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Biomedical subjects

M Philipp

Publications and source records attributed to M Philipp.

At least 19 recordsLinked to original sources
PubMed1992

Development of a rating scale for quantitative measurement of the alcohol withdrawal syndrome.

The alcohol withdrawal syndrome consists of autonomic, neurological and mental symptoms. For its assessment, these symptoms have to be rated in a quantitative and valid manner. We developed a new rating scale for mild and moderate alcohol withdrawal states. Difficulty, discrimination coefficient, internal consistency, and the principal component analysis were assessed. External validation was tested on a separate sample of inpatients. Eight of 12 original items fulfilled test-theoretical criteria. From these a psychosensory and an autonomic factor have been extracted. This instrument can be used repeatedly for clinical assessment as well as for evaluation of the alcohol withdrawal syndrome in clinical drug studies.

Adult↗
PubMed1992

Differentiation between major and minor depression.

Though the concept of Major Depression was generated by clinicians using depressed inpatients as models, a polydiagnostic study in 600 psychiatric inpatients with heterogenous psychological disturbances revealed that all six competing operational definitions of Major Depression (including DSM-III-R and ICD-10) were too restrictive to serve as a general concept of depression. Another polydiagnostic study in 500 primary care outpatients showed that more than two-thirds of all non-chronic depressed cases were below the severity threshold of Major Depression: these patients are classified as Depression Not Otherwise Specified (NOS) by DSM-III-R. Loosening of the over-restrictive time criteria would broaden the concept of Major Depression so as to meet the requirements of a general concept of depression, while the definition of Minor Depression below the threshold of Major Depression would add to a reduction of cases of NOS Depression by more than 80%. For the evaluation of antidepressant drugs in outpatient samples, we propose that patients with these modified definitions of Major and Minor Depression be included, provided they meet a minimum severity criterion of 13 or more points on the Hamilton Depression Scale; four-fifths of the modified Major Depression group and one-third of the Minor Depression group do in fact meet this criterion.

Depression↗
PubMed1992

Brugia malayi: patterns of expression of surface-associated antigens.

Patterns of expression of surface-associated antigens were analyzed in the filarial nematode Brugia malayi immediately prior, and during development in the vertebrate host. Two surface-associated protein molecules, i.e., accessible to surface radioiodination and soluble in aqueous buffers, were investigated: Mrs 29-30,000 and 16,000, both of which are antigenic in infected animals. The Mr 29-30,000 glycoprotein is expressed in a surface-associated manner by adult worms and by fourth-stage larvae, but is not detectable in preparasitic third-stage larvae. The 16,000 component, which appears not to be glycosylated, is surface-associated in adult worms and fourth-stage larvae. In contrast to the 29-30,000 glycoprotein, the 16,000 protein is also expressed both by pre- and postparastic third-stage larvae. However, it becomes surface-associated only after infection. Thus, immediately prior, and during development within the vertebrate host, B. malayi displays at least two different patterns of expression of surface-associated antigens: (i) de novo, intiated either immediately after infection (phase specific) or during genesis of the fourth-stage larva (stage specific); (ii) continuous, but with phase-dependent surface exposure of previously cryptic antigens, during the transition from intermediate to definitive host.

Animals↗
PubMed1992

Nimodipine in acute alcohol withdrawal state.

The effect of the calcium channel blocker, nimodipine, in acute alcohol withdrawal was investigated in a randomized, placebo controlled, double blind study. Thirty-two male patients with a history of alcohol dependence according to DSM-III criteria, but no other substance abuse, were included. A new rating instrument which fulfilled theoretical test criteria was applied to determine the severity of the alcohol withdrawal state. The patients received nimodipine or a placebo on four separate occasions (4 x 60 mg) and, in addition, clomethiazole, according to a standardized procedure. Our investigation has shown that, in the first 48-72 h of alcohol withdrawal, both groups consumed similar amounts of additional clomethiazole medication. Thus, no significant effect of nimodipine on the acute alcohol withdrawal state could be demonstrated. There was some tendency for nimodipine to ameliorate psychosensory dysfunction.

Acute Disease↗
PubMed1991

Animal models in the study of the phenomenon of parasitism: filariae and other parasites.

The Round table has emphasized the absolute necessity of in vivo research showing the complexity of host reaction to the parasite. The results obtained in vitro can only provide a preliminary indication, because any interference with the culture is susceptible of changing the precarious balance of the parasite in that artificial environment. The subject proposed here cannot be treated wholly, but some particular topics could be discussed: 1--searching for appropriate models; 2--parasite strains; 3--some aspects on pathology and drug development; 4--vaccines; what significance in a natural host-parasite relationship can be gathered from a non-natural one?

Animals↗
PubMed1990

Anti-idiotypic antibodies function as a surrogate surface epitope of Brugia malayi infective larvae.

Anti-idiotypic (AB2) antibodies were generated in rabbits following immunization with a murine IgM monoclonal antibody (AB1) recognizing a surface determinant of Brugia malayi infective stage larvae. AB2 specifically inhibited the binding of AB1 to B. malayi larvae. Furthermore, AB2 had the ability to mimic the original antigen since mice immunized with AB2 possessed serum antibodies (AB3) specific for the B. malayi surface determinant. The presence of anti-surface antibodies (AB3 and AB1) induced either by AB2 immunization or by administration of AB1, did not alter the outcome of an intraperitoneal infection of B. malayi larvae in BABL/c mice when compared to untreated animals. AB3 antibodies like AB1, were IgM, thus indicating an isotype restricted response to the B. malayi epitope. There were no detectable cell mediated responses to the surface determinant in mice immunized with AB2, assessed by lymphocyte blastogenesis or IL3 production in vitro in response to the idiotope as presented by living larvae. The lack of cellular responses and/or the previously demonstrated rapid shedding of the epitope may explain the inability of AB1 or AB2 to protect mice against larval challenge in this study.

Animals↗
PubMed1990

Genes that can be mutated to unmask hidden antigenic determinants in the cuticle of the nematode Caenorhabditis elegans.

Rabbit antisera directed against a mixture of proteins solubilized from the wild-type adult Caenorhabditis elegans cuticle were used to isolate mutants, induced by ethyl methanesulfonate treatment, that exhibit alterations in surface antigenicity by immunofluorescence. Genetic mapping and complementation data for four such mutations define two genes, srf-2(I) and srf-3(IV). The mutant phenotypes observed by immunofluorescence appear to result from unmasking of antigenic determinants that are normally hidden in the wild-type cuticle. In support of this hypothesis, surface radioiodination experiments indicate that components labeled on the wild-type surface are missing or less readily labeled on the surface of srf-2 and srf-3 mutants.

Animals↗
PubMed1979

Comparison of the kinetic specificity of subtilisin and thiolsubtilisin toward n-alkyl p-nitrophenyl esters.

The p-nitrophenyl esters of straight-chain fatty acids were used as substrates of the enzyme subtilisin Novo (EC 3.4.4.16) and its chemically produced artificial enzyme thiolsubtilisin. Subtilisin and thiolsubtilisin pH--activity profiles were determined, and kinetic effects of the active site O-S substitution were observed. Among the substrates tested, both enzymes show highest specificity with p-nitrophenyl butyrate. It was also found that subtilisin is more sensitive to changes in substrate chain length than is thiolsubtilisin. Second-order acylation rate constants (k2/Ks) are remarkably similar for both enzymes. However, thiolsubtilisin deacylation rate constants and Km values are lower than analogous subtilisin constants. While thiolsubtilisin deacylation rate constants give a pH profile identical with that of subtilisin, the pH profile of thiolsubtilisin acylation rate constants shows an active site pK value lowered from the subtilisin pK of 7.15 and exhibits an inflection point at pH 8.45, which is absent in subtilisin.

Binding Sites↗
PubMed1979

[Endocrinological prediction of the responsiveness of depressive patients to lofepramine (author's transl)].

In a pilot study of 15 depressive patients of the neurotic and endogenous type we could show that some neuroendocrinological parameters are apt to predict the thymoleptic efficacy of lofepramine. These parameters, which were measured with a simple global stimulation test (insulin hypoglycaemia combined with injection of TRH and LHRH), were as follows: high basal blood glucose; high hypoglycaemic blood glucose; high decrease of blood glucose in comparison to the basal level; low basal TSH; low increase of HGH and low increase of cortisol after hypoglycemia. A synopsis of these parameters allowed a correct classification of 14 out of 15 patients according to therapy response and therapy resistance.

Adult↗
PubMed1979

Prediction of lofepramine-response in depression based on response to partial sleep deprivation.

The improvement of depression after partial sleep deprivation in the second half of the night (sd) is tested for its predictory power for the therapeutical efficacy of pharmacotherapy with lofepramine. In a group of 15 patients with depression, we found that in contradiction to the findings of Wirz-Justice and collaborators (1976), the velocity of the antidepressive effect of sd has no predictive value. On the other hand, the amount of depression improvement after sd is of predictive value. This is independent of the time of occurrence of the improvement peak after sd. An improvement of more than 35% measured in the Bf-S or in the H.DRS on the first or the second day after sd is highly predictive for a good response to three weeks of 210 mg lofepramine per day (p = .05).

Clinical Trials as Topic↗
PubMed1979

A double-blind trial with amitriptyline and lofepramine in the treatment of endogenous depression.

A double-blind trial was undertaken to compare the antidepressant efficacy and the side effects of Lofepramine with those of Amitriptyline in the treatment of endogenous depression. The study involves 22 acutely ill endogenously depressive patients. 11 patients were treated with Lofepramine and the remaining 11 with Amitriptyline. The results demonstrate that both substances are effective in the treatment of depression. However, the therapeutical efficacy of Lofepramine is significantly greater than that of Amitriptyline. Furthermore, the tolerance of Lofepramine is better than that of Amitriptyline, and the side effects of Amitriptyline, especially in blood pressure dysregulation, are greater than those of Lofepramine.

Adult↗
PubMed1978

Chronobiology and its implications for pharmacotherapy of endogenous depression.

An open pilot study on 30 in-patients with endogenous depression showed a clear-cut circadian fluctuation of the therapeutical effect of single doses of lofepramine administered at three different times of the day (8 a.m., and 12 p.m.). A single-dose drug schedule with 210 mg lofepramine at 12 p.m. also proved superior (p less than .05) to the conventional divided-dose drug schedule with 70 mg lofepramine at three times of the day. The chronobiological background and the therapeutical consequences of these findings are discussed.

Adult↗
PubMed1977

Binding rates, O--S substitution effects, and the pH dependence of chymotrypsin reactions.

The pH dependence for acylation of alpha-chymotrypsin by N-acetyltryptophan p-nitrophenyl-, p-nitrothiophenyl-, ethyl-, and thiolethyl esters has been studied by the stopped-flow technique. Values for the acylation rate constant, k2, and the binding constant, KS, were obtained by using measurements of phenolate release, for the p-nitrophenyl esters, and proflavin displacement, for the ethyl esters. The oxygen esters tested have slightly higher k2 values, and substantially higher KS values relative to the analogous thiol esters. Whereas k2/KS for the thiolethyl ester is higher than that for the analogous oxygen ester, the k2/KS values for oxy- and thio-p-nitrophenyl esters are nearly identical. These data are interpreted to indicate rate-determining formation of a tetrahedral intermediate in acylation of alpha-chymotrypsin by p-nitrophenyl esters, and rate-determining breakdown of such an intermediate in the case of the ethyl esters. It is also concluded that the oxygen to sulfur substitution causes a substantial increase in the proportion of nonproductive binding in these substrates. pH dependent k2 and KS values were used to calculate values for k1 and k-1, the binding and debinding rate constants for the two p-nitrophenyl compounds. This is the first such calculation based on experimentally determined acylation rate constants.

Chymotrypsin↗