Probability of pancreatic cancer following diabetes: a population-based study

BACKGROUND & AIMS: Although diabetes occurs frequently in pancreatic cancer, the value of new-onset diabetes as a marker of underlying pancreatic cancer is unknown. METHODS: We assembled a population-based cohort of 2122 Rochester, Minnesota, residents age > or =50 years who first met standardized criteria for diabetes between January 1, 1950, and December 31, 1994, and identified those who developed pancreatic cancer within 3 years of meeting criteria for diabetes. We compared observed rates of pancreatic cancer with expected rates based on the Iowa Surveillance Epidemiology and End Results registry. In a nested case control study, we compared body mass index (BMI) and smoking status in diabetes subjects with and without pancreatic cancer. RESULTS: Of 2122 diabetic subjects, 18 (0.85%) were diagnosed with pancreatic cancer within 3 years of meeting criteria for diabetes; 10 of 18 (56%) were diagnosed <6 months after first meeting criteria for diabetes, and 3 were resected. The observed-to-expected ratio of pancreatic cancer in the cohort was 7.94 (95% CI, 4.70-12.55). Compared with subjects without pancreatic cancer, diabetic subjects with pancreatic cancer were more likely to have met diabetes criteria after age 69 (OR = 4.52, 95% CI, 1.61-12.74) years but did not differ significantly with respect to BMI values (29.2 +/- 6.8 vs 26.5 +/- 5.0, respectively). A larger proportion of those who developed pancreatic cancer were ever smokers (92% vs 69%, respectively), but this did not reach statistical significance. CONCLUSIONS: Approximately 1% of diabetes subjects aged > or =50 years will be diagnosed with pancreatic cancer within 3 years of first meeting criteria for diabetes. The usefulness of new-onset diabetes as marker of early pancreatic cancer needs further evaluation.     

Effects of dietary protein on urinary calcium in normal subjects and in patients with nephrolithiasis.

The effect of high-protein diets on the excretion of calcium in urine was evaluated in four normal persons and in four patients with nephrolithiasis. All subjects were housed in a metabolic unit and given constant metabolic diets each day containing 0.5 g protein/kg and 300–600 mg calcium, 1000 mg phosphorus, and 69 mEq sodium. During the experimental phase, each person received an additional 1.5 g protein/kg/day consisting of purified casein, gluten, lactalbumin, and gelatin. There was a consistent increase in urinary calcium with the high-protein diet, averaging 88% above control in the normals and 82% in the patients. In addition, the normal subjects showed significant (p < 0.05) increases in urinary phosphorus (mean increases, 219 ± 53 mg/d, mean ± SE), nitrogen (8.8 ± 0.9 g/d), titratable acid (19 ± 5 mEq/d), and ammonium (22 ± 3 mEq/d), whereas the patients showed increases in urinary magnesium (18 ± 2 mg/d), nitrogen (12 ± 1.0 g/d), and ammonium (34 ± 2 mEq/d), and in creatinine clearance (14 ± 3 ml/min). In both groups, there was a small increase in the filtered, excreted, and reabsorbed calcium and a small decrease in the percentage reabsorption of calcium. Serum chemical values did not change from values with the low-protein diet. In two of the patients who were known to be hyperabsorbing calcium, sodium cellulose phosphate (chelator of intestinal calcium) reversed the increase in urinary calcium produced by the high-protein diet. In the remaining patients, neither sodium cellulose phosphate nor a low-calcium diet could counteract the increase in excretion of calcium with the diet. It is concluded that a high-protein diet can increase urinary calcium by altering renal function and/or increasing intestinal absorption of calcium and that dietary protein must be considered in the evaluation and treatment of patients with hypercalciuria and nephrolithiasis.     

Thoracic skeletal abnormalities in idiopathic mitral valve prolapse.

Idiopathic prolapse of the mitral valve is a common disorder, but many cases are clinically subtle. Thoracic skeletal abnormalities, reported recently to accompany the syndrome, may serve as an easily identifiable clinical indicator. The prevalence of these abnormalities was defined in 24 patients with proved prolapse of the mitral valve. The valvular syndrome was defined clinically, by echocardiography and, in seven cases, by left ventricular angiography. The skeletal deformities were defined clinically and radiographically. Pectus excavatum was present in 62 percent of the patients, "straight back" in 17 percent and severe scoliosis in 8 percent. Eighteen of the 24 patients (75 percent) had a definite thoracic skeletal deformity. The association of idiopathic prolapse of the mitral valve with these skeletal deformities may represent a forme fruste of Marfan's syndrome. Patients with "straight back" and pectus excavatum should be examined clinically and perhaps by echocardiography to exclude idiopathic prolapse of the mitral valve; when murmurs are present, a diagnosis of "pseudoheart disease" should not be made before mitral valve prolapse has been excluded.     

Effects of factors predisposing to atherosclerosis on formation of coronary collateral vessels

Two hundred eighteen consecutive patients undergoing selective coronary angiography were studied to determine the effects of underlying predisposing coronary risk factors on the formation of intercoronary collateral anastomoses. The presence or absence of hyperlipoproteinemia, diabetes mellitus, glucose intolerance, hypertension or obesity did not influence the formation of these intercoronary collateral channels. Our findings suggest that there are presently no measurable clinical factors that permit prediction of the presence of coronary collateral channels in an individual patient. Factors predisposing to atherosclerosis have a similar distribution in patients with and without such vessels.     

Refractory ventricular arrhythmias in a patient with mitral valve prolapse. Successful control with mitral valve replacement

A 35-year-old woman with proven mitral valve prolapse developed life threatening ventricular arrhythmias which were refractory to medical therapy. She had one episode of "cardiac arrest" presumably due to ventricular tachycardia or possibly ventricular fibrillation, and was successfully resuscitated with closed chest compression. Mitral valve replacement resulted in dramatic control of the ventricular arrhythmias. Over a period of three years following the operation, she has been able to resume an active life with occasional ventricular premature beats and no further episodes of ventricular tachyarrhythmias.     

Renal infarction due to renal artery dysplasia with dissection: Report of a case in a normotensive patient

A previously healthy 44-year-old man with well-documented normotension had a sudden onset of left flank pain and delayed onset of constitutional symptoms, hematuria, and elevations of lactic dehydrogenase, serum glutamic oxaloacetic transaminase, serum glutamic pyruvic transaminase, and creatinine levels. Angiography revealed unilateral renal artery fibromuscular dysplasia with dissection and infarction. In the year since, he has remained well and normotensive without therapy. The literature is reviewed.     

Nifedipine in chronic stable angina: a double-blind placebo-controlled crossover trial

Thirty patients with chronic stable angina pectoris were randomized in a double-blind prospective placebo-controlled crossover trial to assess the efficacy of nifedipine (30 to 60 mg/day orally) in controlling symptoms and objective signs of myocardial ischemia using a symptom-limited treadmill exercise test. Adverse effects that occurred during both nifedipine and placebo treatment were minor and generally well tolerated. Twenty-three patients were analyzed from the crossover phase of the study. Nifedipine significantly reduced the frequency of angina by 55% and nitroglycerin consumption by 59%, and increased exercise time by 34%. These changes were significantly greater than those in the placebo group. Hemodynamic evaluation during exercise revealed a significant reduction in systolic and diastolic blood pressures in the nifedipine group at the onset of angina and at maximal exercise without significant differences in heart rate responses in the nifedipine and placebo groups. The pressure-rate product during submaximal exercise was significantly smaller in the nifedipine group than in the placebo group, but did not differ significantly in the 2 groups at the onset of angina or on maximal exercise. Furthermore, S-T segment depressions that occurred during exercise at the same pressure-rate products were smaller in the nifedipine period than in the placebo period. Thus, it appears that the antianginal effects of nifedipine are caused by a reduced myocardial oxygen demand for a specific work load and possibly by an increased blood supply to ischemic myocardium.     

Serum gonadotropin and steroids associated with breeding activities in the green sea turtle,Chelonia mydas: II. Mating and nesting in natural populations

Circulating levels of gonadotropins (FSH and LH) and sex steroids (estrogen, testosterone, and progesterone) were examined in mating and nesting animals from three breeding aggregations of green sea turtles (Chelonia mydas). Copulating males were characterized by relatively low levels of both gonadotropins and high androgen levels, but the latter did not differ from values previously observed in prebreeding males. Females showed significant changes in all hormones studied, except estradiol. The patterns of changes in gonadotropins and steroids as well as their absolute values were similar among the three natural breeding aggregations and captive turtles studied previously. Serum or plasma LH showed slight but variable increases between mating and nesting animals, whereas FSH was consistently elevated at the time of nesting. Field studies demonstrate that this rise in FSH is a transient surge of no more than a few hours' duration: FSH does not rise until the middle of the nesting process, when oviposition begins, and FSH declines before or immediately after oviposition is completed. Thus, this peak in FSH apparently does not initiate nesting behavior. Testosterone did not differ between mating and nesting in females, but it dropped significantly in the first days following nesting (i.e., in the internesting interval when ovulation occurs). Progesterone values were also similar between mating and nesting samples, but this steroid along with LH frequently showed a pronounced elevation in the 1–2 days postnesting; their elevation was considered to represent the “ovulatory surge”. Since this progesterone and LH surge only occurs if a nesting turtle is allowed to oviposit, the presence of shelled oviducal eggs probably suppresses ovulation.     

The effect of anabolic steroids on lean body mass: the dose response curve

Data from human subjects given various amounts of anabolic steroids show that the resultant increment in lean body mass (LBM) has the features of a typical dose response curve. Low doses produce a very modest effect, while large doses result in a progressive augmentation of the LBM. Endogenous testosterone production during male adolescence is accompanied by a sex differential in LBM that is comparable to the LBM increment generated by exogenous steroids given to adults.     

Extrapancreatic action of sulfonylureas: hypoglycemic effects are not dependent on altered insulin binding or inhibition of transglutaminase

It has been proposed by others that sulfonylureas exert their extrapancreatic hypoglycemic effects by increasing insulin binding through inhibition of receptor-mediated hormone internalization. In this study, we examined the possibility that the drugs act by inhibiting transglutaminase, an enzyme thought important in the internalization process. For ten days, male rats were fed pulverized chow containing either no drug, glipizide (5 mg/kg initial body wt/d), or tolazamide (75 mg/kg initial body wt/d). Prior to sacrifice, the six-hour fasting level of serum glucose was significantly reduced from 96 mg/100 ml in the control rats to 81 and 42 mg/100 ml in the glipizide- and tolazamide-treated rats, respectively. In contrast, the serum level of insulin was similar for all groups. The activity of transglutaminase in the postnuclear fraction of liver homogenate also was the same for all experimental groups. The specific binding of labeled insulin to purified liver plasma membranes was examined over a broad range of insulin concentrations; once again, there was no difference between experimental groups. Thus, the hypoglycemia caused by sulfonylurea administration could not be attributed to increases in insulin binding, inhibition of transglutaminase activity, or enhanced insulin levels. These data support our previous suggestion, based on in vitro studies, that sulfonylureas act predominately on processes beyond the binding portion of the insulin receptor.