Neural migration, pro-inflammatory interleukins and periventricular leukomalacia: involvement in schizophrenia.
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Brain↗
Biomedical subjects
M Huttunen
Publications and source records attributed to M Huttunen.
Cultured allogeneic skin cells are effective in the treatment of chronic diabetic leg and foot ulcers.
Diabetic ulcers on the lower extremities present a difficult treatment problem, and some ulcers respond poorly to conventional topical and cast treatment. The purpose of this study was to assess the effect of cultured allogeneic keratinocyte epithelium and fibroblast-gelatin sponge on the healing of chronic, refractory diabetic leg and foot ulcers. Non-diabetic chronic leg ulcers were treated for comparison. This open study comprised 22 patients with type I or type II diabetes and 16 patients with leg or ankle ulcers of different aetiologies. A total of 26 diabetic and 25 non-diabetic ulcers were treated mainly with keratinocyte epithelium and/or fibroblast-gelatin sponge once weekly until complete healing or until no further healing could be observed despite several repeated treatments. The duration of diabetic ulcers was 10.3+/-15.8 (mean+/-SD) months and the size 3.1+/-6.6 cm2. The diabetic ulcers were located in the heel (7), toe (7), sole (5), leg (6) and Achilles (1). The mean duration of non-diabetic ulcers was 6.8+/-6.0 months and the size 10.5+/-11.8 cm2. A total of 12+/-11 skin cell transplantations were performed for the diabetic ulcers. All but 1 diabetic ulcer healed during the study. The time for 50% reduction in ulcer area was 32+/-32 days, but 99+/-110 days were needed for complete ulcer closure. The longer the ulcer had existed the longer was the healing time. Heel ulcers showed significantly slower healing response than leg, sole and toe ulcers. Preliminary results suggest that both keratinocytes and fibroblasts are equally effective in the healing process. The time required for healing of the diabetic ulcers did not differ markedly from that of the non-diabetic ulcers. The results suggest that cultured allogeneic skin cells used once weekly are effective in the treatment of recalcitrant diabetic ulcers.
Adult↗
The genetic epidemiology of schizophrenia in a Finnish twin cohort. A population-based modeling study.
BACKGROUND: The magnitude of heritability of schizophrenia remains controversial, due in part to limitations of estimates derived from index twin pairs exclusively. We applied structural equation modeling in a total population of twins to determine the significance and magnitudes of the genetic and environmental contributions to schizophrenia. METHODS: All monozygotic (1180 male and 1315 female pairs) and same-sex dizygotic (2765 male and 2613 female pairs) twins born from 1940 to 1957 in Finland were screened for nonorganic psychotic disorder diagnoses as recorded on an inpatient or outpatient basis or from an eligibility review for a disability pension. RESULTS: The lifetime prevalence of schizophrenia was 2.0%, with a marginally higher prevalence in men (2.2%) than women (1.8%). Model fitting indicated that 83% of the variance in liability was due to additive genetic factors, and the remaining 17% was due to unique environmental factors. Sex-limitation modeling revealed no evidence of sex-specific genetic effects and no sex difference in the magnitude of heritability. A multiple threshold model incorporating affective and other psychoses as a phenotype intermediate between schizophrenia and no diagnosis was rejected. CONCLUSIONS: In a population-based twin study of schizophrenia, heritability was estimated at 83%, with the remaining variance in liability attributed to environmental factors not shared in common among co-twins. Despite the notable limitation of using diagnoses ascertained through treatment contacts, the heritability estimate in this study is almost identical to those reported in recent studies of index pairs using standardized applications of DSM-III or later criteria.
Adult↗
Regional gray matter, white matter, and cerebrospinal fluid distributions in schizophrenic patients, their siblings, and controls.
BACKGROUND: Cortical gray matter volume reductions and cerebrospinal fluid (CSF) volume increases are robust correlates of schizophrenia, but their sources have not been established conclusively. METHODS: Structured diagnostic interviews and magnetic resonance imaging scans of the brain were obtained on 75 psychotic probands (63 with schizophrenia and 12 with schizoaffective disorder), ascertained so as to be representative of all such probands in a Helsinki, Finland, birth cohort; 60 of their nonpsychotic full siblings; and 56 demographically similar control subjects without a personal or family history of treated psychiatric morbidity. RESULTS: Patients with schizophrenia and their siblings exhibited significant reductions in cortical gray matter volume and significant increases in sulcal CSF volume compared with controls. The patients, but not their siblings, also exhibited significant reductions in white matter volume and significant increases in ventricular CSF volume. Regional effects were most robust when component volumes were expressed as percentages of overall regional volumes; in this case, for patient and sibling groups, gray matter volume reductions and sulcal CSF volume increases were significantly more pronounced in the frontal and temporal lobes than in the remainder of the brain. None of the group differences varied significantly by sex or hemisphere. CONCLUSIONS: Structural alterations of the cerebral cortex, particularly in the frontal and temporal lobes, are present in patients with schizophrenia and in some of their siblings without schizophrenia; such changes are thus likely to reflect genetic (or shared environmental) effects. Ventricular enlargement is unique to the clinical phenotype and is thus likely to be affected primarily by nonshared causative factors.
Adult↗
Functional changes in back muscle activity correlate with pain intensity and prediction of low back pain during pregnancy.
OBJECTIVE: To assess low back pain (LBP) intensity and subjective disability during pregnancy and compare the pain scores with lumbar motion patterns. DESIGN: A prospective study of pregnant back pain sufferers and healthy controls. SETTING: Kuopio University Hospital, Kuopio, Finland. PARTICIPANTS: Study group consisted of 32 pregnant women with LBP; control group consisted of 21 healthy pregnant women. MAIN OUTCOME MEASURES: Back pain intensity was assessed by visual analog scale (VAS), and subjective disability index was measured by Oswestry Low Back Disability Questionnaire, at 20 and 36 weeks of pregnancy. Back muscle activities were recorded by surface electromyography, and movement sensors were used to detect lumbar motion. RESULTS: In the study group current pain scores (VAS) at first and last trimester correlated strongly (r = .82, p < .00). Pain scores correlated with body weight at the first trimester (r = .54, p = .003) and at the last trimester (r = .67, p < .00). Significant correlation was noted between current pain intensity and back muscle activity level during forward body flexion at first trimester (r = .704, p < .00). Back muscle activity during bending measured at first trimester significantly correlated with pain intensity at last trimester (r = .703, p < .00). Back muscle activity during the first trimester of pregnancy had a negative correlation with current (r = -.57, p = .002) and later subjective disability index (r = -.42, p = .02). It correlated inversely (r = -.54, p = .003) with pain score at last trimester of pregnancy, ie, the lower the back muscle activity at the beginning of pregnancy, the more pain and disability throughout pregnancy. In the control group, three women developed LBP and disability feelings during pregnancy. They had increased muscle activity during flexion at delivery, ie, disturbed flexion relaxation. CONCLUSIONS: Prepregnancy LBP predicts renewed pain during pregnancy, and dysfunction of back muscles has been established in LBP. In this study, disturbance in the relaxation of the back muscles was linearly related to current, and also to later, pain scores. In addition, back muscle activity level was inversely related to the disability index. For the first time, it has been shown prospectively that the function pattern of back extensors seems to predict, and is related to, future back pain. Simple function testing is promising and might be valuable in identifying mothers with a high risk of pregnancy-related back pain and in directing preventive intervention to high risk women by making them aware of self-treatment methods.
Activities of Daily Living↗
Association between HLA-A1 allele and schizophrenia gene(s) in patients refractory to conventional neuroleptics but responsive to clozapine medication.
We report an association between HLA-A1 allele and a subgroup of schizophrenic patients refractory to conventional neuroleptic treatment but responsive to clozapine. The frequency of HLA-A1 was 58% among the schizophrenic patients not responding to conventional treatment but responsive to clozapine but only 10.5% among the patients responding to conventional neuroleptics. The HLA-A1 occurs in 20% of the random Finnish population. Our results indicate that HLA-A1 defines a subgroup of schizophrenic patients with a selective response to neuroleptics.
Adult↗
Neuropeptide- and capsaicin-induced histamine release in skin monitored with the microdialysis technique.
Mast cells are thought to be involved in neurogenic inflammation in skin, and numerous neuropeptides are known to degranulate mast cells. We monitored histamine release in skin in situ with the microdialysis method after skin challenge with neuropeptide injections (10 microM substance P, vasoactive intestinal peptide and calcitonin gene-related peptide), capsaicin injection (30 microM) and 0.1% capsaicin cream with a moist compress. Fractions were collected for 15 min each at 3.0 microliter/min. One hour after insertion of the probe, the baseline histamine level was 4.5 +/- 4.5 nM (mean +/- SD, n = 20). Substance P (250 pmol) induced histamine release peak (66.1 +/- 52.5 nM, n = 8) in the 0-15 or 15-30 min fraction. Thereafter, the histamine concentration declined steadily and rapidly and no second rise was observed. A single substance P injection was sufficient to induce major histamine release in three out of four experiments; and the release kinetics of the second injection (1 h later) mimicked that of the first injection. Vasoactive intestinal peptide (100 and 250 pmol) induced a rapid release of histamine in 4 subjects comparable to substance P, whereas calcitonin gene-related peptide (250 pmol) did not release detectable amounts of histamine in 2 subjects tested. Capsaicin induced a low and rather non-significant release of histamine in 4 out of 5 patients who received capsaicin injection and in 2 out of 5 who were treated with capsaicin cream. The present study shows that neuropeptides substance P and vasoactive intestinal peptide, but not calcitonin gene-related peptide, can induce activation of mast cells and release of histamine into the extracellular space. The low release of histamine by capsaicin suggests low levels of neuropeptides or infrequent morphological contacts between mast cells and sensory nerves in normal human skin. The microdialysis method can be used for studying skin inflammatory reactions involving mast cells.
Adult↗
Comparison of sotalol with digoxin-quinidine for conversion of acute atrial fibrillation to sinus rhythm (the Sotalol-Digoxin-Quinidine Trial).
We randomized 61 patients with paroxysmal atrial fibrillation (AF) ( < 48 hours from onset) to either sotalol or quinidine treatment. Conversion of rhythm was recorded by Holter monitoring. The starting 80 mg dose of sotalol was repeated at 2, 6, and 10 hours if AF persisted (heart rate > 80 beats/min), and if systolic blood was > or = 120 mm Hg. In the quinidine group, if heart rate > 100 beats/min, it was decreased with intravenous digoxin, whereafter 200 mg of oral quinidine sulfate was given maximally 3 times, each dose 2 hours apart. Conversion of AF to sinus rhythm occurred in 17 or 33 patients (52%) taking sotalol, and in 24 of 28 patients (86%) taking quinidine (p < 0.0001). Electric cardioversion was necessary in 39% of the former and in 14% of the latter group. The mean delay from first trial drug to sinus rhythm with the trial medication was 10.2 +/- 7.6 hours in the sotalol group and 4.0 +/- 2.9 hours in the quinidine group (p < 0.01). Treatment was discontinued in 16 patients taking sotalol (48%) because of asymptomatic bradycardia or hypotension, and in 20 taking quinidine (71%) because of rhythm conversion. Asymptomatic wide complex tachycardia (QRS > 0.12 second) was found in 13% and 27% of patients taking sotalol and quinidine, respectively. The longest RR intervals were 6.4 and 3.8 seconds in the sotalol and quinidine groups, respectively. Oral sotalol did not appear as effective as quinidine sulfate treatment in conversion of paroxysmal AF.(ABSTRACT TRUNCATED AT 250 WORDS)
Acute Disease↗
The evolution of the serotonin-dopamine antagonist concept.
Before the dopamine hypothesis of schizophrenia became established, a serotonin (5-hydroxy-tryptamine) 5-HT hypothesis was popular. This was based on the hallucinogenic properties of lysergic acid diethlyamide and abnormal serotonin levels in schizophrenics. Suggestions that serotonin might be involved in the cause of schizophrenia or could be a target for antipsychotic drug action began with the discovery that the antipsychotic agent clozapine is a potent serotonin 5-HT2A antagonist, as well as being a dopamine D2 antagonist. This led to the formulation of the serotonin-dopamine antagonist (SDA) concept for antipsychotics, with wider spectrums of activity and lower extrapyramidal side effects (EPS) liability. The principle of the SDAs is that the drug should be a potent serotonin 5-HT2A antagonist, with slightly less potent dopamine D2 receptor-blocking properties. The clinical experience with risperidone, the first member of the new class of antipsychotics, seems to offer the promise that the SDAs have significant advantages over both the conventional dopamine-blocking neuroleptics and the atypical antipsychotic clozapine. Risperidone has efficacy against both the positive and negative symptoms of schizophrenia and has a low tendency to produce EPS. Only time will tell whether other SDAs will have the same advantages.
Antipsychotic Agents↗
Puerperal endometritis after abdominal twin delivery.
The infectious complications of 122 consecutive abdominal twin deliveries over the period 1984-1989 were analyzed in a prospective clinical study, comparing them with 761 singleton abdominal deliveries over the period 1984-1986. The incidence of endometritis was nearly three-fold after twin deliveries and the incidence of abdominal wound infections nearly two-fold compared with singleton abdominal pregnancies (13.1/4.7% and 5.6/3.0%). The risk of amnionitis was increased ten-fold, 6 hours after rupture of the membranes in abdominal twin delivery, but no connection was found between amnionitis and endometritis, as in singleton abdominal deliveries. Multiple regression analysis indicated only two risk factors as regards puerperal endometritis after abdominal twin delivery: age under 25 years (odds ratio 6.9, 95% confidence limits 1.9-24.8), an association also seen in singleton abdominal deliveries, and a period of more than 6 hours from rupture of membranes to delivery (odds ratio 7.8, 95% confidence limits 2.1-28.5). Multiple pregnancy appears to be associated with an increased risk of endometritis. The etiological factors remain unknown, but a large placental bed and/or immunological factors may be implicated.
Cesarean Section↗
[Does professional sports need psychiatry?].
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Adolescent↗
Cytomegalovirus hepatitis in late pregnancy.
A case of pregnancy complicated by cytomegalovirus hepatitis is represented. The mother had a fulminant disease, but she delivered spontaneously at 31 weeks of gestation. The baby was unaffected.
Adult↗
Which anti-hypertensive to add to a beta-blocker: ACE inhibitor or diuretic?
Thirty-eight patients already treated with atenolol 50 mg once daily were randomly assigned to treatment with either hydrochlorothiazide (12.5-25 mg once daily) or lisinopril (10-20 mg once daily) for 8 weeks in a double-blind crossover study. Eight weeks' treatment with the combination of ACE inhibitor and beta-blocker or the diuretic and beta-blocker produced falls in blood pressure (lying: -8.4 +/- 15.4/ -7.3 +/- 80 mmHg and -6.1 +/- 15.3/ -5.2 +/- 8.8 mmHg [mean +/- SD] for lisinopril and hydrochlorothiazide respectively; standing: -10.2 +/- 14.2/8.2 +/- 9.2 mmHg and -6.8 +/- 14/ -6.3 +/- 10.3 mmHg for lisinopril and hydrochlorothiazide respectively) which were not statistically significantly different. Heart rate was significantly increased on the combination of beta-blocker and diuretic (lying: +4.3 +/- 10.7; standing: +3.2 +/- 10.0 beats/min) compared with a fall on beta-blocker+ACE inhibitor (lying; -0.5 +/- 7.6; standing: -1.5 +/- 7.4). Both therapeutic regimens were equally well tolerated. These results suggest that where patients fail to respond to monotherapy with a beta-blocker the addition of an ACE inhibitor may be as effective as the more traditional option of diuretic therapy.
Adolescent↗
Enoxacin treatment of urinary tract infections in elderly patients.
Sixty-seven elderly patients (61 female, six male) with a mean age of 82 years (range 67-95) were orally treated for 4-14 days with enoxacin (200 or 400 mg bd) for urinary tract infections in a non-comparative open study. Fifty-three patients had features of pyelonephritis, and 17 had indwelling catheters. Clinical and bacteriological assessments were made on day 0, between days 2 and 4, at the end of therapy, 5-9 days post-treatment. Patients whose response continued to be satisfactory were re-examined 4-6 weeks after the last dose. In 20 patients enoxacin concentrations were measured in samples of urine and serum during the study. Enoxacin therapy eliminated the causative pathogens in 98.5% of the patients after 2-4 days treatment and in 100% at the end of therapy. Overall results at the end of treatment were good or excellent in 84% of patients. Sixty patients (90%) at 5-9 days follow-up had a satisfactory response (51 had complete eradication of pathogen and nine re-infection). At 4-6 weeks follow-up, 46 patients (69%) remained completely infection free. Side effects of therapy were, in general, mild or moderate although four patients, all of whom had a history of cerebrovascular disturbance, suffered convulsions during study.
Aged↗
Serum lipid changes in a one-year, multicenter, double-blind comparison of doxazosin and atenolol for mild to moderate essential hypertension.
Proatherogenic changes in serum lipid concentrations have been implicated as one of the major risk factors in the development of coronary artery disease. In a double-blind study, the new alpha 1-adrenoceptor inhibitor, doxazosin, was compared with atenolol for effects on the serum lipid profile. Ninety-six hypertensive patients were treated for up to 1 year with either doxazosin or atenolol once daily. There were statistically significant differences (p less than or equal to 0.01) between doxazosin and atenolol after 20 to 52 weeks of treatment in changes from baseline total triglyceride levels, high density lipoprotein (HDL) cholesterol levels and HDL/total cholesterol ratio. The percentage of change from baseline and the statistical significance of the difference between treatment groups were: total triglycerides, doxazosin -5.9%, atenolol +32.4% (p = 0.01); HDL cholesterol, doxazosin +7.2%, atenolol -5.6% (p = 0.007) and HDL/total cholesterol ratio: doxazosin +8.7%, atenolol -6.2% (p = 0.006). All mean changes were in favor of doxazosin therapy. In addition, doxazosin treatment beneficially decreased total serum cholesterol levels (-1.6%) compared with atenolol (+0.6%), although not to a significant degree. The differences were maintained in the cohort of 67 patients treated for a full year. The favorable change exerted by doxazosin on the lipid profile suggests that it may have a beneficial influence on the lipid risk factor. These results, together with the sustained decrease in blood pressure achieved for up to 1 year of therapy, suggest that doxazosin may reduce the risk of coronary artery disease in susceptible patients.
Adrenergic alpha-Antagonists↗
A long-term double-blind comparison of doxazosin and atenolol in patients with mild to moderate essential hypertension.
The efficacy and safety of doxazosin and atenolol were compared following once-daily administration for up to 1 year, with a minimum of 20 weeks' active treatment. According to response, patients received doxazosin 1-16 mg day-1 or atenolol 50-100 mg day-1. Mean daily doses at the final efficacy assessment (between 20 weeks and 1 year) were doxazosin 11.8 mg and atenolol 94.2 mg. Atenolol produced somewhat greater falls in blood pressure than doxazosin. The differences were statistically significant in the supine but not in the standing position. A small mean reduction in heart rate was produced by doxazosin whereas atenolol produced a marked bradycardia. Analysis of the same patient group at 20 weeks revealed similar overall profiles of activity except that atenolol produced greater falls in blood pressure than in the longer term analysis. Serum concentrations of HDL/total cholesterol ratio were raised in the doxazosin treatment group and lowered in the atenolol group. Triglyceride concentrations fell in the doxazosin group and rose in the atenolol group. Significant differences (P less than 0.001) were observed between treatment groups for these parameters, all differences being in favour of doxazosin. Pharmacokinetics of doxazosin, measured at steady state in 36 patients, showed dose-related plasma concentrations, a mean half-life of about 12 h and relatively low intersubject variation. The incidence of side-effects was slightly greater for patients in the doxazosin group. Drug-related side-effects were mostly mild to moderate in severity with no serious drug-related occurrences in either treatment group. No serious drug-related abnormalities in laboratory biochemistry and haematology tests were observed in either treatment group.
Adult↗
[Developments in psychiatric diagnosis].
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Humans↗
Reduced level of cellular glucocorticoid receptors in patients with anorexia nervosa.
Specific glucocorticoid receptors were measured in circulating mononuclear leukocytes from 12 patients with anorexia nervosa and 21 healthy control subjects. Cells from patients were found to contain a significantly (p less than 0.01) lower level of glucocorticoid receptor (3830 +/- 210 sites/cell, mean +/- SE) than those from controls (4930 +/- 250 sites/cell). A partial glucocorticoid receptor defect may well explain the abnormal cortisol metabolism and glucocorticoid resistance commonly found in patients with anorexia nervosa.
Adolescent↗