International study of objectively measured physical activity and sedentary time with body mass index and obesity: IPEN adult study.

BACKGROUND: Physical activity (PA) has been consistently implicated in the etiology of obesity, whereas recent evidence on the importance of sedentary time remains inconsistent. Understanding of dose-response associations of PA and sedentary time with overweight and obesity in adults can be improved with large-scale studies using objective measures of PA and sedentary time. The purpose of this study was to examine the strength, direction and shape of dose-response associations of accelerometer-based PA and sedentary time with body mass index (BMI) and weight status in 10 countries, and the moderating effects of study site and gender. METHODS: Data from the International Physical activity and the Environment Network (IPEN) Adult study were used. IPEN Adult is an observational multi-country cross-sectional study, and 12 sites in 10 countries are included. Participants wore an accelerometer for seven consecutive days, completed a socio-demographic questionnaire and reported height and weight. In total, 5712 adults (18-65 years) were included in the analyses. Generalized additive mixed models, conducted in R, were used to estimate the strength and shape of the associations. RESULTS: A curvilinear relationship of accelerometer-based moderate-to-vigorous PA and total counts per minute with BMI and the probability of being overweight/obese was identified. The associations were negative, but weakened at higher levels of moderate-to-vigorous PA (>50 min per day) and higher counts per minute. No associations between sedentary time and weight outcomes were found. Complex site- and gender-specific findings were revealed for BMI, but not for weight status. CONCLUSIONS: On the basis of these results, the current Institute of Medicine recommendation of 60 min per day of moderate-to-vigorous PA to prevent weight gain in normal-weight adults was supported. No relationship between sedentary time and the weight outcomes was present, calling for further examination. If moderator findings are confirmed, the relationship between PA and BMI may be country- and gender-dependent, which could have important implications for country-specific health guidelines.

A supercoiled DNA-modified mercury electrode-based biosensor for the detection of DNA strand cleaving agents.

DNA-damaging agents in the environment represent a serious danger to human health. We use a supercoiled DNA-modified mercury electrode as a fast-response biosensor for the detection of DNA strand cleaving agents. The sensor is based on a strong difference between the a.c. voltammetric responses of covalently closed circular (supercoiled) and of open circular (nicked) plasmid DNA. We show that the sensor can detect hydroxyl radicals in laboratory-prepared solutions and in various natural and industrial water samples. The sensor is also capable of detecting unknown DNA-damaging agents in industrial waters.

Torulopsis glabrata fungemia in a diabetic patient.

We have presented a case of a stable diabetic outpatient who had an acute illness that proved to be Torulopsis glabrata fungemia responsive to amphotericin B therapy. Her only apparent additional predisposition was a nonobstructing renal calculus. Fungemia with this organism in an outpatient is most unusual. T glabrata should be an additional consideration in outpatient as well as inpatient illnesses, especially in diabetic women.

Rhabdomyolysis, acute renal failure, and disseminated intravascular coagulation in a man with sickle cell trait.

We have described a patient with sickle cell trait who, after severe exertion, had rhabdomyolysis, acute renal failure, and disseminated intravascular coagulation secondary to sickling. Autopsy showed the characteristic histopathology of sickle cell crisis and not terminal sicklemia.

Exogenous protein as the cause of nephrotic-range proteinuria.

Hematuria and proteinuria developed in a young woman with waxing and waning symptoms suggestive of systemic lupus erythematosus. Quantitatively, the proteinuria was in the nephrotic range, but other manifestations of the nephrotic syndrome were absent. Serologic evaluation demonstrated normal results. The hematuria was subsequently found to be self-induced and related to foreign objects in the bladder. Urine protein electrophoresis confirmed severe proteinuria with a spike in the gamma region. Immunoelectrophoresis demonstrated that the proteinuria was not of human origin. Subsequent urinary protein values were normal. This case exhibits features compatible with Münchausen's syndrome and shows that severe proteinuria may be factitious.

Ureteral involvement complicating eosinophilic cystitis.

A thirty-three-year-old woman was evaluated for eosinophilia, irritative bladder symptoms, and renal insufficiency. Eosinophilic cystitis was documented by bladder biopsy and glomerulonephritis by renal biopsy. As the glomerulonephritis and other symptoms resolved, unilateral ureteral obstruction developed with irreversible loss of right renal function. The distal ureter was found to have eosinophilic infiltration. This entity should be considered in the differential diagnosis of unilateral ureteral obstruction associated with cystitis.

Nephrotic syndrome. Pathogenesis, clinical and therapeutic considerations.

The nephrotic syndrome is the result of a variety of immunologic mechanisms which damage the glomerular capillary wall and cause excessive protein loss. The great number of potential predisposing factors and clinical settings necessitates a thorough history and a careful examination that includes well-defined laboratory studies. Appropriate therapy covers a broad range, from doing nothing more than reducing additional insults, to the aggressive use of combined modalities, depending on the factors involved in the individual case.

Remission and exacerbation of tumor-related nephrotic syndrome with treatment of the neoplasm.

A 61-year-old man presented with nephrotic syndrome in March 1978. Renal biopsy revealed mesangial and endocapillary proliferation with no underlying cause found. One year later, evaluation of back pain resulted in the finding of undifferentiated adenocarcinoma with compression fracture of the T-11 vertebra. Local irradiation relieved the pain and ameliorated the nephrotic syndrome. In 1981 the nephrotic syndrome recurred. Evaluation revealed metastases to the right pelvis and to the brain without an identifiable primary lesion. Irradiation of these lesions reduced protein excretion to 50 to 150 mg/day. A gastric carcinoma was later found. Exacerbation of nephrotic syndrome may herald exacerbation of tumor activity as occurs in Hodgkin's disease. Survival with tumor-related nephrotic syndrome is not invariably poor, and treatment of metastases may be worthwhile in similar patients in whom only partial tumor reduction is possible.

Determinants of serum 1,25(OH)2D levels in renal disease.

Serum 1,25(OH)2D and factors related to its production were studied in 39 patients with various degrees of renal insufficiency. Serum 1,25(OH)2D levels correlated positively with 1/serum creatinine values (r = 0.54, P less than 0.001) and negatively with serum phosphorus (r = -0.39, P less than 0.02) and age (r = -0.33, P less than 0.05). There was no significant correlation between 1,25(OH)2D levels and serum calcium or calcitonin or PTH, although the logarithm of PTH correlated inversely with 1,25(OH)2D levels (r = -0.47, P less than 0.01). Patients who had normal or supranormal 1,25(OH)2D levels despite low GFR tended to have low serum phosphorus values. Serum levels of bone Gla protein (BGP), a biochemical marker for bone metabolism, correlated negatively with 1/serum creatinine (r = -0.39, P less than 0.02) and positively with PTH (r = 0.57, P less than 0.001) and age (r = 0.33, P less than 0.05). Prophylaxis with 1,25(OH)2D should be considered in patients with significantly decreased serum 1,25(OH)2D levels, as seem to occur when serum creatinine is greater than 4.0 mg/dl. However, despite the statistically significant correlation between serum 1,25(OH)2D and 1/serum creatinine, direct measurement should be used to ascertain the serum concentration of 1,25(OH)2D in chronic renal insufficiency.

Crescentic glomerulonephritis complicating idiopathic membranous glomerulonephropathy.

We describe the course of a patient with multiple rectal abscesses and progressive renal dysfunction. A renal biopsy demonstrated a membranous glomerulopathy associated with extensive crescent formation. No underlying cause for the glomerulonephritis could be identified and, specifically, the anti-GBM antibody present in other similar cases was not found. There appears to be a subset of patients with membranous glomerulopathy in whom crescents develop with rapid loss of renal function. Anti-GBM antibody is not necessary in the pathogenesis of this lesion.

Diabetic neuropathic pain: control by amitriptyline and fluphenazine in renal insufficiency.

Seven patients with diabetes of ten to 24 years' duration and renal insufficiency were treated with fluphenazine and amitriptyline in an attempt to control severe pain in the extremities. Six patients had relief of pain within five days of initiation of therapy. One patient had no pain relief despite mood alteration. The relief of pain persisted whether renal function was stable or declining. This form of therapy is safe and as effective in patients with neuropathic pain and mild to moderate renal insufficiency as in patients with normal renal function.

Baroreflex dysfunction in patients with adult-onset diabetes and hypertension.

Ten patients with adult-onset diabetes in whom diabetes antedated the appearance of hypertension were evaluated. These patients had evidence of diabetic autonomic neuropathy, including significant orthostatic hypotension (four patients), impotence (three patients), and evidence of diabetic peripheral sensorimotor neuropathy (nine patients) in clinical testing and nerve conduction study results. Baroreflex function was evaluated by multiple hemodynamic tests, including inhalation of amyl nitrite and intravenous administration of phenylephrine, before and after parasympathetic blockade with atropine, and the cold pressor test; results were compared with results in normal control subjects, patients with essential hypertension, and two subgroups of uremic patients undergoing maintenance hemodialysis. Baroreflex function was significantly abnormal in the diabetic patients and was consistent with combined parasympathetic and sympathetic motor nerve (efferent) dysfunction in the baroreflex arc. There was a significant inverse correlation between the degree of orthostatic hypotension in the diabetic patients and their baroreflex response to phenylephrine (r = -0.680, p less than 0.05). There was no significant correlation between supine hypertension in the patients with diabetes and any of the hemodynamic or biochemical parameters examined. The results suggest that orthostatic hypotension in these patients is related to baroreflex dysfunction. However, baroreflex dysfunction does not appear to be a factor in the development of hypertension in these patients, although more studies with normotensive diabetic patients are needed to confirm this point.

Renal hemodynamic changes during long-term antihypertensive therapy.

Studies of renal hemodynamics were carried out in 84 patients with essential hypertension during long-term antihypertensive therapy with a number of drugs. Renal perfusion was maintained or enhanced despite a fall in mean arterial pressure during therapy with hydrochlorothiazide, furosemide, clonidine, prazosin, and the combination of guanabenz and hydrochlorothiazide. Renal perfusion deteriorated during long-term treatment with propranolol. Renal hemodynamics may be enhanced, maintained, or adversely influenced depending on the choice of antihypertensive agent.

Clinical correlates in hypertensive patients with left ventricular hypertrophy diagnosed with echocardiography.

Seventy-three hypertensive patients were evaluated with M mode and two dimensional echocardiography. Left ventricular hypertrophy was found in 37 patients (51 percent); 29 had concentric hypertrophy and the remaining 8 had disproportionate septal thickening. Factors that did not influence the distribution of patients in the group with left ventricular hypertrophy and normal subjects included (1) duration of hypertension, (2) level of blood pressure, (3) age, (4) body surface area, and (5) race. More of the patients who had a normal left ventricular mass (32 or 89 percent) than of those who had hypertrophy (22 or 59 percent) were receiving two or more antihypertensive drugs. Electrocardiography was very insensitive in identifying left ventricular hypertrophy in these patients. The presence of increased left ventricular mass was associated with a greater incidence of other target organ disease.

Renal papillary necrosis in thyroid carcinoma.

A thirty-four-year-old man with progressive visual impairment was found to have thyromegaly and renal insufficiency at the time of admission. Subsequent evaluation demonstrated bilateral optic neuritis and a thyroid nodule which proved to be a follicular carcinoma. Nephrologic studies revealed bilateral papillary necrosis and chronic interstitial nephritis on biopsy. The patient's renal function stabilized and twenty-four-hour protein excretion diminished after hemithyroidectomy. Carcinoma-related protein production may have played a role in the development of the observed renal lesions. Carcinoma should be a consideration in patients with unexplained papillary necrosis.

Recovery from rapidly progressive glomerulonephritis. Improvement after plasmapheresis and immunosuppression.

Two patients with rapidly advancing renal insufficiency underwent biopsy and were found to have crescentic glomerulonephritis. Patient 1 demonstrated findings compatible with Goodpasture's syndrome. Crescents were present in 100% of his glomeruli. Patient 2 had findings of immune complex-mediated glomerulonephritis and crescents in greater than 90% of his glomeruli. Both patients were treated with high-dose prednisone, cyclophosphamide, and plasmapheresis. Patient 2 additionally required hemodialysis for a brief period. Renal function improved in both patients and has not deteriorated after follow-up of 14 and 18 months, respectively. Repeated renal biopsies were performed in each patient. Our findings suggest that clinical improvement and histologic healing are possible in rapidly progressive glomerulonephritis despite the initial presence of crescents in every glomerulus.

Urinary kallikrein activity and renal vascular resistance in the antihypertensive response to thiazide diuretics.

To evaluate the mechanism of chronic thiazide diuretic action in hypertension, we treated 19 essential hypertensive white men for 1-month periods on placebo alone and hydrochlorothiazide alone. During therapy, mean arterial pressure (MAP) fell, but radioisotopically determined intravascular volume remained unchanged, suggesting other mechanisms of thiazide action upon blood pressure. In the renal circulation, thiazides did not change renal plasma flow or glomerular filtration rate, but renovascular resistance was diminished, probably at the afferent arteriole. Concomitant with the decline in blood pressure and renovascular resistance, urinary kallikrein excretion increased, from subnormal (hypertensive) levels back into the normal range. The kallikrein increase did not correlate with changes in plasma aldosterone. In addition, patients with blood pressure responses (reduction greater than or equal to 10%) to thiazides (n = 12) had greater increases in kallikrein excretion than those without such a blood pressure decrement (n = 7), suggesting a role for renal kallikrein in the hypotensive response to thiazide diuretics.

Hepatic coma after open heart surgery.

Fulminant hepatic failure has been reported in patients with chronic congestive heart failure. Two patients in whom jaundice and coma followed cardiac surgery were studied to find the possible etiology. Clinical, biochemical, and histologic evaluations revealed low cardiac output; elevated levels of bilirubin, lactic dehydrogenase, serum glutamic oxaloacetic transaminase, and alkaline phosphatase; prolonged prothrombin time; and centrizonal necrosis of hepatocytes with sinusoidal dilatation. No other possible causes of hapatic dysfunction and coma were identified. We conclude that acute postoperative congestive heart failure may cause fulminant hepatic failure and metabolic encephalopathy.