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Biomedical subjects

J McGrath

Publications and source records attributed to J McGrath.

At least 73 records · Page 4Linked to original sources

Co-occurrence of executive impairment and amnesic syndrome following sub arachnoid haemorrhage: a case study.

This case study presents a 37 year old man, P.P., who shows evidence of both profound executive impairment and diencephalic amnesia associated with two discrete lesion sites following a Sub Arachnoid Haemorrhage. The executive impairment is unusual in type and severity, amounting to a gross impairment in the initiation and organisation of action. The thalamic lesion provides a rare example of diencephalic damage resulting in an extensive retrograde amnesia of the type that is often associated with Korsakoff's syndrome, but which in this case is not associated with prolonged alcohol abuse. Some of the problems caused by the co-occurrence of two such profound and disabling impairments are discussed.

Adult↗

Training for Norplant implant removal: assessment of learning curves and competency.

OBJECTIVE: To determine the learning curves and rapidity with which clinicians become competent in implant removal using two Norplant removal techniques. METHODS: Twenty-four physicians, none of whom were experienced in the use of Norplant implants, were randomly assigned to learn either the "U" removal technique or the standard technique. The physicians in the two groups received identical training in all other respects. Each physician then performed ten supervised removals. Removal times, procedure problem rates, and the number of procedures performed by the clinicians before they were judged "competent" were assessed for both groups. RESULTS: Data from 240 removals were analyzed. Mean removal times were 38% faster in the "U" group than in the standard group. None of the "U" group procedures took longer than 20 minutes, compared with 11% of removals in the standard group (P < .001). The mean number of cases required before the provider consistently performed all steps adequately was significantly (P < .02) higher in the standard group (5.8 cases) than in the "U" group (3.9 cases). CONCLUSIONS: Using competency-based training methods, the "U" removal technique was learned easily by inexperienced clinicians. It appears to offer significant improvements in speed and achievement of proficiency over the standard technique recommended by the manufacturer. Large-scale programs should consider using competency-based training and the "U" technique as the removal method of choice when providing training in implant removal.

Clinical Competence↗

Ocular abnormalities in chronic schizophrenia: clinical implications.

OBJECTIVE: As part of a randomised double-blind study of a new atypical antipsychotic we sought to determine both the levels of visual acuity and the occurrence of toxic side-effects in a group of patients treated for many years on a variety of antipsychotics. METHODS: Twenty-three inpatients with a DSM-III-R diagnosis of chronic schizophrenia from two separate hospital locations who met the criteria for the double-blind trial were examined for ocular abnormalities at both baseline and at trial completion. RESULTS: At baseline a high prevalence of abnormalities was identified: 19 patients (82.6%) were found to have one or more ocular abnormalities, including lens opacities/cataracts and corneal pigmentation; three patients, with delusions related to the sun, were noted to have solar burns; a high proportion (almost 70%) of patients had untreated visual acuity problems. No further changes were observed at the follow-up examinations. CONCLUSIONS: The possible causes of ocular disturbance in schizophrenia and the reasons for the relatively high ocular morbidity in this group are thought to result from both illness-related factors and the effects of antipsychotic medication. Causality is confounded by a number of issues such as the high prevalence of smoking, poor general health and the variety of antipsychotic medications used in the treatment of psychosis as well as substance abuse. The clinical implications are considered in this paper in relation to the move towards community-based psychiatric services.

Adult↗

Detection of novel LAMC2 mutations in Herlitz junctional epidermolysis Bullosa.

BACKGROUND: Laminin 5, an anchoring filament attachment protein within the lamina lucida of the basement membrane zone involved in the pathogenesis of junctional epidermolysis bullosa (JEB), consists of three polypeptide subunits, the alpha 3, beta 3, and gamma 2 chains which are encoded by the LAMA3, LAMB3, and LAMC2 genes, respectively. To facilitate identification of pathogenetic mutations in LAMC2, a strategy based on direct amplification of genomic DNA by PCR or mRNA by RT-PCR, followed by heteroduplex analysis of the PCR products, was developed. MATERIALS AND METHODS: Primer pairs for amplification of the complete cDNA as well as the 23 individual exons in the genomic DNA, which encode the entire gamma 2 chain of laminin 5, were established. The primers for amplification of exons from genomic DNA were positioned at least 24 bp away from the intron-exon borders in the flanking intronic sequences. For amplification of cDNA generated by RT-PCR, eight primer pairs covering overlapping segments of the entire coding sequence of LAMC2 mRNA were used. The amplified sequences were scanned for pathogenetic mutations and sequence variations in JEB patients and unrelated control individuals by heteroduplex analysis by means of conformation sensitive gel electrophoresis (CSGE). RESULTS: Utilizing the strategy developed in this study, we identified pathogenetic mutations in three patients with the Herlitz (lethal) variant of JEB, and eight intragenic normal polymorphisms, which are useful for linkage analysis, in the LAMC2 gene. CONCLUSIONS: The methodology described in this study is capable of detecting single-base substitutions or small insertions and deletions in the LAMC2 gene. Demonstration of mutations in this gene in JEB patients further emphasizes the role of laminin 5 in providing integrity to the cutaneous basement membrane zone.

Epidermolysis Bullosa, Junctional↗

Lack of in vivo effect of granulocyte-macrophage colony-stimulating factor on human immunodeficiency virus type 1.

Neutropenia complicates HIV disease or its treatment in a large proportion of patients. Hematopoietic growth factor support has been tested in a number of clinical settings in HIV disease and has been demonstrated to be of benefit for specific parameters. One consideration regarding the use of hematopoietic growth factors in HIV disease is their potential effect on HIV viral burden, since alterations in HIV expression have been documented with certain cytokines in vitro. It has also been reported that some cytokines, notably GM-CSF, potentiate the antiviral properties of thymidine analogs such as zidovudine (AZT) in vitro. We tested these observations in vivo. Twelve HIV-positive patients with a CD4 cell count < or = 200/mm3 or HIV plasma viremia who were receiving a stable dose of zidovudine were enrolled into three dose cohorts of yeast-derived GM-CSF at 50, 125, or 250 micrograms/m2 daily by subcutaneous self-injection for 28 days. Measurements of HIV activity included serum acid-dissociated HIV p24 antigen levels, plasma and peripheral blood mononuclear cell (PBMC) limiting dilution HIV culture, and plasma HIV quantitative competitive polymerase chain reaction (PCR). Serum and intracellular zidovudine levels were measured as well as hematologic, immunologic, and toxicity parameters. Virologic measures showed neither significant upregulation nor downregulation of serum acid-dissociated HIV p24 antigen, plasma and PBMC HIV culture, or PCR in association with GM-CSF administration. A trend toward increased intracellular AZT levels was noted, but this did not achieve statistical significance (p = 0.073). CD4 and CD8 lymphocytes were essentially unaffected while absolute neutrophil counts increased with GM-CSF administration as expected. These data suggest that administration of GM-CSF does not perturb HIV activity or immunologic parameters in patients receiving AZT for advanced HIV disease. No potentiation of AZT antiviral effect was demonstrated.

Adult↗

Dermatoglyphic a-b ridge count as a possible marker for developmental disturbance in schizophrenia: replication in two samples.

The aim of this study was to conduct an epidemiological analysis of quantitative dermatoglyphic traits as a marker of prenatal disturbance during the second trimester of life in schizophrenic patients. TFRC (Total Finger Ridge Count) and TABRC (Total a-b Ridge Count) were studied in a sample of 38 schizophrenic patients and 69 healthy individuals. A significant decrease of the a-b ridge count was found in patients compared to controls, with a significant linear trend across the population distribution (OR linear trend = 1.6; 95% CI = 1.0-2.4), indicating that the effect was not confined to a subgroup of cases with values in the lowest range. This finding was replicated in a second, larger sample (OR linear trend = 1.3; 95% CI = 1.0-1.8). The suggestion that a-b ridge count is associated with genetic risk for schizophrenia needs to be investigated further. TFRC did not distinguish between patients and controls. The a-b ridge count may be a continuous risk factor for later schizophrenia, pointing towards a disturbance occurring during the second trimester of prenatal life, a period of critical CNS growth.

Adult↗

Neurogenesis in adult human.

This report describes neurogenesis in the adult human olfactory epithelium in vitro. Olfactory epithelium was collected at autopsy and by biopsy, and grown in serum-free medium. Basic fibroblast growth factor induced the differentiation of bipolar cells which were immunopositive for several neuronal proteins but not glial proteins. [3H]thymidine autoradiography confirmed that these neurones were born in vitro. The results demonstrate that the adult human olfactory epithelium retains the capacity for neurogenesis and neuronal differentiation, at least until the age of 72 years. It is now possible to examine neurones and neurogenesis in biopsies from patients with disorders that may involve a neurodevelopmental or neurodegenerative aetiology such as schizophrenia, bipolar disorder and Alzheimer's disease.

Adolescent↗

Magnesium sulfate adversely affects fetal lamb survival and blocks fetal cerebral blood flow response during maternal hemorrhage.

Magnesium sulfate is commonly used in high-risk pregnancies, even though its actions in the fetus during maternal/fetal stress are not completely understood. The present study tested the hypothesis that magnesium sulfate alters the fetal cerebral blood flow response to hypoxemia produced during maternal hemorrhage. It was conducted in instrumented near-term fetal lambs at 123 days of gestation. Experimental treatment involved four periods of maternal hemorrhage over a 60-min period during fetal infusion of 0.25 g (n = 5) or 0.30 g (n = 6) magnesium sulfate, or normal saline (n = 11). The level of fetal cerx500l blood flow was determined using radiolabeled microspheres. For all three treatment groups, maternal hemorrhage produced fetal hypoxemia and some fetal demise. During fetal infusion of saline, 1 of 11 (9%) of the fetuses died; with the 0.25-g magnesium sulfate regimen, 1 of 5 (20%) died; and with the 0.30-g magnesium sulfate regimen, 3 of 6 (50%) of the fetuses died. Magnesium sulfate caused an increase in the proportion of fetal death produced by maternal hemorrhage (P < 0.05). Among surviving fetuses, hemorrhage-induced hypoxemia increased fetal cerebral blood flow during saline infusion. In contrast, infusion of magnesium sulfate had an inhibitory effect on this compensatory increase in fetal cerebral blood flow (P = 0.003). These data indicate that, in the sheep, magnesium sulfate increases fetal mortality and inhibits the compensatory increase in fetal cerebral blood flow during maternal hemorrhage-induced fetal hypoxemia.

Animals↗

Pedestrian-motor vehicle trauma: an analysis of injury profiles by age.

BACKGROUND: Pedestrian-motor vehicle trauma (PMVT) is a common mechanism of injury in urban populations. STUDY DESIGN: We performed a retrospective review of 273 PMVT victims (16 percent of all patients with blunt injuries) seen at a Level I trauma center over a three-year period. Patients were analyzed by age and grouped as children (age younger than 16 years), adults (age 16 to 59 years), or elderly (age older than 59 years). RESULTS: Children constituted 27 percent of the patients, adults 54 percent, and elderly 19 percent. This mixture had significantly more children and elderly than the population at large or the entire blunt trauma population at our hospital. The majority of patients (66 percent) were male, with females outnumbering males only in the elderly group. Elderly patients were more frequently admitted to the intensive care unit (ICU) and had significantly longer ICU and hospital stays. Injury Severity Scores were successively higher in each age group and significantly higher in the elderly. Extremity trauma was most common in all three groups, followed by head injuries. The elderly patients were more prone to chest and pelvic injuries and the children most often had femur fractures. Operations were performed in 22 percent of the patients; orthopedic procedures were most frequent. The mortality rate was 6 percent, with 69 percent of the deaths occurring during the initial resuscitation efforts. The mortality rate was significantly higher in the elderly patients (13 percent). The majority of accidents occurred during nighttime hours, especially in the adult group. Half of the accidents occurred on the weekend, with the greatest number on Saturday. One-third of the accidents occurred during the months of October to December. CONCLUSIONS: Pedestrian-motor vehicle trauma is a common injury, with distinct epidemiological features that may be useful in accident prevention strategies.

Accidents, Traffic↗

Deletion of chromosome 2q24-q31 causes characteristic digital anomalies: case report and review.

We describe a newborn boy with multiple anomalies, including bilateral split foot and an interstitial deletion of chromosome 2 (q24.2-q31.1). Four additional cases in 2 families involving similar deletions have been reported. Bilateral digital anomalies of hands and feet were seen in all 5 cases, including a wide cleft between the first and second toes, wide halluces, brachysyndactyly of the toes, and camptodactyly of the fingers. Other common manifestations have included postnatal growth and mental retardation, microcephaly, down-slanting palpebral fissures, micrognathia, and apparently low-set ears. Bilateral digital anomalies were reported in 22 of 24 cases with deletions including at least part of region 2q24-q31. Digital anomalies were not prevalent in 18 patients with deletions of chromosome 2q not overlapping 2q24-q31. 2q31.1 appears to be the common deleted segment in all cases with significant digital anomalies, which implies the existence of one or more genes involved in distal limb morphogenesis in this region. HOXD13 and EVX2, located in the proximity of 2q31, were not deleted in our patient by Southern analysis. Bilateral digital malformations of the hands and feet associated with other anomalies should be evaluated by chromosome analysis focused at the 2q24-q31 region.

Abnormalities, Multiple↗

Institutionalizing fertility management/human sexuality training in Colombian nursing schools.

While there is no universally applied definition of the terms, 'institutionalization', 'capacity', 'capability' and 'commitment' have been suggested as subindicators of a self-sustained program. This paper describes efforts to measure these terms in the context of a fertility management/human sexuality (FM/HS) education program for student nurses in Colombia. Interviews with 19 school deans formed the basis of measuring progress towards institutionalization. All the deans supported the idea of having FM/HS instruction, although resource commitment to effectively carry out the instruction varied. Focus groups with professors from participating schools provided insights into the effect of the project on both the students and course teachers. Professors found that students who had taken the course were more effective FM/HS counselors in later practical courses. Responses from interviews with a random sample of students who had or had not attended the course were compared to assess the effect of the course on the nursing students. Although attitudes between the two groups did not differ significantly, knowledge levels about FM/HS were significantly higher among nursing students who had attended the course. In general, the results indicate that the participatory educational approach used in teaching the FM/HS topics was effective in sensitizing both students and teachers to this subject area.

Colombia↗

Mechanistic and developmental aspects of genetic imprinting in mammals.

Genetic imprinting in mammals allows the recognition and differential expression of maternal and paternal alleles of certain genes. Recent results from a number of laboratories indicate that, at least for some genes, gametic imprints, which must exist in order to mark chromosomes or genes as having been transmitted via sperm or ovum, are not by themselves sufficient to determine allele expression. Other postfertilization events are required, and these events are subject to both tissue-specific and developmental stage-specific regulation. Changes in imprinted gene methylation during preimplantation and fetal life indicate that the establishment of additional allele-specific modifications is likely to contribute to imprinted regulation. Disruptions in imprinting processes, loss of imprints, and loss of nonimprinted alleles through uniparental disomy are likely to contribute to a variety of developmental abnormalities and pathological conditions in both mice and humans.

Animals↗

In vivo effects of interleukin 3 in HIV type 1-infected patients with cytopenia.

OBJECTIVE: To determine the safety, tolerance, and hematological and virological effects of the recombinant hematopoietic growth factor interleukin 3 (IL-3) in HIV-1-infected individuals with cytopenia. DESIGN AND METHODS: A phase I single-center trial was conducted with patients in cohorts of three receiving one of four dose levels of self-administered, subcutaneously injected IL-3 (0.5, 1.0, 2.5, or 5.0 micrograms/kg/day). Toxicities, hematological effects, and virological effects were recorded. Viral studies included serum HIV p24 antigen levels, quantitative plasma and peripheral blood mononuclear cell cultures, and quantitative, competitive polymerase chain reaction of patient plasma. RESULTS: Increases in white blood cell counts (WBC) and absolute neutrophil counts (ANC) were noted at the higher dose levels while absolute eosinophil counts (AEC) increased in all patients. The percent changes in WBC from baseline ranged from 52 to 309 and in ANC from 20 to 262 in the 2.5- and 5.0-micrograms/kg/day groups. The mean AEC change was 17-fold (range, 2- to 59-fold). Hemoglobin, hematocrit, platelets, and CD4 and CD8 counts were generally unaffected although individual patients demonstrated increases in hemoglobin and platelet levels. Toxicities were generally mild, but one patient developed a transient local erythematous rash at the sites of IL-3 injection which pathologically demonstrated hypersensitivity vasculitis. Of note, viral studies did not demonstrate any consistent changes in HIV-1 activity. CONCLUSION: These data demonstrate limited hematological effects of IL-3 monotherapy in HIV-1-infected patients with cytopenia. However, should IL-3 be incorporated into combination cytokine therapies for HIV disease, these data suggest that IL-3 does not enhance in vivo HIV-1 activity.

Adult↗

Low avidity recognition of a class II-restricted neo-self peptide by virus-specific T cells.

The specificity with which CD4+ T cells recognize self peptides in vivo was examined in transgenic mice that express an influenza virus PR8 hemagglutinin (HA) polypeptide in many tissues, including the thymus (HA Tg mice). HA Tg and non-Tg mice were analyzed for their T cell responses to the major PR8 HA I-E(d)-restricted CD4+ T cell determinant S1. Negative selection eliminated S1-specific T cells from HA Tg mice. Nevertheless, HA Tg mice retained the ability to mount a T cell response to a closely related analog of the S1 determinant [S1(K113)], and some S1(K113)-specific TCRs displayed a partial reactivity with S1 as indicated by their ability to transmit signals for IL-3 but not IL-2 secretion in response to the neo-self peptide. Moreover, the neo-self S1 peptide antagonized the ability of these TCRs to signal IL-2 secretion in response to the foreign S1(K113) determinant. Thus, TCRs that exhibit a partial reactivity with a self peptide are present in the peripheral T cell repertoire and can be activated by a virus containing an analog of the self peptide. These findings provide a model for the induction of autoimmunity by viruses that are close homologs of self peptides, and suggest a way in which TCRs could react with self peptides during positive selection of developing thymocytes.

Amino Acid Sequence↗

Bullosis diabeticorum. A case report and literature review.

We report a case of bullosis diabeticorum with blisters confined to the lower legs and feet. Histology of a lesion demonstrated a bulla at the dermo-epidermal junction, and ultrastructural studies confirmed the split to be at the level of the lamina lucida which we propose is the site of the pathology in this condition. Immunofluorescence studies were negative, excluding an immunobullous disease. We postulate that in our patient a combination of increased venous pressure and poor vascular supply in diabetic skin, led to the blister formation. The literature on this condition is reviewed.

Aged↗

Differences in social class among psychotic patients at inpatient admission.

A cross-sectional assessment of differences in social class and other sociodemographic variables at hospital admission for patients with psychotic disorders was carried out through a systematic survey of psychotic patients admitted to greater Baltimore psychiatric facilities between 1983 and 1989. Female patients, first-admission patients, and patients with bipolar disorder or other, nonschizophrenic psychosis were more likely to have been admitted to community, university, and private hospitals than to state hospitals. Patients in medium and higher social class categories were 1.29 to 2.57 times more likely to be admitted to community, university, and private hospitals than to state hospitals.

Adolescent↗