Biomedical subjects
Publications and source records attributed to D J Webb.
A patient is described who developed mild hyponatraemia on two occasions when treated with bendrofluazide alone, but severe hyponatraemia when treated with the combination of enalapril and bendrofluazide.
At extracellular pH values close to their pKa values the weak bases, ammonia and procaine, elicited a series of events in non-activated Xenopus eggs, some of which resembled those normally occurring at fertilization. These included: (1) a transient increase in membrane conductance; (2) modification of the microvilli; (3) thickening of the cortical cytoplasm and displacement of the cortical granules; (4) pigment accumulation; (5) contractions and shape changes. However, these eggs did not undergo the cortical reaction nor emit the second polar body. Cortical granule exocytosis of inseminated or artificially stimulated eggs was inhibited if the eggs had been previously treated for 15 min with the weak base and subsequently rinsed. Multiple sperm-entry sites were exhibited by the inseminated eggs, suggesting polyspermy. However, such eggs did not cleave and although sperm had fused with the egg membrane, they were not incorporated. Nevertheless, a transient increase in membrane conductance was evoked, which was longer in duration and had a slightly different form from that normally accompanying fertilization. In these eggs cortical granules were intact but displaced away from the plasma membrane. Prolonged contact with the weak base rendered eggs totally unresponsive to sperm or artificial stimuli but eggs recovered when rinsed sufficiently. These effects of weak bases on unfertilized Xenopus eggs or during fertilization were completely absent at pH 7.4. Although changes in intracellular pH or Ca2+ may be involved in these phenomena, direct action by the weak base itself cannot be ruled out.
Changes in plasma active and inactive renin and angiotensin II in response to tilt and intravenous frusemide were assessed in ten patients with essential hypertension, before treatment and again during chronic therapy with the alpha 1-adrenoceptor antagonist prazosin. During prazosin treatment blood pressure in the patients fell from mean levels 172/108 mmHg to 149/88 mmHg (P less than 0.05). Both before and during prazosin, tilt and frusemide each led to significant elevation of plasma active renin (P less than 0.001) and angiotensin II (P less than 0.05). Inactive renin tended to fall with tilt, and fell significantly following frusemide (P less than 0.05). Active renin (P less than 0.05) and angiotensin II (P less than 0.01) were lower 15 hours after dosing during chronic prazosin therapy than before treatment, but changes after tilt and frusemide were not attenuated during treatment. Chronic prazosin administration does not appear substantially to affect changes in active renin or angiotensin II in response to two standard stimuli, and may be useful in controlling hypertensive patients pending investigation of their renin-angiotensin system.
The fertilization potential in Xenopus eggs under normal circumstances is considered to be a unique event. It is associated with a concomitantly occurring cortical granule exocytosis. If eggs were exposed to weak bases, exocytosis was inhibited but the fertilization potential could still be evoked. After recovery from this first transient increase in membrane conductance, a second could be elicited by a further stimulus. A fertilization potential could be triggered either before or after the egg had undergone an electrically induced activation potential. This suggests that sperm receptors and sperm activated ionic channels in the egg membrane remain functional following the conductance change, at least when the exocytotic event was prevented. A transient conductance increase could only be induced by NH4+ (pH 9.0) in unactivated eggs that had not undergone cortical granule exocytosis. Tremendous variation was noticed between successive activation currents elicited in the same egg. Under voltage-clamp at 0 mV holding potential, the current often changed from inward to outward. Although cortical granule exocytosis may only play a minor role in the transient conductance change triggered at fertilization, it may well be involved in subsequent modifications of membrane conductance.
A case of recurrent eosinophilic granuloma of the mandible following radiation therapy is presented. The lesion was curetted and immediately reconstructed with autogenous bone for strength and lower border continuity. Since radiation therapy in low doses is normally curative for this disease, few recurrences have been reported. It is emphasized that polyostotic disease may have a greater propensity for recurrence and that patients presenting with multiple lesions should be followed up closely, regardless of the mode of therapy.
The treatment of an aggressive giant cell lesion of the mandible by combined curettage and cryosurgery is presented with a 5 year follow-up without recurrence. The difficulty in diagnosing and treating the more persistent central giant cell granulomas as compared to giant cell tumors of the jaws is discussed, and a more conservative first surgical approach is presented.
Studies were performed in normotensive volunteers and hypertensive subjects to examine the effect on forearm blood flow (FBF) of brachial artery infusions of angiotensin I (ANG I), angiotensin II (ANG II), and ramiprilat [the active metabolite of the angiotensin converting enzyme (ACE) inhibitor, ramipril]. Ramiprilat (10 mcg/min for 10 min) produced a 71% mean increase in FBF (n = 8; range, 26-130%; p less than 0.001) in vessels preconstricted with ANG I (64-128 pmol/min), with the effect maximal at the end of ramiprilat infusion and subsiding over 30 min. Doses of ANG I required to produce equivalent reductions of FBF were 2 to 4 times those of ANG II before ramiprilat, but after ramiprilat the dose of ANG I required to produce equivalent constriction was increased 20-fold (n = 6; p = 0.01) while that of ANG II was unaltered. Ramiprilat given alone produced only a small nonsignificant increase in FBF of 7 +/- 4% (n = 12; p = 0.29), though this increase did correlate significantly with plasma renin (r = 0.60; p = 0.04). These results confirm the presence of ACE within human resistance vessels and suggest the possibility that inhibition of ACE at sites other than the pulmonary bed might contribute to the hypotensive action of ACE inhibitors.
All four factors which theoretically may affect the renal vein renin ratio in unilateral renal artery stenosis--increased renin secretion and diminished renal plasma flow on the stenotic side; suppressed renin secretion and renin extraction on the contralateral side--have been assessed. In a series of patients with unilateral renal artery stenosis, the renal vein ratio of active renin was more closely related to the reduction of renal plasma flow than to renin secretion rate on the affected side. On the contralateral side renin secretion was suppressed while angiotensin II was extracted. During long-term treatment with the converting enzyme inhibitor enalapril, peripheral plasma angiotensin II was lowered, while active renin concentration was markedly elevated, both in arterial plasma and in renal venous plasma of the stenotic kidney; the contralateral kidney became a net extractor of active renin. Thus, all 4 factors which theoretically affect the renal vein renin ratio can operate clinically. Both before and during enalapril, the affected kidney secreted inactive renin.
The development of proteinuria, and more rarely nephrotic syndrome, has been seen with the use of the first orally active converting-enzyme inhibitor captopril. Both of these side effects appear to occur more frequently when the drug is used at higher dose, particularly in the presence of renal impairment. We have used enalapril, a new orally active converting-enzyme inhibitor in the treatment of a patient with drug-resistant hypertension and renal impairment who previously developed nephrotic syndrome with captopril. Recurrence of the nephrotic syndrome was not seen in this patient during a period of 20 months on enalapril. On the contrary, urinary protein excretion over the same period was reduced to around 1 g in 24 hours. Our experience would suggest that enalapril may usefully be substituted for captopril in the treatment of hypertensive patients in whom the latter has caused proteinuria or nephrotic syndrome.
Systemic cysticercosis with cerebral involvement is a serious disease that may be encountered with greater frequency in the southwestern United States because of the proximity to areas of endemic disease. Because oral lesions can occur, the dentist and dental specialists, by recognizing and performing biopsies of lesions in patients suspected of having the disease, can provide a valuable service.
The membrane potential of Xenopus eggs was monitored continuously from prior to fertilization until early cleavage. A rapid decay of the initial potential of -33.1 +/- 8.1 (SD) mV (N = 14) upon impalement to a value of -19.3 +/- 4.2 (SD) mV (N = 68) suggested that insertion of the first electrode caused depolarization. Outward and inward rectification were observed when the resting potential was made more positive than about 5 mV or more negative than about -30 mV. Eggs were not activated by this level of current injection. Fertilization and activation evoked a membrane depolarization which was influenced by the external Cl- concentration, the nature of the halide species, and 4,4-diisothiocyanostilbene-2,2-disulfonic acid. Smaller transient depolarizations were associated with the initial stages of the fertilization potential but not with activation. Only when the fertilization potential was significantly diminished, as in high external Cl- or in the presence of Br- or I- solutions did polyspermy ensue. The input resistance of the unfertilized egg was 13.2 +/- 9.8 M omega (N = 26) and decreased about 200-fold at the peak of the fertilization potential to 0.077 +/- 0.020 M omega (N = 9). Ninety minutes after the onset of the fertilization potential and about 6 min after the start of furrow formation the membrane began a series of cleavage cycle-associated hyperpolarizations. These were unaffected by either the external Cl- concentration or other halide species. Reduction in amplitude of the fertilization potential had no apparent effect upon the normal elevation of the fertilization envelope or upon cleavage and later development. The fast electrical block to polyspermy appears to have a lower threshold in Xenopus compared with other species and is also effective at negative membrane potentials.
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The membrane potential of Rana pipiens eggs (-55.0 mV +/- 11.2(16)) was more likely to recover from impalement and was always more negative than that of eggs of Xenopus laevis (-19.3 mV +/- 4.2(68)). It was also much more negative than previously reported. Essentially similar membrane resistance changes were measured in the two frog species through fertilization and cleavage. Small transient depolarizations only associated with the onset of the fertilization potential in Xenopus could be prevented by hyperpolarizing the egg membrane prior to fertilization. Repolarization was variable and longer in Rana and often accompanied by large transient spontaneous depolarizations. Insemination time, the time between fertilization and cleavage and the first cleavage division cycle, were all about twice as long in Rana. Xenopus egg cleavage was invariably accompanied by pronounced transient hyperpolarizations that were essentially absent in Rana.
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The inhibitor of human renin, H142, was studied in nine male volunteers. On three occasions, in random order, volunteers were infused with 5% dextrose or with H142 at 1.0 or 2.5 mg/kg per h for 30 min while supine and thereafter with dextrose for 1 1/2 h. There was a marked reduction in plasma active renin concentration as assayed by an enzyme-kinetic method, with parallel falls in the circulating concentrations of angiotensins (ANG) I and II, all of which rebounded transiently to values above basal after the H142 infusion was stopped. In contrast, total renin concentration as measured by radio-immunoassay rose while ANG I and II fell, subsiding when H142 was discontinued. There was a slight but significant increase in plasma noradrenaline as renin became inhibited; plasma adrenaline was unchanged. H142 produced a slight fall in systolic blood pressure (SBP) and a clearer, highly significant, dose-related fall in diastolic blood pressure (DBP). There was a modest but significant increase in the heart rate. These studies confirm H142 as an effective inhibitor of human renin in vivo.
In a 12-week double-blind randomised study the efficacy of atenolol and a new longer-acting formulation of trimazosin were compared when given once daily in patients with mild to moderate hypertension. Two parallel groups, each consisting of 18 patients, were studied. At randomisation the two groups were well matched for age and sex distribution. They were also well matched for blood pressure, pulse rate and body weight; these latter measurements were recorded at regular intervals during the 12 weeks of study. Atenolol produced substantial reduction in both systolic and diastolic blood pressure, and in heart rate, during 12 weeks of treatment. This therapeutic effect was maintained until the next dose after 24 hours. Trimazosin, by comparison, failed to reduce either systolic or diastolic pressure, or to alter heart rate. Side effects were minor with both agents and compliance with treatment was good. Atenolol caused significant elevation of plasma concentration of triglyceride, with reduction in high density lipoprotein concentration when compared with trimazosin. In conclusion, atenolol was confirmed as an effective agent for the treatment of mild to moderate hypertension. By comparison trimazosin in the longer-acting formulation was ineffective in this study. However, trimazosin may still find a place in treatment if used at higher dose.