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Biomedical subjects

R Unwin

Publications and source records attributed to R Unwin.

32 records · Page 2Linked to original sources
PubMed1993

Use of endoscopic biopsies and microelectrodes to study human gastric acid secretion in vitro.

We have investigated the possibility of measuring acid secretion from human gastric mucosa in vitro as a potential pharmacological preparation. We used open-ended 10 microns-tip, lix-based glass microelectrodes to measure the pH of the mucus layer of gastric biopsies superfused with a HEPES buffered solution in an organ bath. With no drugs added the pH of the mucus layer of biopsies from the body of the stomach stayed constant but the pH of antral biopsies fell slightly by a median of 0.12 pH units over 80 min (P < 0.05). Stimulation of the biopsies with 1-100 microM histamine produced a dose-dependent decrease in pH which was significantly greater in biopsies from the gastric body than from the antrum. 500 pM pentagastrin produced a median fall in pH of 1.20 (P < 0.01) which was prevented by the prior addition of 100 microM omeprazole or 10 microM ranitidine. Omeprazole or ranitidine alone produced slight rises in the median pH of 0.47 (P < 0.05) and 0.26 (P < 0.05) units respectively. Those biopsies which were infected with Helicobacter pylori had a slightly elevated initial pH of about 0.2 of a pH unit (P < 0.05). This novel system provides a means to study human gastric acid secretion in vitro and may be valuable in the testing of new drugs on the stomach.

Adolescent↗
PubMed1992

A comparison of the effects of the selective peripheral alpha 1-blocker terazosin with the selective beta 1-blocker atenolol on blood pressure, exercise performance and the lipid profile in mild-to-moderate essential hypertension.

The effects of six weeks of treatment with the selective peripheral alpha 1-adrenoceptor blocker terazosin, or the selective beta 1-adrenoceptor blocker atenolol on blood pressure, exercise performance and blood lipid profile were compared in a single-blind, randomized, crossover study of 17 patients with mild-to-moderate essential hypertension. Although both drugs significantly reduced blood pressure at rest, atenolol caused a larger fall in supine blood pressure (11/11 and 7.5/7.0 mmHg, atenolol and terazosin, respectively; p < 0.001). Both treatments controlled the pressor response to exercise, although a greater reduction in diastolic blood pressure was observed at the end of exercise on terazosin (74.0 +/- 5.7 and 91.6 +/- 4.0 mmHg, terazosin and atenolol, respectively; p < 0.01). Alpha 1-blocker therapy was not associated with any measurable improvement or deterioration in cardiopulmonary performance and exercise duration. Unlike atenolol, terazosin therapy had the potentially beneficial effect of reducing serum total cholesterol levels and increasing the high-density lipoprotein-cholesterol/low-density lipoprotein-cholesterol ratio.

Adult↗
PubMed1991

Selective alpha 1-adrenoreceptor blockers in the treatment of hypertension: should we be using them more?

It has become apparent in recent years that in the treatment of essential hypertension, reduction of blood pressure alone is not sufficient to reduce significantly the morbidity and mortality from ischaemic heart disease. Since the emergence of a multifactorial approach to the prevention of cardiovascular disease, the potential interaction between antihypertensive therapy and metabolic factors, such as control of blood glucose and lipid levels, has become an important consideration. Abnormal function of the sympathetic nervous system may contribute to both the initiation, or maintenance, of hypertension and the associated metabolic disturbances. The new generation of selective alpha 1-adrenoreceptor blockers, besides lowering blood pressure, appear to have favourable effects on lipid and glucose metabolism. The use of these drugs and their place in the treatment of hypertension are discussed.

Adrenergic alpha-Antagonists↗
PubMed1991

Coupled water transport by rat proximal tubule.

Simultaneous microperfusion of proximal tubules and peritubular capillaries in kidneys of rats anesthetized with Inactin was used to examine water reabsorption by this epithelium. Osmolality of the luminal solution was varied with changes in NaCl concentration and by the addition of raffinose. Capillary perfusates contained either low (2 g/dl) or high (16 g/dl) concentrations of albumin. We used low-bicarbonate perfusates for both lumen and capillary so that we might apply the nonequilibrium thermodynamic model of transport for a single solute (NaCl) to interpret our observations. Linear regression with the volume flux equation Jv = -Lp delta II - Lp sigma delta C + Jav (where Jv is volume flux, Lp is hydraulic conductance, delta II is oncotic force, sigma is osmotic reflection coefficient, delta C is salt concentration difference, and Jav is the component of Jv not attributed to transepithelial hydrostatic or osmotic forces) revealed a tubule water permeability (Pf = 0.11 +/- 0.01 cm/s) and a sigma (0.74 +/- 0.08) in agreement with previous determinations. These transport parameters were unaffected by changes in peritubular protein. We also found that Jav was substantial, approximately three-fourths of the rate of isotonic transport under these perfusion conditions. Further, this component of water transport nearly doubled with the transition from low- to high-protein peritubular capillary perfusion. When expressed as a capacity for water reabsorption against an osmotic gradient, the salt concentration differences required to null volume flux were 13.2 +/- 2.4 and 29.4 +/- 4.0 mosmol/kgH2O under low and high peritubular protein. Our data suggest that this protein effect is, most likely, an increase in solute transport by the tubule epithelial cells.

Absorption↗
PubMed1991

Bicarbonate transport along the loop of Henle. I. Microperfusion studies of load and inhibitor sensitivity.

We microperfused the loop of Henle (LOH) to assess its contribution to urine acidification in vivo. Under control conditions (Na HCO3- = 13 mM, perfusion rate approximately 17 nl/min-1) net bicarbonate transport (JHCO3-) was unsaturated, flow- and concentration-dependent, and increased linearly until a bicarbonate load of 1,400 pmol.min-1 was reached. Methazolamide (2 x 10(-4) M) reduced JHCO3 by 70%; the amiloride analogue ethylisopropylamiloride (EIPA) (2 x 10(-4) M) reduced JHCO3 by 40%; neither methazolamide nor EIPA affected net water flux (Jv). The H(+)-ATPase inhibitor bafilomycin A1 (10(-5) M) reduced JHCO3 by 20%; the Cl- channel inhibitor 5-nitro-2'-(3-phenylpropylamino)-benzoate (2 x 10(-4) M) and the Cl(-)-base exchange inhibitor diisothiocyanato-2,2'-stilbenedisulfonate (5 x 10(-5) M), had no effect on fractional bicarbonate reabsorption. Bumetanide (10(-6) M) stimulated bicarbonate transport (net and fractional JHCO3-) by 20%, whereas furosemide (10(-4) M) had no effect on bicarbonate reabsorption; both diuretics reduced Jv. In summary: (a) the LOH contributes significantly to urine acidification. It normally reabsorbs an amount equivalent to 15% of filtered bicarbonate; (b) bicarbonate reabsorption is not saturated; (c) Na(+)-H+ exchange and an ATP-dependent proton pump are largely responsible for the bulk of LOH bicarbonate transport.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1987

Unusual cranial and abdominal computed tomographic (CT) scan appearances in a case of systemic lupus erythematosus (SLE).

A 35 year old woman presented with headache and fever. Computed brain tomography showed diffuse low attenuation in the cerebral white matter. Several months later, serological tests for systemic lupus erythematosus (SLE) became positive. In spite of immunosuppressive therapy she relapsed after six months of treatment, presenting with abdominal symptoms and signs. On this occasion an abdominal CT scan showed distended and oedematous loops of bowel attributed to an underlying vasculitis. This case illustrates novel CT scan appearances in two systems involved in SLE.

Adult↗
PubMed1987

Cytomegalovirus colitis and oesophageal ulceration in the context of AIDS: clinical manifestations and preliminary report of treatment with Foscarnet (phosphonoformate).

Three patients with biopsy diagnosed invasive cytomegalovirus infection of the colon have been seen in the context of the acquired immune deficiency syndrome (AIDS). Cytomegalovirus colitis presented with fever, abdominal distention, bloody diarrhoea and weight loss. Plain abdominal radiographs showed generalised large bowel dilatation in one patient. Cytomegalovirus infection was shown histologically, but the virus could not be cultured from the stool; no other gastrointestinal pathogens could be demonstrated. The patients were treated with a 14 day continuous infusion of Foscarnet 0.08 mg/kg/min (phosphonoformate, Astra Pharmaceuticals). One patient showed a partial response to therapy, but the cytomegalovirus colitis relapsed; the second patient had a symptomatic response only and the third patient died of non-cytomegalovirus opportunist infection while on treatment. Two other patients with biopsy proven cytomegalovirus ulceration of the oesophagus were seen, presenting with dysphagia, fever and weight loss. Invasive infection of the gastrointestinal tract with cytomegalovirus is now a major clinical problem in AIDS. Treatment with Foscarnet may be initially effective, but does not eliminate cytomegalovirus infection.

Acquired Immunodeficiency Syndrome↗
PubMed1983

Neurotensin stimulates defaecation.

Five normal adults defaecated within 2 1/2 hours of receiving neurotensin 13.5 pmol kg-1 min-1 for 30 min, whereas none did so after control infusions, in a double-blind study. Neurotensin caused borborygmi and production of stools which resembled the normal contents of the proximal and distal colon in terms of consistency and electrolyte content. This evidence suggests that neurotensin had a major effect on propulsive colonic motility. Blood neurotensin concentrations during infusion were about three times higher than normal postprandial concentrations, but plasma neurotensin is raised in some diseases associated with diarrhoea.

Adult↗
PubMed1983

Studies on the renin response to vasoactive intestinal polypeptide (VIP) in the conscious rabbit.

Vasoactive intestinal polypeptide (VIP) has been found within the renal cortex and is believed to be a neurotransmitter. Although it produces systemic vasodilatation and renin release, the exact mechanism of the latter response is uncertain. When infused into conscious rabbits, VIP elicits a rise in plasma renin activity (PRA) and an increase in heart rate. The rise in PRA is unaltered by pretreatment with propranolol, but is attenuated by indomethacin. The tachycardia is inhibited by propranolol, but unaffected by indomethacin. We conclude that the renin response to VIP is in part prostaglandin-dependent and that the heart rate response is due to direct or reflex beta-adrenoceptor stimulation.

Adrenergic beta-Antagonists↗
PubMedDate not supplied

Diminished diuretic and natriuretic response to furosemide in potassium-depleted rats.

Renal clearance and tubule microperfusion experiments were carried out to investigate the effects of chronic potassium depletion upon the renal response to furosemide. Rats kept on a potassium-deficient diet for 3 weeks developed hypokalemia, metabolic alkalosis, and decreased aldosterone levels. These rats responded to an oral administration of furosemide (32 mg/kg) with a blunted excretion rate of urine and sodium. Whereas furosemide increased fractional urine sodium excretion to 5.2% in control rats, the corresponding rate in potassium-depleted rats was 2.8%. The urinary excretion of furosemide was also significantly reduced during potassium depletion from 3.06 mg/kg in control rats to 0.97 mg/kg in potassium-depleted rats. In separate experiments, loops of Henle were pump-perfused with furosemide-containing solutions in control and potassium-depleted rats. No major modification of the inhibitory effects of furosemide on sodium transport was observed when the potassium concentration of the perfusion fluid was kept at the low levels expected in hypokalemic rats. Metabolic alkalosis unaccompanied by potassium deprivation did not decrease the diuretic response to furosemide. These experiments indicate that potassium deprivation reduces the diuretic effects of furosemide by mechanisms including diminished furosemide delivery to its tubule site of action.

Animals↗