The pancreas transplant program--Gothenburg, Sweden.
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Adult↗
Biomedical subjects
G Nyberg
Publications and source records attributed to G Nyberg.
Segmental pancreas transplantation with exocrine drainage to the urinary bladder in humans.
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Adult↗
Beneficial effects of angiotensin converting enzyme inhibition on renal function in patients with diabetic nephropathy.
The effects of angiotensin converting enzyme inhibition with captopril were investigated in patients with diabetic nephropathy and hypertension. After nine days' treatment with captopril glomerular filtration rate was unchanged in 13 patients, whereas renal plasma flow had increased from 265 to 302 ml/min/1.73 m2 body surface area (p less than 0.05) and the filtration fraction had decreased from 14.3 to 12.8% (p less than 0.025). During two years' treatment with captopril in 14 patients the mean arterial blood pressure had fallen by 5 mm Hg (p less than 0.005) and the deterioration in glomerular filtration rate had decreased from 10.3 to 2.4 ml/min/year (p less than 0.005). There was no correlation between the fall in blood pressure and the reduction in the deterioration of glomerular filtration rate. These findings suggest that the effects of angiotensin converting enzyme inhibition on renal haemodynamics protect renal function. Inhibitors of angiotensin converting enzyme should be considered for lowering blood pressure in patients with diabetic nephropathy.
Adult↗
Concentrations of thioridazine and thioridazine metabolites in erythrocytes.
The concentrations of thioridazine and its main metabolites in erythrocytes from 61 thioridazine-treated patients were determined by gas-liquid chromatography. The mean and range of the erythrocyte concentrations, expressed as percentage of the corresponding plasma concentrations, were: thioridazine, 5.1% (2.0-10.6); side-chain sulfoxide, 5.6% (1.6-10.4); side-chain sulfone, 3.3% (1.1-6.8); ring sulfoxide 2.7% (0.8-4.9). The erythrocyte and plasma concentrations were significantly correlated. The erythrocyte/plasma concentration ratios, all the erythrocyte concentrations, but none of the plasma concentrations except ring sulfoxide were significantly positively correlated to the dose of thioridazine. The erythrocyte/plasma concentration ratio was not correlated to age. In vitro experiments indicated no clinically relevant erythrocyte-mediated oxidation of thioridazine.
Adult↗
The effect of isosorbide-5-mononitrate (5-ISMN) Durules on exercise tolerance in patients with exertional angina pectoris. A placebo controlled study.
Twenty-four patients with stable exercise-induced angina pectoris entered a double-blind cross-over study. Isosorbide-5-mononitrate (5-ISMN) 60 mg in a controlled release formulation (Durules) given once daily was compared with identical placebo. The exercise tolerance was determined by bicycle ergometry before and 3 h after a single dose of 5-ISMN and following one week's treatment with 5-ISMN and placebo. Nineteen patients completed the study. Exercise tolerance until the onset of chest pain and until 1 mm ST segment depression increased significantly 3 h after dose. The same increase was seen both after a single dose and the same dose under steady-state conditions. No increase was seen with placebo. The heart rate and systolic blood pressure reactions in the standing position were less pronounced 3 h after dose in steady-state than after a single dose of 5-ISMN. Headache was the only bothersome side-effect reported. The study demonstrates that 60 mg 5-ISMN in a Durules formulation given once daily has a significant anti-anginal effect and that tolerance does not develop.
Adult↗
Onset time of action and duration up to 3 hours of nitroglycerin in buccal, sublingual and transdermal form.
Nitroglycerin in sublingual, buccal and transdermal administration forms were compared in 10 patients with stable exercise-induced angina pectoris with respect to onset time of action and efficacy one and three hours after administration, using bicycle exercise to provoke chest pain. Anti-anginal and anti-ischaemic effects (as judged by influence on electrocardiographic ST depression) began within 2 minutes of application of the buccal and sublingual forms, whereas the transdermal patch did not show such effects within nine minutes of application. One and three hours after application, the sublingual form had no effect whereas both the transdermal and buccal forms significantly increased exercise capacity and improved electrocardiographic ST segment changes. The 2.5 mg buccal tablet was more effective than the 10 mg transdermal patch. An additional observation was that a light snack at 2 hours significantly decreased exercise capacity at 3 hours whether or not active treatment had been instituted.
Administration, Cutaneous↗
Acute and long-term antihypertensive effect of bopindolol once daily or once weekly.
Fourteen male patients, mean age 53 years (range 35-64), were included in an initial 3 months' double-blind crossover study, in which 1-2 mg bopindolol, a nonselective beta blocker with intrinsic sympathomimetic activity (ISA), was compared with 100-200 mg metoprolol regarding effects on blood pressure and heart rate. During the subsequent long-term therapy, eight patients were trained to measure home blood pressure, and in these patients bopindolol 1 mg daily was compared to 8 mg once weekly in a double-blind fashion for 3 weeks on each regimen. Bopindolol (mean dose 1.35 mg/day) caused a significant blood pressure reduction, 26/15 mm Hg, as did metoprolol, 24/3 mm Hg (mean dose 144 mg/day) (NS). Supine and standing heart rates were reduced during both bopindolol and metoprolol treatment. During long-term therapy with bopindolol satisfactory blood pressure control was achieved for 1 year in 11 patients. Heart rate was significantly reduced after 2-3 months' treatment and during the entire 1-year follow-up. Few and well-tolerated side effects were reported. During treatment with bopindolol 8 mg once weekly, the blood pressure control was maintained satisfactorily over the week and no significant differences were observed in comparison with daily administration (1 mg) of the drug.
Adrenergic beta-Antagonists↗
Preparation of serum and plasma samples for determination of tricyclic antidepressants: effects of blood collection tubes and storage.
The effects were tested of eight common types of blood collection tubes and two types of "plasma separators" on the stability of the tricyclic antidepressants amitriptyline, imipramine, clomipramine, and their monodemethylated metabolites in venous blood samples. Although EDTA-containing Venoject lavender and Vacutainer lavender tubes seemed to give the most stable plasma samples, and Venoject red the most stable serum samples, the differences were too small to have practical consequences. Vacutainer royal blue collection tubes gave significant losses of greater than 20% of some of the substances. The tubes with serum separator gel or filter proved unsuitable, since they were responsible for losses of greater than 40%. The losses were not caused by redistribution between blood cells and plasma but occurred mainly as a result of contact between the contents and the caps of the tubes. Experiments with freezing, thawing, and storage of samples showed that freshly sampled blood could be stored at room temperature for 24 h in Venoject green tubes without significant losses. Serum samples could be stored at refrigerator temperature for 4 weeks without important losses. Freezing, thawing, and storage at -20 degrees C did not influence the serum or plasma concentrations.
Antidepressive Agents, Tricyclic↗
Children with inborn errors of phenylalanine metabolism: prognosis and phenylalanine tolerance.
Twenty-three children, who were detected by neonatal PKU screening, were followed for 8-18 years in one paediatric centre. Dietary treatment was started if the blood phenylalanine level exceeded 0.72 mmol/l. All 23 infants were initially given a low phenylalanine diet. The growth and development rates of the children did not differ significantly from those in a reference population, although one child had mild mental retardation and another had a short attention span. Fourteen children were still on a strict phenylalanine-restricted diet on their last follow-up (at 8-18 years of age). In nine children who were initially put on a low phenylalanine diet, it was possible to normalize the diet between 1/2 and 10 years of age, while maintaining the blood phenylalanine levels between 0.25 and 0.72 mmol/l. It seems likely that those of our patients who markedly increased their phenylalanine tolerance during childhood had a regulatory mutation of the phenylalanine hydroxylase system. A continuous reevaluation of each child treated with a low phenylalanine diet reduces the use of unnecessarily restricted diets.
Adolescent↗
Constant glomerular filtration rate in diabetic nephropathy. Correlation to blood pressure and blood glucose control.
Twenty-one patients with diabetes of type I and diabetic nephropathy with reduced glomerular filtration rate (GFR) were followed prospectively with regard to GFR, proteinuria, blood pressure and glucosylated haemoglobin (HbA1). All patients were on antihypertensive treatment. The mean rate of decline in GFR was only 0.38 ml/month = 4.6 ml/year. In one third of the patients, GFR remained constant at a reduced level for at least 24 months. Mean plasma clearance of 51Cr-EDTA in this group was 48.3 +/- 14.6 ml/min/1.73 m2 body surface at entry and 48.0 +/- 13.6 at the time of evaluation. The patients with constant GFR had significantly less proteinuria and lower systolic as well as mean arterial pressure during the study than patients with falling GFR. They also had significantly lower mean HbA1 and fewer very high HbA1 values than patients who deteriorated. The data thus indicate that a combination of good metabolic control and effective blood pressure control may strongly delay the progression of renal insufficiency in diabetic nephropathy. They also show that low degree of proteinuria is a marker of good prognosis.
Adult↗
The somatotopic organization of forelimb cutaneous nerves in the brachial dorsal horn: an anatomical study in the cat.
The projection of forelimb cutaneous nerves to the brachial dorsal horn was studied in the cat by the transganglionic transport method. The results demonstrate a precise somatotopic termination pattern. Afferent nerves from the paw occupy the largest area, with the palm represented most medially in the dorsal horn, followed progressively more laterally by the representations for the palmar and dorsal surfaces of the digits and the dorsum of the paw. The digits are represented in a longitudinal sequence, with the first digit in the caudal part of C6 and the fifth in the caudal part of C8. The projections of the wrist and arm are split, with the line of discontinuity located along the ventral surface of the limb, so that the radial side is represented rostral to the paw and the ulnar side caudal to the paw, with the dorsal surface of the arm represented lateral to the paw. Nerves innervating the skin of the back project to the lateralmost part of the dorsal horn. The degree of overlap or separation of the terminal fields of the nerves along the mediolateral axis of the dorsal horn seems to correspond to the degree of overlap or separation of the peripheral innervation fields. However, along the rostrocaudal axis there appears to be an overlap for which there is no counterpart peripherally.
Afferent Pathways↗
Acute and long-term antihypertensive effect of bopindolol--a nonselective beta-adrenergic blocker with ISA.
14 male hypertensive patients, mean age 53 years first took part in a 3 month, double-blind crossover comparison of 1-2 mg bopindolol, a nonselective beta-blocker with ISA, and 100-200 mg metoprolol. Effects on blood pressure and heart rate were followed. One patient dropped out after the initial phase and the remaining 13 patients were followed for 1 year on bopindolol. 8 patients measured blood pressure at home, and in them bopindolol 1 mg o.d. and 8 mg once weekly were compared in a double-blind fashion, for 3 weeks on each regimen. Finally, after 1 year on bopindolol, treatment was withdrawn and blood pressure and heart rate were followed in 10 of the initial patients. Bopindolol in a mean dose of 1.35 mg/day caused a significant reduction in blood in pressure (26/15 mmHg), as did metoprolol (24/13 mmHg) in a mean dose of 144 mg/day. No significant difference in antihypertensive response was observed. Supine and standing heart rate were reduced both during bopindolol and metoprolol treatment. During long-term therapy with bopindolol, satisfactory blood pressure control was maintained up to 1 year in all patients, the average supine blood pressure being reduced from 173/107 to 144/90 mmHg. During treatment with bopindolol 8 mg once weekly, the blood pressure control was satisfactorily maintained over the week and no significant difference was observed in comparison with daily administration (1 mg) of the drug. When active treatment was withdrawn, a gradual increase in blood pressure and heart rate was observed, the pretreatment values being reached 8 weeks after discontinuation of bopindolol therapy.(ABSTRACT TRUNCATED AT 250 WORDS)
Adrenergic beta-Antagonists↗
The time of onset of action of sublingual nitroglycerin in exercise-induced angina pectoris. A methodological study.
Nitroglycerin 0.5 mg sublingually was tested in two exercise protocols in order to determine the time of onset of the anti-anginal action. When patients stopped exertion after nitroglycerin administered at the time of moderate chest pain and one minute before stopping exercise, no anti-anginal or anti-ischaemic effect was seen compared with a placebo-medicated test given double-blindly. When the patients continued exertion after nitroglycerin administered at the onset of chest pain, a significant decrease in chest pain intensity and an improvement in ST-segment depression was seen. It is concluded that administration of a quick-acting anti-anginal drug at the onset of chest pain during continued bicycle exercise provides a suitable test model to determine the time of onset of action in exertional angina pectoris.
Aged↗
Abnormality of adenylate cyclase regulation in human platelet membranes in renal insufficiency.
Adenylate cyclase in human platelets is under dual control of prostaglandins (PGI2 and PGE1) and catecholamines. The adenylate cyclase complex in membranes of platelets from ten patients with uraemia was investigated. The activation of the platelet cyclase by PGE1 is increased in the uraemic state, Vmax 4436 +/- 607 pmol cAMP mg-1 15 min-1. In the normal state Vmax is 2098 +/- 309 pmol cAMP mg-1 15 min-1. The alpha 2-adrenergic receptor was assayed with 3H-yohimbine binding. The density of receptors was equal in the uraemic (175 fmol mg-1 membrane protein) and the normal (170 fmol mg-1 membrane protein) states. Norepinephrine/3H-yohimbine competition binding revealed that catecholamines were bound with normal affinity in platelets in uraemia. Yet the inhibition of adenylate cyclase through the alpha 2-adrenergic receptor was diminished since Vmax values of adenylate cyclase with PGE1 and PGE2 + norepinephrine did not significantly differ. In the normal state, norepinephrine significantly (P less than 0.05) inhibited the PGE1 stimulated cyclase. It is concluded that platelet adenylate cyclase in the uraemia has an increased capacity for activation which is the result of both a sensitized stimulatory mechanism (prostaglandin mediated) and a deficient inhibitory mechanism (catecholamine mediated). It is suggested that a defect exists in the inhibitory nucleotide binding protein (NI) which is the coupling unit between the adenylate cyclase catalytic subunit (C).
Adenylyl Cyclases↗
Acute diuretic/natriuretic properties of felodipine in man.
The natriuretic/diuretic effect of felodipine was investigated in 2 studies. The first was performed as an open study using intravenous and oral felodipine in healthy male subjects. The second was a double-blind study where a high and a low dose of oral felodipine were given to hypertensive patients on long term treatment with beta-blockers; the different doses of felodipine were chosen to decrease and to have no effect on the blood pressure, respectively. In both studies an oral placebo solution was used as a reference. Felodipine caused a significant increase in natriuresis. Compared with placebo and corrected for total 24-hour excretion, the sodium output during the first 4 hours after drug administration was increased by 219 +/- 53% (mean +/- SEM) after intravenous administration in healthy subjects (p less than 0.01) and by 80 +/- 43% in the first 3 hours after the high dose in hypertensive patients (p less than 0.05). For the same period, the urine excretion was increased by 114 +/- 38% (p less than 0.05) in the healthy subjects and by 36 +/- 22% in the hypertensive patients (not significant). However, the 24-hour excretion of urine, Na+ and K+ was not significantly changed from placebo. A significantly lower blood pressure was recorded after the higher dose (0.10 mg/kg) when given to hypertensive patients, but no such effect was seen after the lower dose (0.01 mg/kg) or in healthy subjects. The changes in diastolic blood pressure seem to be negatively correlated with the diuretic but not with the natriuretic effect.
Adult↗
The central projection of muscle afferent fibres to the lower medulla and upper spinal cord: an anatomical study in the cat with the transganglionic transport method.
The projection of muscle afferent fibres to the medulla oblongata and upper spinal cord was studied in the cat by using transganglionic transport of wheat germ agglutinin-horseradish peroxidase conjugate. The results demonstrate a precise, musculotopic termination pattern in the external cuneate nucleus; thus, fibres from the intrinsic muscles of the paw terminate medially; those from forearm, arm, and shoulder muscles terminate progressively more laterally; and those from neck and thoracic muscles terminate in the ventrolateral and dorsolateral parts, respectively. Muscle afferent fibres to the main cuneate nucleus terminate in the ventral "reticular" region of the nucleus, with a sparse projection also to the ventral part of the rostral and caudal regions, including the base of the dorsal horn. Fibres from the neck muscles terminate slightly more laterally in the ventral region than do those from the limb muscles, but otherwise, and thus contrary to the case in the external cuneate nucleus, no topographic organization was detected. In the spinal cord, projection was found to laminae I and V, and from the musculature of the back of the neck to the central cervical nucleus.
Afferent Pathways↗
Göteborg Metoprolol Trial: mortality and causes of death.
During the 3-month blind treatment period there were 40 deaths in the metoprolol group compared with 62 deaths in the placebo group (p = 0.024). During the first year (after 3 months the 2 groups were treated similarly) there were 64 deaths in the metoprolol group vs 93 in the placebo group (p = 0.017) and during 2 years 92 patients died in the metoprolol group vs 120 in the placebo group (p = 0.043). The relative incidence of different causes of death did not differ significantly between the 2 treatment groups, indicating that metoprolol reduced all causes of death to the same extent as its effect on overall mortality.
Aged↗
Adverse effect of trimethoprim on kidney function in renal transplant patients.
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Creatinine↗