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Biomedical subjects

U C Dubach

Publications and source records attributed to U C Dubach.

At least 73 records · Page 4Linked to original sources

[Nocturnal hypoglycemia in type-I diabetics, an underestimated risk?].

In 22 type I labile diabetics aged 20-64 years, various nighttime blood sugar (BS) values were obtained. Although 13 patients in 15 of 43 nights investigated measured below 2.8 mmol/l (50 mg%) for many hours, two thirds remained symptomless while the remainder suffered from minor hypoglycemic symptoms. The lowest BS values were obtained at about 3 a.m. Prospective as well as retrospective estimation of the hypoglycemic risk was performed with the aid of fasting and bed time BS. Causes and measures for prevention of the unexpectedly large number of episodes of nighttime hypoglycemia are discussed. Additionally, 18 healthy volunteers aged 24-61 years were investigated during 22 nights in regard to BS-values for comparative purposes: the lowest measured BS was 3.7 mmol/l (66 mg%) with an average nighttime BS of 4.9 +/- 1.1 mmol/l (86 +/- 5 mg%).

Adult↗

[Preventive chemotherapy of intrapulmonary residual tuberculosis with isoniazid--example of failed compliance by the physician].

Compliance with the recommendations of the Swiss Society for Tuberculosis and Lung Diseases regarding the treatment of patients with fibrotic pulmonary lesions with isoniazid was evaluated over the period March 1981-October 1982. 42 patients (mean age 53 +/- 16 years) were selected for preventive treatment. Diagnostic procedures were correctly performed in 22 patients (52.4%). 32 patients (76.2%) received the recommended drug initially. In 18 patients (42.9%) isoniazid was correctly prescribed for six months. In only 15 patients (35.7%) was the diagnostic and therapeutic approach correct. The reasons for these quality inadequacies on the diagnostic and therapeutic levels are discussed.

Aged↗

Isolation of a homogeneous glucosidase II from pig kidney microsomes.

The processing of the oligosaccharide precursor chain, (GlcNAc)2(Man)9(Glc)3, of N-glycosylated glycoproteins starts with the action of glucosidase I which excises the terminal (alpha 1-2)-linked glucose residue. Glucosidase II removes the two inner (alpha 1-3)-linked glucose residues. We have purified glucosidase II to homogeneity from pig kidney microsomes. The enzyme is a glycoprotein and contains a single type of subunit of molecular mass approximately equal to 100 kDa. The native enzyme is probably a tetramer. It cleaves glucosidic alpha 1-3 and alpha 1-4, but not alpha 1-1, alpha 1-2 or alpha 1-6 bonds and lacks alpha-mannosidase and glucosidase I activity. The pH optimum is between 6.0 and 7.5. Specific antibodies against the native enzyme and the denatured subunit were prepared. By activity measurements and immune blotting, a similar enzyme was found in rat liver. In the fractionated rat liver, the enzyme was localized in the lumen of the endoplasmic reticulum, probably loosely bound to the inner face of the membrane. Purified Golgi fractions contained only low levels of the enzyme.

Animals↗

Sodium gradient-energized concentrative transport of adenosine in renal brush border vesicles.

The uptake of adenosine in brush border vesicles of the proximal tubule of the rat kidney has been studied with a filtration technique. The initial rate of uptake was almost 6 times greater in the presence of NaCl than in the presence of KCl. The stimulatory effect of Na+ was strictly dependent on a gradient of Na+ (out greater than in). The time course of uptake showed an overshoot with a maximum at 20 s with a gradient of NaCl, but not with KCl. Inosine and 5'-AMP were produced from adenosine within the vesicles. In the presence of an inhibitor or adenosine deaminase adenosine was not significantly metabolized during the first 20 s of uptake. Thus, kinetic parameters of transport could be studied in the absence of interferences with metabolism. A Km of 1.1 microM and a Vmax of 232 pmol X min-1 X mg protein-1 were calculated for the Na+ gradient-dependent transport. The dependency on a Na+ gradient, the capacity for uphill transport and the high affinity for adenosine situate this transport system apart from the mechanisms of transport of nucleosides described so far. It may be relevant in regard to the role of adenosine in the regulation of glomerular filtration.

Adenosine↗

Critical evaluation of the diagnostic use of urinary enzymes.

More basic research has to be done to evaluate the many pathophysiological mechanisms which lead to excretion of enzymes in urine. Special attention is paid to the problem of evaluation of nephrotoxicity of drugs in the animal model. A differentiation of infections in the upper and lower urinary tract may be possible. Correlation of function of a kidney transplant with the aid of urinary enzymes is sometimes possible and the search for enzyme markers in urine for malignancies has to be intensified. Determinations of urinary enzymes are unsuitable for search of kidney disease at present. No nephrological diagnosis is possible with the aid of urinary enzyme determination alone.

Animals↗

Pharmacokinetics of tenoxicam in healthy human volunteers.

Tenoxicam, a thieno-thiazine derivative, belongs to a new chemical class of non-steroidal anti-inflammatory drugs. Single dose kinetics was investigated after intravenous and oral administration to define the disposition and general absorption characteristics of the drug. After intravenous administration of 20 mg tenoxicam to 12 volunteers the time course of the plasma concentrations of unchanged drug followed two-compartment model characteristics. The area under the plasma-concentration time curve in the distribution phase contributed however only 3% or less to the total area. The plasma clearance was low with values ranging from 1.3 to 4.2 ml/min and the volume of distribution Vss was small averaging at 20 to 40% of the total body weight. The median half-life of elimination from the body was found to be 72 hours (range 42 to 100 hours). The disposition was not influenced by sex. Tenoxicam is highly bound to plasma albumin. At pH 7.4 the fraction bound exceeded 99% but was highly dependent on the pH. Plasma protein binding in patients with rheumatic disease was not different from that measured in healthy volunteers. The partitioning of tenoxicam into red blood cells was limited. Erythrocyte concentrations were only 20-30% of the corresponding plasma concentrations. After oral administration of a 20-mg tablet complete and rapid absorption of the drug was observed with maximum plasma levels of 1.7 to 3.6 micrograms/ml reached within 0.5 to 2 hours. Due to the rapid absorption and terminal half-life of the drug its plasma concentration profile after oral administration was very similar to that following intravenous dosing. The pharmacokinetic characteristics of tenoxicam offers a rationale to administer the entire dose in one single portion.

Administration, Oral↗

[Various forms of giant cell arteritis: diagnostic difficulties and significance of biopsies].

15 cases of giant cell arteritis newly diagnosed in the period 1979-1982 at the University Medical Outpatient Clinic, Basle, are presented. 10 cases can be classified as polymyalgia rheumatica, including one patient with aortic arch syndrome and involvement of the femoral arteries. 4 patients had cranial involvement. One patient diagnosed at an early stage exhibited non-characteristic general symptoms only. In 3 patients the diagnosis was suspected immediately, while the others underwent extensive investigations to rule out malignant and infectious diseases. Localized or generalized osteoarthrosis was often present. Most of the patients had severe general symptoms. Elevated sedimentation rate (88 +/- 34 mm 1st hr), anemia (11.6 +/- 1.8 g/dl) and elevation of alpha 2-globulin fraction were constant laboratory findings. Histologic examination of the temporal artery was positive in 2 of 7 cases with polymyalgia rheumatica. Out of 4 cases with cranial symptoms 3 had a positive histologic result. The biopsy result can be improved by removal of a more generous sample of artery segment. Therapy, relapses and complications are discussed.

Aged↗

Epidemiologic study of abuse of analgesics containing phenacetin. Renal morbidity and mortality (1968-1979).

A study group of 623 working women 30 to 49 years old with objective evidence of intake of phenacetin-containing analgesics and a matched control group of 621 women without such intake in 1968 were assessed six times from 1969 to 1978 for laboratory evidence of urinary-tract disorders. The two groups did not differ in development of bacteriuria, hematuria, or proteinuria. However, a low specific gravity of urine (study group vs. control group, 23 vs. 7 per cent) and a raised level of serum creatinine (6.7 vs. 0.9 per cent) were significantly more frequent in the study group (P less than 0.001). Adjusted analyses of mortality over 11 years showed significant differences between the groups in overall mortality (study group vs. control group, 39 vs. 13 deaths; P less than 0.001), mortality due to urinary-tract disorders (P = 0.033), and cardiovascular diseases (P = 0.008). We conclude that heavy users of analgesic mixtures in the course of a decade have a higher incidence of both abnormal kidney function and kidney-related mortality than do casual users and nonusers, but the absolute incidences remain small even among heavy users.

Acetaminophen↗

Nifedipine in hypertensive emergencies.

The effects and safety of using oral nifedipine 10-20 mg as acute antihypertensive treatment were studied in a single-blind placebo-controlled study of 25 consecutive patients with very high blood pressure requiring emergency reduction. In addition the effect of this treatment on cerebral blood flow was investigated using xenon-133 in 10 patients randomly allocated to receive oral nifedipine or intravenous clonidine. Whereas placebo did not alter the blood pressure, oral nifedipine significantly reduced the systolic and diastolic blood pressures in all 25 patients (from 221 +/- 22/126 +/- 14 mm Hg to 152 +/- 20/89 +/- 12 mm Hg after 30 minutes, p less than 0.001). Heart rate increased from 74 +/- 11 to 84 +/- 11 beats/minute (p less than 0.01); this effect was inversely related to age (r = -0.65, p less than 0.01). The falls in systolic and diastolic blood pressures were closely related to the blood pressures before treatment ) r = 0.67, p less than 0.001 for systolic, and r = -0.58, p less than 0.01 for diastolic values). No serious unwanted effects were observed. Measurement of cerebral blood flow after nifedipine showed an increase in flow in four out of five patients. Clonidine, by contrast, reduced cerebral blood flow in all patients by up to 28%. Nifedipine is a simple, effective, and safe alternative drug for managing hypertensive emergencies, especially when continuous monitoring of the patient cannot be guaranteed.

Adult↗

Transport of adenosine by renal brush border membranes.

The transport of adenosine into brush border membrane vesicles from rat kidney is demonstrated. A first, rapid stage of transport is completed by 20 s. It is stimulated by a gradient of sodium. The effect of the concentration of adenosine in the low micromolar range on the initial rate of uptake indicates a saturability. An apparent Km of 1.48 microM and a Vmax of 215 pmol/mg protein/min have been calculated. In the rapid stage of uptake, adenosine is transported into the intravesicular space with no significant binding to the membrane. The following slow uptake is not stimulated by sodium and reaches steady state after about one hour.

Adenosine↗

Activities of enzymes of the tricarboxylic acid cycle in segments of the rat nephron.

The activities of enzymes of the tricarboxylic acid cycle were measured in order to compare the respiratory capacity in different parts of the nephron of the rat. Oxoglutarate dehydrogenase, citrate synthase and isocitrate dehydrogenase were assayed in single nephron segments dissected out of freeze-dried cryostat sections. The activities of the three enzymes per unit weight are higher in the distal segments (thick ascending limb and distal convoluted tubule) than in the proximal tubule. The distal vs. proximal ratios of activities are about 1.5, 2.5 and 2 for oxoglutarate dehydrogenase, citrate synthase and isocitrate dehydrogenase, respectively. Oxoglutarate dehydrogenase shows the lowest activities along the whole nephron and appears to catalyze the rate-limiting step of the tricarboxylic acid cycle. The possibility to estimate the respiratory capacity in the different segments of the nephron on the basis of the activity of oxoglutarate dehydrogenase is discussed. The capacity calculated for the proximal tubule (between 44 and 66 mumol O X min-1 X g-1, depending on the substrate) is in agreement with direct measurements of oxygen consumption as well as with calculations made on the basis of morphometrical data.

Animals↗

Distal tubular segments of the rabbit kidney after adaptation to altered Na- and K-intake. II. Changes in Na-K-ATPase activity.

Na-K-ATPase activity was measured in the convoluted part of the distal tubule (DCT), the connecting tubule (CNT) and the cortical collecting duct (CCD). The segments were microdissected from freeze-dried kidney tissue of rabbits adapted to various salt diets and exposed to large differences in endogenous and exogeneous mineralocorticoids. The Na-K-ATPase activity in the DCT is not influenced by mineralocorticoids. They do influence the activity in the CNT and in the CCD. In the CNT the highest activity was found with a low Na-, high K-diet. At the beginning of the CNT the enzyme activity is higher than in the end portion. While canrenoate-K treatment has no effect on Na-K-ATPase activity in the initial portions of the CNT, this drug decreases the Na-K-ATPase activity significantly in the end portion of the CNT. DOCA treatment has a significant effect on the enzyme activity in the CNT only in the end-portion of the segment, but provokes the highest Na-K-ATPase activity in the CCD. The changes in Na-K-ATPase are found to be associated with corresponding changes in the baso-lateral cell-membrane area in the segments affected.

Adaptation, Physiological↗