How to read clinical journals: X. How to react when your colleagues haven't read a thing.

Physicians receive little instruction on how to interact with colleagues, and even less guidance on what to do when their colleagues are poorly informed. Eight techniques are presented here that may be of use in dealing with colleagues who have clearly not read the literature and are unable to maintain the facade that they have. If employed properly and used judiciously, these techniques may help avoid embarrassment for all and may also improve the exchange of valuable information between professionals.

Antithyroid arthritis syndrome.

We describe a recent clinical case experience of antithyroid arthritis syndrome and literature search from 1965 to 1996 on antithyroid medication and associated arthritis using MEDLINE and EMBASE. The antithyroid arthritis syndrome is a transient migratory polyarthritis that occurs within 2 months of starting thionamide treatment, and resolves within 4 weeks of stopping therapy. Discontinuation of medication is necessary. Alternative forms of treatment for hyperthyroidism should be sought. Nonsteroidal antiinflammatory drug or treatment of the rheumatic complaints is recommended or if unsuccessful, corticosteroid treatment.

Dehydration during fasting increases serum lipids and lipoproteins.

The study was an open, prospective, randomized cross-over design to determine if dehydration during fasting increases lipid concentrations. Fifteen healthy subjects participated, 1 of whom did not complete the study. The subjects fasted once with no fluid replacement and once with salt and water supplementation. Following both fasts, blood was drawn for lipid assessments. Compared to fasting with fluid and salt replacement, fasting with no fluids was associated with higher (mean, 95% confidence interval) total serum cholesterol (8.1%, 4.3-11.9%), HDL cholesterol (7.5%, 1.8-13.1%), LDL cholesterol (10.5%, 2.2-18.8%), apolipoprotein A-1 (8.9%, 5.0-12.8%), and apolipoprotein B (10.5%, 5.2-15.8%). The change in serum triglycerides was not statistically significant (12.4%,-0.5-25.3%). There was a greater reduction in body weight during fasting with fluid restriction compared to fasting with salt and water supplementation (1.8%, 1.3-2.2%). Fasting with fluid restriction results in significantly higher lipid levels and, therefore, variation in hydration of patients could contribute to fluctuation in lipid levels of patients. Care should be taken to ensure that patients are in a standard state of hydration during assessment of lipid levels. We recommend: 1) that patients fast no longer than 12 h, and 2) that, during fasting, patients avoid unnecessary physical activity, avoid hot dry environments, ensure a liberal intake of water, and avoid diuretic substances such as caffeine.

Frusemide causes acute increases in lipid concentrations.

In a randomized double-blind placebo controlled parallel study involving fourteen healthy male volunteers, we examined whether the acute reduction in vascular volume associated with frusemide ingestion would haemoconcentrate lipid particles. Three hours after a single 40 mg oral dose of frusemide, there were 9.6-14.4% increases in lipids and lipoproteins which were highly correlated to changes in body weight. Until further studies determine the extent of haemoconcentration in patients being treated long term with frusemide, we recommend that blood be drawn for lipid analysis prior to frusemide ingestion.

Insulin resistance and action in hypertriglyceridemia.

To define further the characteristics of insulin insensitivity associated with hypertriglyceridemia, the metabolic responses to the euglycemic insulin clamp were evaluated in 6 hypertriglyceridemic male patients and compared to 5 normal male controls. At baseline, the hypertriglyceridemic patients had elevated triglycerides (687 +/- 172 vs 78 +/- 7 mg/dl, P less than 0.005) and free fatty acids (702 +/- 36 vs 444 +/- 42 microM/l, P less than 0.005) concentrations. During the euglycemic insulin clamp, steady-state plasma glucose concentrations were similar in both groups (90.2 +/- 1.5 vs 88.8 +/- 2.3 mg/dl, ns) as were steady state insulin levels (142 +/- 10.1 vs 132.2 +/- 6.8 microU/ml**). The amount of glucose metabolized during the last hour of the clamp (M) was significantly reduced in the hypertriglyceridemic patient (2.9 +/- 0.4 vs 6.2 +/- 0.7 mg.min-1.kg-1, P less than 0.001). Changes in free fatty acid, glycerol, B-hydroxybutyrate, lactate and pyruvate during the euglycemic insulin clamp were similar indicating a preserved antilipolytic, antiketogenic and glycolytic intermediate (lactate + pyruvate) response to insulin and glucose infusion in the hypertriglyceridemic patients. In summary, hypertriglyceridemia is associated with insulin resistance as it relates to muscle glucose utilization. However, this is not universal, as a number of other insulin responsive pathways appear to be unaffected.

Recurrent hypoglycemia secondary to drug-dispensing error.

We present three patients who developed hypoglycemia due to inadvertent dispensing of sulfonylurea drugs. Each patient had a similar clinical course characterized by hypoglycemia that remitted during hospitalization and recurred after discharge. The cause of the hypoglycemia was determined only after close inspection of the patients' medications, not the label on the container. Our experience suggests that hypoglycemia due to drug-dispensing error may be more common than is generally recognized.

Detecting Elevated Cholesterol Levels: Part 1: How accurate is the Reflotron?

To assess accuracy of blood cholesterol measurements in the office, fingerprick blood cholesterol assays by a dry reagent chemistry analyzer were compared in 151 patients with simultaneous venipuncture cholesterol assays by standard laboratory methods. Compared with the laboratory assay, seven of eight analyzers had total absolute biases less than 5%. Variability in results was comparable to that of community laboratories.

Detecting Elevated Cholesterol Levels: Part 2: Prevalence and feasibility considerations.

The Reflotron dry chemistry reflectance photometer was studied as a case-finding method in physicians' offices. A total of 713 adult patients had their risk factor profiles determined along with fingerprick blood cholesterol measurements. Blood cholesterol levels were classified into three categories, (<5.2 mmol/L), 51%; borderline high (5.2 to 6.1 mmol/L), 28%; and high (≥6.2 mmol/L), 21%. The physicians' predictions from clinical risk factor profiles of which patients had elevated serum cholesterol levels were inaccurate.

Growth hormone suppression and nonproliferative diabetic retinopathy: a preliminary feasibility study.

We used the long acting somatostatin analogue SMS 201-995 in order to examine the feasibility and effect of medical suppression of growth hormone in nonproliferative diabetic retinopathy. Six insulin-dependent diabetic subjects with nonproliferative retinopathy were studied. After eight weeks of SMS 201-995 administration, 24-hour integrated plasma growth hormone concentrations had declined by 47.0 +/- 9.3% of pretreatment values (p less than 0.01), and insulin requirements fell from 40.7 +/- 6.7 units per day to 32.2 +/- 6.9 units per day (p less than 0.01). Plasma levels of somatomedin-C were low before SMS 201-995 (0.5 +/- 0.1 U/ml) and remained unchanged at eight weeks (0.6 +/- 0.1 U/ml; p = ns). During SMS 201-995 administration, best corrected visual acuity improved in both right eyes (53.8 +/- 2.57 to 59.8 +/- 0.7 letters, p less than 0.05) and left eyes (54.8 +/- 2.8 to 61.7 +/- 1.23 letters, p less than 0.03). Fluorescein angiography and stereo fundus photography demonstrated concurrent improvement in retinopathy level in only two subjects. Following cessation of SMS 201-995 treatment, visual acuity returned to pretreatment levels in both right eyes (54.5 +/- 2.4 letters, p = ns compared to baseline) and left eyes (55.8 +/- 2.6 letters, p = ns compared to baseline). These results demonstrate that growth hormone was only partially suppressed by SMS 201-995 in insulin-dependent diabetic subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

The effects of SMS 201-995 (sandostatin) on metabolic profiles in insulin-dependent diabetes mellitus.

GH has been implicated in the pathophysiology of various acute and chronic complications of diabetes mellitus. As a consequence, there has been a great deal of interest in developing methods for suppressing GH secretion in diabetes. SMS 201-995 is a long-acting somatostatin analog which inhibits the secretion of numerous hormones, including GH. To determine the metabolic and hormonal responses to SMS 201-995 independent of endogenous insulin suppression, we studied six patients with insulin-dependent diabetes mellitus while they received 150 micrograms SMS 201-995, sc, daily for an 8-week period. This treatment resulted in no change in 24-h glucose profiles, although the mean insulin dose decreased by 19%, while hemoglobin A1c decreased significantly (0.084 +/- 0.023 to 0.067 +/- 0.011, P = 0.04). The 24-h profiles of blood lactate, plasma free insulin, glucagon, FFA, blood glycerol, and beta-hydroxybutyrate were unchanged, whereas that of blood alanine increased significantly (7.8 +/- 0.4 to 10.6 +/- 0.9 mmol/L.h; P = 0.01). GH secretion declined in five of the six patients; the mean values before and during SMS 201-995 treatment were 102 +/- 23 and 68 +/- 12 micrograms/L.h, respectively (P = NS), for the six patients. [In the five patients in whom GH secretion declined, the mean values before and during SMS 201-995 treatment were 115 +/- 23 and 63 +/- 14 micrograms/L.h, respectively (P = 0.01).] These results suggest that SMS 201-995 may be administered to patients with insulin-dependent diabetes mellitus without a deleterious effect on metabolic control.

Determination and kinetic analysis of non-insulin mediated glucose uptake in type 1 (insulin-dependent) diabetes mellitus.

In man, total glucose uptake is the sum of insulin mediated glucose uptake and non-insulin mediated glucose uptake. The later pathway has not been examined in Type 1 (insulin-dependent) diabetes mellitus. In order to assess non-insulin mediated glucose uptake in Type 1 diabetes, we measured steady-state rates of glucose uptake during glucose clamps at 5.27, 9.71 and 12.5 mmol/l using low (0.25 mU.kg-1.min-1), intermediate (0.75 mU.kg-1.min-1) and high (1.50 mU.kg-1.min-1) insulin infusion rates in 10 subjects with Type 1 diabetes. For insulin infusion rates of 0.25, 0.75 and 1.50 mU.kg-1.min-1 as plasma glucose rose from 5.27 to 9.71 mmol/l, total glucose uptake increased by 35, 43 and 52 percent respectively (p less than 0.05 for each insulin infusion rate). For all three insulin infusion rates, there was no significant increase in total glucose uptake as plasma glucose increased from 9.71 to 12.5 mmol/l. At each glycaemic level, glucose uptake correlated significantly with plasma free insulin (r = 0.81, p less than 0.01 at 5.71 mmol/l; r = 0.84, p less than 0.01 at 9.71 mmol/l; r = 0.73, p less than 0.02 at 12.5 mmol/l). Linear regression analysis to a point corresponding to plasma free insulin equalling zero, yielded values for non-insulin mediated glucose uptake (mmol.kg-1.min-1) of 0.11, 0.14, 0.18 at plasma glucose of 5.27, 9.7 and 12.5 mmol/l respectively. Thus, increasing plasma glucose concentrations were associated with increasing rates of non-insulin mediated glucose uptake. For each insulin infusion rate used, the percent of total glucose uptake accounted for by non-insulin mediated glucose uptake remained independent of plasma glucose concentration, but decreased as insulin infusion rate increased.(ABSTRACT TRUNCATED AT 250 WORDS)

Triglyceride-rich lipoprotein metabolism during acute hyperinsulinemia in hypertriglyceridemic humans.

Chronic endogenous hyperinsulinemia is associated with increased rates of triglyceride production in humans. The effect of acute exogenous hyperinsulinemia on triglyceride production was studied in seven hypertriglyceridemic men before and during six hours of hyperinsulinemic-euglycemic clamping, and in two men before and during six hours of hyperinsulinemic-hyperglycemic clamping. Apparent triglyceride production rates were assessed qualitatively by examining the rate of decline of 3H-glycerol-labeled plasma triglyceride specific activity in the preclamp period, and again when a new steady state had occurred, during the final three hours of the clamp. During the euglycemic (91.2 +/- 3.0 mg glucose/dL plasma) clamps, plasma insulin levels were increased by 700% (0.76 +/- 0.12 to 5.3 +/- 0.29 ng/mL, P less than .001) and plasma glucagon levels decreased by 19%, compared with baseline. The apparent triglyceride production rate did not increase in five of six men during the euglycemic-hyperinsulinemic clamp, or in either man during the hyperglycemic-hyperinsulinemic clamp. During the clamp period the triglyceride declined in the plasma by 23.4 +/- 3.1%; and the apolipoprotein B by 10.5 +/- 1.5%. Hyperinsulinemia with euglycemia was also associated with a decline in the ratio of triglyceride to apolipoprotein B in the triglyceride-rich lipoproteins. This was more pronounced in very low density lipoprotein (VLDL) than in intermediate density lipoprotein (IDL). In this study, hyperinsulinemia led to a decrease in the plasma glucagon concentration. This decrease was positively correlated with the decrease in the slope of the triglyceride specific activity v time curve. Hence, the changes in triglyceride production were not due to an increase in plasma glucagon concentration.(ABSTRACT TRUNCATED AT 250 WORDS)

The relationship of cardiac diastolic dysfunction to concurrent hormonal and metabolic status in type I diabetes mellitus.

The presence of diabetic cardiomyopathy and its relationship to concurrent hormonal and metabolic status have not been defined in patients with uncomplicated type I diabetes mellitus. Accordingly, radionuclide left ventricular angiograms and simultaneous metabolic profiles were obtained in 8 type I diabetic patients who had no major diabetic complications and in 11 normal subjects. Occult coronary artery disease was excluded by electrocardiogram exercise testing. Hemodynamics and systolic function did not differ between the groups. However, the peak filling rate (PFR; end-diastolic volumes per s) was less in the diabetic patients at rest [mean, 4.1 +/- 0.2 (+/- SE) vs. 4.8 +/- 0.2; P less than 0.05] and during aerobic (6.8 +/- 0.2 vs. 8.30 +/- 0.3; P less than 0.01) and anaerobic exercise (8.8 +/- 0.3 vs. 9.8 +/- 0.4; P less than 0.05). The time to PFR was prolonged in the diabetic patients at rest (174 +/- 10 vs. 133 +/- 7 ms; P less than 0.01) and during anaerobic exercise (126 +/- 5 vs. 103 +/- 6 ms; P less than 0.01). Plasma glucose and insulin levels were elevated in the diabetic patients at rest and during exercise. Otherwise, the metabolic and hormonal levels did not differ between the groups. In the diabetic patients, no single metabolic or hormonal parameter correlated with PFR or time to PFR. Impairment of diastolic filling also did not correlate with level of glycosylated hemoglobin or duration of diabetes. The alteration in diastolic filling present in type I diabetic patients who have no other diabetic complications may represent the earliest functional effect of diabetic cardiomyopathy.