Bradykinin-forming components in Kuwaiti patients with type 2 diabetes.

Diabetes is the most common risk factor in inducing hypertension, nephropathy and retinopathy. The bradykinin (BK)-forming system has been proposed to protect cardiovascular and renal functions. We therefore evaluated urinary active and proactive kallikrein, total kininogen, plasma tissue kallikrein, plasma creatinine, plasma glucose and plasma HbA1c in newly diagnosed untreated type 2 diabetic patients and healthy subjects. In diabetic patients, urinary and plasma tissue kallikrein concentrations were significantly increased. In addition, plasma prekallikrein levels were also significantly higher. However, urinary kininogen values were significantly reduced in diabetic patients when compared with healthy subjects. This is the first investigation among Kuwaiti Arab patients with type 2 diabetes showing abnormal activities in the BK-forming system. High levels of plasma prekallikrein may be a risk factor for developing high blood pressure as well as nephropathy. The urinary and plasma tissue kallikrein concentrations were higher in diabetic patients, which could indicate the hyperactivities of these components, and may result in increased levels of plasma glucose to induce diabetes. Furthermore, the urinary kininogen levels were reduced in diabetic patients. These alterations might reflect the utilization of urinary kininogen to form BK, a potent inflammatory agent. However, this hypothesis needs further investigation.

Optimal use and interpretation of the aldosterone renin ratio to detect aldosterone excess in hypertension.

With the introduction of the aldosterone/renin ratio as a screening test, the detection rate of primary aldosteronism has increased considerably. Nevertheless, no consensus has so far been reached regarding the cutoff points, operating characteristics or indeed even the reference values for reporting the aldosterone/renin ratio using plasma active renin (ng/l or mU/l) measured by immunoradiometric assay. We review the characteristics of this ratio in normal individuals, essential hypertension and primary hyperaldosteronism in an attempt to reach an agreement regarding its optimum use and interpretation - both using the renin activity or concentration. It seems that the optimal cutoff for patients with primary aldosteronism is above 30 ng/dl per mug/l/h or 800 pmol/l per mug/l/h or 130 pmol/ng or 80 pmol/mU. We explore enhancing measures such as captopril loading or use with a plasma aldosterone cutoff as well as pitfalls with the test such as confounding medications or the need for confirmatory testing. For the latter, demonstration of autonomous aldosterone production via salt loading is widely used, but may not be most advantageous and may even be contraindicated in patients with severe hypertension. The renin stimulation test may be an alternative being safe, well tolerated, and cost effective.

Normal measurement of orbital structures: implications for the assessment of Graves' ophthalmopathy.

Compute tomography anatomy of the orbits is well described, but only a few reports are available on normal measurements of the extraocular muscles (EOM) and globe position (GP). We obtained CT images from patients who were referred to our department for CT of the paranasal sinuses using a standard protocol for evaluation of normal orbital measurements. Our study suggests that optimum results are attained with the use of a coronal scan at a window level and width setting that results in an optimum image at the maximum muscle width for assessment of EOM and an axial scan at the mid-GP for GP and interzygomatic line. Based on our normal values, a right-to-left ratio of more than 1.4 for EOM diameter or 1.2 for GP is indicative of asymmetry. An absolute diameter of EOM > 8 mm and GP < 2 mm are abnormal.

Ovarian steroids modulate neuroendocrine dysfunction in polycystic ovary syndrome.

OBJECTIVE: Neuroendocrine dysfunction in polycystic ovary syndrome (PCOS) was addressed by studying the steroid hormone changes in women with PCOS with either high or normal LH levels leading to inferences regarding the primacy of elevated LH in the pathophysiology of PCOS. METHODS: A cross-sectional study was designed in an academic clinical facility involving 234 women with PCOS. Patients were divided into two groups based on an LH/FSH ratio < or >1 and hormonal and metabolic studies were performed in both groups. Factors were determined by binomial logistic regression that predicted group membership of these women. RESULTS: Higher follicular phase estradiol (E2) and androstenedione (A4) levels as well as greater insulin sensitivity were the only factors that predicted the presence of neuroendocrine dysfunction with elevated A4 being necessary for neuroendocrine dysfunction. CONCLUSIONS: It was concluded that uncoupling of hypothalamic E2 inhibition by elevated ovarian A4 associated with E2 related sensitization of pituitary LH leads to neuroendocrine dysfunction in PCOS.