[Guidance of coworkers and team development].
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Humans↗
Biomedical subjects
R Vogel
Publications and source records attributed to R Vogel.
The increase of suicides in psychiatric hospitals in southwestern Germany according to diagnostic subgroups.
In this paper, results are shown of a study on suicides committed by psychiatric inpatients in four state mental hospitals in Baden-Württemberg, Federal Republic of Germany during the 15 years from January 1, 1970 up to the end of 1984. There was a mean suicide rate of 195 per 100,000 admissions. A comparison of 5-year sequences showed a significant increase of so-called hospital suicides in two of the hospitals at the end of the seventies and the beginning of the eighties. A statistical analysis of a trend of increase using nonparametric methods (Spearman rho, Kendall tau) showed a significant increase in the number of suicides and suicide rates in all four hospitals. In a second step, the same statistical procedure testing for an increase in the fifteen years was used for the group of schizophrenic (N = 106) and depressed (N = 55) inpatients who committed suicide. An impressive and highly significant increase was found especially in schizophrenic male inpatients with the ICD-9 diagnosis 295.3 (paranoid-schizophrenia), and within that group, in inpatients with 3 or more inpatient treatments. There was also an increase in the depressed group, especially in female depressives, but only significant at the 5% level in the trend analysis.
Data Interpretation, Statistical↗
Mapping of the prekallikrein-binding site of human H-kininogen by ligand screening of lambda gt11 expression libraries. Mimicking of the predicted binding site by anti-idiotypic antibodies.
High molecular weight (H-)kininogen, a non-enzymatic cofactor of the contact activation system, has on the COOH-terminal part of its light chain a unique binding site which complexes prekallikrein or factor XI with high affinity and specificity. In a conventional protein fragmentation approach, the prekallikrein-binding site was mapped to positions 556-595 of the human H-kininogen sequence (Tait, J. F., and Fujikawa, K. (1986) J. Biol. Chem. 261, 15396-15401). To gain more insight into the minimum structural requirements of the prekallikrein-binding site, we have developed an alternative strategy employing the lambda gt11 expression cloning system. A ligand assay was established which probes for the binding site in H-kininogen or recombinant fusion proteins thereof by complexation with prekallikrein, followed by a specific antibody against prekallikrein and a secondary labeled antibody. A cDNA library constructed in lambda gt11 from random fragments of a cDNA clone encoding the COOH-terminal part of the kininogen light chain was screened by the ligand assay, and 17 positive clones were identified. Analysis of their inserted cDNA sequences revealed a consensus sequence of 119 nucleotides which maps to the extreme 3' end (positions 1759-1877) of the coding part of the prekininogen mRNA. The consensus sequence encodes positions 569-607 of the kininogen light chain and overlaps by 27 residues (positions 569-595) with the binding segment identified previously by the fragment approach. Analysis of successively shortened peptides revealed that the common segment of 27 residues but not truncated versions thereof contains the essential structural elements for prekallikrein binding. This conclusion was corroborated by the finding that anti-idiotypic antibodies toward a monoclonal antibody directed to the binding segment of 27 residues bear internal image(s) of the binding site of H-kininogen. It is pointed out that the methodology described in this study may prove generally useful in the cloning and mapping of high affinity binding sites of proteins.
Amino Acid Sequence↗
High molecular weight kininogen-binding site of prekallikrein probed by monoclonal antibodies.
A panel of monoclonal antibodies against human prekallikrein was raised in mice and characterized with respect to the major antigenic epitopes. Of 18 antibodies, nine were directed against the light chain portion performing the proteolytic function of activated kallikrein, and nine recognized the heavy chain mediating the binding of prekallikrein to high molecular weight (H-)kininogen. Among the anti-heavy chain antibodies, one (PK6) interfered with the procoagulant activity of prekallikrein, and prolonged in a concentration-dependent manner the activated partial thromboplastin time of reconstituted prekallikrein-deficient plasma (Fletcher type). Antibody PK6 was subtyped IgG1,k and had an apparent Kass of 6.8 +/- 0.44.10(8) M-1 for prekallikrein. Functional analyses revealed that PK6 does not interfere with prekallikrein activation by activated Hageman factor (beta-F XIIa), and has no effect on the kininogenase function of activated kallikrein. Monoclonal antibody PK6 but none of the other anti-heavy chain antibodies completely prevented complex formation of prekallikrein with H-kininogen, and readily dissociated preformed complexes of prekallikrein and H-kininogen. Likewise, Fab' and F(ab')2 fragments of PK6 blocked H-kininogen binding to prekallikrein. A synthetic peptide of 31 amino acid residues encompassing the entire prekallikrein binding region of H-kininogen effectively competed with PK6 for prekallikrein binding indicating that the target epitope of PK6 is juxtaposed to, if not incorporated in the H-kininogen-binding site of prekallikrein. Extensive cross-reactivity of PK6 with another H-kininogen-binding protein of human plasma, i.e. factor XI, suggested that the structure of the target epitope of PK6 is well conserved among prekallikrein and factor XI, as would be expected for the kininogen-binding site shared by the two proteins. It is anticipated that monoclonal antibody PK6 will be an important tool for the precise mapping of the hitherto unknown kininogen-binding site of prekallikrein.
Antibodies, Monoclonal↗
Synthesis and secretion of hirudin by Streptomyces lividans.
To examine the secretory production of heterologous proteins by Streptomyces lividans, we fused the DNA encoding the signal peptide of the alpha-amylase inhibitor tendamistat, derived from S. tendae with a synthetic gene encoding the thrombin inhibitor hirudin. The analysis of secretion by immunoblots revealed an efficient translocation of hirudin through the membrane, with no detectable immunoreaction among the cellular proteins. The secreted hirudin was stable in the shaking culture for about 6 days. A comparison of the hirudin secreted by S. lividans and recombinant reference hirudin from yeast by immunoblots and thrombin inhibition assays shows that hirudin from Streptomyces has a lower specific activity, which may be due to a different aminoterminal sequence or to inexact processing of the precursor.
Amino Acid Sequence↗
The effect of timolol, betaxolol, and placebo on corneal sensitivity in healthy volunteers.
This study in sixty healthy volunteers investigated the effect of a single drop of either 0.5% timolol ophthalmic solution, 0.5% betaxolol ophthalmic solution, or placebo on corneal sensitivity as measured by the Cochet-Bonnet anesthesiometer. Corneal sensitivity was measured immediately prior to the drop and then 1, 3, 6, 10, 15 and 30 minutes after drop instillation. The timolol treated eyes showed a significant decrease at one minute after instillation. An increase in sensitivity occurred in the placebo group at 15 and 30 minutes. In the eyes treated with betaxolol, a significant reduction in corneal sensitivity was seen at every time point through the 10-minute measurement.
Administration, Topical↗
Sulfadiazines reduce gingivitis and plaque formation in beagle dogs.
The effect of zinc sulfadiazine (ZnSD) and silver sulfadiazine (AgSD) on reducing plaque formation and gingivitis was studied in 12 beagle dogs over a 14-week period. 12 beagle dogs were scaled, root planed and pumiced to bring them to a similar level of gingival health, prior to placing them on a diet of Purina Dog Chow softened with canned gravy and molasses to promote the build-up of plaque and the initiation of gingivitis. At the end of 8 weeks, the dogs were determined to have substantial bacterial plaque accumulation and apparent gingivitis. Thereafter, 4 dogs were treated 2 x daily with topical applications of 3% zinc sulfadiazine; 4 dogs were treated with 2% silver sulfadiazine while 4 dogs were treated with placebo gel serving as control over a 14-week treatment period. By week 2, the zinc and silver sulfadiazine dogs showed a significant decrease in gingival index which was maintained throughout the study. Additionally, by week 2, the % of sites with bleeding was also seen to decrease significantly in the experimental groups. The plaque index remained consistent in all 3 groups until week 6 when the 2 experimental groups indicated significant decrease in plaque accumulation as compared to controls. Probing depths were also seen to decrease significantly in the experimental groups after 10 weeks of therapy. The mean stain index was similar in all 3 groups of dogs throughout the study. Data indicate that both zinc and silver sulfadiazine inhibit plaque formation and reduce existing gingivitis in beagle dogs.
Administration, Topical↗
Sulfadiazines prevent plaque formation and gingivitis in beagles.
The effect of zinc sulfadiazine (ZnSD) and silver sulfadiazine (AgSD) on developing plaque formation and gingivitis was studied in 12 beagle dogs over a 14-week period. Plaque and gingival indices were used to measure plaque formation and gingivitis. During a 2-wk baseline period each dog was brought to optimal gingival health with prophylaxis and tooth brushing. Thereafter, 4 dogs were treated twice daily with topical application of 3.0% zinc sulfadiazine; 4 dogs were treated with 2.0% silver sulfadiazine while 4 dogs treated with placebo gel served as controls over a 12-wk treatment period. At wk 2 of treatment, all three groups of dogs showed an increase in plaque build-up on their teeth from baseline. By wk 6, plaque accumulation on the teeth was significantly less in dogs treated with either ZnSD or AgSD compared to control dogs. At wk 2 of treatment, gingival inflammation was increased from baseline in all three groups. Thereafter, over the course of the 12-wk treatment period, gingival inflammation in the ZnSD and the AgSD treated dogs was significantly less than the placebo treated dogs. The data indicate that both ZnSD and AgSD inhibit developing plaque formation in beagles. This significant inhibition of plaque formation was accompanied by a significant reduction in gingival inflammation.
Administration, Topical↗
Association between intraocular pressure and loss of visual field in chronic simple glaucoma.
This paper reports the analyses on data from 747 patients with chronic simple glaucoma (CSG) recorded in the King's College Hospital glaucoma data base between January 1970 and February 1985, having a mean follow-up time of 5.1 years (mode 8 years) with the object of determining the relationship of intraocular pressure (IOP) and visual field loss in CSG. A highly significant negative relationship was found between the presenting visual field coefficient (FC) and the untreated IOP (r = -0.26, p = 0.0001) - that is, the higher the IOP on detection, the worse is the visual field. A weak negative correlation was present between the change of FC per year and the treated IOP (r = -0.06), p = less than 0.05). At treated IOPs less than or equal to 18 mmHg visual field loss averaged 0.6 unit per year and for IOPs greater than 18 mmHg the average loss was 1.2 units per year. The data confirm both the importance of a raised IOP in the causation of chronic glaucomatous visual field loss and the importance of reducing the IOP in patients with chronic simple glaucoma.
Adolescent↗
Subcutaneous fat necrosis with thrombocytopenia in a newborn infant.
A case of subcutaneous fat necrosis (SCFN) in a newborn who had suffered from asphyxia secondary to meconium aspiration is described. During the third week of life, bluish-red subcutaneous nodules were noticed. A biopsy of the lesions showed subcutaneous necrosis with fat cells containing needle-like crystals with reactive inflammatory infiltrates. Peripheral transient thrombocytopenia was observed prior to the appearance of subcutaneous fat necrosis. The good prognosis is stressed.
Asphyxia Neonatorum↗
Methotrexate-induced leukoencephalopathy is treatable with high-dose folinic acid: a case report and analysis of the literature.
An episode of leukoencephalopathy is reported in a 13-year-old girl who, after standard radiotherapy for a posterior fossa medulloblastoma, received 8 treatments with a protocol containing a 4-hour infusion of 500 mg/m2 methotrexate and 12 mg intrathecal methotrexate. The leukoencephalopathy, documented clinically and by CT and EEG, cleared after 2350 mg of leucovorin (citrovorum factor, folinic acid) was given in addition to the 135 mg given as part of the therapy. A review of the literature suggests that leukoencephalopathy may be prevented by high doses of leucovorin and can be treated by high doses, if lower doses were used initially. When high dose leucovorin was not used, residual neurological damage is not unusual.
Adolescent↗
[Integration and reintegration of first admission psychiatric patients].
In the framework of a prospective follow-up study, development and outcome of the occupational and social status in 258 first-admission psychiatric patients was investigated. Interviews were made at the time of discharge, 1 year and 5 years later. For that reason prospective data exist on the prehospital and hospital time as well as on short-term and long-term course. Social adjustment, occupational rehabilitation, early retirement, social status and pre- and post-hospital occupational integration were investigated. It must be placed on record, that psychiatric patients are subjected to severe negative changes in their occupational and social life even after the first hospital treatment. Type and quantity of disintegration depended on the diagnostic group. Schizophrenic patients differed from the other patients in every intergration area.
Alcoholism↗
Characterization of the simian adenovirus type 30 inverted terminal repeat.
The presence of an inverted terminal repeat (ITR), which plays an important role in the initiation of DNA replication, is one of the characteristic properties of adenoviruses (Ads). We have established the nucleotide (nt) sequences for the ITR of simian adenovirus type 30 (SV30), a subgroup-III oncogenic virus. This repeat consists of 185 nt, representing the longest ITR found in an Ad so far. It contains multiple copies of internal repeats, as well as the consensus sequences of the putative binding sites for replication and transcription factors. The conserved features of the known ITRs are also found in SV30. Interestingly, the ITR of SV30 is more closely related to that of Ad5 (human), than to that of SA7 (simian).
Adenoviridae↗
Biologic and cytogenetic characteristics of leukemia in infants.
Clinical features, leukemic cell characterization, chromosomal findings, and treatment outcome were analyzed in a retrospective study of 30 cases with acute leukemia of infancy, 24 infants with acute lymphoblastic leukemia (ALL), and six cases with acute nonlymphoblastic leukemia (ANLL). Extensive bulky disease with organomegaly, central nervous system (CNS), and skin involvement were prominent features at diagnosis with a higher frequency in ANLL as compared to ALL. Four of six ANLL patients were classified as monocytic or myelomonocytic. In the ALL group nine of 24 (36%) were non-L1 morphology and six of 17 (33%) were common ALL antigen (CALLA) negative, the majority of them (five of six) were included in the non-L1 group. Immunophenotyping revealed four cases with early B-cell (three patients: Ia+B4+, and one patient: Ia+) and two cases with T-cell. Mixed lineage leukemia was found in five infants. Heavy chain immunoglobulin gene rearrangement was present in six cases tested, two CALLA+, two with Ia+B4+, and two were undifferentiated mixed lineage leukemia. Chromosomal aberrations were detected in ten of 18 patients, mostly in ANLL and CALLA negative ALL. Translocations were detected in six patients, involving 4q21-23 and 11q23 in three and two cases, respectively. The probability of five-year DFS were 27% for the whole group. The worst prognosis was observed in infants younger than 6 months of age, in whom the leukemia cell characteristics was compatible with stem cell: ANLL, very early pre-B, or undifferentiated mixed type. The chromosomal aberrations found in all cases included translocation with the seemingly nonrandom breakpoints at 4q21 and 11q23, and breakpoints that corresponded to known fragile sites. This finding may be suggestive of an underlying genetic predisposition associated with the poor prognosis of leukemia of infancy.
Female↗
Changing therapy from timolol to betaxolol. Effect on intraocular pressure in selected patients with glaucoma. Timolol-Betaxolol Study Group.
Three hundred fifty-three patients whose intraocular pressure was controlled with a timolol maleate ophthalmic solution were studied. Following a baseline period, half were switched (masked and randomized) to treatment with a betaxolol hydrochloride ophthalmic solution and were followed up for 12 weeks. Intraocular pressure, signs, and symptoms were recorded at weeks 1, 4, 8, and 12. Those patients switched to the betaxolol ophthalmic solution had a significant increase in both ocular side effects (burning/stinging and tearing) and intraocular pressure at weeks 4, 8, and 12 when compared with those patients who continued to receive timolol.
Adrenergic beta-Antagonists↗
Beneficial effects of ascorbic acid on preimplantation mouse embryos after exposure to cyclophosphamide in vivo.
To study mechanisms of embryotoxicity in early pregnancy, we have evaluated the genotoxic and embryolethal effects of ascorbic acid (AA) alone or in combination with cyclophosphamide (CPA). Female mice were exposed on day 3 of pregnancy. Embryotoxicity was investigated at term and genotoxicity shortly after treatment using the chromosomal aberration test and the sister chromatid exchange (SCE) assay as sensitive end points. Additionally, cytotoxic effects were determined by a proliferation test. AA was not found to be embryotoxic, cytotoxic, or genotoxic when given alone. In combination with 10 mg/kg CPA, however, which induced 50% aberrant metaphases, 100% increase SCE frequency, and a strong inhibition of cell proliferation, AA in a dose range of 25-1,600 mg/kg did not change SCE and proliferation, but reduced the rate of aberrant metaphases significantly. This anticlastogenic effect was clearly correlated to a beneficial effect on embryolethality at term when 200 mg/kg ascorbic acid was given in combination with 40 mg/kg CPA. The results suggest that during early pregnancy AA is not genotoxic even at so-called megadoses doses, but it seems to protect early embryos against damage induced by genotoxic agents like CPA.
Animals↗
Work and psychiatric illness: the significance of the posthospitalization occupational environment for the course of psychiatric illnesses.
The value of the reintegration and rehabilitation of inpatients vocationally was studied. Certain of the vocational experiences (unemployment and stressful working conditions) of former psychiatric inpatients were examined, with attention being paid to their stabilizing or destabilizing effect on symptomatic behaviour. A cohort of 230 first-time admissions for treatment of various disorders were interviewed while hospitalized and 1 year later. A 20-item list prepared by INFAS was used for indexing stressful working conditions. Psychopathological states were assessed with the help of the Present State Examination of Wing et al. (1973). The results indicate that mentally ill persons (especially those with organic or affective disorders), when confronted with unemployment after discharge from hospital, will usually respond by developing new or worse syndromes. Stressful working conditions appear to have very different effects in schizophrenia and affective disorders, viz. deterioration and amelioration of psychopathological syndromes respectively.
Humans↗
Overview of efficacy and local tolerability of a new timolol/pilocarpine combination.
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Administration, Topical↗