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Biomedical subjects

H Malmgren

Publications and source records attributed to H Malmgren.

At least 37 records · Page 2Linked to original sources
PubMed1993

1.5-Mb YAC contig in Xq28 formatted with sequence-tagged sites and including a region unstable in the clones.

A contig of 20 yeast artificial clones (YACs) has been assembled across 1.5 Mb of Xq28 and formatted with nine previously reported probes and nine STSs developed from the sequence of probes and end fragments of YACs. YAC end fragments were obtained by subcloning, Alu-vector PCR, or primer-ligation PCR methods. Eighteen of the YACs were recovered from a library specific for Xq24-q28; two that fill a gap were obtained from a second library made from total human DNA. One region, containing probes pX78c and 2A1.1, was unstable in YACs, but it was possible to generate a self-consistent map of DNA over the entire contig. Overlaps were confirmed by Southern blot analyses of YAC DNAs, and pulsed-field gel electrophoresis confirmed the extent of the contig and identified at least four CpG islands in the region.

Base Sequence↗
PubMed1993

Organic mental disorders as hypothetical pathogenetic processes.

A new diagnostic system for organic psychiatry is presented. We first define "organic psychiatry", and then give the theoretical basis for conceiving organic-psychiatric disorders in terms of hypothetical psychopathogenetic processes, HPP:s. Such hypothetical disorders are not strictly identical to the clusters of symptoms in which they typically manifest themselves, since the symptoms may be concealed or modified by intervening factors in non-typical circumstances and/or in the simultaneous presence of several disorders. The six basic disorders in our system are Astheno-Emotional Disorder (AED), Somnolence-Sopor-Coma Disorder (SSCD), Hallucination-Coenestopathy-Depersonalisation Disorder (HCDD), Confusional Disorder (CD), Emotional-Motivational Blunting Disorder (EMD) and Korsakoff's Amnestic Disorder (KAD). We describe their usual etiologies, their typical symptoms and course, and some forms of interaction between them.

Affective Symptoms↗
PubMed1993

Normal pressure hydrocephalus: psychiatric findings before and after shunt operation classified in a new diagnostic system for organic psychiatry.

23 patients with normal pressure hydrocephalus (NPH) underwent psychiatric examinations prior to and 80 days to 10 months after a ventriculo-peritoneal shunt operation. A global evaluation of the effect of the operation on the patients' mental symptoms indicated appreciable improvement in 10 cases and slight improvement in a further 4.8 patients were assessed as unchanged, and one as mentally deteriorated. The psychiatric analyses was based on a new diagnostic system created by two of the authors (G.L., H.M.). The patients manifested varying, often complex psychiatric symptom constellations with symptomatological components from two or more organic mental disorders. Before the operation a mild or a moderately severe somnolence-sopor-coma disorder (SSCD) was diagnosed in 10 cases. After the operation all these patients became free from symptoms of SSCD. This was the most unequivocal change in connection with the operation, and the elimination of all symptoms of SSCD was the single factor which most effectively contributed to the total therapeutical result in these patients. All 23 cases were considered to have symptoms of a more or less severe astheno-emotional disorder (AED) preoperatively. The degree of severity of this disorder could not be determined with satisfactory certainty in some of the patients with complex symptoms. Amongst the 17 cases where the preoperative symptomatology allowed for a reasonably precise calculation of the degree of severity of AED, 6 were assessed as markedly improved after the operation and 10 as largely unchanged. In one patient, symptoms of the AED increased when the postoperative course was complicated by a subdural haematoma. Symptoms of an emotional-motivational blunting disorder (EMD) were diagnosed in 5 cases before the operation. After the operation 3 of these patients were symptom free in this respect while 2 unchanged. Slight or moderately severe symptoms of Korsakoff's amnestic disorder (KAD) were before the operation found in 7 cases: at the postoperative examination 6 of these cases were improved, of which 4 were free from such symptoms; one was unchanged. According to our experience, confident prognoses concerning the effect of the shunt operation on symptoms of SSCD can be made preoperatively, while, for a particular patient, the therapeutic effect on AED, EMD and KAD is often difficult, or sometimes impossible, to foresee. This article contains three case reports which represent different forms and courses of the mental symptom patterns.

Affective Symptoms↗
PubMed1993

The semantic status of diagnostic criteria for organic mental syndromes and disorders in DSM-III and DSM-III-R.

After a general introduction referring to the contemporary debate about psychiatric classification, the nature of so-called "diagnostic criteria" in psychiatry is discussed with special reference to DSM-III(-R) and to organic mental syndromes and disorders. A set of diagnostic criteria for a disease category can be intended alternatively (i) as stating logically necessary and/or sufficient conditions for the diagnostic concept in question, or (ii) as providing contingent (probabilistic) indicators of the disease. In one possible interpretation, a main aim of DSM-III and DSM-III-R has been to formulate type (i), logical criteria, which amounts to an attempt to strictly identify syndromes or disorders with complex (polythetic) sets of easily observable symptoms and signs. It is shown that a logical interpretation would lead to such unwanted consequences for clinical and scientific practice that it could not possibly have been intended by the authors of DSM-III and DSM-III-R. But neither can the alternative interpretation in terms of type (ii), contingent or probabilistic indicators be consistently upheld. The conclusion of the essay is that the semantic status of the diagnostic criteria in DSM-III and DSM-III-R is fundamentally blurred. This unclarity may very well lead to divergent interpretations of the concepts and to corresponding uncertainties in their clinical and scientific application.

Delirium↗
PubMed1993

Psychiatric classification and empiricist theories of meaning.

The philosophical background of the contemporary debate over psychiatric classification is reviewed in some detail. It is shown that the philosophy behind DSM-III and DSM-III-R is based on a theory about the semantic status of operational definitions, which was abandoned several decades ago by empiricist philosophers of science. It is argued that the newer empiricist and realist theories of meaning developed after 1960, particularly the idea of an indirect specification of meaning through contingent operational criteria, offer a better foundation for psychiatric classification.

Diagnosis, Differential↗
PubMed1993

Linkage mapping of a severe X-linked mental retardation syndrome.

A four-generation Swedish family with a new type of X-linked mental retardation syndrome was recently reported by Gustavson et al. The complex syndrome includes microcephaly, severe mental retardation, optical atrophy with decreased vision or blindness, severe hearing defect, characteristic facial features, spasticity, seizures, and restricted joint motility. The patients die during infancy or early in childhood. Twenty-one family members, including two affected males, were available for study. Linkage analysis was conducted in the family by using 11 RFLP markers and 10 VNTR markers spread along the X chromosome. A hypervariable short tandem repeat of DXS294 at Xq26 showed a peak two-point lod score of 3.35 at zero recombination fraction. Calculations using the same markers revealed a multipoint peak lod score of 3.65 at DXS294. Crossover events with the centromeric marker DXS424 and the telomeric marker DXS297 delimit a probable region for the gene localization. It is noteworthy that hte disease loci of two other syndromes with overlapping clinical manifestations recently were shown by Turner et al. and Pettigrew et al. to be linked to markers at Xq26.

Abnormalities, Multiple↗
PubMed1992

Infantile autism--fragile X: molecular findings support genetic heterogeneity.

Twenty-two members of 18 families with autism have been examined for the presence of mutations and abnormal methylation in the FMR-1 region at Xq27.3. All patients fulfilled diagnostic criteria of infantile autism. A characteristic pattern of insertion and methylation were detected after Southern blot analysis in 7 autistic individuals expressing the fragile site at Xq27.3. Normal DNA patterns were observed in 15 autistic boys cytogenetically negative for the fragile site. The results indicate a lack of involvement of the FMR-1 region in infantile autists negative for fragile X expression.

Adolescent↗
PubMed1991

Capture PCR: efficient amplification of DNA fragments adjacent to a known sequence in human and YAC DNA.

We have devised a procedure, termed capture PCR (CPCR), that permits the rapid isolation of DNA segments situated adjacent to a characterized nucleotide sequence. In this procedure, a DNA sample is restriction-digested and a linker, comprising two base-paired oligonucleotides, is added to the ends by ligation. Multiple extension reactions are performed using a biotinylated primer derived from the known sequence, permitting the subsequent isolation of extension products on a streptavidin-coated support. The enriched fragments are amplified exponentially using another specific oligonucleotide, hybridizing 3' to the biotinylated primer in combination with one of the linker oligonucleotides, now functioning as a PCR primer. The convenience of CPCR is greatly enhanced by using a novel streptavidin-coated manifold, which is constructed so that it projects into each individual well of a microtiter plate. The procedure permits the simultaneous isolation of fragments from large numbers of DNA samples and minimizes the risk of contamination between reactions. We have applied this method to identify DNA sequences located downstream of known sequences in the human genome. The technique has also been used to identify end fragments of sequences cloned in a yeast artificial chromosome (YAC) vector. The reactions can be initiated directly from yeast colonies and provide access to DNA sequence information for these end fragments in a minimal number of steps. With the aid of the present technique, we have isolated over 100 end fragments from YACs derived from the human X chromosome. Isolated end sequences have been used to order YAC clones into a contig.

Base Sequence↗
PubMed1989

The polymorphic marker DXS304 is within 5 centimorgans of the fragile X locus.

The fragile X syndrome, which is the most common cause of inherited mental retardation, poses important diagnostic problems for genetic counseling. The development of diagnostic strategies based on DNA analysis has been impaired by the lack of polymorphic markers very close to the disease locus. Here we report that the polymorphic probe U6.2 (locus DXS304) is much closer to the fragile X locus than all the previously reported markers. A recombination fraction of 0.02 between DXS304 and the fragile X locus was estimated by multipoint linkage analysis (confidence interval 0.002 to 0.05). Our data suggest that DXS304 is distal to the fragile X locus. This marker thus represents a major improvement for carrier detection and prenatal diagnosis in fragile X families.

Chromosome Mapping↗
PubMed1989

Linkage analysis of families with fragile-X mental retardation, using a novel RFLP marker (DXS 304).

A new polymorphic DNA marker U6.2, defining the locus DXS304, was recently isolated and mapped to the Xq27 region of the X chromosome. In the previous communication we describe a linkage study encompassing 16 fragile-X families and using U6.2 and five previously described polymorphic markers at Xq26-q28. One recombination event was observed between DXS304 and the fragile-X locus in 36 informative meioses. Combined with information from other reports, our results suggest the following order of the examined loci on Xq: cen-F9-DXS105-DXS98-FRAXA-DXS304-(DXS52-F8 -DXS15). The locus DXS304 is closely linked to FRAXA, giving a peak lod score of 5.86 at a corresponding recombination fraction of .00. On the basis of the present results, it is apparent that U6.2 is a useful probe for carrier and prenatal diagnosis in fragile-X families.

Chromosome Mapping↗
PubMed1985

Intramuscular bioavailability of chlorazepate as compared to diazepam.

Dipotassium chlorazepate (DPC) and diazepam (DZM) were given i.m. and i.v. to 6 healthy volunteers in doses of 20 mg (48.9 mumol) DPC and 15 mg (52.0 mumol) DZM. The interval between the injections was at least 1 week. Plasma samples were analyzed for DPC and DZM by HPLC. The bioavailability of DPC and DZM after i.m. administration, determined from computer calculated AUCs, was 1.04 and 0.85, respectively.

Adult↗
PubMed1983

Pharmacokinetics of chlorazepate after intravenous and intramuscular administration.

Dichlorazepate (DPC) was given to eight healthy volunteers aged 22-38 years (five males and three females). The dose was 20 mg (48.9 mumol) given either as an IV or an IM injection. The interval between the injections was at least 1 week. Plasma samples were analysed for desmethyldiazepam (DMD) by HPLC before and after acid hydrolysis. The kinetics after both IV and IM administration could be explained by a one or two compartment open model. By comparing values before and after hydrolysis an estimate of di- and/or monopotassiumchlorazepate (MPC) could be made. The bioavailability was almost 100% after IM administration. The plasma half lives of DPC and DMD were independent of the form of administration (2.42 and 46.0 h respectively after IV and 2.29 and 45.1 h respectively after IM injection).

Adult↗
PubMed1980

Pharmacokinetics of dipotassium chlorazepate in patients after repeated 50 mg oral doses.

Dipotassium chlorazepate (DPC) was administered to ten patients (five males and five females), ages 18-37 years (mean 27.4), as a once daily dose of 50 mg until a steady state was reached. Plasma concentrations of the main metabolite N-desmethyldiazepam (DMD) were monitored by a high pressure liquid chromatographic (HPLC) method during the medication period and for 5 days after withdrawal of the drug. The plasma half life (t1/2), the elimination coefficient (K beta), the steady state concentration (Css), and the apparent volume of distribution (V beta), were calculated at steady state and the mean values +/- SEM were 44 +/- 5 h. 0.0184 +/- 0.0026 h(-1), 1590 +/- 163 ng/ml and 1.41 +/- 0.17 l/kg, respectively. A moderate inter-individual variability was observed. There was no tendency towards dose dependent elimination.

Adolescent↗
PubMed1978

Comparison studies of chlorazepate administered as a divided daily dose and as a single dose at night.

The residual effects of dipotassium chlorazepate administered as either a single daily dose of 20 mg at bedtime or a divided daily dose (5 + 5 + 10 mg) were studied in a placebo-controlled, double-blind trial comprising 12 out-patients. The following tests were used to determine changes in perceptual wakefulness, performance ability, fine motor skills, and coordination: critical flicker fusion test, car driving in a simulator, and the "bead and needle tests." In addition, the patients underwent a clinical assessment and also filled out a self-rating scale for judging factors related to the tests. No significant differences were found between the dosage schedules or between the active medication and the placebo. The clinical results were not dependent on the dosage schedule.

Adult↗
PubMed1977

Pharmacokinetics of N-desmethyldiazepam in healthy volunteers after single daily doses of dipotassium chlorazepate.

Dipotassium chlorazepate was administered to 12 healthy volunteers (8 males and 4 females), aged 22-38 years, as a single daily dose of 20 mg for 14 days. Plasma concentrations of N-desmethyldiazepam were monitored with a gas-chromatographic method during the medication period and for 5 days after withdrawal of the drug. The plasma half-life (t1/2), the elimination coefficient (Kbeta), the concentration (Css), and the apparent volume of distribution (Vbeta) were calculated at steady state, and the mean values +/- SEM were 53 +/- 6 h, 0.0147 +/- 0.0013 h-1, 884 +/- 73 ng/ml, and 1.13 +/- 0.08 1/kg, respectively. A moderate interindividual variability was observed regarding these parameters. There was no tendency toward a biexponential elimination. A significant difference in the apparent volume of distribution was found when males and females were compared.

Adult↗
PubMedDate not supplied

Carrier detection of the fragile X syndrome using flanking loci DXS98, DXS105, and DXS304.

Diagnosis of the carrier status of the fragile X [fra(X)] syndrome was made in 2 unrelated women who did not express the fragile site. Both were related to several individuals with a typical fra(X) phenotype and the marker X chromosome. A restriction fragment length polymorphism (RFLP) approach was used with probes that flank the fra(X) locus (FRAXA). The loci used for risk calculations of the fra(X) genotype were DXS98 and DXS105 on the centromeric side and a recently characterized locus, DXS304, on the telomeric side. Coincidence correction for the distances between marker loci and FRAXA was made according to the Kosambi function. The DNA marker test gave the risk for one female to be a carrier of 99.7-99.9%. In another family a female was excluded from being a carrier with a probability of greater than 99.7%. The DNA marker U6.2, defining the locus DXS304, has increased the reliability of DNA based diagnosis of carrier status for females-at-risk. It is concluded that DNA analysis can serve as a valuable complement to chromosome analysis in families informative for the more closely linked flanking markers.

DNA Probes↗