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Biomedical subjects

G N Smith

Publications and source records attributed to G N Smith.

At least 55 records · Page 3Linked to original sources
PubMed1997

Increased incidence of preeclampsia in women conceiving by intrauterine insemination with donor versus partner sperm for treatment of primary infertility.

OBJECTIVE: Reports suggest that there is an increased incidence of preeclampsia after a previously normal pregnancy if there is a change in paternity. We hypothesize that there is a higher incidence of preeclampsia (proteinuric hypertension) in women conceiving by intrauterine insemination with donor sperm versus intrauterine insemination with partner sperm. STUDY DESIGN: This was a retrospective cohort study. In women with primary infertility all pregnancies achieved by either partner or donor intrauterine insemination carried to birth of a fetus (> 20 weeks) were identified. The medical records were examined for the maternal and pregnancy outcome data. The relative risk and 95% confidence interval were calculated for the risk of preeclampsia. The baseline data were compared with t tests, chi 2 analysis and Fisher's exact test where appropriate. RESULTS: Forty-four patients in the partner intrauterine insemination group and 37 in the donor insemination group were identified as having primary infertility. Three cases of mild preeclampsia were found in the partner insemination program and nine cases of preeclampsia (five severe, four mild) in the donor insemination program (relative risk 1.85, 95% confidence interval 1.20 to 2.85). CONCLUSIONS: There is a higher incidence of preeclampsia in women conceiving by intrauterine insemination with washed donor sperm compared with intrauterine insemination with washed partner sperm. This supports, indirectly, an immunologic basis for preeclampsia. The antigenic factor would appear to be located on the sperm as opposed to the seminal fluid itself.

Cesarean Section↗
PubMed1997

A comprehensive method of assessing routine CT scans in schizophrenia.

Morphological brain abnormalities are common in schizophrenia, although the aetiological and clinical significance of these findings is largely unknown. Substantial between-subject variability suggests that large samples are needed to study the full implications of brain pathomorphology. Computerized tomography (CT) is frequently used routinely in schizophrenia, and large numbers of scans are available for study. This article describes the development and statistical properties of a rapid and simple method of assessing CT scans. The CT Rating Scale for Schizophrenia (CTRSS) is minimally affected by variability in scanning procedures, is reliable, and accurately estimates area and volumetric measures of brain spaces. By promoting the comprehensive assessment of large numbers of routinely obtained scans, the CTRSS would allow the investigation of variables that may systematically affect results (e.g. gender and age) and variables with low prevalence. The CTRSS provides a useful adjunct to technologically more sophisticated methods of assessment such as magnetic resonance imaging (MRI).

Adult↗
PubMed1997

Inhibition of recombinant human neutrophil collagenase by doxycycline is pH dependent.

OBJECTIVE: To examine, as part of an evaluation of the role of matrix metalloproteinase (MMP) inhibition in the amelioration of cartilage damage by doxycycline, the effect of pH on the inhibition of activity and reduction in stability of recombinant human neutrophil collagenase (rhMMP-8) by doxycycline in vitro. METHODS: After activation with trypsin, rhMMP-8 was assayed using a peptolide substrate and a colorimetric assay. The rate of hydrolysis in the presence and absence of 30 microM doxycycline was measured over a pH range of 6.5-7.9. The molecular weight changes that accompanied activation of the proenzyme by acetylphenylmercuric acetate (APMA) in the presence and absence of doxycycline at pH 6.9 and 7.5 were studied by Western blotting. RESULTS: At pH values above 7.1, doxycycline inhibited the activity of the enzyme. At pH values below 7.1, no inhibition was observed. When doxycycline was present during activation with APMA at pH 7.5, significant amounts of small (< 30 kDa) fragments were generated. In contrast, when doxycycline was present during activation with APMA at pH 6.9, no small fragments were detected. CONCLUSION: The ability of doxycycline to inhibit matrix rhMMP-8 activity or to promote its degradation is lost at pH values lower than 7. Although relatively high pH values may exist in adult articular in some pathological situations, at lower pH the effect of doxycycline on proenzyme levels in the extracellular matrix may be due to an effect on the regulation of synthesis of the proenzyme, rather than to direct inhibition of the active enzyme or reduction in the level of enzyme by proteolysis.

Anti-Bacterial Agents↗
PubMed1996

Obstetric complications and age-related changes in brain morphology in schizophrenia.

Birth problems can lead to changes in brain morphology in the general population and an increased prevalence of both birth problems and altered brain morphology are found in patients with schizophrenia. The purpose of this study was to test the hypothesis that these two findings are related. Birth history and the size of ventricular and sulcal spaces from nine regions of the brain were assessed in 80 male subjects with schizophrenia. No differences were found between patients with and those without a history of birth problems for the size of any brain space; however, ventricular size increased significantly with age in patients who had no birth complications but not in patients with a history of birth problems. The size of cortical sulci increased with age in patients with and those without a history of birth problems. These results suggest that region-specific rates of change in size may identify clinically meaningful patients subgroups.

Adolescent↗
PubMed1996

The sonographic finding of persistent umbilical cord cystic masses is associated with lethal aneuploidy and/or congenital anomalies.

Advancements in sonographic technology have led to improved prenatal detection of fetal anomalies. Umbilical cord cystic masses are being detected prenatally and several case reports have appeared in the literature. We report three new cases in which umbilical cord cystic masses were detected prenatally; two cases in the later half of pregnancy and one case in the first trimester. The literature was reviewed and summaries of the 23 reported cases of persistent second- and third-trimester umbilical cord cystic masses and their implications are discussed. There is a high association (18 of 23 cases) with lethal chromosomal anomalies and/or congenital malformations suggesting that the finding of an isolated umbilical cord cystic mass should lead to further detailed sonographic evaluation.

Adult↗
PubMed1996

Activation of recombinant human neutrophil procollagenase in the presence of doxycycline results in fragmentation of the enzyme and loss of enzyme activity.

OBJECTIVE: To determine if reduction of collagenase activity in vitro by doxycycline (doxy) is related to activation of the proenzyme, and to determine how exogenous Ca++ and Zn++ affect the reduction. METHODS: Recombinant human neutrophil procollagenase was activated with trypsin or APMA. Activity was assayed on a small peptolide substrate or on 14C-acetylated collagen fibers. The molecular weight of the proenzyme, active enzyme, and enzyme fragments was determined by Western blotting, using a polyclonal antiserum raised against the recombinant proenzyme. Similar experiments were performed in the presence of EDTA, EGTA, 1,10-phenanthroline, or doxy. The effects of exogenous Ca++ and Zn++ were also tested. RESULTS: Doxy inhibited activity of the enzyme against both substrates. If the drug was present during activation, the yield of activity was lower than when it was added after activation of the proenzyme. Western blotting showed that activation in the presence of doxy resulted in the appearance of lower molecular weight fragments and accumulation of less active enzyme. APMA generated prominent 28- and 26-kd fragments while trypsin cleavage yield 40- and 30-kd fragments. Fragmentation of the enzyme also occurred in the presence of EDTA or EGTA, but not 1,10-phenanthroline. It was prevented by Ca++ concentrations greater than 50 mM, but was not altered by addition of Zn++ in concentrations as high as 500 microM. Inhibition of collagenase activity by doxy could be overcome by 100 mM Ca++, but addition of Zn++ had no effect. CONCLUSION: These data suggest that doxy alters the conformation of procollagenase or collagenase by binding enzyme-associated Ca++, rendering the proteins more susceptible to proteolysis and resulting in irreversible loss of enzyme protein.

Calcium↗
PubMed1995

The temporal lobes, reversed asymmetry and the genetics of schizophrenia.

Mechanisms determining temporal lobe structural asymmetries may be involved in the pathogenesis of schizophrenia. To investigate the temporal lobes in familial schizophrenia, computed tomographic scans were obtained from 51 subjects (seven families). Enlargement of sylvian fissures and temporal lobe sulcal spaces was observed in family members with schizophrenia. The posterior one-third of the sylvian fissure was larger on the left side in subjects with schizophrenia, and larger on the right side in unaffected individuals. This disturbed pattern of posterior sylvian fissure asymmetry suggests that adjacent language regions may be affected in schizophrenia. An intermediate degree of disturbance in subjects who had schizophrenia-related illnesses or were obligate carriers suggests that genetic factors may be important determinants of temporal lobe asymmetries in familial schizophrenia.

Adult↗
PubMed1995

Developmental abnormalities and cortical sulcal enlargement in psychosis.

Neurodevelopmental abnormalities and cortical sulcal enlargement both occur in schizophrenia. To test the hypothesis that these abnormalities were related, CT scans from 164 psychotic patients (80 with schizophrenia) were reviewed. Neurodevelopmental abnormalities were observed in 11%. Abnormalities were equally prevalent in schizophrenia and other psychotic disorders. Cortical sulcal enlargement was observed in 39% of patients with schizophrenia, and was not associated with developmental abnormalities. Different mechanisms may contribute to distinct structural abnormalities.

Adolescent↗
PubMed1995

Methyldopa hepatotoxicity in pregnancy: a case report.

A case of hepatotoxicity in a multiparous Native woman, who was begun on a regimen of methyldopa for control of chronic hypertension, is described. The patient was first seen for clinical evidence of hepatotoxicity approximately 3 weeks after initiation of treatment. At presentation the aspartate aminotransferase level was 1800 IU/L and alanine amniotransferase was 2415 IU/L. There was also a significant prolongation of clotting time, which required therapy. Resolution of symptoms occurred after cessation of the medication. Although methyldopa is considered to have a wide margin of safety in the treatment of chronic hypertension in pregnancy, potentially serious adverse effects can occur. It is important to monitor serum aminotransferase levels after initiation of methyldopa therapy.

Adult↗
PubMed1995

Regional cortical anatomy and clozapine response in refractory schizophrenia.

Regional measures of cortical sulcal and ventricular enlargement on computed tomography scan were studied in a clinical sample of patients treated with clozapine. Cortical sulci were significantly enlarged in clozapine nonresponders compared to responders. The Clinical Global Impressions score at discharge was related to the size of the posterior frontal and lateral temporal sulci, with large sulci predicting a poorer response to clozapine treatment.

Adult↗
PubMed1995

Obstetric complications and severity of illness in schizophrenia.

A history of obstetric complications (OCs) is common in schizophrenia and may lead to a severe form of the disorder. In order to test this possibility, three questions were identified: (1) Is a history of OCs in schizophrenia common in patients with a severe form of illness? (2) Do patients with OCs have more impaired function, greater severity of illness, and poorer treatment outcome than those with no identified OCs? (3) Are OCs associated with an early age at onset of illness? Obstetric history, clinical indices of functioning, and illness severity were obtained for 83 severely ill patients with schizophrenia. The proportion of patients with a history of OCs was greater in this study than has been reported previously. Subjects with a history of OCs had better functioning than those with no OCs at the time of admission but no group differences were found at discharge. No difference in age at onset of illness was found between patients with and without an OC history.

Activities of Daily Living↗
PubMed1995

Comparative study of sodium nitroprusside induced vasodilation of human placental veins from premature and full-term normotensive and preeclamptic pregnancy.

The objective of this study was to determine whether nitrovasodilator (nitric oxide donor) drug induced relaxation is different between preeclamptic and normotensive pregnancy. Human placental veins were collected at the time of delivery from normotensive (n = 6 premature, n = 6 full term) and preeclamptic (n = 6 premature, n = 3 full term) women and cut into rings. Cumulative concentration-response curves were performed on 5-hydroxytryptamine-contracted rings for the nitrovasodilator agent, sodium nitroprusside (SNP). The EC50 values were determined from the SNP concentration-response curves of the individual subjects, and were compared across gestational age and between preeclamptic and normotensive pregnancy by two-way ANOVA. There was no difference in the SNP EC50 values for normotensive and preeclamptic human placental veins in either the premature or full-term study groups. However, for both normotensive and preeclamptic pregnancy, the SNP EC50 value for full-term placental vein was greater than that for premature tissue. The sensitivity of human placental veins to SNP is similar between preeclamptic and normotensive pregnancy at similar gestational ages, but is increased in premature compared with full-term pregnancy in both preeclamptic and normotensive pregnant women.

Child, Preschool↗
PubMed1995

A clinical study of clozapine treatment and predictors of response in a Canadian sample.

OBJECTIVE: To study the clinical response to clozapine in patients with refractory schizophrenia. METHOD: Open trial of clozapine in 61 consecutively-treated patients. RESULTS: Following clozapine, the level of function of patients was improved relative to admission (p = 0.0001) and to the highest level in the previous year (p = 0.0001). Severity of illness was decreased (p = 0.0001). Overall, 31% of the patients were classified as responders to clozapine and the responders were all identified by 32 weeks of treatment. Poor functioning in the previous year was associated with less favourable response. At a mean interval of 26 months following discharge, 72% of the patients were continuing clozapine treatment. CONCLUSIONS: This open trial of patients who were treated consecutively indicates a comparable degree of response to clozapine as observed in controlled clinical trials, and that level of functioning in the previous year was the best predictor of response.

Adolescent↗