A prospective study of local recurrence after resection and low stapled anastomosis in 183 patients with rectal cancer

Local recurrence is the most serious complication of anterior resection for rectal cancer, usually occurring during the first two years after surgery. Over a five-year period, from 1981 to 1986, 183 patients underwent anterior resection for rectal carcinoma at the Surgery Ward of the University of Ferrara. Patients were followed for two years postoperatively. All operations were performed with staplers and classified according to Dukes, with 43 cases of Dukes' A; 83 cases of Dukes' B; and 57 cases of Dukes' C. In the first 24 months after surgery, the tumor recurred locally in 44 of the 183 patients (24 percent. Dukes' stage, grading distal resection margin, and histopathologic differentiation of the distal rectal ring left in the stapler after anastomosis were assessed to determine a prognostic indicator for the recurrence of the tumor. The stage:recurrence ratio was as follows: A, 1 (2 percent); B, 21 (25 percent); and C, 22 (39 percent). The grading:recurrence ratio was: G1, 1351 (25 percent); G2, 24110 (22 percent); and G3, 722 (32 percent). The ratio between distal rectal resection margin and recurrence was: 0 to 2 cm, 1527 (56 percent); 2 to 4 cm, 1674 (22 percent); and over 4 cm, 1382 (15 percent). Histopathologic examination of the distal rectal ring was negative for all patients. These data confirm the direct relationship between class and local recurrence and indicate histologic grade and distal resection margin as significant prognostic parameters only when interpreted in the light of staging.     

Effects of short-term high dose intake of evening primrose oil on plasma and cellular fatty acid compositions, α-tocopherol levels,and erythropoiesis in normal and Type 1 (insulin-dependent) diabetic men

Summary In addition to their usual diet, nine Type 1 (insulin-dependent) diabetic men and ten male control subjects took 20 g d,ga-tocopheryl acetate enriched evening primrose oil (14.45 g 182c,6, 1.73g 183c,6, 400 mg d,-tocopheryl acetate) daily for one week. At start, diabetic patients had more 140, 150 and 18 2c,6, and less 160, 161c,7, 181c,7, 183c,6, 203c,9, 203c,6, 204c,6 and 226c,3 in plasma, erythrocytes and/or platelets. Furthermore, they had lower 161c,7/160, 181c,7/160, and 204c,6/203c,6 ratios and a higher 203c,6/183c,6 ratio. In diabetic patients, -tocopherol levels in erythrocytes were lower, whereas those in plasma were normal. In both groups, oil intake changed fatty acid profiles. Most markedly, 203c,6 increased, whereas the ratios 203c,6/ 183c,6 and 204c,6/203c,6 decreased. 204c,6 increased in control subjects, but not in diabetic patients. Erythrocytes and platelets responded differently in their fatty acid profiles, -tocopherol rose in plasma and, although less for diabetic patients, in erythrocytes. In diabetic patients as well as in control subjects, erythrocyte count, haemoglobin level, mean corpuscular haemoglobin content and concentration increased and glycosylated haemoglobin percentage decreased without an apparent decline in blood glucose levels. Plasma -thromboglobulin and platelet factor 4 decreased, especially in diabetic patients. In conclusion, diabetic patients had abnormal fatty acid patterns, suggesting an impaired 9, 6 and 5 desaturation and an enhanced chainelongation, and had lower erythrocyte a-tocopherol levels; and short-term high dose intake of evening primrose oil increased 203c,6 in both groups, but 204c,6 only in control subjects, gave fatty acid responses which were different for erythrocytes and platelets, enhanced erythropoiesis, and lowered indices of in vivo platelet activation.     

Colonic mucosal T lymphocytes in ulcerative colitis: Expression of CD7 antigen in relation to MHC class II (HLA-D) antigens

T-cell subsets and their activation state were examined by double-label immunofluorescence of cryostat tissue sections of the colon from 21 patients with ulcerative colitis (UC) and 30 histologically normal controls. Expression of MHC class I (HLA-A, B, C) and class II (HLA-D) antigens was studied in parallel. In the normal colonic mucosa, the CD4CD8 ratio in the epithelial compartment approximated 11, and in the lamina propria, 2.551. Of the CD8⁺ (cytotoxic/suppressor) subset, approximately half did not express the CD5 pan-T marker in either compartment. Virtually no Leu 8⁺ cells were observed, implying that the CD4⁺ subset consisted of helper, rather than suppressor-inducer cells. Classical markers of T-cell activation (CD25, HLA-D) and proliferation were absent, and strong expression of the CD7 immunostimulation marker was approximately equal in both CD4 and CD8 subsets. The epithelium was uniformly negative for class II antigens, but positive for class I. In UC, there were no significant alterations in CD4CD8 ratios in either compartment, and there were no changes with respect to phenotype of the subsets. In 11 of 19 patients (mainly with total colitis), enterocytes were HLA-D⁺. In this HLA-D⁺ group, there was an increase in the percentage of CD4⁺ cells coexpressing CD7; this difference was significant (P<0.02) in the lamina propria. Increased expression of CD7 was also found by the CD6⁺ T cell subset (P<0.05). These results suggest that class II expression is mediated by immunostimulated T helper cells in UC, with consequences for antigen presentation and maintenance of the chronic inflammatory state.HLA-D is used as a generic term for class II major histocompatibility complex (MHC) gene products (HLA-DR, DP, DQ) unless specified otherwise.     

Different ratio of myosin heavy chain isoforms in arterial smooth muscle of spontaneously hypertensive rats

Summary The relative proportion of the two putative heavy chains of smooth muscle myosin (MHC1 and MHC2) was determined in the caudal and femoral arteries of spontaneously hypertensive rats (SHR) and normotensive (WKY) rats at 16 weeks of age. The heavy chain polypeptides with M_r 204000 and 200000 were resolved electrophoretically under denaturing conditions in porous polyacrylamide gels. Both proteins reacted strongly with a monoclonal antibody (2C4) to smooth muscle MHC. In caudal arteries the ratio of MHC1/MHC2 was 3.11 in SHR rats compared with 1.81 in WKY rats (p<0.005) and similarly in femoral arteries, 2.81 vs 1.51 (p<0.001). In the portal vein there was no significant difference, 1.71 vs 1.51. The possibility that the higher MHC ratio in the SHR is the genetically mediated defect in arterial smooth muscle cells leading to the hypertension is discussed as an alternative to the elevated systemic blood pressure causing the altered MHC ratio.     

Gewinnung von Granulozyten zur Transfusion mit dem IBM-Blutzellseparator von gesunden Spendern

Zusammenfassung Durch Variation der mit dem IBM-Zellseparator zur Gewinnung von Leukozyten gebräuchlichen Methoden konnte gezeigt werden, daß die Antikoagulierung mit einer Kombination von Heparin und ACD, die Verwendung von Neoplasmagel^® sowie die Reduzierung des extrakorporalen Blutvolumens die besten Voraussetzungen zur Gewinnung von Granulozyten sind. So konnten von einem gesunden Spender in 6 h im Mittel (n=5) 1,6x10¹⁰ Granulozyten isoliert werden bei einem Reinheitsgrad von Granulozyten: Lymphozyten: Thrombozyten: Erythrozyten=11,211151. Die Ergebnisse konnten darüber hinaus durch Erhöhung der Granulozytenausgangszahl beim Spender mit Prednisolon gesteigert werden auf eine mittlere Ausbeute (n=5) von 5,6x10¹⁰ bei einem Reinheitsgrad von Granulozyten: Lymphozyten: Thrombozyten: Erythrozyten=10,23,240. Die Viabilität der isolierten Granulozyten wurde geprüft durch Untersuchung ihres Verhaltens nach Markierung mit DF³²P und autologer Transfusion. Gegenüber nicht isolierten, im Vollblut markierten Granulozyten zeigte sich beiobne Prednisolon isolierten Granulozyten eine Verminderung, beimit Prednisolon isolierten Granulozyten eine Erhöhung der Transfusionseffektivität.

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Summary By varying the common methods for separating leukocytes with the IBM cell separator the anticoagulation with a combination of Heparin and ACD, the use of Neoplasmagel^® as well as the reduction of the extracorporal blood volume have shown to be the best conditions to separate granulocytes. From 5 healthy donors a mean yield of 1.6x10¹⁰ granulocytes could be obtained during six h with a degree of purity of granulocytes: lymphocytes: thrombocytes: erythrocytes=11.211151. These results could be improved by increasing the count of granulocytes in the donor's blood with prednisolone in another 5 donors to a mean yield of 5.6x10¹⁰ with a degree of purity of granulocytes: lymphocytes: thrombocytes: erythrocytes=10.23.240. The viability of separated granulocytes was proved by investigating their circulation after labeling with³²P and autologous transfusion. Comparing with granulocytes which were not separated but labeled in fresh whole blood the effectivity of transfusion was diminished when separated granulocytes were transfused without stimulation with prednisolone and was increased when separated granulocytes were transfused after stimulation with prednisolone.

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Studie im Rahmen des Assoziationsvertrages EURATOM-GSF No. 031-64-I BIAD und des Sonderforschungsbereiches 37 der Universität München.     

Immediatevs. Salvage resection after local treatment for early rectal cancer

PURPOSE: There is an increasing awareness of local procedures to treat early stage rectal cancer. Abdominoperineal resection (APR) or low anterior resection (LAR) has been recommended if adverse pathologic findings are encountered in the local excision specimen. No data compare the impact on survival of immediate resection for adverse featuresvs. salvage resection for clinical recurrence. METHODS: We reviewed retrospectively 155 patients who underwent initial curative treatment of invasive rectal cancer by excision (91), snare-cautery (44), and fulguration (20). RESULTS: Twenty-one patients underwent APR/LAR immediately after initial local treatment, whereas another 21 patients underwent salvage APR/LAR for local recurrence. The disease-free survival after APR/LAR was 94.1 percent for the immediate group and 55.5 percent for the delayed group (P<0.05). CONCLUSION: This decreased survival observed after delayed resection supports the recommendation for immediate APR/LAR when adverse pathologic features are present in the excision specimen. Presented at the Annual Cancer Symposium of the Society of Surgical Oncology, New York, New York, March 15 to 18, 1992.     

Role of defecography in predicting clinical outcome of rectocele repair

PURPOSE: The aim of this study was to evaluate the role of defecography in predicting clinical outcome of rectocele repair. METHODS: Between January 1988 and July 1994, 74 consecutive patients (median age, 54 (range, 35–81) years) with a rectocele and symptoms of obstructed defecation were studied prospectively. After preoperative evaluation by a standardized questionnaire, physical examination, and defecography, a combined transvaginal/transanal rectocele repair was performed. At follow-up, all patients had defecography. Long-term results were qualified by an independent observer after a median follow-up of 58 (range, 14–89) months as excellent, good, or poor. RESULTS: Rectocele repair was considered excellent in 37 patients and good in 13 patients. Defecography six months after surgery did not show persistent or recurrent rectocele in any of the patients. Size of the rectocele, barium-trapping in the rectocele, internal intussusception, rectal evacuation, and perineal descent did not appear to influence clinical outcome. Radiologic evidence of anismus did not correlate with longterm results of rectocele repair. CONCLUSIONS: Combined transanal/transvaginal repair of rectocele is an efficient therapy in patients with obstructed defecation. Various defecographic parameters (size of rectocele, internal intussusception, rectal evacuation, perineal descent, radiologic signs of anismus) do not appear to influence clinical outcome of surgery. The main value of defecography is the objective demonstration of rectocele and any associated abnormalities such as an enterocele preoperatively and again in objective assessment of the postoperative results.     

Clinical and pathologic factors associated with delayed diagnosis in solitary rectal ulcer syndrome

Solitary rectal ulcer syndrome (SRUS) often goes unrecognized or is misdiagnosed. Of 98 patients with a final clinicopathologic diagnosis of SRUS, an initially incorrect diagnosis had been made in 25 patients (26 percent). In these 25 patients with a misdiagnosis, the median age was 43 years and the female-to-male ratio was 3.21. The median duration of incorrect diagnosis was five years (range, three months to 30 years), and seven patients received prednisone (>30 mg/day) for a mistaken diagnosis of inflammatory bowel disease. The main clinical symptoms were rectal bleeding (84 percent) and a disturbance of bowel function (56 percent). Rectal prolapse was present in 13 patients. Original rectal biopsy specimens from 23 patients were reviewed; inadequate specimens and failure to recognize diagnostic features of SRUS contributed to delayed diagnosis in 13 and 10 patients, respectively. The most common clinicopathologic mis-diagnoses in SRUS patients with rectal ulcers or mucosal hyperemia were Crohn's disease and mucosal ulcerative colitis. In patients with polypoid SRUS, diagnostic confusion was usually with a neoplastic polyp. Persistent bowel symptoms and rectal lesions led to review of the presentations and repeat biopsy directed toward the edge of the rectal ulcers or from within the polypoid or hyperemic rectal lesions, finally establishing the diagnosis of SRUS. Intractable symptoms led to surgery in 15 patients (60 percent), with symptomatic improvement in over two-thirds.     

Influence of insulin on cyclic 3′,5′-AMP phosphodiesterase activity in liver,skeletal muscle,adipose tissue,and kidney

Summary Influence of insulin on liver glycogen metabolism and on lipolysis appears to be mediated by a decreased intracellular 3,5-AMP concentration. Reduced formation of 3,5-AMP had been shown in adipose tissue incubated with insulin. The influence of insulin on 3,5-AMP degradation has been investigated. — 3,5-AMP phosphodiesterase (PDE) activity was reduced in liver, adipose tissue and, insignificantly, in skeletal muscle of insulin deficient, i.e. alloxan diabetic or starved rats. I.V. injection of a low dose of insulin (0.5 U/kg) or stimulation of endogenous insulin secretion by injection of glucose led to a rapid increase of PDE activity in these tissues. 15 min after insulin injection liver PDE activity was increased. The maximal effect occurred after 30–45 min. Renal PDE activity was not decreased in alloxan diabetes, insulin injection has been found ineffective. —In vitro, there was an activating effect of crystalline insulin on PDE purified from beef heart. Insulin concentration required for duplication of enzyme activity was of the order of 2 · 10^–5 M. Treatment with actinomycin D nearly prevented stimulation of liver PDE by insulin. This may indicate that the action of insulin on PDE activity is essentially based on an increased enzyme synthesis. — Owing to the influence of insulin secretion on liver and adipose tissue 3,5-AMP concentration, glycogen metabolism and lipolysis can be quickly adapted to food intake.

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Der Einfluß von Insulin auf die 3,5-AMP-Phosphodiesterase-Aktivität in Leber, Skeletmuskulatur, Fettgewebe und Niere

Zusammenfassung An der Steigerung der Glykogensynthese der Leber und der Verminderung der Lipolyse durch Insulin ist eine Abnahme der 3,5-AMP-Konzentration wesentlich beteiligt. Die 3,5-AMP-Bildung ist in Fettgewebe, das mit Insulin inkubiert wird, vermindert. Insulin beeinflußt jedoch auch den 3,5-AMP-Abbau. -Die 3,5-AMP-Phosphodiesterase (PDE)-Aktivität des Fettgewebes, der Leber und, in geringerem Grade, der Skeletmuskulatur ist im Insulinmangel vermindert, d.h. bei alloxandiabetischen oder hungernden Ratten. I.v. Injektion von 0,5 E/kg Insulin oder eine erhöhte Abgabe von Insulin aus dem Pankreas nach Glucoseinjektion führen in diesen Geweben zu einem raschen Anstieg der PDE-Aktivität. Dieser ist in der Leber schon 15 min nach Insulingabe nachweisbar und erreicht nach 30–45 min sein Maximum. In der Niere ist kein Einfluß von Insulin auf die PDE-Aktivität nachweisbar. — Aus Rinderherz isolierte PDE wirdin vitro durch Insulin aktiviert, jedoch werden2 · 10^–5 M zur Verdopplung der Aktivität benötigt. Actinomycin D verhindert die Steigerung der Leber-PDE-Aktivität nach Insulininjektion. So kann die Wirkung des Hormons im wesentlichen auf eine gesteigerte PDE-Synthese zurückgeführt werden. — Durch diesen Einfluß der Insulininkretion auf die 3,5-AMP-Konzentration in Leber und Fettgewebe können Glykogenstoffwechsel und Lipolyse rasch an die Nahrungsaufnahme angepaßt werden.

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Influence de l'insuline sur l'activité de la 3,5-AMP-phosphodiestérase dans le foie, le muscle strié, le tissu adipeux et le rein

Résumé L'influence de l'insuline sur le métabolisme du glycogène hépatique et sur la lipolyse semble s'exercer par l'intermédiaire d'une diminution de la concentration de 3,5-AMP intracellulaire. Onamontré une diminution de la formation de 35-AMP dans le tissu adipeux incubé avec de l'insuline. L'influence de l'insuline sur la dégradation du 3,5-AMP est étudiée. — L'activité de la 3,5-AMP-phos-phodiestérase (PDE) est diminuée dans le foie, le tissu adipeux et, de façon non-significative, dans le muscle strié des rats qui manquent d'insuline, c-à-d les rats rendus diabétiques par l'alloxane ou les rats privés de nourriture. L'injection intraveineuse d'une faible dose d'insuline (0.5 U/kg) ou la stimulation de la sécrétion d'insuline endogène par une injection de glucose provoquent une augmentation rapide de l'activité de la phosphodiestérase dans ces tissus. 15 min après l'injection d'insuline, l'activité de la phosphodiesterase du foie est augmentée. L'effet maximum est atteint après 30–45 min. L'activité de la phosphodiestérase rénale n'est pas diminuée dans le diabète alloxanique, l'injection d'insuline s'est avérée inefficace.In vitro, l'insuline cristalline a un effet activant sur la phosphodiestérase purifiée du coeur de boeuf. La concentration d'insuline requise pour doubler l'activité de l'enzyme est de l'ordre de 2 · 10^–5 M. Le traitement avec actinomycin D empêche la stimulation par l'insuline de la PDE dans le foie. Ceci peut indiquer que l'action de l'insuline sur l'activité de la phosphodiestérase est essentiellement basée sur une synthèse accrue de l'enzyme. A cause de l'influence de la sécrétion d'insuline sur la concentration en 3,5-AMP du foie et du tissu adipeux, le métabolisme du glycogène et la lipolyse peuvent s'adapter rapidement à la prise de nourriture.

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Non-Standard Abbreviations G 6 P Glucose-6-phosphate - UDPG UDP-glucose - FFA non-esterifled, free fatty acids - 3,5-AMP cyclic adenosine-3,5-monophosphate - PDE 3,5-AMP phosphodiesterase This study was supported by the Deutsche Forschungsgemeinschaft.Deceased October 31, 1967.     

Risk of human immunodeficiency virus (HIV) transmission by anti-HIV-negative blood components in Germany and Austria

In order to estimate the residual risk of transfusion-transmitted HIV infection we have analyzed the data from two transfusion centers in Austria (Vienna) and Germany (Göttingen) from 1985 to 1994. In Vienna, an incidence of 142000 positive anti-HIV tests in repeat donors and a prevalence of 17000 in first-time donors were found in 1993. In Göttingen, the indicence was 167000 and the prevalence 17900 from 1985 to 1993. Based on a mathematical model which takes (a) the window period and (b) the false-negative rate of anti-HIV tests, as well as (c) human and operational errors into consideration, we have calculated the residual risk of HIV infection. The residual risk (third generation anti-HIV test) was found to be 1520000 (95% confidence interval 11340000-1210000), and 1900000 (95% confidence interval 12340000-1380000) for Vienna and Göttingen, respectively, in 1993. Look-back studies from 1985 till 1994 revealed transfusion-transmitted HIV infections in three recipients (for 1.9 million donations in Vienna) and one recipient (for 160000 donations in Göttingen) of blood components. Based on our model, as well as on prevalence and incidence rates of HIV infection, it is also possible to predict the efficacy of additional measures introduced to further decrease the risk of transfusion-transmitted HIV infection through blood components.     

Bone marrow and peripheral blood globin chain biosynthesis in iron deficiency

Summary Globin chain synthesis was studied in 13 iron-deficient patients. The mean whole-cell globin / ratio in the peripheral blood of 11 patients was 1.05±0.06 which is similar to the value 0.99±0.08 obtained for 10 controls. The ratios odtained for stroma-free globin were not significantly different from those of whole cell preparations. In contrast, the / ratio of bone marrow was 0.73±0.14 in 10 iron deficient patients, which is significantly lower than that of controls. Two other patients had decreased / ratios in the peripheral blood, probably because of the presence of an -thalassemia gene. These results demonstrate a reduced rate of synthesis of chains relative to that of chains in the bone marrow of iron-deficient patients that is not demonstrable in the peripheral blood.This work was partly supported by Fundação de Amparo à Pesquisa do Estado de São Paulo, Brazil     

Weakened cellular scavenging activity against oxidative stress in diabetes mellitus: regulation of glutathione synthesis and efflux

Summary Glutathione functions to scavenge oxidants or xenobiotics by covalently binding them and transporting the resulting metabolites through an adenosine 5-triphosphate-dependent transport system. It has been reported that the intracellular concentration of glutathione decreases in diabetes mellitus. In order to elucidate the physiological significance and the regulation of anti-oxidants in diabetic patients, changes in the activity of the glutathione-synthesizing enzyme, -glutamylcysteine synthetase, and transport of thiol [S-(2,4-dinitrophenyl)glutathione] were studied in erythrocytes from patients with non-insulin-dependent diabetes and K562 cells cultured with 27 mmol/l glucose for 7 days. The activity of -glutamylcysteine synthetase, the concentration of glutathione, and the thiol transport were 77%, 77% and 69%, respectively in erythrocytes from diabetic patients compared to normal control subjects. Treatment of patients with an antidiabetic agent for 6 months resulted in the restoration of -glutamylcysteine synthetase activity, the concentration of glutathione, and the thiol transport. A similar impairment of glutathione metabolism was observed in K562 cells with high glucose levels. The cytotoxicity by a xenobiotic (1-chloro-2,4-dinitrobenzene) was higher in K562 cells with high glucose than in control subjects (50% of inhibitory concentration. 300±24 mol/l vs 840±29 mol/l, p<0.01). Expression of -glutamylcysteine synthetase protein was augmented in K562 cells with high glucose, while enzymatic activity and expression of mRNA were lower than those in the control subjects. These results suggest that inactivation of glutathione synthesis and thiol transport in diabetic patients increases the sensitivity of the cells to oxidative stresses, and these changes may lead to the development of some complications in diabetes mellitus.Abbreviations ATP Adenosine 5-triphosphate - NIDDM non-insulin-dependent diabetes mellitus - GSH -glutamylcysteinyl glycine - GSSG glutathione disulphide - -GCS -glutamylcysteine synthetase - mRNA messenger ribonucleic acid - DNA deoxyribonucleic acid - C₅₀ 50% inhibitory concentration - CDNB 1-chloro-2,4-dinitrobenzene - GS-DNP S-(2,4-dinitrophenyl)glutathione - PSL photostimulated luminescence     

Effect of β-adrenergic stimulation on free fatty acid content in subepicardial and subendocardial layers of the dog heart in situ. Separation and assay by capillary gas chromatography

Summary The effects of -adrenergic stimulation produced by an infusion of isoproterenol (1 g·kg^–1 min^–1, 30 min) were studiedin situ in the anaesthetized dog placed under a total cardiopulmonary bypass. Samples of the subepicardial and the subendocardial layers were homogenized separately prior to the extraction and methylation of free fatty acids (FFA). Gas chromatography on Carbowax 20 M capillary columns was used for the quantitation of myristic (C 140), palmitic (C 160), palmitoleic (C 161), stearic (C 180), oleic (C 181), linoleic (C 182), and arachidonic (C 204) acids.Within 5 min, isoproterenol decreased the tissue content of FFA significantly. The decrease was more pronounced in the endocardial layer where the FFA concentration reached its minimum at the 5th or the 15th min. In the epicardial layer, all the FFA reached their minimal concentration at the 30th min of the isoproterenol infusion. In both layers, lactate content remained unchanged at 5 and 15 min and rose at the 30th min only and content in phosphorylated compounds (ATP, creatine-phosphate—CP) did not show any significant variation during the -stimulation period. A significant correlation was found between the chronotropic effect of isoproterenol and the reduction of FFA concentration.With the technical assistance of Agnès Bacconin.     

Impaired alveolar gas exchange in acute pancreatitis

We evaluated the alveolar–arterial oxygen difference (A-a) and the ratio between P_ao₂ and the fractional concentration of inspired oxygen (P/F) in acute pancreatitis. Eleven patients had mild uncomplicated disease, six showed acute abdominal fluid collections, six had acute abdominal collections and asymptomatic x-ray lung involvement, three presented transient dyspneic episodes, and four had severe acute pancreatitis requiring prolonged oxygen therapy. In the uncomplicated disease, respiratory function was normal; in the six patients with abdominal collections only, A-a increased by 50% and P/F decreased by 20–30%; in the six patients with abdominal collections and asymptomatic x-ray lung involvement, A-a increased by 50–70% and P/F decreased by 40%; the three patients with dyspneic episodes showed a twofold increase in A-a and a 40% decrease in P/F; the four patients with severe pancreatitis had a two- to threefold increase in A-a and a 40–50% decrease in P/F. Hence respiratory function is normal only in uncomplicated pancreatitis; in the presence of complications, disturbance of gas exchange always occurs, requiring careful control and treatment.     

Ischemic colitis: Patterns and prognosis

We identified 47 patients with nonocclusive ischemia of the large intestine over a seven-year period. The mean age at presentation was 56.2 years, with a 221 male predominance. Associated medical illnesses were diabetes (17 percent), renal failure (5 percent), and hematologie disorders (5 percent). Six patients developed ischemic colitis after aortic surgery. The mean delay in diagnosis was 1.8 days (range, three hours to 23 days). The right colon was involved in 21 patients (46 percent). Overall, 15 of 16 patients were successfully treated non-operatively with bowel rest and antibiotics; one patient who was managed nonoperatively died. Among the 31 requiring intestinal resection, enteric continuity was reestablished in 14. Second-look laparotomy in eight patients revealed further ischemia in two (20 percent). Mortality in the operative group was 29 percent (9 of 31). No patient has developed recurrent ischemia (mean follow-up, 5.3 years). Ischemic colitis often occurs without an obvious predisposing event, may involve all segments of the large intestine, and frequently requires surgery. While its course may be self-limited, elderly and diabetic patients, as well as those developing ischemia following aortic surgery or hypotension, continue to have a poor prognosis.Read at the meeting of The American Society of Colon and Rectal Surgeons, Boston, Massachusetts, May 12 to 17, 1991.     

Colectomy for constipation: Physiologic investigation is the key to success

The results of total abdominal colectomy (TAC) with ileorectal anastomosis as a treatment for colonic inertia (CI) were prospectively assessed. One hundred sixtythree patients were evaluated for chronic constipation between July 1988 and November 1990. Patients underwent pancolonic transit times, anorectal manometry, cinedefecography (CD), and electromyography (EMG). CI was defined as diffuse marker delay on transit study without evidence of puborectalis contraction on CD or EMG. Sixteen patients (10 percent; 15 females and 1 male) with a mean age of 45 years (range, 24–75 years) with CI underwent TAC. Preoperative bowel frequency ranged from three per week to one per month; all 16 patients evacuated only with high doses of laxatives, enemas, or both. TAC was performed with no postoperative mortality or major morbidity; three patients were readmitted four times for successful conservative treatment of partial small bowel obstruction. At a mean followup of 15 months (range, 2–35 months), these 16 patients reported a mean frequency of spontaneous bowel evacuations of 3.5 per day (range, one to six per day). Patient satisfaction with the operation was excellent or good in 15 cases (94 percent). Thorough preoperative physiologic evaluation permits the selection of a small group of patients with CI who may benefit tremendously from TAC.Read at the meeting of The American Society of Colon and Rectal Surgeons, Boston, Massachusetts, May 12 to 17, 1991.     

K-value and low insulin secretion in a non-obese white population: predicted glucose tolerance after 25 years

Aims/hypothesis Insulin resistance and insulin deficiency are proposed as risk factors for IGT and type 2 diabetes. We assessed the predictive value of initial parameters for the outcome of an OGTT performed 24.3±2.9 years later in an unselected healthy non-obese population.Methods The K-value of an IVGTT was determined in 267 healthy subjects (mean±SD: age 31.0±12.0 years, BMI 21.8±2.8 kg/m²). First-phase insulin response to a glucose infusion test was estimated as an incremental 5- or 10-min (I5 or I10) value, and as insulinogenic indices (I5/G5 or I10/G10) adjusted for insulin sensitivity determined by homeostasis model assessment for insulin resistance ([I5/G5]/HOMA-IR).Results At follow-up, six subjects had type 2 diabetes and 47 had IGT; 214 retained normal glucose tolerance. Insulin sensitivity and early (30 min) insulin response decreased with decreasing outcome OGTT. Blood glucose (2 h) at OGTT correlated positively with initial age and BMI, and negatively with I5/G5, (I5/G5)/HOMA-IR and K-value. In multiple linear regression analysis, (I5/G5)/HOMA-IR, I10, K-value, age, HOMA estimate of insulin secretion, and fasting plasma glucose were significantly associated with 2-h OGTT blood glucose. Similar results were obtained on comparing differences between subjects with normal and decreased (IGT+diabetes) glucose tolerance.Conclusions/interpretation In 267 non-obese healthy subjects, initial K-value and first-phase insulin response to glucose adjusted for insulin sensitivity, but not insulin sensitivity itself, were strong predictors of the outcome of an OGTT performed 25 years later. Thus, in contrast to obese or other high-risk populations, in lean subjects, decreased beta cell function, but not insulin resistance itself, determines future glucose tolerance.This paper is dedicated to Rolf Luft, our mentor and collaborator over several decades, on the occasion of his 90th birthday.     

Decreased mid-to-late diastolic decay of diastolic coronary artery flow velocity in pressure-overloaded left ventricular hypertrophy

Summary This study was carried out to investigate the characteristics of coronary arterial flow in left ventricular hypertrophy secondary to systemic hypertension. The blood velocities in the left anterior descending coronary artery (LAD) were measured by a No. 3F 20 MHz Doppler catheter in 23 hypertensive patients with left ventricular hypertrophy (systolic/diastolic pressure: 181 ± 15/100 ± 4 mmHg) and 13 patients with atypical chest pain, but without left ventricular hypertrophy and any abnormal hemodynamic findings. All patients had normal coronary arteriograms. The LAD blood velocity waveforms in pressure overloaded left ventricular hypertrophy were characterized by both a decreased mid-to-late diastolic deceleration rate (V/T) and a normalized value of V/T by peak diastolic velocity [V/(T · Vpeak)], as well as delayed early diastolic inflow (time for diastolic rise; TDR). The values of the V/(T · Vpeak) in the patients with hypertensive left ventricular hypertrophy and in the normotensive controls were 1.26 ± 0.61 and 3.03 ± 1.18/s, respectively (P < 0.001). The TDR was 145 ± 56 and 66 ± 15 ms (P < 0.001). In patients with hypertensive left ventricular hypertrophy, the V/(T · Vpeak) correlated well with the degree of hypertrophy (r = 0.75,P < 0.01) and with the TDR (r = 0.82,P < 0.01). The coronary flow reserve, calculated from the ratio of the diastolic mean velocity after intracoronary injection of papaverine to the resting flow velocity increased with the V/(T · Vpeak) (r = 0.68,P < 0.01). In conclusion, the increase in blood flow in the later part of diastole may compensate for the decrease in early diastolic inflow and may cause the reduction in the coronary flow reserve in pressure-overloaded LV hypertrophy.Supported, in part, by Kawasaki Medical School Grant (No. 1-102) for Project Research, Japan.     

CD4+ and CD8+ subsets: Naive and memory cells in the peripheral blood of patients with systemic sclerosis

Summary Systemic Sclerosis (SSc; scleroderma) is associated with several immunological abnormalities, including altered proportion between lymphocyte subsets. Peripheral blood lymphocyte subsets from 25 patients with SSc were studied by two-colour flow cytometry using monoclonal antibodies against CD45RA and CD29 markers, which allow a dissection of CD4+ and CD8+ populations into naive and memory subsets. A decrease of the percentage of CD8+ (p<0.05) and of CD8+ CD29+ (p<0.001) cells was observed compared to that in 20 age and sex-matched controls. These abnormalities were not significantly associated with the extension of cutaneous disease or other clinical features of SSc nor with treatment, pattern of autoantibodies or HLA phenotype.     

Effect of polyinosinic-polycytidylic acid on chemically induced tumorigenesis by methylcholanthrene in mice

Summary Polyinosinic-polycytidylic acid administered intraperitoneally inhibits the formation of chemically induced tumors by methylcholanthrene in mice. The experiments show that poly (IC) is an effective suppressor of tumor formation when given simultaneously with the cancerogenic compound, or soon thereafter (before 4 weeks). Once the tumorigenesis was started (after 8 weeks), poly (IC) treatment becomes ineffective.The mechanism of inhibition of tumor formation by poly (IC) was studied by measuring the immune response of treated mice. Mice treated with methylcholanthrene alone exhibit a 50% inhibition of the immune response towards sheep red blood cells. Animals injected with poly (IC) after the methylcholanthrene treatment did not show any significant change. However, a pretreatment with poly (IC) causes a complete reversal of immunosuppression caused by methylcholanthrene.

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Zusammenfassung Polyinosin-Polycytidylsäure (Poly IC), intraperitoneal verabreicht, hemmt die Bildung von chemisch induzierten Tumoren durch Methylcholanthren in Mäusen. Die Versuche zeigen, daß Poly (IC) ein wirksamer Hemmstoff der Tumorbildung ist, wenn es gleichzeitig mit Methylcholanthren oder bald danach (vor Ablauf von 4 Wochen) gegeben wird. Wenn die Tumorgenese einmal begonnen hat (nach 8 Wochen), wird die Poly (IC)-Behandlung unwirksam.Der Hemmungsmechanismus der Tumorbildung durch Poly (IC) wurde durch Messung der Immunantwort von behandelten Mäusen untersucht. Nur mit Methylcholanthren behandelte Mäuse zeigen eine 50%ige Hemmung der Immunantwort in Gegenwart von Schaferythrocyten. Behandelt man die Tiere zuerst mit Methylcholanthren und anschließend mit Poly (IC), so bleibt die Immunantwort unbeeinflußt. Ändert man diese Reihenfolge, indem das Poly (IC) vor Methylcholanthren eingespritzt wird, so wird die immunsuppressive Wirkung des Methylcholanthrens vollkommen aufgehoben.