measuring peak uptake, late uptake, and clearance of the nuclear tracer. The left ventricle was divided in 13 segments in the bull's-eye target plot. Peak and late MIBG uptake was increased in the anterolateral segments (2,3,7,8) compared to the inferoposterior and septal segments, in controls and in patients. No difference was observed between controls and patients in the inferoposterior and septal segments. In contrast, a significantly higher MIBG uptake was observed in patients compared to controls in the anterolateral segments (   94 ± 4%   vs   81 ± 11%, P < 0.03   for peak uptake;   94 ± 5%   vs   79 ± 12%, P < 0.01   for late uptake). No difference was observed in MIBG clearance in any segment in either study group. Cardiac sympathetic innervation is highly heterogeneous, though predominant in anterolateral segments in normal subjects. Patients with idiopathic VF exhibit the same distribution, though have a significantly greater density of sympathetic terminals in the anterolateral segments than controls, which may promote ventricular arrhythmias. (PACE 2003; 26[Pt. II]:357–360)     

特发性房颤患者心房电生理特点的临床观察

【目的】分析特发性房颤（idiopathic atrial fibrillation,IAF）患者与正常对照在基础状态及不同联律间期早搏刺激后心房有效不应期（effective refractory period,ERP）,不应期离散度（ERPdispersion,ER—PD）的差别,探讨IAF的发病机制。【方法】2005年4～7月住院的21例无器质性心脏痛室上性心动过速患者,其中6例伴有阵发性房颤。所有患者室上速射频消融成功后,程控刺激高右房（high right atrium,HRA）,冠状窦远端（coronary sinus distal,CSD）,测出上述两个部位基础刺激时（S1S1 500ms）心房ERP。保持基础刺激不变,分别给予不同联律间期的S2早搏刺激（S1S1不应期＋20ms,＋70ms,＋120ms,＋170ms）,通过发放S3测出不同S2早搏刺激后心房ERP。以基础及早搏刺激后HRA与CSD不应期的差值作为ERPD。【结果】6例IAF患者在HRA予S2早搏刺激（S1S1不应期＋20ms）时诱发房颤,HRA的ERP在基础及各种联律早搏刺激时明显短于对照组（P〈0．05）,CSD刺激时ERP两组无差别（P〉0．05）,IAF组ERPD较对照明显增大（P＜0．05）。（S1S1不应期＋20ms）的S2刺激较其他S2刺激使心房ERP缩短最为明显（P＜0．05）。【结论】HRA短ERP,增大的ERPD是IAF患者发病的电生理基础。短联律间期早搏刺激使ERP缩短更为明显,是房颤发作的始动因素。     

儿童特发性血小板减少性紫癜骨髓巨核细胞的研究

本研究观察特发性血小板减少性紫癫(ITP)患儿骨髓巨核细胞形态与造血功能的改变，初步分析其血小板减少的发生机制。采用巨核细胞CI41α单克隆抗体免疫酶标染色观察骨髓涂片中小巨核细胞的计数与分类，采用血浆凝块法体外培养骨髓单个核细胞，用免疫酶标法进行巨核细胞集落检测，计数巨核细胞集落形成单位(CFU—MK)和爆式巨核细胞集落形成单位(BFU—MK)。结果表明：ITP患儿骨髓小巨核细胞检出率与对照组无显著差异，而Ⅰ型淋巴样小巨核细胞很少见；小巨核细胞总数及CFU—MK和BFU—MK集落形成率明显高于对照组；在培养体系中可以观察到正在释放血小板的成熟的巨核细胞。发现1例慢性ITP患儿骨髓巨核细胞集落形成率降低。结论：Ⅱ、Ⅲ、Ⅳ型小巨核细胞增多是ITP的病理特征，这些小巨核细胞在体外培养条件下可发育成熟为正常的巨核细胞，并释放血小板；免疫损伤导致血小板减少及巨核细胞成熟障碍可能并不是ITP发病的唯一机制，部分病例尤其是慢性ITP，其发病可能与患者巨核细胞本身质的异常有关。     

Fractional Intestinal Absorption and Retention of Calcium Measured by Whole-Body Counting. Application of a Power Function Model

By application of a power function model, fractional intestinal calcium absorption was investigated with a new technique involving whole-body counting after successive oral and intravenous administration of standard doses of ⁴⁷Ca. The fractional calcium retention 7 days after the oral load of ⁴⁷Ca was also measured. Fractional calcium retention averaged 30.3% in normal subjects and 11.5% in 11 patients with intestinal malabsorption. In the same groups fractional calcium absorption averaged 46.6% and 16.4%, respectively. Fractional calcium retention and intestinal calcium absorption were significantly correlated to body surface area, and there was a welldefined relation between fractional retention and absorption of calcium. These studies demonstrate that measurements of fractional retention and fractional intestinal absorption of calcium can be combined by the use of a whole-body counter, that fractional retention and intestinal absorption are proportional to total body surface area and therefore probably also to the total bone mass, and that fractional retention and absorption are so closely interrelated that fractional absorption can be estimated from fractional retention with reasonable accuracy in normal subjects.     

脾切除治疗慢性特发性血小板减少性紫癜疗效观察

目的观察脾切除对特发性血小板减少性紫癜(ITP)的治疗效果。方法对1996年～2007年内科治疗无效的58例ITP患者行脾切除手术,并对其临床疗效进行观察。结果术后l周内血小板恢复正常(≥10&;#215;109/L)者45例(77.6%),术后2月随访总有效率82.7%(48/58)。术后50例获随访&;gt;6月,总有效率为80%(40/50),10例复发。结论对内科治疗无效或复发的ITP脾切除治疗有效,术后血小板回升较早者预后较好。     

Effects of 1,25-Dihydroxycholecalciferol on Intestinal Calcium Transport in Cortisone-Treated Rats

The administration of glucocorticoids may decrease intestinal calcium absorption in vivo and the active transport of calcium in rat duodenum in vitro. It has been suggested that this apparent "anti-vitamin D-like" effect of steroid hormones may be related to alterations in vitamin D metabolism. In order to test this hypothesis, vitamin D-deficient control and cortisone-treated rats were given an intraperitoneal injection of 5.5 IU of 1,25-dihydroxycholecalciferol (1,25-DHCC), the probable end-organ active vitamin D metabolite in the intestine, and 16 h later studies of duodenal calcium transport were performed in modified Ussing chambers. In the vitamin D-deficient state, cortisone administration was associated with a diminution in J(MS), J(Net), and the flux ratio (J(MS)/J(SM)). While the magnitude of the increases in J(MS) and J(Net) that resulted from 1,25-DHCC treatment were approximately the same in control and cortisone-treated animals, 1,25-DHCC failed to restore these parameters to "normal levels" in the steroid-treated rats. Furthermore, contrary to the results obtained in the saline-treated controls, 1,25-DHCC failed to reduce J(SM) in the duodenum from cortisone-treated rats. The cortisone-related defect in calcium transport was due to alterations in both unidirectional calcium fluxes (decrease in J(MS) and increase in J(SM)), such that the J(Net) and the flux ratio (J(MS)/J(SM)) were only approximately 50% of the levels achieved in vitamin D-deficient control animals repleted with the same dose of 1,25-DHCC.The administration of 1,25-DHCC was accompanied by a marked increase in the serum calcium levels of control rats, but there was no such response in the cortisone-treated group.The results support the concept that under the conditions of these experiments in the rat the apparent antagonism between glucocorticoids and vitamin D may be due to steroid hormone-related alterations in end organ function that are independent of any direct interaction between the hormone and the vitamin and that cannot be reversed by the vitamin.