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Biomedical subjects

M Philipp

Publications and source records attributed to M Philipp.

At least 19 recordsLinked to original sources

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

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

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

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

Irreversible inhibition of a monoclonal antibody by a nitrophenyl ester.

TEPC-15 is a phosphorylcholine-binding mouse myeloma protein which reacts with an ester-containing phosphorylcholine, the p-nitrophenyl ester of 6-(phosphorylcholine)hexanoic acid (PEPCH). The rate of nitrophenolate release mediated by the antibody is pH-dependent and increases with increasing pH. The antibody becomes inactive during the reaction with the ester. The inactive antibody is not reactivated even after treatment with hydroxylamine. Antibody activity is associated with the Fab' fragment. These observations together with the pH profile of the reaction suggest that the ester acylates a lysine side chain near the antibody-binding site.

Antibodies, Monoclonal

The concept of major depression. I. Descriptive comparison of six competing operational definitions including ICD-10 and DSM-III-R.

All operationalized diagnostic systems contain a diagnostic category, which corresponds to the concept of major depression. Yet, these corresponding definitions are not identical. Up to now, no comprehensive comparisons of the competing diagnoses have been published. We will therefore present a series of studies, describing six different operational definitions of major depression according to their content and construction and empirically comparing them in large inpatient and outpatient samples. This first paper presents a descriptive comparison of the definitions given in the Feighner Diagnostic Criteria, the Research Diagnostic Criteria, the Diagnostic and Statistical Manual of Mental Disorders, third edition and third edition, revised, and in two developmental drafts of the ICD-10 diagnostic criteria for research (draft April 1987-I87; draft April 1989-I89). The descriptive comparison will demonstrate that there are many similarities, especially concerning the symptom-criteria of major depression. Classificatory relevance could only be assumed for those differences found for cut-offs, for time criteria and especially for exclusion criteria. Whether these differences are negligible and whether patients classified by different diagnostic systems are really comparable will be examined in subsequent publications.

Depressive Disorder

The concept of major depression. II. Agreement between six competing operational definitions in 600 psychiatric inpatients.

Six operational definitions of the concept of major depression were submitted to empirical evaluation in 600 psychiatric inpatients. Special attention was given to the comparison of major depression in DSM-III-R and ICD-10. The data base created by a polydiagnostic interview revealed relevant classificatory differences between the six definitions under study. Sources of different diagnostic base rates were: inclusion or omission of anhedonia as an obligatory mood criterion; minimal number of syndrome criteria required for the syndrome diagnosis; different width and reference points of time criteria; exclusion rules for co-existing schizophrenic symptoms and for previous nonaffective and manic episodes. The empirically evaluated overlap between pairs of diagnostic definitions was less than excellent in most of the diagnostic definitions under study; only the DSM-III and DSM-III-R definitions agreed with each other to a highly comparable degree. The relatively good agreement of the 1989 draft definition of ICD-10 for major depression ("mild depression") with the other five operational definitions (kappa = 0.69) led us to expect that this definition should receive sufficient international acceptance.

Depressive Disorder

The concept of major depression. III. Concurrent validity of six competing operational definitions for the clinical ICD-9 diagnosis.

The comparative validity of six operational diagnoses of major depression was evaluated in 600 psychiatric inpatients using the independently assessed clinical ICD-9 diagnoses as a yardstick. Agreement with, and positive predictive value for the ICD-9 categories of pure (endogenous and psychogenic) depression served as validation criteria; sensitivity of major depression diagnoses for detecting ICD-9 bipolar depressions was additionally used for examining the adequacy of width, time and exclusion criteria of the competing operational definitions. Three essential results were found. First, the "old" diagnostic definitions of RDC and FDC are superior to all newer definitions because they define the time criteria and the schizophrenic exclusion criteria more adequately than, for example, both DSM-III and DSM-III-R definition. Secondly, the current ICD-10 definition of 1989 ("mild", "moderate" or "severe" depression) comes closer to the concurrent validity of RDC and FDC than DSM-III, DSM-III-R and the previous ICD-10 definition of 1987. Thirdly, using the criterion of identifying a high proportion of ICD-9 bipolar depressions, all six competing diagnostic systems are too restrictive. Evaluations of predictive and criterion-related validity will be needed to substantiate these findings.

Affective Disorders, Psychotic

The impact of the endogenous subtype on the familial aggregation of unipolar depression.

The endogenous/non-endogenous distinction of unipolar major depression is widely accepted, as is the family study approach to the validation of diagnostic distinctions. Rates of affective disorders were examined in 689 first-degree relatives of 184 patients with unipolar major depression and were compared with 312 first-degree relatives of 80 healthy controls. Only unipolar depression and alcoholism were more common in families of depressed probands compared with families of healthy controls. As a variety of diagnostic definitions of endogenous depression have been proposed, probands and relatives were diagnosed in a polydiagnostic manner. None of the five diagnostic definitions of endogenous depression was able to identify patients with an increased familial risk of unipolar depression.

Arousal

Identification of minor affective disorders and implications for psychopharmacotherapy.

Five hundred general practice patients with functional complaints were studied with the Polydiagnostic Interview (PODI) to see whether DSM-IIIR criteria were able to specify affective disorders satisfactorily. Almost one third of the patients received the diagnosis of depression not otherwise specified (NOS). When Research Diagnostic Criteria were applied to these patients more than 70% received specific diagnoses. A modification of DSM-IIIR algorithms enabled us to further specify diagnoses in subjects with depression NOS. On the 17-item Hamilton Depression Scale many of these patients reached scores of 13 or more which is severe enough to justify a therapy trial with antidepressants.

Adjustment Disorders

Can the scanning tunneling microscope sequence DNA?

A revolutionary new microscope, the scanning tunneling microscope (STM), can image some surfaces at atomic resolution, even in air or water. It can produce high-resolution images of DNA, and we outline what we know of its mechanism, concluding that it may be able to sequence DNA. This application would require major advances in sample preparation in order for the technique to compete with conventional methods. On the other hand, the STM may provide a very useful alternative to gels for probing sequence-directed structural features.

Base Sequence

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

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

Comparison of the ICD-10-classification with the ICD-9- and the DSM-III-classification of mental disorders.

The diagnostic concepts in ICD-10 show better congruence with those in DSM-III than with those in ICD-9. The diagnostic definitions used by ICD-10 and DSM-III for the majority of diagnoses turn out to be similar; the definitions of anxiety disorders and schizoaffective disorders are, however, still at variance. Consequently, the empirical results from the WHO field trial in German-speaking countries reveal a high degree of overlap between the two systems; the degree of overlap between ICD-9 and ICD-10 was lower, but still surprisingly high overall. These empirical results support the validity of ICD-10.

Humans

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

Antigenic and dynamic properties of the surface of Onchocerca microfilariae.

We analyzed the antigenicity and stability of the surface of skin microfilariae (mf) of Onchocerca cervicalis, a horse parasite. These mf express antigens on their surface that are cross-reactive with the cattle parasite O. lienalis and with the human parasite O. volvulus. The surface of living O. cervicalis mf was radioiodinated using Iodogen and the labeled components were solubilized in buffers containing sodium dodecyl sulphate (SDS), or extracted with the milder detergent octyl-beta-D-glucopyranoside (OGP). Electrophoresis of this material showed seven prominent bands, one of which (14 kDa) was specifically precipitated by antisera from rabbits immunized with mf from either O. cervicalis, O. lienalis, or O. volvulus, and by human sera obtained from infected individuals in Chiapas, Mexico. Other components were precipitated by either the rabbit or the human sera. In addition, antisera from mice immunized with O. cervicalis mf bound specifically to the surface of freeze-thawed uterine O. lienalis and O. volvulus mf as detected by immunofluorescence. This fluorescence was lost from the surface of O. cervicalis mf in a temperature-dependent fashion. Live mf incubated on ice with mouse anti-mf antisera and secondary FITC-GAM, showed uniform surface fluorescence. When these mf were incubated at 37 degrees C, but not at 0 degrees C, the fluorescent pattern changed with time. First, small non-fluorescent patches arose, followed by an increasingly wide belt devoid of fluorescence, and finally, no visible fluorescence. These changes in the mf surface suggest potential mechanisms for immune evasion by filarial parasites.

Animals

A lambda gt11 cDNA recombinant that encodes Dirofilaria immitis paramyosin.

The cDNA synthesized from mRNA of Dirofilaria immitis female adult worms was cloned into the expression vector lambda gt11. Screening the library with a hyperimmune rabbit antiserum raised against adult worm homogenates yielded several antigen positive clones. One of these clones, lambda cDi2, was recognized by rabbit antisera raised against either D. immitis L-3, adult, Brugia malayi L-3 or Onchocerca volvulus adult worm antigen, as well as by antisera from humans naturally infected with O. volvulus or Wuchereria bancrofti. Affinity-purified anti-lambda cDi2 antibodies reacted with a 97-kDa protein on Western transfers of adult D. immitis antigen extracts that were reduced with beta-mercaptoethanol. The whole rabbit anti-D. immitis adult antiserum depleted of anti-lambda cDi2 antibodies exhibited decreased reactivity to this 97-kDa band. A monoclonal antibody (IA6) that specifically binds Schistosoma mansoni paramyosin also recognised a 97-kDa protein in D. immitis extracts upon Western transfer. The deduced amino acid sequence of partial DNA sequence from lambda cDi2 showed some similarity to nematode myosin, and gave a stretch of 82 amino acids that is 91.5% identical to Caenorhabditis elegans paramyosin: thus, lambda cDi2 encodes D. immitis paramyosin.

Amino Acid Sequence

[Chronic paranoid-hallucinatory psychosis as the initial manifestation of an HIV infection?].

In a 36-year-old patient an acute onset of psychosis occurred, probably due to HIV infection. For one year HIV-infection with reduced T4/T8 ratio had been known without clinical manifestation (stage IV B of the CDC-classification). He developed chronic delusional hallucinations, which persisted for more than one year in spite of adequate psychoactive drug therapy. So far AIDS-related dementia has not become evident. Focal lesions caused by opportunistic infections or tumour were excluded by computed tomography and magnetic resonance imaging. The latter revealed several small lesions and the brain scan showed a nonhomogeneous pattern of cerebral blood flow. CSF-examination disclosed a mild lymphocytosis and raised protein concentration. A classification as an organic, HIV-induced delusional hallucination seems to be justified.

Acquired Immunodeficiency Syndrome