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Biomedical subjects

P Metz

Publications and source records attributed to P Metz.

13 recordsLinked to original sources

Intracavernous self-injection with vasoactive intestinal polypeptide and phentolamine in the management of erectile failure.

A total of 52 men, median age 55 years (range 28 to 74 years), with erectile failure was treated with vasoactive intestinal polypeptide and phentolamine. Impotence was classified as psychogenic in 3 patients, psychogenic/arteriogenic in 3, arteriogenic in 25, arteriogenic/neurogenic in 4, neurogenic in 5, venous leakage/psychogenic in 2, venous leakage/neurogenic in 1 and following venous leak surgery in 9. The patients were treated with 30 micrograms vasoactive intestinal polypeptide and 0.5 to 2.0 mg. phentolamine. A total of 1,380 self-injections was given and the number of injections per patient varied from 5 to 245. No patient had priapism, corporeal fibrosis or other serious complications. After sexual stimulation all patients obtained erection sufficient for penetration. Following ejaculation rigidity decreased normally. The median duration of treatment was 6 months (range 1 to 22). Nine patients discontinued treatment. One patient with severe arteriosclerosis experienced decreased effectiveness of the drug and received a penile prosthesis. Five patients elected not to perform self-injection any longer, 1 psychogenic impotent patient was cured, and 1 patient discontinued therapy due to palpitation and sweating. One patient died of a myocardial infarction not associated with this therapy.

Adult

Low dose loop diuretics in essential hypertension. Experience with torasemide.

Diuretics belong to the class of antihypertensive drugs recommended for first-line therapy of essential hypertension. Although they are widely and effectively used for the treatment of hypertension, the question remains whether their possible negative influence on metabolic and electrolyte parameters could partly offset the benefit of blood pressure reduction with respect to reduction of coronary artery disease. Recently published data demonstrate that much lower doses of thiazides exert the same antihypertensive effect as the higher doses used in the past and even prescribed today. These lower doses produce relatively little change in biochemical parameters. Thus, the postulated risks can be avoided by using the lowest effective dose. Traditionally, loop diuretics of the furosemide (frusemide) type are rarely used as first-line antihypertensive agents. They seem to display less efficacy coupled with an intense diuresis when used in standard available doses. However, there is evidence that newly developed loop diuretics, in lower doses than used in congestive heart failure, are effective antihypertensive agents. For example, torasemide 2.5mg once daily, which does not exert a significant diuresis over 24 hours compared with placebo, lowers elevated blood pressure to a similar extent than thiazides or related compounds. This antihypertensive effect is accompanied by less, if any, changes in metabolic or electrolyte parameters compared with widely used standard diuretics such as hydrochlorothiazide, indapamide or chlorthalidone. The influence on serum potassium and magnesium is similar to or even less than fixed combinations of hydrochlorothiazide and triamterene or amiloride. Thus, low-dose torasemide constitutes an alternative to established thiazide antihypertensive therapy.

Diuretics

Purification and characterization of glucose-6-phosphate dehydrogenase from Pseudomonas W6.

Glucose-6-phosphate dehydrogenase (EC 1.1.1.49) has been purified from methanol grown Pseudomonas W6 by a simple procedure involving dye-ligand affinity chromatography on Cibacronblue F3G-A-Sephadex and Procion Red HE-3B-Sepharose. The purification procedure yielded a homogeneous enzyme with (1) high specific activity of 390 and 500 units/mg with NADP and NAD, respectively, and (2) low concentrations of contaminating activities. The molecular mass of the native enzyme was estimated to be 123 +/- 5 kDa. For the polypeptide chain after SDS denaturation a molecular mass of about 61 kDa was calculated. The kinetic behaviour of glucose-6-phosphate dehydrogenase exhibiting activity with either NADP or NAD was studied with respect to the substrate and coenzyme affinities and to ATP inhibition of enzyme activity. The applicability of prepared glucose-6-phosphate dehydrogenase as an auxiliary enzyme in clinical tests is discussed.

Chromatography, Affinity

Interaction of bacterial glucose-6-phosphate dehydrogenase with triazine dyes: a study by means of affinity partitioning and kinetic analysis.

The interaction of glucose-6-phosphate dehydrogenase (EC 1.1.1.49) from Pseudomonas W6 with 33 triazine dyes bound to poly(ethylene glycol) has been screened by means of affinity partition in an aqueous two-phase system composed of poly-(ethylene glycol) and dextran. Regarding the strength of interaction expressed by the affinity partitioning effect three groups of dyes can be distinguished showing high, medium or low interaction to the enzyme. The different influence of the structurally related dyes Cibacronblue F3G-A, Procion Blue MX-3G and Procion Blue MX-R on the partitioning of glucose-6-phosphate dehydrogenase is discussed. Both coenzymes of this glucose-6-phosphate dehydrogenase, NADP+ and NAD+, are able to diminish the dye-enzyme interactions but to a different extent. In the case of Procion Red HE-3B less than 0.2 mM of NADP+ abolished completely the dye-protein interaction indicating that the dye binding site might be closely related to the nucleotide binding site. This does not hold for a series of other dyes revealing strong interactions to the enzyme. In these cases higher NADP(+)-concentrations are necessary to weaken the dye-enzyme interactions. Only small influences on the interaction between the dye and glucose-6-phosphate dehydrogenase were found with 1 mM NAD+. The different effects of the two coenzymes are discussed with respect to separate binding sites for them and to different conformational states induced. The competition of Procion Red HE-3B with NADP+ and NAD+ for the binding site of glucose-6-phosphate dehydrogenase was also demonstrated by inhibition studies. The Ki-values of Procion Red HE-3B with NAD+ and NADP+, respectively, were calculated.

Bacterial Proteins

Covalent cross-linking of photosensitive phospholipids to human serum high density apolipoproteins (apoHDL).

Human serum high density apolipoproteins were reassociated with three different lecithin species substituted with radioactively labelled photosensitive azido fatty acids, bis([3H]-16-azidopalmitoyl)-, bis([3H]12-azidooleoyl)- and bis([3H]18-azidolinoleoyl)glycerophosphocholine. The lipoprotein particles were reconstituted from a mixture of azido-labelled phosphatidylcholine and non-labelled dioleoylglycerophosphocholine (1:9). Excess lipid was separated from the homogeneous particles by Bio-Gel A-5m. The molecular weight, stoichiometry, fluorescence and circular dichroism of the reconstituted particles were determined before and after photoactivation with covalent cross-linking of the phospholipids with the apoproteins. The physical parameters of the reconstituted lipoproteins remained unperturbed by the cross-linking reaction between the generated nitrenes and apolipoprotein A-I and A-II. Thus the hydrophobic interactions of the phospholipid molecules with the apoproteins have been proved for the first time by a chemical method.

Apolipoproteins

Covalent binding of photosensitive 1-(12-azido-[9,10(-3)H2]oleoyl)glycero-3-phosphocholine (lysolecithin) to human serum high density apolipoproteins.

Human serum high density apoproteins were complexed with increasing concentrations of 1-(12-azido-[9,10(-3)H2]oleoyl)glycero-3-phosphocholine up to the saturation concentration (72 mol lysolecithin per mol apo HDL). Ultraviolet irradiation generated the nitrene which led to crosslinking with the two main apolipoproteins AI and AII. Methods are described for the removal of excess, unbound lipid and the column chromatographic separation of the lipopolypeptides AI and AII.

Apolipoproteins

Retroperitoneal approach for implantation of aorto-iliac and aorto-femoral vascular prosthesis.

During the period 1963--76, sixty-nine patients underwent aorto-iliac of aorto-femoral by-pass operation at the department. Fifty-two of the operations were performed through a retroperitoneal approach. The operative procedure is described. The approach is found gratifying and the statement of earlier authors concerning fewer cases of paralytic ileus and smoother convalescence is confirmed.

Aorta, Abdominal

Occult traumatic dislocation of the patella.

In series of patients with clinically established traumatic patellar dislocation other authors have found surgical and radiological lesions pathognomonic for this condition. In a series of patients admitted with hemarthrosis, and with no knowledge of having had dislocation of their patella, we found the same lesions thus illustrating that a syndrome of occult traumatic patellar dislocation exists. The vertical location of the patients' patellae was found normal measured by the index of Insall and Salvati (9). The intercondylar groove measured by the method of Brattström (4) was found in almost all cases to be under the upper normal limit. Their knee caps were normal following the descriptions of Knutsson. None had valgus knees beyond normal upper limits and none had general laxity of joints, thus indicating that this syndrome may be found in normal knees.

Adolescent

Surgical treatment of occlusive arterial disease of the legs.

During the period 1959-68, a total of 982 patients were submitted to treatment for arteriosclerotic vascular lesions in the lower limbs in Department M, Bispebjerg Hospital, Copenhagen. Conservative treatment solely was undertaken in 425 cases, while in addition 271 limbs were amputated after varying periods of conservative therapy or observation. Primary lumbar sympathectomy was undertaken in 25 patients. In the remaining 261 patients, indications were found for arterial reconstruction. In 25 cases explorative intervention only was undertaken. In the remaining 236 patients, 255 reconstructive interventions were undertaken during the period. These comprised 113 thrombendarterectomies, 71 of which were in vessels distal to the inguinal ligament, and 142 by-pass operations. In the latter procedures, five bifurcation prostheses were introduced, 40 simple prostheses with proximal anastomosis to the aorta or the iliac arteries, and 53 synthetic prostheses and 44 venous prostheses with proximal anastomoses to the femoral artery. Eight patients (3.4 percent) died postoperatively, while amputation had to be resorted to in 20 (8 percent). On discharge, pulsation distal to the site of operation was found in 61 percent of the patients discharged, one year later in 44 percent of the survivors and five years later in 23 percent. A total of 62 (24 percent) limbs were amputated on an average of 14 months after operation. 224 cases could be assessed after an average of 4 4/12 years. In 58 cases there was definite clinical improvement and pulsation distal to the site of operation. In 44 cases, pulsation had been present after operation and definite clinical improvement, but no pulsation distal to the reconstructed vessel was found at the follow-up examination. In 122 cases no evident beneficial effect of operation could be demonstrated at follow-up examination. The indications for operation and the incidence of operation are discussed, and the results compared with those of previous publications.

Adult