Hypoglycemic drugs.

There are an estimated 14 million individuals in the United States with diabetes mellitus. These individuals suffer a very high incidence of podiatric complications. This article focuses on the pharmacologic agents used in the management of hyperglycemia in the patient with diabetes mellitus, including insulin and sulfonylureas.     

The evoked K-complex: all-or-none phenomenon?

The functional significance and topographical variation of the different components of the evoked K-complex were examined. In the first experiment, the intensity of the stimulus (80 and 60 dB SPL) and its rise-and-fall time (2 and 20 milliseconds) were manipulated during nonrapid eye movement sleep. In the second experiment the tonal frequency (500, 1,000 and 2,000 Hz) of the stimulus was manipulated. In the first experiment, nine stimuli were presented every 10 seconds, whereas in the second, 20 consecutive stimuli were presented. The evoked K-complex consisted of two different negative components peaking at approximately 350 and 550 milliseconds, respectively, and followed by a positive component peaking at approximately 900 milliseconds. K-complexes were easier to elicit for high-intensity fast rise-and-fall time stimuli than for low-intensity slow rise-and-fall time stimuli. The probability of occurrence was not affected by the tonal frequency of the stimulus. When a K-complex was evoked, the amplitude and latency of N350, N550 and P900 remained invariant regardless of its intensity, rise-and-fall or its tonal frequency. The N550-P900 portion of the K-complex therefore appears to be an all-or-none phenomenon. On trials in which a K-complex could not be elicited, N350 was still visible although much attenuated. In these trials, its amplitude was further reduced when stimulus intensity was lowered. N350 might need to reach a certain critical threshold before the much larger N550-P900 complex is elicited.     

ANGIOTENSIN CONVERTING ENZYME (ACE) INHIBITORS AND KININ METABOLISM: EVIDENCE THAT ACE INHIBITORS MAY INHIBIT A KININASE OTHER THAN ACE

1. Angiotensin converting enzyme (ACE) converts angiotensin I to angiotensin II, and also metabolizes bradykinin-(1–9) to bradykinin-(1–7) and bradykinin-(1–7) to bradykinin-(1–5). Increases in endogenous kinin levels may contribute to the therapeutic effects of ACE inhibitors. 2. ACE inhibitors increase vascular levels of both bradykinin-(1–9) and its ACE cleavage product bradykinin-(1–7), at doses below the threshold for ACE inhibition, leading to the proposal that ACE inhibitors may also inhibit a non-ACE kininase which cleaves both kinin peptides; this non-ACE kininase may be the major pathway of kinin metabolism in the vasculature and some other tissues. 3. In support of this proposal, ACE inhibitors potentiate bradykinin-(1–9) effects at doses which have little or no effect on ACE activity, as indicated by angiotensin I conversion to angiotensin II. ACE inhibitors also potentiate the actions of ACE-resistant kinin analogues, which may be susceptible to metabolism by a non-ACE kininase. 4. Identification and characterization of the putative non-ACE kininase which is inhibited by ACE inhibitors may reveal novel approaches to the tissue-specific modulation of kinin levels.     

Use of intracavity saline instillation and transvaginal ultrasonography to detect tamoxifen-associated endometrial polyps.

There is sometimes a discrepancy between the apparent thickness of postmenopausal endometria, as determined by transvaginal ultrasonography, and the examination of endometrial biopsies. We describe a case which showed that tamoxifen (20 mg/day over 12 months) decreased impedance to blood flow in the uterine arteries and increased the apparent thickness of the endometrium. Conversely, the analysis of biopsies suggested the presence of an atrophic endometrium. The introduction of sterile saline into the uterine cavity during a repeat ultrasound scan revealed the presence of a large, free-floating endometrial polyp, which was subsequently difficult to see by hysteroscopy.     

Pseudopapilloedema in the linear naevus syndrome.

This case report describes the ophthalmic findings in a child with the linear naevus syndrome. The patient was referred by the Department of Paediatric Neurology with 'unilateral papilloedema'. This was thought to be a form of pseudopapilloedema, a finding that has not been previously described in this syndrome.     

Diagnosis and management (by subxiphoid pericardiotomy) of large pericardial effusions causing cardiac tamponade.

To determine the clinical features, course and outcome of patients with cardiac tamponade, 57 consecutive patients with new, large pericardial effusions were prospectively studied. Twenty-five patients (44%) developed cardiac tamponade with venous hypertension and a pulsus paradoxus greater than 10 mm Hg. Electrocardiography, radiographic studies and echocardiography did not differentiate patients with and without tamponade. All 57 patients underwent thorough diagnostic evaluation followed by subxiphoid pericardial biopsy and drainage. A diagnosis was obtained in 53 patients (93%). Collagen vascular disease was significantly more frequent in the 25 patients with than in the 32 without cardiac tamponade (24 vs 3%; p less than 0.05). The frequency of malignant and uremic effusions was equal in both groups, whereas radiation-induced effusions seldom produced tamponade. At 1-year follow-up, 3 patients (12%) with tamponade had recurrent effusions, and 1 needed reoperation. This was not significantly different from the 32 patients without tamponade. Twelve-month mortality was also similar in both groups (36 vs 44%). This prospective series disclosed several unexpected findings: (1) Cardiac tamponade occurred in almost 50% of patients with new large pericardial effusions; (2) both malignancy and collagen vascular disease occurred with equal frequency as etiologies, whereas radiation-induced tamponade was unusual; (3) thorough clinical evaluation resulted in few idiopathic etiologies; and (4) subxiphoid pericardiotomy was effective for both diagnosis and therapy of tamponade.     

Innovative endpoint determination system for antifungal susceptibility testing of yeasts.

Fungal infections and antifungal resistance are increasingly recognized. Antifungal susceptibility testing remains unstandardized, and a particularly important problem is endpoint determination. In this paper we propose the yeast metabolic reduction of the tetrazolium salt 2,3-bis(2- methoxy-4-nitro-5-sulfophenyl)-5-[(phenylamino)carbonyl]-2H-tetraz olium hydroxide (XTT) as a colorimetric endpoint which is quantitative and objective. Amphotericin B, fluorocytosine, and fluconazole dose-response curves were obtained, and a metabolic MIC could be determined by using precise criteria.     

Protein kinase C activity in blood vessels from normotensive and spontaneously hypertensive rats.

This study investigates the effects of phorbol dibutyrate (PDB) on protein kinase C (PKC) activation, as assessed by the translocation of PKC activity from the cytosolic to the particulate fraction, in aortas and mesenteric arteries from spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY). The basal distribution of PKC activity between the cytosolic and particulate fractions of SHR and WKY aortas, and mesenteric arteries, was not significantly different. PDB induced a concentration-dependent decrease in cytosolic PKC activity in SHR and WKY aortas. PDB (0.01 microM) decreased cytosolic PKC activity to a greater magnitude in SHR aorta as compared to WKY aorta, while 1.0 microM PDB decreased cytosolic PKC activities to similar magnitudes in SHR and WKY aortas, and mesenteric arteries. These results suggest that the increased sensitivity of SHR vessels to contraction by phorbol esters may be due, at least in part, to the greater sensitivity of PKC in these vessels to phorbol ester activation.