Nitric oxide-mediated gastric hyperemia decreases ethanol-induced gastric mucosal injury in uremic rats. We investigated whether the recently described endothelium-derived nitric oxide-mediated gastric hyperemia in the uremic rat protects the gastric mucosa against ethanol injury. Uremia was induced by subtotal nephrectomy. Basal gastric mucosal blood flow, measured by a hydrogen gas clearance technique, was significantly higher in uremic than control rats. Continuous intragastric perfusion with 40% ethanol produced significantly less gross and histological lesions in uremic than in control rats. The administration of 3 mg/kg of NW-nitro-L-arginine methyl ester, a specific inhibitor of nitric oxide biosynthesis, decreased resting gastric mucosal blood flow to control levels in uremic rats, but had no effect on basal gastric blood flow in control rats. This pretreatment with the inhibitor of nitric oxide biosynthesis increased 40% ethanol-induced gastric mucosal lesions in uremic rats to the same level as that observed in control rats, but had no effect on lesions in control rats. In conclusion, this study suggests that in the uremic rat, gastric hyperemia, mediated by increased endothelium-derived nitric oxide, attenuates ethanol-induced gastric mucosal injury.


Superior mesenteric artery is more important than inferior mesenteric artery in maintaining colonic mucosal perfusion and integrity in rats. Mucosal hemodynamics (by reflectance spectrophotometry) and mucosal damage (by histologic examination) following acute colonic ischemia were evaluated in different anatomic locations in the colon of anesthetized rats. The reflectance spectrophotometer provides an index of mucosal hemoglobin concentration (IHB) and an index of oxygen saturation of hemoglobin (ISO2). The patterns of ischemia without congestion (decreases IHB, decreases ISO2) during superior mesenteric artery occlusion, and ischemia with congestion (increases IHB, decreases ISO2) during portal vein occlusion, previously demonstrated in the stomach and duodenum, are also applicable to the colon. The significant linear correlations between changes (as percent of baseline) in IHB, ISO2, and hydrogen gas clearance suggest that changes in these indices are adequate indicators of changes in colonic mucosal perfusion. Superior mesenteric artery ligation produced significant reductions in both indices, and an increase in damage in the mucosa of the cecum, transverse colon, splenic flexure, and left colon, but not the rectum. Inferior mesenteric artery ligation produced only slight reduction in these indices and minimal damage only in the mucosa of the splenic flexure. These results support the hypothesis that the superior mesenteric artery is more important than the inferior mesenteric artery in maintaining colonic perfusion and colonic mucosal integrity in the rat.


Role of capsaicin-sensitive afferent neurons in mucosal blood flow response of rat stomach induced by mild irritants. The role of capsaicin-sensitive sensory nerves in gastric mucosal blood flow (GMBF) responses to mild irritants was investigated in the rat stomach mounted on a lucite chamber using hypertonic NaCl and 0.2 N HCl. Exposure of the mucosa to hypertonic NaCl (0.5, 0.75, 1 M) for 10 min caused a reduction in the transmucosal potential difference (PD) in a concentration-related manner, followed by an increase of luminal pH and GMBF. In contrast, mucosal application of 0.2 N HCl caused no or little change in PD and pH, but increased GMBF significantly. Functional ablation of capsaicin-sensitive sensory nerves significantly inhibited the increase of GMBF after exposure to these irritants, although the PD and pH responses induced by 1 M NaCl remained unaltered by this treatment. Pretreatment with indomethacin (5 mg/kg, subcutaneously) significantly attenuated the GMBF responses to 1 M NaCl and 0.2 N HCl and inhibited the increase of pH caused by 1 M NaCl. Mucosal application of capsaicin (0.1 mg/ml for 10 min) produced an increase of GMBF without being accompanied by change in PD and pH, and this effect was significantly blocked by either indomethacin or chemical deafferentation. These results suggest that capsaicin-sensitive sensory nerves as well as endogenous prostaglandins may be involved in the mechanism of GMBF responses induced by mild irritants, and the latter might sensitize these nerves to mucosal irritation. PD reduction may be obligatory for pH but not GMBF responses.


Sequence of gastric mucosal injury following ischemia and reperfusion. Role of reactive oxygen metabolites. The mechanisms of gastric mucosal injury following a period of ischemia remain unclear. The aim of this study was to determine the relative contributions of ischemia, reperfusion, and reactive oxygen metabolites to mucosal injury induced by temporary occlusion of the celiac artery. Rats were subjected to 30 min of gastric ischemia in the presence of 100 mM HCl. Reperfusion periods ranged from 1 min to 24 hr. Drug treatments included allopurinol (100 mg/kg) or a combination of superoxide dismutase (15,000 units/kg), catalase (90,000 units/kg), and desferrioxamine (50 mg/kg). Mucosal injury was assessed by quantitative histology and the extent of macroscopic hemorrhage. Approximately one third of the total injury to the volume of the mucosa (11.8 +/- 9.1%) was due to ischemia alone. Another third was blocked by allopurinol or superoxide dismutase, catalase, and desferrioxamine (22.1 +/- 6.9%, P less than 0.001; and 25.9 +/- 4.6%, P less than 0.01), respectively, compared with control (32.5 +/- 5.1%). In contrast, extensive surface mucosal injury (62.2 +/- 27.6%) occurred primarily during ischemia and was not affected by antioxidants. Macroscopic hemorrhage was halved by treatment with allopurinol (17.5 +/- 12.6%, P less than 0.01) or superoxide dismutase, catalase, and desferrioxamine (15.9 +/- 14.5%, P less than 0.01). We conclude that temporary celiac occlusion results in gastric mucosal damage that consists of both ischemic and reperfusion components. The majority of surface mucosal injury occurred during ischemia, whereas injury to the volume of the mucosa and the vasculature occurred equally during reperfusion and was associated with reactive oxygen metabolites.


Intestinal fatty acid-binding protein as a sensitive marker of intestinal ischemia. Determination of the serum level of intestinal fatty acid-binding protein has been used to detect rat intestinal ischemia following ligation or 30-min occlusion of the superior mesenteric artery. The normal values were under the minimal detectable level of less than 2 ng/ml in all the 10 rats. The serum fatty acid-binding protein level increased rapidly, to 340.7 +/- 54.6, 438.5 +/- 40.1, 388.1 +/- 37.4, and 292.2 +/- 95.7 ng/ml (P less than 0.01) at 1, 2, 4, and 8 hr after ligation, respectively. It also increased, to 347.2 +/- 127.7 ng/ml (P less than 0.01) at 1 hr, after a 30-min transient occlusion and then returned to a normal level. Histological studies showed destruction of the villi, disappearance of the mucosa, and transmural necrosis with the progress of time after ligation, while no remarkable morphological change was observed following 30-min transient occlusion. These observations strongly suggest that the intestinal fatty acid-binding protein is a useful biochemical marker for intestinal ischemia, particularly in the early reversible phase.


Mealtime versus nighttime acid inhibition. A clinical pharmacological study with ranitidine. This study was carried out in order to compare the effects of mealtime and bedtime regimens of ranitidine on gastric acidity. Fifteen duodenal ulcer patients in clinical remission were randomized to receive in single-blind fashion either placebo, ranitidine 300 mg at night (2200 hr) or ranitidine 150 mg three times a day given before each of the three daily meals (1800, 0800 and 1200 hr). Over 24 hr, the two active treatments produced a significantly greater acid inhibition than placebo, while the single daily regimen was superior to the three times a day regimen of ranitidine in terms of both rise in pH values (P less than 0.001) and duration of action expressed as time spent above 3.0 pH units (P less than 0.05). The analysis of these two parameters during fractioned periods of the circadian cycle showed that the three divided doses of ranitidine were more effective during the daytime (P less than 0.01) and the evening (P less than 0.001), whereas the bedtime dose of ranitidine was superior during the night (P less than 0.0001). Thus a short-lasting antisecretory action, which is, however, capable of fully controlling the high acidity of postprandial periods, might be the key to understanding the results of several recent clinical trials in which the suppression of daytime gastric acidity has been shown to promote similar or even faster duodenal ulcer healing rates than the suppression of nocturnal acidity.


Omeprazole heals mucosal ulcers associated with endoscopic injection sclerotherapy. Endoscopic injection sclerotherapy (EIS) is a standard and definitive therapy for bleeding esophageal varices. While the overall complication rate of the procedure is low, a substantial minority of patients treated by EIS develop refractory mucosal ulceration and/or esophageal strictures. However, despite the prophylactic use of H2 blockers and sucralfate in our EIS protocol, we observed a number of patients who developed nonhealing esophageal and/or gastroduodenal ulceration. We conducted an open trial in which we enrolled nine patients who had refractory ulcer disease. Patients that enrolled in the trial exhibited complete healing of their mucosal ulcers. These results suggest that acid is an important contributory factor in the pathogenesis and perpetuation of EIS-associated mucosal ulceration. Patients with alcohol-associated liver disease may be at increased risk for the development of EIS-associated complications.


Effect of oral contraceptive use on reoperation following surgery for Crohn's disease. The influence of oral contraceptive (OCP) use as a risk factor for the development of Crohn's disease is disputed. We wished to determine if OCP use affected the risk of recurrence (defined as need for a second surgery) in women who had already undergone a resection for Crohn's disease. We hypothesized that if contraceptive use was a risk factor for disease development, it could influence recurrence. Using a mail questionnaire, we surveyed 138 women regarding their OCP use following surgery for Crohn's disease. All participants were between ages 16 and 35 at the time of their initial surgery which occurred between 1966 and 1984. Ninety-seven women (70%) responded. Mean follow-up was 9.9 years (range 4-27). Forty-six women required a second surgery. The recurrence rate as determined by actuarial analysis, was 27.2% (95% confidence intervals (CI95 16.5-38.1) and 58.0% (CI95 37.8-78.2) at 5 and 10 years, respectively. Thirty-two women took OCP in the first year following surgery. Eleven OCP users (34.4%) required additional surgery compared to 34 (53.1%) of nonusers. Using life table analysis, the percentage requiring a second surgery was 25.0% (CI95 6.9-43.1) and 40.7% (CI95 1.5-80%) at 5 and 10 years, respectively, for users compared to 28.4% (CI95 6.9-43.1) and 64.0% (CI95 40.5-87.5) for nonusers (Lee Desu, P greater than 0.05). When surveyed about their reasons for using OCP, most women stated that their disease did not affect their decision to use contraceptives.(ABSTRACT TRUNCATED AT 250 WORDS)


Prooxidant properties of 5-aminosalicylic acid. Possible mechanism for its adverse side effects. There is a growing body of experimental and clinical evidence to suggest that oral or rectal administration of 5-ASA or 5-ASA conjugates is associated with significant adverse side effects including pancreatitis, hepatitis, and renal toxicity. The objective of this study was to assess the ability of 5-ASA to interact with low-molecular-weight iron to yield oxygen-derived free radicals and to determine whether these oxidants could damage model biological compounds. We found that 5-ASA was very effective at chelating ferric iron (Fe3+), and it rapidly reduced Fe3+ to the ferrous form (Fe2+). Addition of the 5-ASA/Fe2+ chelate to solutions containing polyunsaturated fatty acids or deoxyribose resulted in lipid peroxidation and oxidative carbohydrate degradation, respectively. These results are consistent with the formation of the highly reactive (and cytotoxic) hydroxyl radical. Formation of this free radical species was confirmed by the ability of hydroxyl radical scavengers (dimethyl sulfoxide, dimethyl thiourea) to inhibit the 5-ASA/Fe-mediated oxidative reactions. Maximum hydroxyl radical formation was achieved at a 5-ASA-to-Fe3+ ratio of 1.0 (20 microM 5-ASA and 20 microM Fe3+). Increasing this ratio significantly inhibited OH. formation with a concomitant reduction in lipid peroxidation and deoxyribose degradation. Finally, we demonstrated that 5-ASA promotes the reductive release of Fe3+ from ferritin. Data obtained in this study suggest that 5-ASA may, under certain conditions, promote the formation of potentially injurious free radical species. These oxidative reactions may contribute to some of the adverse side effects known to be associated with the newer preparations of 5-ASA.


Low bone mineral density in patients with inflammatory bowel disease. To assess the prevalence and risk factors for low bone mineral density in inflammatory bowel disease, we studied 61 consecutive patients, mean age 36 +/- 11 years. Twenty-seven had a Crohn's disease and 34 ulcerative colitis (including 13 with ileoanal anastomosis). Three patients, two women and one man (32, 70, and 45 years old, respectively) had vertebral crush fractures. Bone mineral density measured by dual energy x-ray absorptiometry at spine and femoral level was more than 2 SD below normal values in 23% of the patients, all of them having received steroid therapy. Eighteen patients (29%) had never received steroid therapy; their bone mineral density was not different than those who had. Univariate analysis showed a positive correlation between bone mineral density and body weight or oral calcium intakes, and a negative correlation with steroid daily dose. After ileoanal anastomosis, bone mineral density was not different from other groups and showed a positive correlation with time elapsed since coloproctectomy. We concluded that bone mineral density is low in patients with inflammatory bowel disease and exposes them to the risk of bone fracture. Bone mineral density after ileoanal anastomosis may increase with time after surgery.


Influence of shock on development of infection during acute pancreatitis in the rat. This study tested the hypothesis that hypovolemic shock elicits or promotes the development of infection during acute pancreatitis. Pancreatitis was induced in rats by ligation of the common biliopancreatic duct; nonlaparotomized animals served as controls. After 24 hr, the animals were subjected to either sham-shock (instrumented only) or to shock by withdrawal of blood through a femoral artery line by maintaining the mean arterial blood pressure at 30 mm Hg for 1 or 2 hr. After completion of the shock period, the shed blood was returned to the animal. All animals were sacrificed 24 hr later and specimens obtained from portal and systemic blood, liver, spleen, pancreas, and mesenteric lymph nodes for bacteriologic culture using standard techniques. The pancreas was also analyzed by morphometric techniques. The histologic changes of pancreatitis induced by biliopancreatic obstruction were characterized by marked edema with accompanying mild inflammation, hemorrhage, and necrosis. Concomitant with these morphologic findings was an associated translocation of enteric organisms to the mesenteric lymph nodes without spread to distant organs. Shock by itself induced only a mild edema in the pancreas and did not cause bacterial translocation. Furthermore, shock failed to aggravate the morphologic alterations of acute pancreatitis and did not promote bacterial spread to mesenteric nodes over that observed with pancreatitis alone. Thus, we conclude that periods of severe shock lasting up to 2 hr do not play a major role in the pathogenesis of infection in our model of pancreatitis.


Use of famotidine in severe exocrine pancreatic insufficiency with persistent maldigestion on enzymatic replacement therapy. A long-term study in cystic fibrosis. In patients with pancreatic exocrine insufficiency, the use of pancreatic enzyme does not abolish steatorrhea in some cases. We carried out a long-term prospective study in an attempt to clarify the effectiveness of the associated use of famotidine to enzymatic supplementation on fat absorption and nutritional parameters of patients with pancreatic insufficiency due to cystic fibrosis. We studied 10 patients, mean age 12.5 years, with persistent steatorrhea on enzymatic supplementation. A double-blind crossover design was used and famotidine (1 mg/kg/day) or placebo was given as adjuvant to enzymatic preparations for either of two six-month periods. A statistically significative reduction in fecal wet weight (P less than 0.0001), an improvement in the coefficient of fat absorption (P less than 0.01) and in the steatocrit values (P less than 0.028) were found on famotidine. Moreover, the weight and the height increases were greater after famotidine than after placebo period (respectively, P less than 0.012 and P less than 0.01); also the serum calcium and triglycerides levels were higher after the period on famotidine (respectively, P less than 0.0025 and P less than 0.025). No adverse effects of famotidine were noted. These data suggest that famotidine is a useful adjuvant to pancreatic enzyme therapy in patients with severe pancreatic insufficiency and persistent maldigestion on large doses of pancreatic supplements; in fact, famotidine improves not only fat absorption but the nutritional status of the patients.


Phlegmonous gastritis associated with HIV-1 seroconversion. Endoscopic and microscopic evolution. A 40-year-old man presented with peritonitis. Diagnosis of phlegmonous gastritis was made by laparotomy. Conservative treatment combined with antibiotics was successful. Multiple endoscopies with biopsies illustrate the natural history of this disease. The patient developed HIV-1 seroconversion during hospital stay. Prompt diagnosis and treatment may improve the prognosis of this often lethal disease.


Antibiotic-associated colitis and cystic fibrosis. The use of antibiotics in patients with cystic fibrosis is widespread, and fecal carriage of Clostridium difficile occurs in up to 50% of these patients; however, antibiotic-associated colitis appears to be a rare occurrence. The reasons why this is so remain unknown. A case of antibiotic-associated colitis occurring in a patient with cystic fibrosis is described. Possible mechanisms for the rarity of antibiotic-associated colitis are reviewed and implications for prompt diagnosis and therapy are discussed.


High systolic blood pressure increases prevalence and severity of retinopathy in NIDDM patients. To determine whether the severity of retinopathy is higher in a group of NIDDM patients with sBP greater than or equal to 140 mmHg compared with NIDDM patients with sBP less than 140 mmHg. Ophthalmoscopy and FAG were conducted among a group of NIDDM patients with either a sBP above (n = 54) or below (n = 55) 140 mmHg. The groups were matched according to diabetes duration, metabolic control (HbA1c), and AER. Patients with sBP greater than 140 mmHg had a higher prevalence of retinopathy, as established according to a rating scale (4.9 +/- 3.8 vs. 3.2 +/- 3.3, P less than 0.02); furthermore, their BMI values were higher (28.1 +/- 4.5 vs. 24.9 +/- 4.1 kg/m2, P less than 0.001). The group of normotensive subjects showed the highest rate of low grading (0-2) values. However, the highest prevalence rates of 8-10 grading values (proliferative retinopathy) were found in the hypertensive group. These data suggest that sBP values greater than or equal to 140 mmHg favor the onset of retinopathy in NIDDM patients during their 1st 10 yr of disease.


Homogeneity in pattern of decline of beta-cell function in IDDM. Prospective study of 204 consecutive cases followed for 7.4 yr. To study the natural history of beta-cell function from onset of IDDM to expected deterioration of insulin (C-peptide) secretion and to identify different patterns of decline, if any. A cohort of 204 consecutive newly diagnosed IDDM (clinical criteria) patients were followed prospectively for 7.4 yr (range 6-9 yr), measuring fasting C-peptide at onset, 1, 3, 6, 9, 12, and then every 6 mo until 106 wk (range 104-135 wk). Then, postprandial C-peptide was measured. Fasting C-peptide was 0.17 nM (range 0.11-0.25 nM) at onset followed by an annual increase rate of 0.16 nM/yr (range 0.06-0.48 nM/yr) to a peak of 0.28 nM (range 0.23-0.34 nM/yr) after 25 wk (range 12-39 wk). The subsequent annual decline rate of fasting C-peptide was 0.08 (0.05-0.12) and of postprandial C-peptide 0.03 nM/yr (range 0.02-0.06 nM/yr). None of these parameters showed bimodality in their distribution. However, some parameters were important. In men, fasting C-peptide at onset was lower, but the initial C-peptide increase rate was more pronounced compared to women. Furthermore, insulin-free remission was related to higher C-peptide levels throughout the study. C-peptide was higher during the 1st yr of diabetes in subjects greater than 30 yr of age at onset compared with younger diabetic patients. Stepwise multiple regression analysis showed that age, male sex, and fasting C-peptide at onset were of some predictive value for the C-peptide levels at 5 yr. However, simple group comparisons revealed no significant differences. No major heterogeneity exists in the pattern of decline of beta-cell function in IDDM, although small differences in pattern could be identified in both sexes, in different age-groups, and in relation to achieving insulin-free remission.


Granulocytes and three-phase bone scintigraphy for differentiation of diabetic gangrene with and without osteomyelitis. In diabetic gangrene, concomitant osteopathy and soft-tissue infection often render laboratory and roentgenographic signs unreliable as indicators of osteomyelitis. In this situation, scintigraphic methods can be helpful. Relying on the long-term clinical course as the final indicator of presence or absence of osteomyelitis, we prospectively compared in 31 patients three-phase bone scintigraphy with either indium-labeled autologous granulocytes (n = 20) or 123I-labeled antibodies against granulocytes (n = 11). Three-phase bone scintigraphy and imaging with indium-labeled autologous granulocytes yielded sensitivities and specificities of 95 and 70% for bone scintigraphy and 77 and 100% for granulocyte scintigraphy, respectively. One patient with severe angiopathy and proved osteomyelitis had a negative bone scintigraphy but a positive scintigraphy with labeled antibodies against granulocytes. One patient with aseptic bone necrosis presented with a formally false positive result with both methods. In contrast to former retrospective studies, three-phase bone scintigraphy compares very well with granulocyte scintigraphy. The care of most patients can be managed with clinical data and this widely available scintigraphic method.


Asymptomatic hyperglycemia and atherosclerotic vascular disease in the elderly. OBJECTIVE--To investigate the relationship between asymptomatic hyperglycemia (IGT or newly diagnosed NIDDM) and atherosclerotic vascular disease. RESEARCH DESIGN AND METHODS--A representative cross-sectional population sample of 1431 subjects (511 men, 920 women; 65-74 yr old). Altogether, 312 men and 515 women had NGT, 84 men and 158 women had IGT, 33 men and 59 women had newly diagnosed NIDDM, and 82 men and 188 women had previously diagnosed NIDDM. Participation rate was 71%. Main outcome measures were prevalence rates of CHD, stroke, and intermittent claudication. RESULTS--There was no difference in the prevalence of definite or possible MI verified at hospital between subjects with asymptomatic hyperglycemia and NGT (15.5 vs. 13.3% in men, 6.3 vs. 5.3% in women). Men with asymptomatic hyperglycemia had 1.5 x higher prevalence of angina pectoris (29.4 vs. 19.3%, P less than 0.05), major Q-QS changes (21.1 vs. 12.0%, P less than 0.05), ischemic ECG changes (59 vs. 45%, P less than 0.05), and silent MI on ECG (14.8 vs. 7.9%, P less than 0.05) compared to men with NGT. Women with asymptomatic hyperglycemia had more often ischemic ECG changes compared to women with NGT (48.3 vs. 39.7%, P less than 0.05). There was no difference (NS) in the prevalence of verified stroke (3.5 vs. 4.6% in men, 2.7 vs. 2.5% in women) or claudication (7.0 vs. 7.7% in men, 4.6 vs. 4.3% in women) between subjects with asymptomatic hyperglycemia and NGT. In multiple logistic regression analyses, the association between risk factors and MI or ischemic ECG changes in subjects with asymptomatic hyperglycemia was not consistent. CONCLUSION--Elderly subjects with asymptomatic hyperglycemia (particularly men) tended to have an increased prevalence of CHD. Thus, asymptomatic hyperglycemia in the elderly is not a benign phenomenon but is associated with cardiovascular morbidity.


Twice-daily humulin ultralente insulin decreases morning fasting hyperglycemia. To test whether a two-injection regimen of HUL/R would improve FBG and metabolic control in pediatric IDDM patients with a dawn rise in FBG compared with our standard twice-daily therapy, HL/R. Seventy-seven patients with fasting hyperglycemia (prebreakfast mean FBG greater than or equal to 8.3 mM (150 mg/dl) during the preceding 2 wk) were evaluated with twice-weekly midsleep (0230-0330) FBG for 2 wk. Forty-seven patients (61%) had a mean dawn rise between midsleep and prebreakfast of greater than or equal to 2.8 mM (50 mg/dl). Patients continued on HL/R for an additional 4 wk, after which 31 patients were then randomized into a double-blind 12-wk trial of either HUL/R (n = 14) or HL/R (n = 17) administered before breakfast and the evening meal. Midsleep FBG was obtained twice weekly with weekly insulin adjustment as needed to optimize glycemic control. FBG was monitored and verified with memory glucometers (Glucometer M). HbA1c levels were measured at the time of physician visits at 0, 6, and 12 wk. Prebreakfast FBG was lower in the HUL/R-treated patients (10.6 +/- 0.6 vs. 12.6 +/- 0.6 mM [191 +/- 6.4 vs. 227 +/- 11.2 mg/dl], P less than 0.02). The dawn rise was diminished in the HUL/R patients (0.5 +/- 0.5 vs. 2.6 +/- 0.7 mM [9 +/- 8.3 vs. 46 +/- 11.7 mg/dl], P less than 0.02). FBG at lunch, dinner, bedtime, and midsleep were similar in both groups, and HbA1c did not differ between groups or change significantly in either group during the 12-wk trial. Insulin dose, percentage R, day-night dosage split, and episodes of hypoglycemia (FBG less than 3.3 mM [60 mg/dl]) were similar in both groups. A 12-wk trial of twice-daily HUL/R improved fasting glycemia in pediatric patients with a dawn rise but did not improve metabolic control as measured by HbA1c.


Severe hypoglycemia incidence and predisposing factors in 85 pregnancies of type I diabetic women. To evaluate the incidence and predisposing factors of severe hypoglycemia (SH) in pregnant women with insulin-dependent (type I) diabetes mellitus. SH (impairment of consciousness due to hypoglycemia subsequently treated with glucagon or i.v. glucose) was recorded in all pregnant type I diabetic women (n = 77) who attended our pregnancy clinic during 85 pregnancies from 1986 to 1990. Ninety-four SHs were reported during 35 pregnancies. Of 94 SHs, 84% occurred before the 20th gestational wk (median 12th wk) and 77% during sleep. In the group with SH, there was no permanent maternal sequelae, and there was a favorable fetal outcome (no perinatal death and no congenital malformation). Mean HbA1c values were not different between the group with and without SH for the first half (6.4 +/- 1.1 vs. 6.3 +/- 0.9%) and 2nd half (5.4 +/- 0.6 vs. 5.5 +/- 0.7%) of pregnancy. The percentage of women with SH before pregnancy (51 vs. 28%, P less than 0.05) and the incidence of SH patients before pregnancy (0.49 vs. 0.08 SH/patient/yr) was different between the group with and without SH. SH is frequent during pregnancies of type I diabetic women with near normoglycemia. The risk for SH is particularly pronounced during the first half of pregnancy and in women with a history of SH.


Plasma endothelinlike immunoreactivity levels in IDDM patients with microalbuminuria. To determine whether plasma endothelin, a potent vasoconstrictor and growth factor for vascular smooth muscle, is elevated in microalbuminuric insulin-dependent diabetes mellitus patients. Plasma endothelinlike immunoreactivity was measured by radioimmunoassay in 15 microalbuminuric diabetic patients, 12 normoalbuminuric diabetic patients, and 12 control subjects. The mean levels of plasma endothelinlike immunoreactivity were raised in the normoalbuminuric patients (8.4 pM [range 4.8-12.7 pM]; P less than 0.01) and the microalbuminuric patients (10.2 pM [range 5.6-31.1 pM]; P less than 0.001) compared with control subjects (6.1 pM [range 4.5-7.6 pM]). Plasma endothelinlike immunoreactivity was also higher in the microalbuminuric patients compared with the normoalbuminuric patients (P less than 0.05). The increase in plasma endothelinlike immunoreactivity further confirms endothelial dysfunction in diabetes and this increase in plasma endothelin may contribute to the vascular disease prevalent in diabetes.


Use of blood glucose data by families of children and adolescents with IDDM. Prospective evaluation of the use of blood glucose test results for treatment actions by families of youth with IDDM. Forty-seven patients with IDDM used reflectance meters with memory for SMBG for 28 days. Parents kept weekly diaries of six types of uses of SMBG data. We collected SMBG data from the reflectance meters, HbA1 and serum fructosamine assays, and measures of behavioral factors that could affect use of SMBG data. Families recorded a mean of 4.85 data-based actions during the 28-day study, and 74% of the families reported at least one such action. Fifty percent of recorded actions consisted of management of hypoglycemia and, among the remainder, only 18% were anticipatory, proactive actions. Partial correlation analysis showed that families with more frequent use of SMBG data had less parent-child conflict about diabetes, more diabetes knowledge, and better overall treatment adherence. Use of SMBG data was unrelated to objective indices of the need for treatment adjustments or to diabetic control. Most families made active use of their SMBG data, but few of these actions were proactive. Behavioral factors were stronger predictors of family use of SMBG data than were objective indices of the need for treatment adjustments. The results illustrate the need for further research on use of SMBG data and methods to enhance its impact on diabetic control.


Immediate HbA1c results. Performance of new HbA1c system in pediatric outpatient population. This study compared the performance of a new device that uses an IA to measure HbA1c in 9 min with a 1-microliter capillary blood sample with AC and CE methods in both nondiabetic and diabetic pediatric patients. Two hundred seven pediatric subjects (103 nondiabetic, 104 with insulin-dependent diabetes mellitus) had HbA1c measured with the IA method and compared with total GHb values determined by AC and HbA1 by the CE method with the same whole-blood capillary aliquot. Glucose values were also obtained from the same blood samples. Correlations and regression analyses show excellent correspondence between the three assays. The correlation between the AC and CE methods is 0.98 (P less than 0.001) with a slope of 1.615 +/- 0.0125 and intercept of 4.00 +/- 0.20. The correlation between the IA and AC methods is 0.99 (P less than 0.001) with a slope of 0.608 +/- 0.007 and intercept of 1.326 +/- 0.066. The correlation between the IA and CE methods is 0.97 (P less than 0.001), with a slope of 0.983 +/- 0.018 and intercept of 1.122 +/- 0.153. The average difference and average percentage difference between methods were also significant (P less than 0.001), reflecting the differences in GHb components measured. There was a significant correlation (P less than 0.001) between each method and glucose values (IA r = 0.72, AC r = 0.70, CE r = 0.73). Within-run precision for IA ranged from 1.7 to 3.5% and between-run precision 2.7 to 4.1%. Study results suggest that the IA method gives extremely accurate and reliable values over the clinical range of interest. The instrument is small, portable, easy to use, and provides information within 9 min for both physicians and patients.


Comparison of two commonly used standard IVGTTs. To compare the magnitude and reproducibility of the FPIR measured during two different IVGTT protocols in nondiabetic subjects. Nine control subjects each had two pairs of IVGTTs with either a 4-min infusion of 0.5 g/kg glucose or a 1-min infusion of 0.3 g/kg glucose. Blood glucose and serum insulin were measured before and 1, 2, 3, 5, and 10 min after completion of the glucose infusion. The FPIR was measured with either 1 + 3-, 2 + 3 + 5-, or 1 + 3 + 5-min serum insulins, areas under the insulin curve (0-5 or 0-10 min), or the ratio of serum insulin to blood glucose area. The FPIR was higher in eight of nine subjects with the short-infusion test, but the within-subject variation of the two methods was identical. Reproducibility was not significantly improved with an integrated insulin area or insulin-to-glucose ratio measurement. Reproducibility of the FPIR measured during IVGTT is not significantly affected by the duration of the glucose infusion. However, the magnitude of the difference in FPIR observed between the two protocols highlights the need for standardization of the methodology if the IVGTT is to be used in studies of the preclinical stage of IDDM.


Smokers with IDDM experience excess morbidity. The Colorado IDDM Registry. OBJECTIVE--To determine whether there is an association between smoking and the self-reported morbidity of people with IDDM and to evaluate the nature of a possible interaction between smoking and IDDM in increasing the risk of morbidity among smokers with IDDM. RESEARCH DESIGN AND METHODS--Subjects were non-Hispanic whites aged 18-28 yr who participated in the Colorado IDDM Registry Follow-up Survey (case subjects, n = 24) or the 1985 NHIS (control subjects, n = 5876). Assessments of self-reported morbidity included any hospitalization in the past year; bed days, sick days, and limited-activity days in the past 2 wk; and ratings of poor health. The criteria outlined by Saracci were used to determine whether smoking was associated with greater morbidity among IDDM case compared to control subjects (smoking by IDDM interaction). RESULTS--Age- and sex-adjusted ORs, estimated from logistic regression, showed that people with IDDM reported excess morbidity compared with control subjects, regardless of smoking status. Smokers with IDDM reported morbidity 3-10 times as often as nonsmoking control subjects and were 2-3 times more likely to report morbidity than nonsmokers with IDDM. The smoking by IDDM interaction was more than multiplicative for all morbidity measures. Fifty to 75% of excess morbidity in young smokers with IDDM over simple additive effects was related to the interaction between smoking and IDDM. CONCLUSIONS--There was excess reported morbidity among people with IDDM who smoked, greater than that expected from the combined effects of smoking and IDDM. Smoking cessation in young people with IDDM may alleviate some of this excess, but more study is needed to determine whether smoking serves as an indicator of poor IDDM care practices or has a physiological impact that compounds the morbidity experienced by people with IDDM.


Diabetic ketoacidosis. A rare complication of gestational diabetes. To describe a case of severe DKA in an otherwise healthy pregnant woman. We describe 2.5 yr of close follow-up of a Bedouin woman who was hospitalized for DKA while pregnant with her 11th child. Plasma glucose returned to normal levels immediately after delivery of a dead conceptus. Four months later, while normoglycemic, the patient became pregnant again. During the subsequent pregnancy, GDM was diagnosed at week 20 of gestation. Tight plasma glucose control was achieved with an insulin regimen, and the patient delivered a healthy girl at term. Plasma glucose again returned to normal and remained so to date, 18 mo postpartum. An OGTT and a euglycemic hyperinsulinemic clamp were performed between pregnancies; another OGTT was performed at week 14 of the last pregnancy. Plasma glucose, insulin, and C-peptide were measured in blood samples during these procedures. We established beyond doubt that the patient developed GDM and returned to essentially normal glucose tolerance after her last (12th) delivery. During the 11th pregnancy, gestational diabetes was complicated by severe DKA. GDM is a common abnormality of glucose metabolism during pregnancy, which affects fetal development and leads to peripartum complications. Our report stresses that under certain circumstances, gestational diabetes can be complicated by DKA and become life-threatening to the mother and fetus.


Telephone modem access improves diabetes control in those with insulin-requiring diabetes. To assess whether modem access improves diabetes control in IDDM patients. Forty-two patients participated in the study and were followed for 12 wk. The patients were randomly divided into two groups at baseline, a modem group and a control group. There were no significant differences between HbA1c, random blood glucose, and weight between the groups at the beginning of the study. Patients were asked to perform five blood glucose determinations/day (before breakfast, before lunch, afternoon [1500], before dinner, and at bedtime) twice/week. The modem group transferred their data over the phone once/week. The control group would bring in their results on their regular visits every 6 wk. Patients in the modem group were counseled every week over the telephone after transferring results to adjust insulin and food intake if necessary. In the modem group, HbA1c improved from 0.106 to 0.092 (13.20%). The control group improved from 0.112 to 0.102 (8.9%). There was no significant change in weight, random blood glucose, or insulin. The use of telephone modem-based patient-monitoring systems in diabetes clinical research seems to stimulate the patient to keep closer control of blood glucose levels. It might be especially useful in rural settings, for which this study was designed.


Glycemic control in early IDDM. The Wisconsin Diabetes Registry. A cohort (n = 277) was followed from diabetes diagnosis to evaluate longitudinal glycemic control, urinary C-peptide levels, and certain features of diabetes self-management. Unselected cases with IDDM, who were less than 30 yr of age, were identified at diagnosis from a 28-county area in Wisconsin. Subjects were asked to submit blood every 4 mo for GHb testing, to report aspects of diabetes self-management every 6 mo, and to collect a 24-h urine specimen 4 mo after diagnosis. In the 1st yr of diabetes, the rate of increase (0.23%/mo) in GHb was significant for the cohort (P less than 0.001) and for almost all age and sex subgroups. In the 2nd yr, there was no significant rate of increase for the cohort as a whole (P greater than 0.10). Adolescent males (10-19 yr of age) had a mean GHb level for year 2 higher than males of other age-groups and higher than female adolescents (P less than 0.001). Adolescent males had a significant rate of increase in GHb for year 2 (P = 0.02), unlike all other age and sex subgroups. Adolescents had higher initial 24-h urine C-peptide levels than children less than 10 yr of age (P less than 0.01). During the 2nd yr of diabetes, the percentage of adolescent males reporting three or more insulin injections/day was lower than any other subgroup. These data-suggest that glycemic control stabilizes during the 2nd yr of IDDM, except in adolescent males, and that this may be due partly to aspects of self-management.


Assessment of glucose tolerance test criteria for diagnosis of diabetes in Chinese subjects. To examine and compare WHO diagnostic criteria for diabetes mellitus. The relationship between FPG and 2-h glucose are examined in 680 OGTTs with a quadratic regression model and ROC analysis. Simultaneous measurements of HbA1 and fructosamine are also compared with multiple linear regression. Two hundred eighteen subjects (32%) had 2-h glucose greater than or equal to 11.1 mM, of which only 86 had FPG greater than or equal to 7.8 mM. Only 2 subjects had FPG greater than 7.8 mM and 2-h glucose less than 7.8 mM. Of subjects with 2-h glucose less than 7.8 mM (n = 332), only 9 had FPG greater than 6.0 mM. From the quadratic model, the predicted FPG corresponding to 2-h glucose = 11.1 mM was 5.7 mM, whereas the predicted 2-h glucose corresponding to FPG = 7.8 mM was 15.2 mM. ROC analysis showed that, with 2-h glucose greater than or equal to 11.1 mM as indicating diabetes, an FPG of 5.6 mM gave an intersect for sensitivity and specificity of 87%. HbA1 and fructosamine correlated more closely with 2-h glucose and area under the OGTT curve than with FPG. Given that a 2-h glucose cutoff of 11.1 mM can be justified from other studies, our results suggest that the FPG cutoff of 7.8 mM when used for screening purposes should be reduced. At a suggested value of 7.0 mM, specificity remains 98.5%, whereas sensitivity increases to 57%.


Fibrinolytic system during long-distance running in IDDM patients and in healthy subjects. Endurance exercise has been advocated in diabetes mellitus to improve both metabolic control and prevent atherosclerotic complications. The response of the fibrinolytic system during prolonged exercise has not been studied in diabetes. In seven male marathon runners with IDDM and eight healthy nondiabetic male control subjects, matched for age and degree of training, we studied fibrinolytic and coagulation parameters during a 3-h 32-km outdoor running session. Measurements included t-PA, u-PA, PAI-1, PAP (as a measure of in vivo activation of fibrinolysis), FbDPs, FGN, vWF, and VIII:C. In both IDDM and control subjects, levels of t-PA, u-PA, PAP, vWF, and VIII:C continued to rise throughout the exercise, whereas PAI-1 showed a similar decline in both groups. FbDP rose slightly in both groups, and FGN remained unchanged. t-PA levels during exercise correlated closely with exercise intensity. These findings indicate that continued stimulation by exercise does not deplete endothelial PA stores. Differences between IDDM and control subjects were seen only for t-PA, vWF, and u-PA. The AUC during exercise (AUC0.5-3.0) of t-PA in IDDM was insignificantly lower than in control subjects (53 +/- 19 vs. 67 +/- 31 ng.ml-1.h), but the ratio of t-PA to exercise intensity was lower in IDDM (0.24 +/- 0.11 vs. 0.31 +/- 0.13, P less than 0.05). The AUC0.5-3.0 of vWF was lower in IDDM than in control subjects (569 +/- 268 vs. 880 +/- 265%.h, P less than 0.05). The AUC0.5-3.0 of u-PA was higher in IDDM than in control subjects (15.1 +/- 3.5 vs. 11.2 +/- 1.8 ng.ml-1.h, P less than 0.05). Despite a defect in the exercise-induced endothelial release of vWF and t-PA, the overall potential to activate fibrinolysis is intact in IDDM, possibly by enhancement of u-PA after exercise. Our data suggest that in IDDM, as in nondiabetic subjects, long-distance running may slow the progression of atherosclerosis by stimulating fibrinolysis.


Factors predicting course of beta-cell function in IDDM. The purpose of this study was to determine whether the severity o clinical presentation, sex, age, HLA type, and the presence of IAs and ICAs could predict the variation of residual insulin secretion as measured by the serum C-peptide response to a Sustacal meal. A cohort of 151 newly diagnosed IDDM children (mean age 10.2 +/- 4.6 yr) was followed prospectively for 3 yr. Thirty-five patients (12 males, 23 females) were still secreting C-peptide after 36 mo. We found that age (P = 0.0001), sex (P = 0.003), presence of ICA (P = 0.006), severity of clinical presentation (P = 0.001), and symptom duration (P = 0.002) significantly predicted the rate of loss of C-peptide secretion. The risks of accelerated C-peptide disappearance decreased with increasing age, the risk ratios being 0.25 for the older group (greater than 12 yr) compared with the younger group (less than 6 yr) and 0.50 for the intermediate group (6-12 yr) compared with the younger group. The risk for the presence of ICA was 1.7, and the risk for males was 1.7 also. There was a significant negative correlation between ICA titers and C-peptide at 18 and 24 mo after diagnosis (P = 0.04). There were no significant differences in HbA1 values between patients who secreted C-peptide and those who did not. We conclude that younger age of onset, male sex, high titers of ICA, severe clinical presentation, and shorter symptom duration significantly predict accelerated rates of loss of C-peptide secretion.


Fundus pigmentation and the dark-adapted electroretinogram. Dark-adapted electroretinograms were obtained over a 3.6-log range of stimulus intensities from 17 black and 15 white normal subjects. Subjects were grouped on the basis of light or dark fundus pigmentation, determined from digitized fundus photographs. B-wave amplitudes for each group were fitted by the Naka-Rushton equation, and the measures Vmax, log K, and n were determined. The luminance-response functions revealed that subjects with light fundi had larger b-wave amplitudes at all luminance levels. There was a significant difference between groups for Vmax and n but not for log K. A comparison of b-wave implicit times showed no significant difference between subjects with dark and light fundi. Ancillary tests and multiple regression analysis suggested that the relationship between Vmax and fundus pigmentation could not be attributed to age, gender, refractive error, axial length or intraocular pressure. The results have implications for the collection of normative electroretinographic data and for the interpretation of electroretinogram results.


Color electroretinography. A method for separation of dysfunctions of cones. Electroretinograms to white and color stimuli were recorded in four normal subjects and nine subjects with different cone dysfunctions, including protanopia, cone dystrophy, cone dystrophy with supernormal b-waves at dark adaptation, cone dystrophy with missing b-waves during light adaptation and rod-cone dystrophy with blue cone hypersensitivity. Color stimuli were obtained with Kodak Wratten filters in blue, blue-green, green, yellow and red. Electroretinograms to all stimuli were recorded during dark and light adaptation with different stimulus intensities and to 30-Hz flicker stimulation. In protanopia, responses to red during light adaptation and flicker stimulation were reduced. All cone dystrophies showed reduced amplitudes and prolonged implicit times to red when dark adapted. The light-adapted responses were equally reduced to all color stimuli in cone dystrophy and cone dystrophy with supernormal b-waves. Contrary to other cone dystrophies, in cone dystrophy with missing b-waves, responses to red were severely reduced and responses to green were preserved, indicating a predominantly red cone dysfunction. Blue cone hypersensitivity was clearly distinct from other dystrophies in having large response to blue and blue-green and much smaller responses to all other colors in all stimulus conditions. The electroretinogram with color stimuli allowed separation of different cone dysfunctions and identification of new retinal dysfunction syndromes.


Spectral characteristics of rapid off-response in congenital deuteranomaly in one of monozygotic female twins. The spectral sensitivity of the rapid off-response in the electroretinogram was studied in monozygotic female twins. One case was diagnosed as congenital deuteranomaly, and the other was normal. The log ratio of the sensitivity at 480 nm to the sensitivity at 620 nm (log S480/S620) was within the deutan range in the first case and within the normal range in the second. The two case were determined to be different at the retinal receptor level by study of the rapid off-response. This result of the rapid off-response was consistent with the results of the psychophysical examinations.


Electrophysiologically determined contrast sensitivity in patients with ocular hypertension and chronic glaucoma. Subjectively assessed contrast sensitivity has been found to be abnormal in many patients with glaucoma. We previously reported the use of onset-offset visual evoked potential measurements to determine contrast threshold objectively. We now studied 216 patients (79 with ocular hypertension and 137 with chronic simple glaucoma) with this technique. In comparison with an age-matched control group (68 subjects), mean contrast threshold was found to be significantly different in both patient groups, the degree of significance being greater in the patients with chronic simple glaucoma. Additionally, the slope of the CI-CII amplitude versus log contrast plot was shown to be depressed in the majority of affected eyes in patients with unilateral chronic simple glaucoma. This measure appears to give an indication of suprathreshold contrast processing and is related to the difference in luminance between pattern elements, rather than the quality of the border or "edge" between them. The data support not only an increase in contrast threshold (reduced sensitivity) in early glaucoma and some patients with ocular hypertension but also a suppression in suprathreshold function that is not readily measurable with standard psychophysical methods. The findings are consistent with recent theories concerning the effect of early chronic simple glaucoma on the function of Y-type units of the M (magnocellular)-type pathways.


Cortical potentials to pattern reversal and luminance onset under ramp stimulation conditions in glaucoma. Stimulus quantities with a ramp-like temporal course evoke cortical potentials that are delayed and attenuated in comparison with responses evoked by a step-like course. This delay probably depends on temporal transfer characteristics of the activated precortical visual system. In a pilot study, luminance onset and pattern-reversal stimulation using this technique (light-emitting diode stimulator; transition time, 50 ms) were applied to 18 glaucomatous eyes with early visual field damage. The visual evoked cortical potential latency shifts between ramp and step mode were compared with visual field indices (mean defect, corrected loss variance). The pattern-reversal stimulation in ramp mode yielded a significant difference between the glaucoma group and normal subjects (p less than 0.004). The difference between groups with pattern-reversal stimulation in step mode was not significant (p = 0.15). From the determined visual field indices, only the mean defect showed a significant correlation to the measured visual evoked cortical potential latency shift, with both luminance-onset and pattern-reversal stimulation. In glaucoma with early malfunction, the precortical transmission and processing of lower and middle temporal frequencies, which are predominant in ramp-like temporal stimulus courses, are obviously more affected than the transmission of higher frequencies. The ramp stimulation technique for visual evoked cortical potentials might be of interest as a tool to detect early and specific functional defects in glaucoma.


Pattern flash visual evoked potentials in patients with homonymous hemianopia. Visual evoked potentials from seven horizontally spaced electrodes were recorded from normal subjects and subjects with homonymous hemianopia in response to hemifield pattern flash stimulation. Stimulation produced a large early peak that was positive on the scalp contralateral to the hemifield and negative on the ipsilateral scalp. From computer fitting of the amplitudes versus electrode position, the position of the equivalent source was found to be in the contralateral hemisphere. The horizontal orientation of the dipole source was approximately tangential (parallel) to the occipital scalp surface with negative polarity toward the medial fissure. In normal subjects, visual evoked potential amplitudes at the first peak were positive on the left and negative on the right for right hemifield stimulation. Left hemifield stimulation showed the opposite results. Three patients with homonymous hemianopia showed normal visual evoked potential results from their functional hemifields and nearly flat results from their hemianopic hemifields. The normal visual evoked potentials originated in their intact cortical hemispheres.


The topographic distribution of the magnetic P100M to full- and half-field stimulation. Visual evoked magnetic responses were recorded to full-field and left and right half-field stimulation with three check sizes (70', 34' and 22') in five normal subjects. Recordings were made sequentially on a 20-position grid (4 x 5) based on the inion, by means of a single-channel direct current-Superconducting Quantum Interference Device second-order gradiometer. The topographic maps were consistent on the same subjects recorded 2 months apart. The half-field responses produced the strongest signals in the contralateral hemisphere and were consistent with the cruciform model of the calcarine fissure. Right half fields produced upper-left-quadrant outgoing fields and lower-left-quadrant ingoing fields, while the left half field produced the opposite response. The topographic maps also varied with check size, with the larger checks producing positive or negative maximum position more anteriorly than small checks. In addition, with large checks the full-field responses could be explained as the summation of the two half fields, whereas full-field responses to smaller checks were more unpredictable and may be due to sources located at the occipital pole or lateral surface. In addition, dipole sources were located as appropriate with the use of inverse problem solutions. Topographic data will be vital to the clinical use of the visual evoked field but, in addition, provides complementary information to visual evoked potentials, allowing detailed studies of the visual cortex.


The application of Laplacian analysis in the recording of half-field pattern-onset evoked potentials. The Laplacian operator in electroencephalographic measurements consists of a mathematical combination of the responses from a number of electrodes (e.g., five in a crosswise montage). It enhances activity from sources lying underneath the area covered, relative to activity from outside this area. Thus, by appropriate positioning, the contributions of extrastriate and striate sources can be recorded selectively. To quantify the contribution of each hemisphere to half-field onset evoked potentials, the responses in two Laplacian operators, one over each hemisphere, were analyzed and compared to monopolar derivations and a bipolar derivation between the two hemispheres. Both the Laplacian and bipolar analyses were helpful in interpretation of the responses.


Visual evoked potentials specific for motion onset. Motion-onset visual evoked potentials were studied in 140 subjects by means of motion-onset stimulation either on a television screen or through back projecting via a moving mirror. The motion-onset visual evoked potentials were characterized in 94% of the population by a dominant negative peak with latency in the range of 135-180 ms. Motion-onset visual evoked potentials with a dominant positive peak, as described in the literature, seemed to be a variant of pattern-off visual evoked potentials, caused by the pattern-disappearance effect at the onset of motion with a high temporal frequency (the multiple of the spatial frequency of the structure and the velocity of motion) of more than 6 Hz. Such visual evoked potentials occur mainly when the stimulus is limited to the macular area only. Additionally, other stimulus and recording conditions were found to be suitable for acquiring the specific motion-onset potentials without their contamination by pattern-related components. These conditions were as follows: an aperiodic moving pattern (e.g., random dots) with a low contrast (less than 0.2); a short duration of motion (less than or equal to 200 ms) and a sufficient interstimulus interval (at least five times longer than the motion duration) to decrease the adaptation to motion; and extramacular stimulation and recording of visual evoked potentials from unipolar lateral occipital leads. Such leads should be used because of the lateralization of these visual evoked potentials (mainly to the right occipital area), which is consistent with their assumed extrastriate origin.


The c-wave of the direct-current-recorded electroretinogram and the standing potential of the albino rabbit eye in response to repeated series of light stimuli of different intensities. In 10 experiments on five albino rabbits, the direct-current electroretinogram and the standing potential of the eye were recorded in response to repeated light stimuli (duration, 10 s; interval, 70 s), presented in four series, each consisting of 25 light flashes. Light intensities were, in order of presentation to the eyes, 3, 2, 1 and 0 log rel units (series I, II, III and IV, respectively) below the maximum output of the system. Thirty minutes of dark adaptation preceded each series. At the end of series I, the mean amplitudes of the b- and c-waves were higher and that of the a-wave relatively unchanged compared with the corresponding initial amplitudes. During series II-IV, there was a marked decrease in mean a- and b-wave amplitudes between the first and the following electroretinogram responses, and at the end of the three series, the amplitudes were still significantly reduced compared with the corresponding initial values. The mean c-wave amplitude was also markedly decreased immediately after the first electroretinogram recording, but it later recovered to a large extent. A peak in the c-wave amplitude was discerned about 14-18 minutes after the start of the recordings. A standing potential minimum during the second light stimulus was followed by a peak after about 10-13 minutes. The partially parallel behavior of the c-wave and the standing potential suggests the operation of a pigment epithelial mechanism behind the recovery of the c-wave amplitude. The final amplitudes of the b- and c-waves, and to a large extent also of the a-wave, were about the same irrespective of stimulus intensity. The adaptational processes in the rabbit appear to be more complicated than was previously thought. When electroretinogram amplitudes and standing potential levels are discussed and when one experiment is compared with another one, it is important that adaptational and stimulus conditions, as well as time course, are well controlled and clearly specified.


[Proteinuria and atherogenic risk].

[Proteinuria and atherogenic risk]. The relationship between blood-lipid levels and severity of proteinuria was examined retrospectively in 30 patients (12 males, 18 females; mean age 39 [18-58] years). All patients had histologically confirmed glomerulonephritis (minimal change: n = 7, perimembranous: n = 8, focal sclerosing: n = 6, rapid progressive: n = 3, mesangio-proliferative: n = 4, membrano-proliferative: n = 1, diabetic glomerulosclerosis: n = 1). None was taking lipid-lowering drugs. Patients were classified according to the degree of proteinuria. In group 1 (proteinuria less than 5 g/d, n = 13) the LDL-HDL ratio averaged 4.4; in group 2 (proteinuria 5.0-10.0 g/d, n = 10) the average ratio was 8.8, and in group 3 (proteinuria greater than 10.0 g/d, n = 7) 13.3. Total cholesterol concentration also rose with increasing proteinuria (to 300 +/- 87 mg/dl, 375 +/- 168 mg/dl and 464 +/- 143 mg/d, respectively). The size of the LDL-HDL ratio and the level of total cholesterol did not correlate with the degree of excretory renal failure. These results point to an impressive correlation between the degree of proteinuria and the level of LDL-HDL ratio as a measure of atherogenic risk for a given patient.


[Bleeding gastric and duodenal varicose veins: endoscopic embolisation using tissue adhesives]. Endoscopically guided intravascular injections of the tissue glue N-butyl-2-cyanoacrylate have since 1990 been performed in eight patients (seven men, one woman; median age 59.5 [40-72] years) with cirrhosis of the liver (alcoholic: n = 6, posthepatic, n = 2), decreased haemoglobin (6-10 g/dl) and transient shock symptoms (n = 5) due to gastric (n = 7) or duodenal varices (n = 1). Gastric acid production was suppressed with omeprazole. Neither balloon catheters nor drugs were used to lower portal vein pressure. Initial haemostasis was achieved in all patients. One patient with consumption coagulopathy died of recurrent bleeding from varices in the body of the stomach which could be only temporarily arrested. Another patient had a recurrence of bleeding from varices in the cardia 3 months after the initial treatment: it was again controlled by endoscopic sclerotherapy with tissue glue. All other patients remain free of bleeding after a mean observation time of 8.4 months.


[Mitral insufficiency after percutaneous balloon valvuloplasty in mitral stenosis. Incidence and progression]. Percutaneous balloon valvoplasty of the mitral valve was performed in 126 patients (24 men, 102 women; mean age 55.0 +/- 12.1 years) with mitral stenosis. The mean transmitral valve gradient fell from 12.4 +/- 6.1 to 6.0 +/- 3.2 mmHg, while the valve opening area increased from 1.0 +/- 0.2 to 1.55 +/- 0.3 cm2. After percutaneous balloon valvoplasty 36 patients still had no mitral regurgitation, while the grade of mitral regurgitation remained the same in 47 (grade I: n = 35; grade I: n = 12). Mitral regurgitation, previously not present, occurred in 25 patients, but was severe in only three (grade III: n = 1; grade IV: n = 2). Previously present mitral regurgitation increased in 18 of 65 patients, in four to grade III, in one to grade IV. In three patients acute grade IV mitral regurgitation resulted from a tear in a leaflet of a fibrotic valve which was not or only slightly calcified, requiring emergency surgery. Followup observations over 16.9 (1-60) months showed no change in most patients, but three developed mitral regurgitation. The latter underwent elective surgery, as did one patient with acute mitral regurgitation. Thus a total of seven patients (5.6%) required surgery for mitral regurgitation after percutaneous balloon valvoplasty.


[Diphtheria immunity in school beginners and after reimmunization with d-vaccine]. The antitoxin immune status against diphtheria was determined in 814 children, aged 6-7 years, 5-6 years after first immunization. All children were then re-immunized with d-vaccine. 4-8 weeks later antitoxin was again measured to assess the immunogenic effect of the booster injection (reduced toxoid dosage of 5 IU/0.5 ml). Although all children had been completely immunized as infants, 149 of them (18.3%) presented inadequate or no immunity to diphtheria. The booster injection resulted in a reliably protective antibody concentration of 0.1 IU/ml serum even in children with low or no longer demonstrable residual immunity. The high proportion of inadequately protected children and the further continual loss of antitoxin antibodies makes booster injection mandatory at the time of beginning school as well as in juveniles and adults. The Standing Immunization Commission of the Federal German Health Office recommends this re-immunization every 10 years in the form of combined tetanus-diphtheria immunization with Td vaccine.


[Endoscopic sonography in extrahepatic obstructive jaundice]. In a prospective study, 37 patients (20 women, 17 men, mean age 75 [41-93] years) with extrahepatic obstructive jaundice were investigated, within 24 hours of admission, by transcutaneous ultrasound (US), endoscopic ultrasound (EUS) and endoscopic retrograde cholangiopancreatography (ERCP). EUS was always performed after US and immediately before ERCP, and the findings were recorded without any knowledge of the results of ERCP (the 'gold standard'). Dilatation of the common bile duct was demonstrated by all three methods. Concretions in the distal common bile duct causing obstructive jaundice were demonstrated by EUS in 15 out of 16 cases, but in only seven cases by US. All 21 cases with an underlying malignant cause were correctly diagnosed by EUS and ERCP, and the level of the biliary obstruction was accurately determined; using US this was possible in only 15 (70%) and 18 (85%) cases. In comparison with ERCP, which imaged the tumour only indirectly, EUS showed the tumour itself and allowed local and regional staging in all cases. EUS is superior to US for elucidating the cause of biliary outflow obstruction and allows reliable local and regional staging. It is of additional benefit in deciding on appropriate therapy. A disadvantage is the impossibility at present of undertaking surgical therapy during EUS investigations.


[Fatal pulmonary embolism after lysis therapy in post-traumatic renal vein thrombosis]. A 30-year-old man was hospitalized because of increasing dyspnoea for 4 weeks. Chest X-ray demonstrated an infiltrate in the right upper lobe and enlargement of the central pulmonary arteries. Lung perfusion scintigraphy revealed, typical of embolism, absent perfusion of the entire right upper lobe, as well as segmental embolism in the left upper and basal lobes. Phlebography of the legs and pelvis was unremarkable. Intravenous heparin treatment was begun (initially 1,250 IU/h, then dosage adjusted according to the partial thromboplastin time). Nonetheless the patient's condition deteriorated the next day and the respiratory failure increased (pO2 61 mm Hg despite oxygen supply). Streptokinase was then infused in ultra-high dosage, 9 million units over 6 hours. But the patient died of cardiocirculatory failure 4 hours after the streptokinase infusion had been finished. Autopsy revealed fulminant recurrent pulmonary embolism with occlusion of the right main pulmonary artery. The emboli had their origin in renal vein thrombosis extending into the inferior vena cava, which had probably been caused by slight trauma to the flank during a game of squash 6 weeks previously.


[Scanning electron microscopic findings of the navicular bone and deep flexor tendon in podotrochlosis of horses]. In 25 adult horses the podotrochlea of 49 forelimbs was examined by means of light and electron microscopy in order to correlate clinical and morphological findings. According to the clinical diagnosis the animals were divided into three groups: lameness due to syndrome of podotrochlosis (group 1) or due to tendopathy (group 2) and horses without lameness (group 3). The most striking pathological findings of the navicular bone and the opposite surface of the deep flexor tendon were found in horses with podotrochlosis, consisting of loss of cartilage and tendon matrix with denudation of collagen fibrils, superficial degeneration and necrosis, focal occurrence of fissures and far-reaching defects, sometimes accompanied by adhesions between tendon and navicular bone surface. In radiologically only slightly altered tendons and navicular bones light and scanning electron microscopy often revealed moderate to severe pathological changes, which sometimes could also be seen in clinically healthy horses. The distribution of the lesions indicate that in course of podotrochlosis the initial alterations caused by repeated microtraumata start at the surface of the deep flexor tendon and subsequently spread to the opposite facies flexoria of the navicular bone. An involvement of the cartilage and the synovial layer of the hoof joint in cases with podotrochlosis could only be rarely observed and is to regard as a secondary manifestation.


[PCB concentrations in hair, blood, tissues and secretions of chronically-exposed dairy cows, fattening bulls and calves. 1. Course and relation of some polychlorinated biphenyls in hair, milk and tissues in exposed nursing cows and conventionally raised dairy cows]. 20 cows contaminated chronically with PCB were kept as nurse cows or in a tie-stall. The contamination in different substrates (hair, milk, blood, feces) was examined for a period up to 8 months. The distribution of PCB in the carcass of some animals was registered in addition. The system of keeping nurse cows turned out to be useful in order to overcome a contamination situation. Drying off gravid animals in the first step helps solving problems of handling contaminated milk. With low contaminated animals a short dry off period is sufficient, so that the milk--after calving--is marketable (report II, in preparation). In case of nurse cows with two calves post partum a continuous decline of PCB-concentrations in the milk can be observed. With biological half life periods of 2-4 months, milk with PCB 153-concentrations of 0.15-0.20 mg/kg fat will be marketable within this period. Cows milked by milking-machines show a decline of PCB in the milk similar to nurse cows. Two animals had a limited increase p.p., probably caused by mobilization of fat in the high lactation stage. Over longer periods, the biological half-life-periods were comparable to nursing cows. Hair is easy to sample and store; it is useful as a diagnostic substrate beside the milk in order to estimate the degree of contamination in individual animals. The ratio of PCB-concentrations between perirenal fat and hair is 1:0.95 (s = +/-0.192); the ratio of PCB-concentrations between perirenal fat and milk is 1:0.77 (s = +/- 0.122).(ABSTRACT TRUNCATED AT 250 WORDS)


[Evaluation of fixed glucocorticoid-antibiotic combinations]. Fixed combinations of glucocorticoids and antibiotics are widely used for the treatment of bacterial infections because they can cause a rapid relief of the inflammatory symptoms. However, hitherto a decisive improvement of the clinical efficacy of the combination as compared to single antibiotic therapy could not be proved. Without a real clinical advantage the combined use of glucocorticoids causes severe side effects like immune suppression with increased risk of infections, gastrointestinal lesions and depression of endogenous hydrocortisone which all will occur even after short-term use and may last for several weeks. Glucocorticoids exhibit a markedly longer duration of action than antibiotics with the risk of cumulation of the glucocorticoid. Thus, there is no kinetic compatibility as it has to be claimed for a rational combination. Due to the negative risk-benefit relation the systemic use of such combinations has to be rejected. For the topical treatment of skin disorders, however, the short-term use of combinations of corticosteroids and antibiotics with comparable pharmacokinetics on the skin like aminoglycoside antibiotics can be of clinical benefit.


[Liver diseases of fattening bulls].

[Liver diseases of fattening bulls]. The authors report on occurrence, causes and diagnostics of liver affections observed in fattening bulls in Ukrainia between 1982 and 1988. For this purpose, 2747 bulls in 10 fattening plants had been controlled clinically once during the last month of their final fattening period (lasting, according to the feeding schedule, from the 4th until the 12th, or from the 6th until the 18th month of life), and 1318 of them were controlled for eventual hepatic lesions at slaughter. The authors found an increase in liver affections during the final fattening period. The type of lesion found preferentially in the different fattening plants showed a certain correlation with feeding used in these: The prevalence of liver lesions (i.e. in 87.2% of the animals controlled) were found in fattening bulls fed cereal branstraw-pellets; among these, liver abscesses were most frequent (i.e. 55.2% of all lesions observed in this group). Steatosis of the liver was prevalent in fattening bulls receiving eating offalls (i.e. 82.7% of all lesions found in that group), whereas liver cirrhosis was prevalent in fattening bulls fed with sugar beet chips-silage. In Holstein-bulls, liver lesions were about double as frequent as in Fleckvieh-bulls (i.e. 37.3 and 16.7% of the livers controlled were found involved, respectively). Diagnostical value of several clinical parameters controlled is discussed (i.e. size and sensitivity of liver percussion field, activity of SDH, LDH, AST and ALT in serum, serum concentration of vitamin A, D3-25 and E, concentration of Vitamin A in liver, and concentration of cholic acids and of their glucoconjugates in bile).


[Arnold Schell (1821-1900), departmental veterinarian and dozent of the Agricultural Academy in Bonn--contemporary historical profile of a personality]. In the early 19th century numerous scientific educational institutions in the field of agriculture came into existence. Motives were new knowledges in agriculture, science and economics. After a transient establishment of an agricultural institute at the University of Bonn (1819-1826) in 1847 an independent academy of agriculture, later a college resp. a faculty were founded in Poppelsdorf nr. Bonn. Instructions on veterinary science, which was regarded as an auxiliary subject included animal diseases and anatomy as well as physiology of domestic animals. These subjects were taught for 48 years by Prof. Arnold SCHELL, honorary lecturer (1850-1898), being simultaneously Departmentstierarzt in Cologne and Kreistierarzt (district veterinary officer) in Bonn. SCHELL published articles with variable topics. He took an active hand as member of the executive committee (from 1860) and as head of the local section Bonn in the Landwirtschaftliche Verein für Rheinpreussen. He organized the Verein Rheinpreussischer Tierärzte, and he was for many years its president. As delegate of this association he advocated the corporate concerns in the Deutsche Veterinärrat and in the Centralvertretung der tierärztlichen Vereine Preussens. SCHELL was a distinguished teacher and conveyor between veterinary science and agriculture, he was engaged in problems of animals husbandry and epidemic law, he contributed essentially to the development of the veterinary corporation. He was decorated with top honors as Kronenorden III. class and Roter Adlerorden IV. and III. class.


[Leibniz and veterinary medicine--a contribution to Leibniz research]. This study examines LEIBNIZ' idea of Veterinary medicine in a biographical context. It is based on material from the Leibniz-Archives of the Niedersächsische Landesbibliothek Hannover, primary sources as well as the correspondence between LEIBNIZ and F. HOFFMANN and B. RAMAZZINI. Critical analysis of LEIBNIZ' proposal to establish a medical administrative authority and an analysis of further sources corroborate the view of LEIBNIZ as a progressive thinker who included the epidemiology of veterinary medicine (the preventive approach) in his conception. In this way he conceived of veterinary medicine in scientific terms which is going to be the relevant approach today.


Anterior skull base reconstruction with the pericranial flap after craniofacial resection. No one reconstructive method is always satisfactory, especially when considering repair of a region such as the anterior skull base. Increased morbidity and mortality is directly related to failure of the reconstruction to adequately isolate the cranial cavity from the respiratory tract. Those surgeons performing craniofacial resections for lesions of the paranasal sinuses and anterior skull base must be familiar with a variety of reconstructive techniques which they can utilize depending upon the surgical defect that must be closed. For those small to moderate size defects of the anterior fossa we recommend using the inferiorly based pericranial flap to effect a repair. For larger defects extending laterally from the midline to involve a portion of the orbital roof, a laterally based flap of temporalis and pericranium can be used to provide successful anterior skull base reconstruction. Larger defects of the cranio-orbito-facial region will require additional methods of repair utilizing distant vascularized flaps.


Management of head and neck burns.

Management of head and neck burns. Successful treatment of acute head/neck burns requires assessment and protection of the airway, prevention of further injury to damaged surface structures, and timely and diligent debridement and wound closure. Rehabilitation methods and modalities help to preserve function and control scarring. Reconstructive surgery should be designed to improve function and appearance, primarily by correction of the skin/tissue defect which healed by scar contracture. Thoughtful timing and application of logical surgical principles offer the opportunity of recovery to a level better than merely acceptable.


Loracarbef (LY 163892) vs amoxicillin/clavulanate in bacterial maxillary sinusitis. Loracarbef (LY 163892), a beta-lactam antibiotic (carbacephem), was compared with amoxicillin/clavulanate potassium in a 10-day, single-blind, randomized parallel trial in the treatment of acute bacterial maxillary sinusitis. Based on posttherapy aspirate and culture, there was a 95.2% bacteriologic cure rate in patients receiving loracarbef (400 mg twice daily) and an 86.7% cure rate in patients receiving amoxicillin/clavulanate (500/125 mg three times daily) (p = 0.359). Loracarbef was comparable in efficacy to amoxicillin/clavulanate with a more desirable safety profile.


Subglottic and tracheal malignancies.

Subglottic and tracheal malignancies. Subglottic and tracheal malignancies are the least frequently encountered laryngeal cancers. When these tumors are encountered, they have often reached advanced size prior to producing symptoms. Once symptoms are brought to the attention of the otolaryngologist, rapid and accurate diagnosis is essential to effect the earliest possible treatment and to minimize morbidity and mortality associated with this problem. Illustrative cases are presented including a highly unusual case that presented with cardiac-like chest pain. A review of the literature including the pertinent anatomy, pathophysiology, and methods of diagnosis and treatment is presented. Increased familiarity with this disease process and a high index of suspicion on the part of the otolaryngologist may lead to improved survival patterns in patients with these malignancies.


Otogenic brain abscess: the Syracuse experience. A review is presented of five cases of otogenic brain abscesses (from among 34 cases of brain abscesses of all causes) treated during a 16-year period at a major university hospital in upstate New York. Although the morbidity and mortality rates are high for patients with brain abscess, advances in the microbial isolation methods, specificity of antimicrobial agents, and earlier diagnosis by CT scans have all contributed to an improved outcome for this dreaded disease.


Late development of lateral sinus vein thrombosis. The incidence of lateral sinus vein thrombosis has been reduced by the use of antibiotics, but it is still a major complication of middle ear disease. Patients without active acute or chronic middle ear infection, however, develop this deadly complication. CT scan is helpful in diagnosis, but mostly the final diagnosis is made by surgical exploration. A case of a 23-year-old patient who developed lateral sinus vein thrombosis without an active middle ear disease is presented. The pertinent literature is discussed.


Recurrent meningitis and a congenital perilymph fistula. In any child with recurrent meningitis, the presence of a congenital perilymph fistula must be entertained. All of the patients must have an audiologic assessment, and if a sensorineural loss is demonstrated, CT of the temporal bones should be performed. CT is excellent in identifying malformations within the temporal bones, fistulous tracts, soft tissue densities in the middle ear, and defects in the tegmen tympani. Although MRI may provide superior discrimination of the audiovestibular and facial nerves and cerebellopontine angle, presently it does not offer any distinct advantages over CT in evaluation of the inner ear. When a fistula is suspected, an exploratory tympanotomy is recommended, and any CSF leak is sealed with muscle.


CSF anatomy with emphasis on relations to nasal cavity and labyrinthine fluids. Cerebrospinal fluid, occupying the subarachnoid space, is elaborated in an active process by the choroid plexus. It supports the brain and spinal cord and acts in lieu of a lymphatic system for central nervous tissue. Whether or not absorption of CSF into dural venous sinuses is an active or passive process is still controversial. A very thin layer of bone separates the posterior ethmoid air sinus from the subarachnoid space. There appears to be potential in man for flow of cerebrospinal fluid into the perilymphatic space of the inner ear, but it seldom occurs.


Neurosurgical approaches to cerebrospinal fluid rhinorrhea. The evolutionary concepts of pinpointing and treating cerebrospinal fluid (CSF) fistulas over the past few decades are reviewed taking into consideration the dynamic character of CSF circulation. The localization of the site of leakage is greatly facilitated by the judicious use of a variety of radioisotope and radiological techniques. The most recent are Metrizamide CT Cisternography and Magnetic Resonance Imaging. It is asserted that still the most challenging cases are those with intermittent liquorrheas, and those patients in which the site of the fistula is not easily defined. The authors will describe their personal experience with intracranial surgical repair of fistulas located in the anterior fossa.


Complications of interstitial radioactive iodine implants for recurrent pituitary adenomas. Three cases of recurrent pituitary adenoma elected to be treated with I125 implants are presented. The I125 implants caused significant delayed changes in the tissues surrounding the sella turcica which lead to the development of refractory cerebrospinal fluid (CSF) rhinorrhea. All three cases developed meningitis and two had pneumocephalus. This complication lead to the death of two patients and required intensive therapy in the third to achieve recovery.


Extracranial approaches to the repair of cerebrospinal fluid rhinorrhea. This paper presents a review of the extracranial evaluation and treatment of cerebrospinal fluid (CSF) rhinorrhea. Diagnosis with attention to a careful history and physical with maneuvers which exacerbate drainage and thorough physical exam along with imaging techniques are discussed. The common etiologies of CSF rhinorrhea including trauma, spontaneous leakage, tumor, and iatrogenic injury are included. Management consists of conservative measures including the avoidance of straining maneuvers which increases intracranial pressure. Periodic drainage of CSF via lumbar puncture or continuous drainage via flow-regulated systems may also be of benefit in attempts of conservative management. Failure of conservative management, constant leakage, pneumocephalus, and recurrent meningitis are indicators for surgical repairs. Ethmoid-cribiform plate region repairs are generally approached by external ethmoidectomy and the development of mucoperiosteal flaps from various donor sites which are then rotated to the leak area to seal the defect. Frontal sinus leaks are usually repaired via an osteoplastic flap technique with direct repair of the dural defect or the use of fascial graft tucked under the bony defect, then obliterated with abdominal fat. CSF rhinorrhea presents a diagnostic and surgical challenge to the otolaryngologist. After diagnosis and localization, operative repair using extracranial approaches is accepted as the initial method of intervention in these cases.


Cerebrospinal fluid rhinorrhea: a review of the literature. CSF rhinorrhea may be spontaneous or traumatic, the majority of cases being traumatic and presenting within the first three months. Spontaneous leaks imply an underlying abnormality which must be identified prior to treatment. Diagnosis and identification of the site of the leak is often inaccurate, even with meticulous care given to placing and removing the nasal pledgets. Once the leak is identified, medical or surgical treatment may be attempted. Recurrent leaks are common and serial operative procedures have been reported to stop even small leaks.


Spontaneous cerebrospinal fluid rhinorrhea. The diagnosis of CSF rhinorrhea requires the performance of a thorough history and physical examination. Often no objective findings can be found and further evaluation will be required. In our experience, metrizamide CT cisternography yields the most information for localization of the fistula. When indicated, patients can be protected against meningitis by using prophylactic antibiotics for 4-6 weeks to allow a fistula to close spontaneously. If the fistula fails to close during this time, surgical closure with dural or muscle graft with or without waxing of the bone is the treatment of choice.


Assessment of medical impairment: problems v diabetes traumatic. The modern concept of diabetes is first considered, i.e a susceptibility to diabetes which can be inherited. The environment may then interact with this susceptibility to determine which persons actually develop clinical complaints and the timing of its onset. The clinical types of established potential and latent diabetics are described together with the proof required for trauma to be accepted as a cause of diabetes rather than exposing a previous diabetic or latent state. Despite an extensive search of the literature and questioning of experts both in Kenya and outside, in the absence of predisposing factors no evidence of trauma being the direct cause of the diabetic syndrome has been found. The one exception may be where there has been definite gross physical injury to the pancreas, but even in this case the evidence is scanty and not very convincing and such cases must be very rare. Trauma may precipitate latent diabetes and its complications and make control more difficult. A percentage assessment is suggested.


Reference values for FEV1 and FVC in male adolescents and young adults of Ibo origin. Forced vital capacity (FVC) and one second forced expiratory volume (FEV1) were measured in 245 healthy Nigerian Ibo males aged 12-23 years. Analysis showed strong correlation between anthropometric factors (age, height, weight) and spirometric measurements (r----0.808-0.994). In the young adult group (18-23 years), FEV1 did not correlate so strongly with weight, however (r----0.654). Prediction equations, based on age and height have been developed for use among male Ibo adolescents and young adults.


Acute renal failure as seen at Kenyatta National Hospital. Forty seven patients with acute renal failure were studied prospectively over a two-year period at the Kenyatta National Hospital. There were 20 males and 27 females. The mortality rate was 40.4%. Most patients had medically oriented problems. Complications that were associated with a high mortality were infections and the presence of neuropsychiatric manifestations.


Keloids: a study of the immune reaction to sebum. A controlled study of the "immune reaction to sebum" pathogenesis of keloids was carried out at the University College Hospital, Ibadan, Nigeria; on 22 humans using a homogenate solution of liquid paraffin and vernix caseosa from neonates. The 22 human volunteers comprised two groups, 11 of which were keloid formers and 11 non keloid formers. 0.1cc of sterile liquid paraffin was injected intradermally into the anterior aspect of the left forearm. The mean reaction in keloid formers was 11.55mm while in non keloid formers, it was 8.18mm. Although a higher reaction was demonstrated in this study, in keloid formers, this was found not to be significant (p less than 0.05), thus suggesting that sebum may not be an important factor in the pathogenesis of keloid.


Insulinoma in pregnancy presenting as a seizure disorder: a case report. We present the clinical course and problems in the management of a 30 year old Nigerian lady who was admitted with fasting hypoglycaemia due to a pancreatic islet cell tumour (insulinoma) during the first trimester of pregnancy. Her case was initially misdiagnosed as idiopathic epilepsy. The outcome was fatal mainly because the poor clinical state of the patient limited our treatment options. This condition though uncommon, is potentially easily recognisable and treatable, as long as there is a high index of suspicion.


Unusual form of motor neuron disease in Kenya. Over the period November 1978 to October 1988, 46 cases of motor neuron disease were seen at Kenyatta National Hospital, Nairobi. One case was seen in private practice. A bimodal age distribution of the disease was identified with a peak in the fourth decade of life and another peak in the sixth decade of life. The disease seen in the fourth decade of life was different as seen in other parts of the world in that the majority of patients tended to present with very rapidly progressive disease despite the primary presentation with limb symptoms and signs. Serum cholinesterase activity in five of these patients and five of the classical motor neuron disease revealed no abnormalities. This unusually rapidly progressive disease in young adults has not been described anywhere. The disease seen in older age groups and especially in patients over fifty years of age was not different from the one seen in other parts of the world.


Cerebellar ataxia in childhood: a review of clinical features, investigative findings and aetiology in 30 cases. The symptoms, neurological deficits and aetiology of cerebellar ataxia were reviewed in 30 children aged from 4 to 16 years, who had been extensively investigated. Fourteen (46.6%) children had perinatal problems, and in 6 (20%), ataxia resulted from these perinatal events. Besides unsteady gait, a common presenting complaint was delayed motor milestones, noted in 15 (50%) patients. In most children (76.6%), clinical examination indicated involvement of more than one of the three main cerebellar divisions, viz archicerebellum, paleocerebellum and neocerebellum. Hypotonia, found in 11 (36.6%) children, was the third most common sign after gait and truncal ataxia. A variety of aetiological factors was identified, the two most frequent being hydrocephalus in 7 (23.3%) children, and perinatal problems in 6 (20%). The findings are discussed against the background of current literature on the subject.


Rarity of dementia (by DSM-III-R) in an urban community in Nigeria. Dementia of the elderly, a public health problem world-wide, is underdocumented in black Africa. We carried out a door-to-door survey in Idikan in NW3 ward, a political and administrative unit, with a population of 9000: in Ibadan city, Nigeria, to determine the burden of dementia. Census and demographic listing was done by trained clinical students who concurrently administered a modified Mini Mental State Examination as a screening instrument to those aged 40 years or more. Only 2 out of 932 subjects refused: 293 (31%) were aged 65 years or more. Those who were positive to the screening test and 20% of negatives were investigated by neurologists. Decline in cognitive function significantly correlated with age, female sex and low level of education. Impaired cognition was present in 41 (4.4%) but was due to depressive disorders in 7 (0.6%) patients. In none of the remaining 34 (3.8%) subjects could a diagnosis of dementia as defined by DSM-III-R be justified.


Bacteraemia in febrile out-patient children. In order to study the occurrence of bacteraemia, 634 consecutively febrile children aged less than or equal to 14 years with Initial rectal temperature or 39 degrees C and above were evaluated. The overall frequency of bacteraemia was 7.7% (49 cases). Salmonellae, Streptococci and Staphylococci accounted for 57%, 16% and 14% respectively. No statistically significant difference was noted between cases and controls with regard to the nutritional status mean age in months +/- SD (55.9 +/- 49.1 vs 39 +/- 41), and haemoglobin levels in g/dl +/- SD (11.1 +/- 1.5 vs 11.1 +/- 1.5) (P greater than 0.05). None of the parameters studied was a strong predictor of bacteraemia and systemic bacterial infection did not strongly correlate with the magnitude of the clinical illness.


Clinical and bacteriological study on childhood empyema in south eastern Nigeria. Forty-eight children with empyema thoracis were seen over a seven-year period (December, 1982 to November 1989) in the University of Calabar Teaching Hospital, Calabar, Nigeria. This number accounted for 0.2% of all paediatric admissions during the period. The peak age incidence was 2 years and under. Pneumonia was the antecedent illness in about all cases, but surprisingly, measles played an insignificant role. Late consultation and severe morbidity were constant feature with anaemia and cardiac failure as frequent complications of the disease. Staphylococcus aureus, the predominant causative organism was resistant to penicillin and ampicillin but sensitive to gentamicin, cloxacillin and erythromycin. The initial use of the parenteral gentamicin or cloxacillin in treating children with empyema is therefore recommended. This study demonstrates the rarity and low fatality (6%) of childhood empyema in Calabar, but protracted hospitalisation and exorbitant medication involved make it an important disease. Perhaps, it can be completely eliminated if parents are educated enough to avoid late reporting of childhood respiratory disease.


Megaloblastic anaemia in Zimbabwe: spectrum of clinical and haematological manifestations. An analysis of 100 cases (43 males and 57 females) with confirmed megaloblastic anaemia is presented. The age distribution showed two peaks with 18% in the third and fourth decades and 25% in the seventh decade. Anaemia of moderate to severe degree occurred in all patients and accounted for the commonest triad of symptoms at presentation viz: weakness (73%); breathlessness (40%) and headaches (33%). Macrocytosis or macroovalocytosis and neutrophil hyper-lobulation were found in all cases; MCV greater than 100fl in 84%; pancytopenia in 47%; and megaloblastic haematopoiesis found in all patients varied from moderate to gross in severity. Thus, the finding of macrocytic anaemia with a high MCV particularly in excess of 100fl, neutrophil hypersegmentation, and characteristic megaloblastic changes in the bone marrow should dictate further appropriate investigations to help in establishing the specific diagnosis if appropriate therapeutic intervention is to be ultimately instituted.


Comparative study of superficial cancer in Tanzania. Examination of the Tanzania Cancer Registry from 1978 to 1988 showed squamous cell carcinomas to be the most frequent form of superficial malignancy, followed by Kaposi's sarcoma and then malignant melanoma. Males were more afflicted than females, and the lower limbs were predominant sites of the lesion. In terms of relative importance of various types of superficial cancers, the pattern seen in Tanzania was similar to that in another East African country. In a West African country, Kaposi's sarcoma was not common. On the other hand, among blacks in the USA, basal cell carcinomas were almost similar in frequency to squamous cell carcinomas.


Consanguineous marriages in the province of Trabzon, Turkey. This study involved 999 married women, aged between 15 and 49, at the twelve health centres in the province of Trabzon in order to determine the ratio of consanguineous marriages, the factors affecting this situation, the ratios of abortion and the mortality of children in the first year. This ratio of consanguineous marriages was found 20 percent. The education levels of the great majority of these were low. The average age was 18. These were most frequently between children of paternal aunts and maternal uncles (39%) and these marriages, the ratio of abortion and children mortality were higher than others (P less than 0.05). Furthermore, it has been established that the kind of marriage has considerably decreased in Trabzon lately, but we believe that this reduction will be higher in the future since the education levels rapidly increase.


Adult empyema in Zaria, Nigeria.

Adult empyema in Zaria, Nigeria. The clinical records of 41 adult patients who were treated for empyema thoracis at the ABU Hospital, Zaria from 1974 to 1986 have been reviewed. Twenty six (63%) of the patients were younger than 34 years. Bacterial pneumonia, pulmonary tuberculosis and chronic bronchitis were the underlying illnesses in 32 (78%) while advanced malignancies were present in two others. Gram-negative bacilli were as important as the gram-positive cocci as causative agents in the 16 patients whose pleural aspirates were culture-positive. Closed chest tube drainage was most often effective when combined with antibiotics. Overall, 5 patients died, 2 absconded, 34 were discharged home but the default rate from the follow up clinic was high.


Raw milk as a source of enterotoxigenic Staphylococcus aureus and enterotoxins in consumer milk. Staphylococcus aureus strains were isolated from 183 of 300 raw milk samples collected at the Kenya Co-operative Creamery (Dandora). 97 of these 183 trains were assayed for the production of enterotoxin A, B, C and D. Seventy two (74.2%) of these were found to produce either a single or a combination of enterotoxins. Raw milk is a potential source of enterotoxigenic S. aureus in milk and milk products, especially if there is defective pasteurisation.


Layman's perception of antimicrobial agents: a challenge to health education strategy in Zimbabwe. In many developing countries there has not been any systematic analysis of societal beliefs and attitudes towards drug entities, the meaning which is attributed to drugs and their effects and how such meanings might influence drug consumption and health seeking behaviour. It is in many developing countries that a lot of antimicrobial agents are available freely over the counter or on the street. This is said to make the assessment of the therapeutic outcome during their use often very difficult. The present study has shown that continued health education while at the same time paying attention to societal beliefs and attitudes towards infectious diseases and medicines used, is required. The specific aims must be to reinforce beliefs that facilitate appropriate use of antimicrobial agents and to discourage those that impede it.