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Biomedical subjects

P Wahl

Publications and source records attributed to P Wahl.

At least 19 recordsLinked to original sources

Gastroschisis: what part can the obstetrician play?

In order to assess the contribution of antenatal diagnosis to the management of gastroschisis, the antenatal and postnatal data from 24 cases of gastroschisis observed between 1974 and 1990 were re-examined. The frequency of antenatal diagnosis (29%), polyhydramnios (21%), atresia of the small intestine (29%), length of pregnancy (36.6 +/- 2 weeks of amenorrhea), proportion of cesarean sections (21%), birth weight (2230 +/- 430 g) and the Apgar score after 5 min (9.0 +/- 1.5) were comparable to findings reported elsewhere. The overall mortality rate for the period studied was high (41%), and was not influenced by any antenatal parameter or by the mode of delivery; its recent fall (P = 0.01) is explained by the development of therapeutic methods. These results are consistent with other recent studies and suggest that antenatal diagnosis does not enable an accurate assessment of the prognosis to be made and has no major influence on the mortality rate in gastroschisis.

Abdominal Muscles

Diffusion of proteins in Sepharose Cl-B gels.

The reduced diffusion coefficient, D/D0, of fluorescein-labelled globular proteins in the agarose gels Sepharose Cl-2B, 4B and 6B were measured by the FRAP method. Comparison of the partition coefficients of the native and the labelled proteins in the gel showed that the fluorescein residues did not introduce new interactions between the solute and the gel matrix. D/D0 decreased as a function of the Stokes radius. The variation of D/D0 as a function of the partition coefficient of the proteins in the gel did not agree with a previously published prediction. This is in contrast with the diffusion of globular proteins in ACA34 gel, in which the sieving matrix is made of cross-linked polyacrylamide.

Chromatography, Gel

Stereoselective effects of AMOA on non-NMDA receptors expressed in Xenopus oocytes.

Pharmacological characterization of the action of the novel non-N-methyl-D-aspartate (non-NMDA) antagonist AMOA (2-amino-3-[3-(carboxymethoxy)-5-methylisoxazol-4-yl]propionate) on glutamate receptors was investigated in Xenopus oocytes injected with mouse brain mRNA. AMOA (150 microM) produced a nearly parallel shift to the right of the dose-response curve for kainate-induced currents. AMOA was found to have two different effects on AMPA receptors: 1) currents elicited by low concentrations of AMPA (6 microM) were inhibited by AMOA with an IC50 value of 160 +/- 19 microM and 2) currents elicited by high concentrations of AMPA (100 microM) were potentiated with an IC50 value of 88 +/- 22 microM. The maximal potentiating effect of AMOA on AMPA currents was around 170%. Furthermore, the two opposing effects of AMOA on AMPA responses are specific for the L-configuration of AMOA. This unusual antagonistic/agonistic property of AMOA may explain its unusual properties with regard to antagonism of non-NMDA receptor-mediated events previously described.

Animals

[The risks of pyrimethamine-sulfadoxine combination in the prenatal treatment of toxoplasmosis].

Some of the alternative treatments to avoid termination of pregnancy in cases where the fetus is affected by toxoplasmosis is to treat it as soon as the diagnosis has been made. The authors who already have experience of using pyrimethamine with sulfadoxoine (Fansidar) in the post-natal treatment of congenital infection, thought after reviewing the literature that this association of drugs would be harmless if applied during pregnancy. The principal risk that arises in the fetus is the teratogenicity of each of the components of pyrimethamine and sulfadoxine and also their associations. In animals pyrimethamine can increase the frequency of cleft palates probably because of its antifolinic action but there is no formal proof that it is teratogenic in human beings. Furthermore, the theoretical risk of karnicerus in the new born using the Sulfonamide has not been demonstrated. In the mother the main but rare risk (1 in 75,000) seems to be for the production of severe skin lesions such as Lyell and Stevens-Johnson which could be brought about by sulfonamides, but not particularly sulfadoxine.

Antimalarials

An approach to several problems in using large databases for population-based case-control studies of the therapeutic efficacy and safety of anti-hypertensive medicines.

In this paper we discuss approaches to two distinct problems in using large computerized databases to conduct population-based case-control studies. The first topic, concerning case ascertainment, is a methodologic problem, and the second, concerning confounding by indication, is an analytic problem. The first involves attempting to ascertain all incident cases of coronary disease among enrollees of Group Health Cooperative of Puget Sound (GHC), a large health-maintenance organization. Methodologic studies reported here have helped us improve the efficiency of using the large computerized databases for case ascertainment at GHC. The second problem involves the issue of confounding by drug indication. Drugs such as beta-blockers have multiple indications, including the treatment of both high blood pressure and angina. These two indications may make it difficult in an observational study to determine whether beta-blockers may prevent coronary disease in patients with high blood pressure. We discuss here our current thinking about the best analytic approach to this problem.

Adrenergic beta-Antagonists

Development of binding sites for excitatory amino acids in cultured cerebral cortex neurons.

Binding of [3H]glutamate, [3H]AMPA (RS-alpha-amino-3-hydroxy-5-methyl-4-isoxazolo-propionate) and [3H]kainate was investigated in membranes prepared from cerebral cortex of 4-day-old and adult mice and from cerebral cortex neurons cultured for different periods of time (2, 4, 8 and 14 days). For all ligands, the number of binding sites increased as a function of development both in vivo and in culture. A significant number of binding sites for the ligands could be demonstrated on the cultured neurons already after 2 days in culture. Scatchard analysis of the binding data showed a single population of binding sites for glutamate (KD approximately 200 nM) and kainate (approximately 6 nM) regardless of the developmental stage in vivo or in culture. In case of [3H] AMPA binding two binding sites with KD values of approximately 6 nM and 100-200 nM could be demonstrated both in vivo and in culture. Binding of [3H]glutamate to cultured neurons could be displaced by N-methyl-D-aspartate (100 microM) and quisqualate (3 microM) in an additive manner but D,L-4-aminophosphonobutyrate (100 microM) had no effect. AMPA binding to cultured neurons was much more (40-fold) sensitive than kainate binding to the newly developed AMPA selective antagonist NBQX (2,3-dihydroxy-6-nitro-7-sulphamoyl-benzo(F)quinoxaline) indicating that kainate and AMPA bind to independent binding sites. Monitoring membrane potentials in the cultured neurons using the lipophilic cation TPP+ (tetraphenylphosphonium) it was demonstrated that potassium (55 mM) as well as glutamate, AMPA and kainate (100 microM) could depolarize the neurons both at early (2 days) and late (9 days) developmental stages in culture. The demonstration of functionally active receptors for the 3 excitatory amino acids in both immature (2 days in culture) and mature (8-9 days in culture) neurons is discussed in the light of previous studies of the development as a function of the culture period of effects of excitatory amino acids in neurons. It is concluded that no simple correlation exists between expression of binding sites for the excitatory amino acids and their ability to induce cytotoxicity and neurotransmitter release.

Amino Acids

[Nocturnal paroxysmal hemoglobinuria disclosed during pregnancy. Apropos of a case].

Paroxysmal nocturnal haemoglobinuria (PNH) is a rare, acquired, intrinsic haemolytic anaemia believed to occur with an incidence of 1.5 per million in France. The disease is characterised by acute and chronic intravenous haemolysis and pancytopenia, without leukocytopenia. Pregnancy is rare and a high incidence of spontaneous abortion has been reported. The case reported here describes the successful outcome of a pregnancy where PNH was diagnosed. A 25 year old primigravida was admitted for evaluation of pancytopenia discovered in the 32nd week of an hypertensive pregnancy. On admittance R.B.C. were 1.67 x 10(12)/1, W.B.C. 3.4 x 10(9)/1 and platelets 12 x 10(9)/1; Hb was 6.8 g/dl and MGV 126 mu 3. Initial arterial pressure was 160/90 mm/Hg, with oedema and proteinuria 0.7 g per day. Obstetrical parameters were good and physical examination revealed to spontaneous haemorrhage, no jaundice, no dark urine, no organomegaly, no consumptive coagulopathy (C.C.) and no biological liver abnormalities. The patient received saline-washed packed red cells and fresh platelets. R.B.C. increased to 2.5 x 10(12)/1 and remained stable and platelets decreased to 5 x 10(9)/1 with increased arterial pressure and proteinuria, and appearance of C.C. A Caesarean section was performed, under general anaesthesia, and a male healthy baby weighing 2750 g was delivered. The post operative course was uneventful, except for a parietal haematoma which needed surgical evacuation. Because of the low platelet count, no heparin was given and the patient had no thrombosis and no infection.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

[Improved prognosis of Type I and Type II diabetics with nephropathy].

Between 1966 and 1985, 72 type I and 75 type II diabetics developed persistent proteinuria. These patients were divided into two groups according to time of onset of proteinuria (1966 to 1975 and 1976 to 1985, respectively). In these groups, we investigated both the quality of antihypertensive treatment and metabolic control as well as the course of nephropathy and life prognosis. Control of hypertension was markedly improved in type I and type II diabetics with later onset of proteinuria (1976 to 1985), compared with patients who developed proteinuria between 1966 and 1975. However, metabolic control was improved only in type I diabetics. Compared with the previous decade, prevalence of renal insufficiency was lowered by one-third in type I and type II diabetics with later onset of proteinuria (1976 to 1985). During the six-year observation period, 32% of type I and 72% of type II diabetics who developed proteinuria between 1966 and 1975 died, whereas all type I and 54% of type II diabetics with later onset of proteinuria (1976 to 1985) survived. The study shows that conservative treatment methods, especially lowering of blood pressure, may improve prognosis for proteinuric type I and type II diabetic patients.

Adolescent

Cutaneous reactive hyperemia in short-term and long-term type I diabetes--continuous monitoring by a combined laser Doppler and transcutaneous oxygen probe.

Using a recently designed combined laser Doppler/transcutaneous oxygen probe postocclusive reactive hyperemia response was investigated in 10 healthy subjects and 33 patients with type I diabetes mellitus. From the foot dorsum sensing site simultaneous recordings of the red cell flux of the superficial skin microvasculature and cutaneous PO2 were obtained at identical measuring position and conditions. Whereas cutaneous PO2 response exhibited an uniform monophasic curve with a significantly reduced percentage increase of PO2 in short-term (p less than 0.05) and in long-term type I diabetic patients (p less than 0.001), four different laser Doppler hyperemic flux patterns were observed. Hyperemia types A and B were biphasic, type C had only a monophasic course. Apparently in type C the initial fast component of the myogenic response is missing; in type D no increase in flux or PO2 could be measured. Comparison of prevalence of these hyperemia types showed a significantly (p less than 0.05) higher prevalence of the monophasic or even absent hyperemic response in type I diabetes. The reduction in viscoelastic properties of the small arteries and arterioles in patients with type I diabetes may account for these changes which is most likely cofactor in the pathogenesis of diabetic microangiopathy.

Adult

[Microalbuminuria screening in diabetics].

Nocturnal albumin excretion rate was measured in 133 diabetics and the results were compared with those in first morning urine and urine spontaneously voided later in the morning. Albumin concentrations greater than 20 mg/l in the first morning urine indicated a raised albumin excretion rate of 20-200 micrograms/min (sensitivity 86%, specificity 98%). Simultaneous creatinine measurement and calculation of the albumin/creatinine ratio did not increase sensitivity or specificity. An albumin concentration greater than 20 mg/l in spontaneously voided day urine pointed to a raised albumin excretion rate (sensitivity 90%, specificity 60%). These results suggest that determining the albumin concentration in the first voided morning urine is suitable as screening test for microalbuminuria.

Adult

Plasma insulin levels in Japanese and Japanese-American men with type 2 diabetes may be related to the occurrence of cardiovascular disease.

Sixty-eight second-generation Japanese-American (Nisei) men 45-74 years old and 26 Tokyo Japanese men 40-72 years old with type 2 diabetes were given 75 g glucose by mouth, and their venous blood levels of glucose and insulin were measured at 0, 30, 60, 90, 120, and 180 min. Blood glucose levels were similar for the two groups but the Nisei had higher levels of insulin at all time points (P less than 0.006). The Nisei men had a higher mean body mass index (P less than 0.001) and the Tokyo men had had diabetes for a longer duration (P less than 0.001). Data were also compared following selection of a subgroup of Nisei men (n = 39) with a diabetes duration of 2-25 years, making this group more similar to the Tokyo men with respect to this variable. The Nisei still had significantly higher plasma insulin levels. Because of a significant (P less than 0.01) positive correlation between plasma insulin and body mass index in Nisei, but not in Tokyo men, data comparing the Nisei subgroup and Tokyo men were re-examined by analysis of covariance. With an adjustment for body mass index in the analysis, all differences in plasma insulin, except for the fasting insulin level, were no longer significant between the Nisei and Tokyo men, suggesting that body mass index was responsible for these differences.

Aged

The use of the Magnetip double-J ureteral stent in urological practice.

The Magnetip* double J type ureteral stent has been used in a wide variety of clinical urological settings. We reviewed the use of the stent in 50 patients. In 45 patients stents were placed in conjunction with extracorporeal shock wave lithotripsy, stone manipulation, obstruction due to pregnancy or malignancy, pyeloplasty and ureteroneocystostomy. In 83 per cent of the attempts the stent was placed successfully. Retrieval with the Magnetriever* was accomplished in 86 per cent of the cases (100 per cent in female and 76 per cent in male patients). Details of stent use are described.

Adult

Similar risks of nephropathy in patients with type I or type II diabetes mellitus.

It is commonly assumed that in patients the risks of developing nephropathy and uraemia are high in type I and low in type II diabetes mellitus. Since type II occurs mostly in elderly individuals with limited life expectancy and high cardiovascular mortality, the true risk may have been underestimated, as many patients do not survive to experience renal complications. To assess renal risk further, we evaluated all patients with type II and type I diabetes mellitus without severe secondary disease who were followed in the outpatient clinic between 1970 and 1985. The cumulative risk of proteinuria after 20 years of diabetes mellitus was 27% in type II and 28% in type I, the findings after 25 years were 57% and 46% respectively. The cumulative risk of renal failure, i.e. serum creatinine greater than 1.4 mg/dl, after 3 years of persisting proteinuria was 41% in both type II and type I, and after 5 years of proteinuria were 63% and 59% respectively. We conclude that the renal risk is similar in patients with type II and type I diabetes mellitus.

Adolescent

Glutamate-induced increase in intracellular Ca2+ in cerebral cortex neurons is transient in immature cells but permanent in mature cells.

The free cytosolic Ca2+ concentration ([Ca2+]i) of cultured cerebral cortex neurons was determined using a fluorescent Ca2+ chelator (Fluo-3) after exposure of the neurons to glutamate. Mature neurons (8 days in culture) responded within 45 s to 100 microM glutamate by an increase in [Ca2+]i from 75 to 340 nM, an increase that during the following 6 min of exposure reached 400 nM. This increase in [Ca2+]i could not be reversed by removal of glutamate. In the absence of extracellular CaCl2, only part of the initial, rapid, glutamate-induced increase in [Ca2+]i was observed in these neurons. In contrast to these findings, neurons cultured for only 2 days (immature neurons) exhibited only a small (from 75 to 173 nM) increase in [Ca2+]i after exposure to 100 microM glutamate, and this rapid increase in [Ca2+]i tended to decline on prolonged exposure to glutamate. Moreover, after removal of glutamate, the increase in [Ca2+]i was fully reversible. Pharmacological characterization of the response to glutamate in mature neurons showed that the N-methyl-D-aspartate (NMDA) receptor antagonists phencyclidine and D-2-amino-5-phosphonovalerate phosphonovalerate blocked 75 and 90%, respectively, of the response, whereas the non-NMDA antagonist 6-cyano-7-nitroquinoxaline-2,3-dione had little effect.

Animals

[Acute thrombosis of mitral Starr prosthesis. Value of color coded two-dimensional doppler echocardiography].

In a case of acute thrombosis on mitral Starr valve two-dimensional doppler-echocardiography rapidly showed that parts of the transprosthetic jets had disappeared, while conventional continuous wave doppler ultrasound confirmed the presence of a severe haemodynamic obstacle. With colour-coded doppler ultrasound, there only remained a jet that was parallel to the posterior wall of the left ventricle. This jet was of unusual pattern, with the presence of turbulence and high velocities in aliasing colour. The effectiveness of a thrombolytic treatment was demonstrated by the reappearance of the missing diastolic jets with return to normal velocities. Comparison between a post-thrombolysis colour-coded doppler examination and a reference examination confirmed that the valve was now functioning normally. Thus, while conventional doppler recordings accurately quantify prosthetic dysfunctions leading to stenosis, two-dimensional doppler recordings rapidly provide an anatomical information. By showing changes in the transprosthetic jets they indicate the precise location and extent of valve obstruction.

Echocardiography, Doppler

Impact of hypertension on prognosis in IDDM.

In Type I diabetes, hypertension is usually associated with the development of diabetic nephropathy. In proteinuric patients hypertension has a deleterious effect on the progression of microangiopathy and macroangiopathy, which in turn impairs their quality of life and long-term prognosis. As shown in numerous studies, hypertension accelerates loss of renal function. After kidney transplantation, the percentage of functioning grafts is much lower in diabetic patients who remain hypertensive. Furthermore, the rate of development of proliferative retinopathy, a common complication in proteinuric diabetics, increases in the presence of hypertension. Finally, hypertensive blood pressure values at the start of maintenance hemodialysis are significant predictors of cardio-vascular death among diabetics of renal replacement therapy. It has recently been demonstrated that during the last two decades blood pressure control has improved in proteinuric Type I diabetic patients. These results are associated with better renal prognosis and higher life expectancy.

Cardiovascular Diseases

[Hyperthyroidism and pregnancy. A retrospective multicenter study Nord-Picardie-Champagne. Report of 48 cases].

In 92,130 pregnancies followed between 1980 and 1987, 48 cases of hyperthyroidism were reported including 38 Grave's diseases, 5 toxic adenomas, 4 multinodules goiters. In comparing the results with those mentioned in the literature, a number of conclusions may be reached. In case of hyperthyroidism treated before the pregnancy or discovered at the beginning, there is, in every other case, an aggravation at the end of the first trimester, then a stabilization in the 2nd or 3rd trimester and finally an aggravation in the post-partum period. There is a high rate of abortions (35 p. cent), a delayed intra-uterine growth in half of the cases. The problem of the treatment is of paramount importance; there is no problem with Beta-blockers but the SAT are not without danger: risk of hypothyroidism and fetal goiter, but also risk of maternal hypothyroidism. From the 15th week, the doses should therefore be decreased, and sometimes the treatment discontinued and replaced with Beta-blockers. The best SAT drug during pregnancy is the propylthioracile which is the least likely to cross the fetal barrier. Surgery is only exceptionally indicated. In a woman who is cured from her Grave's disease, recurrences are always possible, and also fetal hyperthyroidism caused by crossing of thyreostimulins immunoglobins, even in case of maternal euthyroidism.

Adult