Serum hsCRP and visfatin are elevated and correlate to carotid arterial stiffness in spinal cord-injured subjects.

STUDY DESIGN: Cross-sectional comparison, control group. OBJECTIVES: To investigate the relationship between carotid arterial stiffness and circulating markers for cardiovascular disease (CVD) in spinal cord-injured (SCI) subjects compared with able-bodied (AB) individuals. SETTING: University Research Laboratory, University of Louisville. METHODS: SCI (n=14) and AB (n=13) subjects between 20-52 years of age were recruited to participate in the study. B-mode Doppler ultrasound was used to obtain carotid artery diameter measurements. Arterial stiffness was assessed via the stiffness index and distensibility coefficient. Markers of CVD risk were obtained by fasting blood draw. RESULTS: Carotid arterial stiffness index (P=0.061) and distensibility coefficient (P=0.370) were not different between the SCI and AB groups. The SCI group had higher high-sensitivity C-reactive protein (hsCRP) (P=0.046), triglycerides (P=0.017), leptin (P=0.040) and visfatin (P<0.001) compared with the control group. Visfatin (r=0.559, P=0.047), hsCRP (r=0.633, P=0.037), insulin (r=0.637, P=0.019) and HOMA (r=0.614, P=0.026) significantly correlated with carotid arterial stiffness index in the SCI group. CONCLUSION: This study demonstrated that SCI subjects are at a high cardiovascular risk as indicated by elevated hsCRP levels. Elevations in hsCRP and visfatin may contribute to accelerated atherogenic processes in the SCI population.

Beta-cell sparing in transplanted islets by vascular endothelial growth factor.

We have reported that vascular endothelial growth factor (VEGF) promotes the revascularization of transplanted islets, thereby reducing the initial number required to prevent diabetes. The present study was undertaken to assess other mechanisms of beta-cell sparing by VEGF. For in vitro studies, islets were cultured for 14 days with versus without 20 ng/mL VEGF. Viability, necrosis, and apoptosis were examined by specific staining (Alcein AM, propidium iodide, and annexin/phosphatidylserine). The effects of VEGF on islets were also examined in a proteomic study. In vivo streptozotocin-treated diabetic Lewis rats received 1000 Lewis or Sprague-Dawley islets beneath the renal capsule. Oxygen levels at the transplant site were monitored by a Clark-type oxygen electrode. Fasting blood glucose served as an indicator of islet survival and function. VEGF enhanced oxygen levels at the transplant site. Syngeneic recipients were euglycemic for over 6 months, whereas control islets failed within 30 to 60 days. VEGF prevented allograft rejection for over 14 days, whereas controls were rejected within 6 to 7 days. Immunostaining suggested that VEGF inhibited the presentation of MHC II antigen and promoted islet survival by the inhibition of necrosis and apoptosis. Our proteomic study suggested VEGF preserved systems required for cellular preservation (heat shock proteins) and insulin secretion. VEGF promotes the preservation of isolated and transplanted islets by a variety of mechanisms, including enhanced oxygenation and inhibition of immune rejection, necrosis, and apoptosis. The provision of exogenous VEGF may be a useful adjunct to islet transplantation.

Myasthenia gravis in conjunction with Graves' disease: a diagnostic challenge.

OBJECTIVE: To describe an association between Graves' disease and myasthenia gravis and discuss the clinical features and laboratory tests that may help distinguish these two diseases. METHODS: The clinical, laboratory, and electrophysiologic findings in a patient with Graves' disease and myasthenia gravis are presented. RESULTS: A 28-year-old African American man was admitted to the University of Louisville Hospital with generalized muscle weakness, exophthalmos, diplopia, weight loss, and mild dysphagia. The diagnosis of Graves' disease with ophthalmologic involvement was suspected clinically and confirmed by an undetectable thyrotropin level (<0.03 mIU/mL), high total thyroxine (20.5 mg/dL), and increased homogeneous 123I thyroid uptake. Because of the generalized muscle weakness and mild dysphagia, assessment was done by a neurology team, and severe thyrotoxic myopathy was diagnosed. He was treated with 131I and b-adrenergic blocking agents and scheduled for follow-up as an outpatient. Two weeks later, the patient presented in acute respiratory failure. The neurology team was reconsulted because of suspected myasthenic crisis. Anti-acetylcholine receptor antibodies were undetectable in the serum, and computed tomography of the chest showed no thymic enlargement. Repetitive nerve stimulation testing, however, showed findings consistent with an abnormality of the neuromuscular junction. The patient responded dramatically to an anticholinesterase agent and corticosteroids. CONCLUSION: The overlapping clinical features may cause diagnostic confusion when myasthenia gravis and Graves' disease coexist, and numerous tests may be needed to distinguish these two conditions, which have differing treatments and prognoses.

Does concurrent acute ethanol ingestion during omeprazole therapy affect pituitary gonadal axis in male subjects?

OBJECTIVE: Literature suggests that both ethanol and omeprazole may affect the endocrine system. We studied the effect of concurrent use of ethanol and omeprazole on the pituitary gonadal axis in healthy males. METHODS: Serum testosterone, luteinizing hormone, and follicle stimulating hormone levels were assessed in a fasting state before and after ingestion of 0.5 g/kg bodyweight of ethanol. Subjects then received omeprazole therapy (20 mg 2x/d for one week) followed by assessment of hormone levels before and after ethanol ingestion as done previously. RESULTS: Total testosterone levels before and after ethanol at baseline declined an average of 46.6 ng/dL (n = 8; p = NS). The testosterone levels before and after ethanol following omeprazole therapy rose an average of 55.4 ng/dL (n = 8; p = NS). There was no significant difference in the change of ethanol induced testosterone concentrations as a result of omeprazole therapy. Similarly the free testosterone, follicle stimulating hormone, and luteinizing hormone were also not affected by ethanol or omeprazole alone or in combination. CONCLUSIONS: We conclude that omeprazole and/or acute ingestion of ethanol do not affect the pituitary gonadal axis in healthy male subjects.

Massive chylothorax complicating cirrhosis of the liver.

Chylothorax is an unusual complication of cirrhosis of the liver. This condition is probably underdiagnosed because appropriate tests are not usually done. We describe the case of a 54-year-old man with cirrhosis of the liver and massive chylothorax. Despite chest tube drainage and intensive supportive therapy, there was a fatal outcome. Our case highlights the difficulties in the management of this complication and draws attention to the possible dangers of certain therapeutic procedures.

Interstitial insulin during euglycemic-hyperinsulinemic clamp in obese and lean individuals.

Transcapillary insulin transport has been considered a rate-limiting step of insulin action. However, direct measurement of interstitial insulin levels during physiologic levels of insulinemia have not been performed. We determined changes in interstitial insulin in eight healthy non-obese men and seven healthy obese men by microdialysis during a euglycemic-hyperinsulinemic clamp. Interstitial insulin was determined in the subcutaneous tissue of the abdomen and thigh. Steady-state insulin concentrations were reached approximately 10 minutes after the start of insulin infusion in the subcutaneous tissue of the abdomen and thigh and returned to basal levels approximately 10 minutes after the infusion was discontinued. There was no difference in the rapidity of change in interstitial insulin between obese and lean individuals at either site studied, irrespective of the pattern of fat distribution. The relative change in dialysate insulin concentration during the euglycemic clamp did not differ between obese and lean individuals at either site studied. It was also unaffected by the waist to hip ratio. The rapid change in interstitial insulin concentration could be of physiologic significance in determining the effects of changes in circulating insulin concentration. We conclude that transcapillary insulin transport in adipose tissue is unaffected by obesity and the pattern of fat distribution in healthy men. It is also concluded that when interstitial insulin is determined directly, transcapillary insulin transport is rapid and does not demonstrate a significant lag phase.

Alterations in upper gastrointestinal motility in Helicobacter pylori-positive nonulcer dyspepsia.

OBJECTIVE: To study the association between gastrointestinal motility and Helicobacter pylori (HP) among patients with nonulcer dyspepsia (NUD). METHODS: We examined the gastric emptying and orocecal transit times (OCTT) in patients with NUD who were colonized with Helicobacter pylori (n = 27). NUD was defined as dyspeptic symptoms for at least 3 months in the absence of gastrointestinal pathology as seen on endoscopy and ultrasound. Subjects with diabetes mellitus, thyroid disorder, or abdominal surgery except appendectomy were excluded. The HP-negative patients with NUD (n = 38) served as controls. Solid phase gastric emptying was assessed by radionuclide scintigraphy. OCTT was determined by measuring exhaled breath hydrogen upon administration of lactulose. RESULTS: The two groups were similar with respect to age, sex, race, and history of smoking. Gastric emptying (t1/2) was 64.96 +/- 3.61 min in the HP-negative and 61.0 +/- 6.59 in the HP-positive group (p = NS). The OCTT was 130.9 +/- 17.26 minutes in the HP-negative and 84.28 +/- 11.07 in the HP-positive group (p = 0.03). There was no difference in the prevalence of nonhydrogen producers between the two groups. There was no correlation between gastric emptying and OCTT (p > 0.05). CONCLUSIONS: OCTT is faster among HP-positive patients with NUD than among HP-negative patients. However, gastric emptying is similar in the two groups.

Lack of delay in hepatic insulin transit as indicated by concordance of insulin secretory and peripheral insulin pulses.

The liver is an important site of insulin metabolism and action. It has often been assumed that the liver may diminish the amplitude of the insulin secretory waveform without altering hepatic insulin transit time. However, the significant extraction and metabolism of hepatic insulin has the potential to delay hepatic insulin transit. To examine hepatic insulin transit, we studied the concordance of calculated insulin secretory peaks with peripheral insulin peaks in 12 healthy men of varying body weight and fat distribution. Adiposity was determined by percent body fat, and fat distribution by the waist to hip ratio. Arterialized peripheral venous samples for insulin and C-peptide assays were obtained every 2 minutes for 90 minutes. Pancreatic insulin secretion rates were estimated with individual C-peptide kinetics using a two-compartment model. Concordance between insulin secretory peaks and peripheral insulin peaks was assessed by the hypergeometric probability model. A significant concordance between secretory and peripheral insulin pulses was demonstrated in seven of 12 subjects (P < .00001). The mean pulse intervals for insulin secretion were similar to the mean pulse intervals for peripheral insulin. The degree of concordance between the insulin secretory peaks and peripheral insulin pulses was unrelated to adiposity or body fat distribution. Significant synchronicity exists between insulin secretory peaks and peripheral insulin peaks in healthy men. We conclude that despite significant hepatic insulin extraction and metabolism, hepatic insulin transit may not be delayed in healthy men.

Thyroid disease in the elderly.

Thyroid disease in the aged, both hypothyroidism and hyperthyroidism, may be subtle or may be present with no clinical symptoms and signs, and is therefore difficult to diagnose on the basis of clinical evaluation. The help of the laboratory is essential in making the diagnosis of disease of the thyroid. Therapeutic strategies are different in the aged than in the younger adult with thyroid disease. It is essential for geriatricians, and all clinicians who care for the elderly, to have a solid understanding of thyroid function and dysfunctions in this group of patients so that they diagnose diseases of the thyroid correctly and treat them appropriately.

Congenital adrenal hyperplasia diagnosed in a man during workup for bilateral adrenal masses.

We studied an asymptomatic 55-year-old man who was found to have markedly enlarged adrenal glands on an abdominal computed tomographic scan and was scheduled to have adrenal biopsy because of suspicious findings on an adrenal magnetic resonance image. However, hormonal studies revealed congenital adrenal hyperplasia due to 21-hydroxylase deficiency. Treatment with dexamethasone decreased the size of the adrenal glands. This is, we believe, the first report of congenital adrenal hyperplasia in an adult, diagnosed during the evaluation of an incidental adrenal lesion. Although congenital adrenal hyperplasia can present with varying severity and remain undiagnosed into adulthood, it is usually not considered in the evaluation of asymptomatic adult adrenal masses. We emphasize the need for proper hormonal studies in the evaluation of incidental adrenal lesions.

Heat stress of cultured GC cells enhances triiodothyronine-induced growth hormone production by action within the 5'-flanking region of the rat growth hormone gene.

We studied the effect of incubation at 41 C on a clone of GC cells that had previously been stably transfected with a gene construct, pGHXGPT, containing -1800 to +8 of the rat growth hormone promoter fused to the structural gene for E. Coli xanthine guanine phosphoribosyl-transferase. The effect of incubation of the clone containing pGHXGPT at 41 C was to enhance triiodothyronine induction of growth hormone secretion (2-fold, p < 0.01) and of xanthine quanine phosphoribosyl-transferase activity (3-fold, p < 0.01). We conclude that the increase in triiodothyronine-induced growth hormone production during heat stress occurs by stimulation of the growth hormone promoter.