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Biomedical subjects

G van Melle

Publications and source records attributed to G van Melle.

At least 19 recordsLinked to original sources
PubMed1992

Paternal selection favoring mutant alleles of the retinoblastoma susceptibility gene.

Penetrance and segregation rates of mutant Rb-1 alleles were assessed in all 51 members of eight kindreds with hereditary retinoblastoma by concomitant ophthalmologic examination and determination of seven intragenic restriction fragment length polymorphisms (RFLPs). Penetrance was in the range reported in the literature except for one family in which it was only 42.8%. However, the odds of transmitting a mutant Rb-1 allele from one generation to the next were 25:9 in this population, much above the Mendelian 1:1 ratio (P less than 0.025). This preferential transmission was discovered through the use of molecular information. Further analysis revealed that this distortion was due to preferential inheritance among children of male carriers (18:4, P less than 0.005). No difference from a 1:1 segregation ratio could be detected among the children of female carriers (7:5). These findings were consistent with a review of relevant data in the literature.

Alleles↗
PubMed1992

A four-proton-families model for pH-dependent enzyme activation: application to intestinal brush border sucrase.

Current concepts of pH-dependent enzyme function are expanded to consider enzymes with up to four key proton families. In an earlier paper the authors extended classical theory to explain the existence, in the acid ionization reaction, of two functionally distinct, V and K, proton families, exemplified by the 1988 sucrase three-proton-families model of Vasseur et al. They now propose that enzymes having two distinguishable proton families at each side of the pH-activity curves exist in nature although there is no previously published evidence of their existence. The resulting, more general, four-proton-families model is treated as a useful framework from which submodels can be derived by simplification, the simplest being the 1911 linear model of Michaelis and Davidsohn, which took into account two proton families out of the theoretical maximum of four proposed here. It is shown that whether a three-proton-families or a four-proton-families model can explain sucrase better is not merely a question of theory but also involves the practical question of having enough data, at each side of the pH spectrum, to permit making an unequivocal choice between the two alternatives. The paper concludes with a discussion of substrate-induced pK shifts according to both models.

Animals↗
PubMed1992

Aqueous humor analysis after Nd:YAG laser capsulotomy with the laser flare-cell meter.

Using the laser flare-cell meter (Kowa FC-1000), we conducted a prospective study analyzing the effect of Nd:YAG posterior capsulotomy on the quantity of aqueous particles, aqueous flare, and intraocular pressure in 65 eyes (58 patients). Aqueous particles increased at six hours, followed by flare rise which was significant at 18 hours after capsulotomy. Only 22 eyes (34%) had a significant flare rise over prelaser values. Anti-inflammatory therapy was necessary in only one patient. The mean intraocular pressure value did not rise significantly after capsulotomy. Acute intraocular hypertension (AIOHT) (> 7 mm Hg increase) occurred between three and six hours after laser therapy in 12 patients (19%), was related in time to particle rise, and always responded to a single dose of acetazolamide. Acute intraocular hypertension was strongly correlated with elevated aqueous particles (P < .0001) and somewhat correlated with flare rise (P < .036), but was not correlated with the intraocular lens position (bag or sulcus fixation). Our findings strongly suggest that trabecular meshwork clogging by debris generated by the capsulotomy is the mechanism at the origin of AIOHT.

Adult↗
PubMed1992

Pure motor stroke: a reappraisal.

We studied the correlations between the pattern of weakness, stroke type, topography, and etiology in 255 patients whose first stroke was manifested by isolated hemiparesis. They represented 14% of consecutively admitted stroke patients. The weakness distributions were as follows: face, upper limb, and lower limb (FUL) (50%); face and upper limb (FU) (29%); upper limb (U) (10%); and upper and lower limb (UL) (9%). Twenty-nine percent of the patients had dysarthria, which was of no localizing value. Less than one half of the patients had a deep infarct, and one third had a potential embolic source from the heart or large arteries. Logistic regression analysis showed that history of hypertension and type of weakness distribution were the main factors accounting for lesion localization: patients with FUL distribution and hypertension had a 90% probability of deep infarct; patients either with FUL distribution but no hypertension or with UL distribution and hypertension each had 70% probability of deep infarct. Pure motor monoparesis was almost never caused by a deep infarct. We suggest that the assumption of a lacunar etiology to a pure motor stroke should be applied only to patients with FUL involvement.

Brain↗
PubMed1991

[Chronic backache and occupational rehabilitation: prognostic factors].

The professional outcome in 65 patients with chronic low back pain who stayed in the Invalidity Insurance Medical Observation Center from 1982 to 1987 was studied retrospectively. The group studied was composed of 51 males and 14 females aged 28 to 61 years. Thirty-one out of 65 patients (48%) returned to work, 4 to full time employment (active group), whereas 34 did not return to work (inactive group). Data established during our initial observation served to compare the 2 groups by means of a logistic regression. No significant difference was found between the 2 groups of height, weight, age, family situation, severity of the X-ray findings and the existence of an associated psychiatric diagnosis were compared. On the other hand, the absence of professional training, female gender and the presence of a radicular syndrome significantly decreased the proportion of patients returning to work. If these 3 risk factors were absent, the chance of resuming work was 72%; if one was present it was 50%, and if there were 2 or 3 risk factors it was 28%.

Adult↗
PubMed1991

[Ozone, ventilatory function and bronchial reactivity].

Forty adult hospital workers were followed prospectively in 1989 by monthly assessment of the lung function and bronchial responsiveness to methacholine in a rural region in Switzerland. No correlation was demonstrated between these values and the concentrations of tropospheric ozone. Nevertheless, this is not incompatible with previous studies showing impairment of ventilatory function in subjects exposed to ozone, for several reasons: ozone levels in 1989 were low, the indoor concentrations were lower than outdoors and the volunteers performed little or no physical activity.

Adult↗
PubMed1991

Prognostic factors in papillary carcinoma of the thyroid.

In a retrospective study of 119 patients, followed for 1 to 30 years after treatment of a papillary carcinoma of the thyroid, the authors searched for possible prognostic factors of the risk of recurrence. Microcarcinomas, anaplastic tumors and Hürthle cell carcinomas were excluded from the study. In a univariate analysis, age (greater than 45 years), sex (male), loss of histologic differentiation, size (greater than 3 cm), presence of carcinomatous lymphangitis, extrathyroid extension, and presence of metastasis at diagnosis were associated with a higher recurrence rate; type of growth and multifocality were not significant. In a multivariate analysis (logistic regression), age, size, and carcinomatous lymphangitis were significant predictors for women, whereas metastasis at diagnosis and cystic growth were significant for men.

Adult↗
PubMed1991

Absence of metabolic effects of the topical carbonic anhydrase inhibitors MK-927 and sezolamide during two-week ocular administration to normal subjects.

Potential systemic effects of the racemic carbonic anhydrase inhibitor MK-927 and its S-enantiomer, sezolamide hydrochloride, after topical ocular administration were investigated in a double-masked, randomized, placebo-controlled study in 16 healthy volunteers. A controlled diet was started 4 days before initiation of treatment and continued throughout the study. For 14 days six volunteers received bilaterally one drop of 2% MK-927 (1.2 mg) q.i.d., six received one drop of 1.8% sezolamide (1.1 mg) q.i.d., and four received the common vehicle q.i.d. Blood and urine electrolytes and acid-base profiles were measured before and on days 1, 7, and 14 of treatment, and 24-hour urine samples were collected daily. All values were compared with those on the pretreatment day. Taking the circadian variations of the parameters into account, no significant treatment effect was observed in either the daily profiles or the 14-day cumulative sodium, potassium, and citrate excretions. Because the usual variability of the measured biologic parameters has been reduced markedly by the stringent requirements of this study, it can be concluded that the induction of clinically significant metabolic changes by topically administered MK-927 or sezolamide is unlikely.

Administration, Topical↗
PubMed1991

[Lausanne study of retinoblastoma, 1986-90: deletion of esterase D locus in a collective of 128 patients].

Activity and phenotype of red blood cell esterase D were systematically determined in a population of 128 retinoblastoma patients from 99 families and compared to 158 controls, in order to detect a chromosome 13q14 deletion. Among these patients 12 were healthy carriers and 116 affected carriers of a mutant allele of the retinoblastoma susceptibility gene (110 retinoblastoma, 5 retinoma, 1 phtisis bulbi). 4 patients were found to have decreased ESD levels in connection with 13q14 deletion which was confirmed by chromosome analysis. The data presented here suggest that ESD quantification has a high specificity and sensitivity for the detection of homogenous chromosome 13 deletions in retinoblastoma patients.

Carboxylesterase↗
PubMed1991

Prognostic value of serum proteins synthesized by breast carcinoma cells.

Several breast carcinoma cell lines or explants of such tumors, as well as examples of lactating or dysplastic breast tissue, synthesized three serum proteins (alpha 2-Zn-glycoprotein, alpha 1-antichymotrypsin, and alpha-lipoprotein) in vitro. These proteins were detected by immunoperoxidase techniques in 126 breast carcinomas that had been evaluated clinically for more than six years. Alpha-2-Zn-glycoprotein was present in 58% of the carcinomas, whereas alpha 1-antichymotrypsin was seen in 55% and alpha-lipoprotein in 52%. These markers showed a relationship with clinical outcome. Alpha-1-antichymotrypsin and alpha-lipoprotein were unfavorable determinants, whereas alpha 2-Zn-glycoprotein was detected in lesions with a favorable evolution. Taken individually, these markers have similar but rather weak associations with five-year survival rates; roughly 20% of patients in the "favorable" group died, compared with 33% in the "unfavorable" group. Alpha-2-Zn-glycoprotein in grade 1 tumors was a marker with marginally favorable significance, but alpha 1-antichymotrypsin significantly worsened the prognosis of grade 2 and 3 tumors. Furthermore, stratification of patients according to the number of positive unfavorable markers yielded striking results. Eight percent of patients with none of the unfavorable markers were dead at five years, compared with 55% of those whose lesions expressed three unfavorable markers.

Biomarkers, Tumor↗
PubMed1990

[Cardiac sources of cerebral embolism and infarction: results of the Lausanne register for cerebrovascular accidents].

We studied 305 patients with a first stroke and a potential cardiac source of embolism (PCSE), on the basis of the Lausanne Stroke Registry. We have compared these patients with 1006 patients with stroke but without PCSE, admitted into the Registry during the same period, in order to assess the potential role of PCSE and the coexistence of other causes of stroke. Analysis of the various types of PCSE suggests that some neurologic characteristics are more frequent in patients with than without PCSE (infarcts of the posterior division of middle cerebral artery with Wernicke's aphasia and lateral hemianopia; maximal neurologic deficit at onset; haemorrhagic infarcts).

Arrhythmias, Cardiac↗
PubMed1990

Primitive megalencephaly in children: natural history, medium term prognosis with special reference to external hydrocephalus.

We studied 74 children with primitive megalencephaly retrospectively with attention directed to familial megalencephaly, birth history, enlarged pericerebral subarachnoid space (SAS) (idiopathic external hydrocephalus), head and statural growth dynamics, developmental and school prognosis, morphological findings and development of subdural haematoma. In the megalencephalic children, no significant differences were found between those with normal or those with enlarged pericerebral SAS. Out of 62, 31 children (50%) were already megalencephalic at birth. Of 74, 37 children (50%) showed variable degrees of developmental delay which in 18 was transient. Eight out of 74 were mentally retarded. Of 52 children at school age, 42 attend normal schools and 10, of whom 7 are mentally retarded, attend special schools. Three children showed subdural haematoma resulting from apparently minor trauma or occurring spontaneously. We suggest that idiopathic external hydrocephalus represents a variant of primitive megalencephaly with transient increase of intracranial pressure and that it could predispose to the development of idiopathic (spontaneous or non-traumatic) subdural haematoma.

Brain↗
PubMed1990

[Organ donation for transplantation. Survey of opinions of physicians and paramedics in the province of Vaud].

In 1987, two media campaigns were organized in Switzerland to promote donor cards. The purpose of this study was to test their impact on the medical community. Questionnaires were sent to qualified practitioners, doctors in training and intensive care nurses. It is concluded that the campaigns for organ donation must be repeated and that their quality can be improved. It is however more urgent to improve the level of knowledge among doctors and other health professionals.

Attitude of Health Personnel↗
PubMed1989

Substrate- and alkali-metal-ion-induced pK shifts in intestinal brush-border sucrase, according to the three-protons model.

To define adequately enzyme activation/inhibition mechanisms as a function of pH, it is necessary to characterize the effector-induced pK shifts on both the free enzyme and on the enzyme-substrate complex. On the basis of our recent three-protons model for sucrase [Vasseur, van Melle, Frangne & Alvarado (1988) Biochem. J. 251, 667-675], we show how the 'fundamental' pK values, deduced from the classical double-logarithmic transformations, are insufficient to generate the required information. This insufficiency derives from the fact that, for sucrase, the acid ionization constant, K1, is a molecular constant that involves complex, V-type plus K-type, activatory and inhibitory kinetic effects. As a consequence, substrate-induced pK shifts cannot be interpreted correctly only by using the fundamental pK approach, because an unequal number of key protons is involved, depending on whether the free enzyme or the enzyme-substrate complex is considered. We demonstrate how this problem can be solved by using the 'theoretical' pK values, derived from the reciprocals of the Michaelis pH functions, i.e. Cha's fractional concentration factors. The procedure we propose, which is general, has the advantage of yielding all the macroscopic pK values for any given model, as calculated from the microscopic pK values. Furthermore, it permits predicting pK shifts as a function of [S] and/or [A] (where S is the substrate and A is the allosteric modifier), an objective that cannot be attained by using the double-logarithmic plot approach. Finally, we describe the relation existing between the fundamental and the theoretical pK values.

Animals↗
PubMed1989

A method for writing enzyme rate equations: application to the estimation of the number and size of key proton families.

We develop a method to derive the rate equation for enzyme models that include pH-dependent activation. Our presentation is based on a kinetic model recently described for sucrase, the three-key-proton model of Vasseur and coworkers, which considers the existence, in the acid ionization reaction, of two functionally distinct prototropic groups, respectively responsible for either V-type or K-type kinetic effects. In contrast, as concerns the basic ionization reaction, the model conforms to classical concepts of pH-dependent activation, whereby a single proton participates in either V-type or K-type effects but not in both at the same time. Enzymes with more than three key protons have been described, indicating that, rather than isolated protons, groups of protons should be considered, and therefore the model can be better described as a three-proton-family model, where a proton family is defined as one or several protons that are gained or lost as a block and perform the same kinetic function. The resulting model is treated here as a useful framework upon which other models can be built. To facilitate the writing of the rate equations, we define two new entities: (1) intralevel coefficients, which describe the various combinations of the enzyme with either the substrate(s), the allosteric effector(s), or both at a given protonation level, and (2) interlevel coefficients, which describe the interplay between the various protonation levels. The resulting rate equation can be used in a global fit procedure permitting in a single computer run the estimation of (1) the entire set of dissociation and microscopic ionization constants of the model, (2) the number and kinetic function of proton families characterizing the enzyme under consideration, and (3) the number of key protons constituting each family, which is derived from the derivatives of the kinetic parameters, Vm/Km, Vm, and Km.

Enzymes↗
PubMed1988

[Differentiation of a normal population and of a cohort of patients presenting with a history of idiopathic thromboembolism as identified with fibrinolytic tests].

To identify persons at risk for development of thromboembolic disease, fibrinolytic and blood coagulation parameters of normal controls (n = 40) and patients (n = 40) have been compared. Four fibrinolytic parameters, i.e. fibrinolytic activity at rest (FAr), fibrinolytic response after 10 minutes of venous occlusion (delta FA10'), and resting antigenic levels of the plasmatic inhibitor of the plasminogen activators (PAI-1) and of urokinase (u-PA), showed significant differences between the two study groups. The separate and combined discriminant analysis of FAr and delta FA10' values revealed that individuals with FAr below 0.63 UI/ml or a delta FA10' below 0.98 UI/ml are at risk for development of thromboembolic disease.

Adult↗