Temporal evaluation of estrogenic endocrine disruption markers in smallmouth bass (Micropterus dolomieu) reveals seasonal variability in intersex.

A reconnaissance project completed in 2009 identified intersex and elevated plasma vitellogenin in male smallmouth bass inhabiting the Missisquoi River, VT. In an attempt to identify the presence and seasonality of putative endocrine disrupting chemicals or other factors associated with these observations, a comprehensive reevaluation was conducted between September 2012 and June 2014. Here, we collected smallmouth bass from three physically partitioned reaches along the river to measure biomarkers of estrogenic endocrine disruption in smallmouth bass. In addition, polar organic chemical integrative samples (POCIS) were deployed to identify specific chemicals associated with biological observations. We did not observe biological differences across reaches indicating the absence of clear point source contributions to the observation of intersex. Interestingly, intersex prevalence and severity decreased in a stepwise manner over the timespan of the project. Intersex decreased from 92.8% to 28.1%. The only significant predictor of intersex prevalence was year of capture, based on logistic regression analysis. The mixed model of fish length and year-of-capture best predicted intersex severity. Intersex severity was also significantly different across late summer and early spring collections indicating seasonal changes in this metric. Plasma vitellogenin and liver vitellogenin Aa transcript abundance in males did not indicate exposure to estrogenic endocrine disrupting chemicals at any of the four sample collections. Analysis of chemicals captured by the POCIS as well as results of screening discrete water samples or POCIS extracts did not indicate the contribution of appreciable estrogenic chemicals. It is possible that unreported changes in land-use activity have ameliorated the problem, and our observations indicate recovery. Regardless, this work clearly emphasizes that single, snap shot sampling for intersex may not yield representative data given that the manifestation of this condition within a population can change dramatically over time.

Isolation, characterization and molecular identification of a novel aquareovirus that infects endangered fountain darter Etheostoma fonticola.

The fountain darter Etheostoma fonticola (FOD) is a federally endangered fish listed under the US Endangered Species Act. Here, we identified and characterized a novel aquareovirus isolated from wild fountain darters inhabiting the San Marcos River. This virus was propagated in Chinook salmon embryo (CHSE)-214, rainbow trout gonad-2 and fathead minnow cells at 15°C. The epithelioma papulosum cyprini cell line was refractory at all temperatures evaluated. High throughput sequencing technologies facilitated the complete genome sequencing of this virus utilizing ribosomal RNA-depleted RNA extracted from infected CHSE-214 cells. Conventional PCR primer sets were developed for the detection and confirmation of this virus to assist diagnostic screening methods. Phylogenetic analysis suggests this virus belongs to the Aquareovirus A genus. This research provides requisite initial data critical to support hatchery and refugia biosecurity measures for this endangered species.

Effect of alpha-adrenergic blockers, ACE inhibitors, and calcium channel antagonists on renal function in hypertensive non-insulin-dependent diabetic patients.

In the present study we investigated the effect of a selective alpha 1-adrenergic blocker (doxazosin), an angiotensin-converting enzyme (ACE) inhibitor (captopril), and a calcium channel antagonist (nifedipine) on renal function in hypertensive non-insulin-dependent diabetic patients. 30 NIDD hypertensive patients (age = 50 +/- 3 years; BMI = 30 +/- 1 kg/m2) (mean +/- SEM) were studied before and after a 12-week period of antihypertensive treatment. Ten patients were treated with doxazosin (Cardura) (2-8 mg once daily or 8 mg b.i.d.), 9 with captopril (Capoten) (25-50 mg b.i.d.), and 11 with nifedipine (Procardia-XL) (30-60 mg once daily). Blood pressure, creatinine clearance, 24-hour urinary protein excretion, fasting plasma glucose concentration and glycosylated hemoglobin were measured before and after drug treatment. Fasting plasma glucose and glycosylated hemoglobin (HbA1c) were similar in all three groups prior to the start of antihypertensive therapy and did not change significantly from baseline in any treatment groups. In the doxazosin group creatinine clearance rose from 99 +/- 8 to 122 +/- 8 ml/1.73 m2.min (p < 0.01), while 24-hour urinary protein excretion declined from 2.66 +/- 0.05 to 1.76 +/- 0.02 mg/day/ml/1.73 m2.min (p < 0.01). In diabetics treated with captopril creatinine clearance rose from 93 +/- 6 to 109 +/- 9 ml/1.73 m2.min (p < 0.05), while the 24-hour urinary protein excretion fell from 2.70 +/- 0.05 to 2.03 +/- 0.04 mg/day/ml/1.73 m2.min (p < 0.05). In patients treated with nifedipine creatinine clearance did not change (97 +/- 6 vs. 94 +/- 7 ml/1.73 m2.min), while 24-hour urinary protein excretion decreased from 2.84 +/- 0.04 to 1.95 +/- 0.03 mg/day/ml/1.73 m2.min. Systolic and diastolic blood pressure were similar in doxazosin (150 +/- 3/95 +/- 2 mm Hg), captopril (153 +/- 3/93 +/- 1), and nifedipine (155 +/- 4/93 +/- 1) groups prior to the start of antihypertensive therapy and declined to 143 +/- 3/84 +/- 3 (doxazosin), 139 +/- 3/82 +/- 3 (captopril), and 141 +/- 3/84 +/- 1 (nifedipine) mm Hg (all p < 0.01 vs. pretreatment). In summary, both doxazosin and captopril treatment were associated with significant rises in GFR, while all three antihypertensive agents caused a significant decline in proteinuria. These results indicate that alpha-adrenergic blockers, ACE inhibitors, and calcium channel antagonists can safely and effectively be used in the clinical management of non-insulin-dependent diabetic patients with hypertension.

Exercise-induced acute renal failure associated with ibuprofen, hydrochlorothiazide, and triamterene.

Nonsteroidal anti-inflammatory drugs predispose to acute renal failure in conditions associated with decreased RBF. Such conditions include advanced age, hypertension, chronic renal insufficiency, diuretic use, and any condition decreasing effective circulating volume. Strenuous exercise also causes marked reductions in RBF. The patient discussed developed severe acute renal failure after strenuous exercise and therapeutic doses of ibuprofen and hydrochlorothiazide-triamterene. Urinalysis showed a nephritic sediment with red blood cell casts. Renal biopsy showed acute tubular necrosis and arteriolar nephrosclerosis. Although exercise-associated acute renal failure is uncommon, susceptible patients with exercise-induced renal ischemia and prostaglandin inhibition may develop this complication.

Microalbuminuria in non-insulin-dependent diabetes mellitus. Implications for renal survival.

Microvascular and macrovascular disease cause considerable mortality and morbidity both among patients with non-insulin-dependent diabetes mellitus and those with insulin-dependent diabetes mellitus. Furthermore, non-insulin-dependent and insulin-dependent diabetes mellitus overlap in their pathogenesis as well as short- and long-term complications. In the diabetic patient, genetic susceptibility as well as other factors, ie, microalbuminuria, hypertension, high protein intake, blood glucose control, etc, ultimately culminate in a diffuse disease process, eg, diabetic vascular and/or renal disease. Early predictors of susceptibility for development of renal disease in diabetic subjects would help focus our treatment strategies. The role of microalbuminuria as a prognostic marker for the major complications of insulin-dependent diabetes mellitus has been previously reviewed. We reviewed the role of microalbuminuria as prognostic marker for progression of diabetic renal disease in subjects with non-insulin-dependent diabetes mellitus. We examined treatment strategies to lower microalbuminuria and its associated impact on disease progression.

Painless giant cell thyroiditis diagnosed by fine needle aspiration and associated with intense thyroidal uptake of gallium.

A 52-year-old woman presented with fever, goiter, and no evidence of pain or tenderness in the thyroid. A diagnosis of silent thyroiditis was made after obtaining evidence of biochemical thyrotoxicosis, intense gallium-67 citrate thyroidal localization, and cytologic thyroiditis. Fine needle aspiration biopsy of the thyroid revealed numerous giant cells in all areas of the thyroid, typical of subacute thyroiditis. This is believed to be the first time painless thyroiditis is reported with the classic cytologic feature of painful subacute thyroiditis.

Necrosis of thyroid nodules after fine needle aspiration.

In a series of 200 fine needle aspirations (FNA) of the thyroid, necrosis around the needle tract was histologically evident in 2 of 30 cases with surgical follow-up. In one case of a differentiated thyroid carcinoma, necrosis with involution of the nodule was the dominant finding. This suggests that FNA can induce necrosis and apparent clinical regression of thyroid neoplasms. We believe, however, that a positive cytologic diagnosis coupled with a clinical suspicion of neoplasm should lead to surgical intervention, despite clinical regression following FNA.

The effects of oral fructose, sucrose, and glucose in subjects with reactive hypoglycemia.

We have evaluated the acute effects of orally administered 100-g loads of fructose, sucrose, or glucose given as drinks and of 100-g loads of fructose and sucrose given in cakes on the postprandial serum glucose, insulin, and cortisol responses in seven subjects with reactive hypoglycemia. We defined reactive hypoglycemia as a serum glucose nadir of 65 mg/dl or less, symptoms compatible with hypoglycemia occurring at or after the serum glucose nadir, a hypoglycemic index of greater than 1.0, and a rise in serum cortisol to greater than 20 micrograms/dl after the serum glucose nadir. The data demonstrated that (1) pure fructose given as a drink resulted in relatively flat serum glucose and insulin responses and did not cause a hypoglycemic reaction in any of the subjects, compared with the glucose drink, which caused a hypoglycemic reaction in any of the subjects; (2) ingestion of pure sucrose as a drink elicited significantly flatter serum glucose and insulin responses than did the glucose drink and was associated with some episodes of chemical hypoglycemia and symptoms, but did not result in a hypoglycemic reaction by our definition in any patient; and (3) ingestion of fructose cake led to serum glucose and insulin responses that were lower than those caused by ingestion of sucrose cake, but ingestion of neither fructose nor sucrose cake led to a hypoglycemic reaction by our definition in any patient. In conclusion, the use of fructose as a sweetening agent given either alone, in a drink, or with other nutrients in a cake resulted in markedly flatter serum glucose and insulin responses in subjects with reactive hypoglycemia. Fructose may thus prove useful as a sweetening agent in the dietary treatment of selected patients with reactive hypoglycemia.

Refined carbohydrate as a contributing factor in reactive hypoglycemia.

To assess the effects of diet on symptoms in patients with idiopathic reactive hypoglycemia, we obtained by dietary recall histories the dietary composition from eight of these patients. The data obtained represented the dietary content of each individual before and after instruction on a diet containing 100 gm of carbohydrate daily. Neither the percentage of carbohydrate or fat nor the total grams of protein or fat changed significantly after dietary instruction. In contrast, the percentage of refined carbohydrate decreased (P = .003) and the percentage of protein increased (P = .003). The total grams of refined carbohydrate and total carbohydrate both decreased significantly (P = .01 and .05, respectively), but the fall in refined carbohydrate (from 147 to 20 gm) accounted for the entire fall in total dietary carbohydrate. All values except those of refined carbohydrate were within 95% confidence limits of the average diet in Western culture. Despite continuing intake of a normal quantity of total carbohydrate (mean, 221 gm), all patients had symptomatic improvement. These data suggest that reducing the amount of dietary refined carbohydrate may be important in the treatment of idiopathic reactive hypoglycemia, and that quantitative reduction in total carbohydrate may be of lesser importance.