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Biomedical subjects

A Smith

Publications and source records attributed to A Smith.

At least 361 records · Page 20Linked to original sources

[Diffusion- and perfusion-weighted MR imaging during the hyperacute phase of stroke].

The sensitivity of diffusion-weighted MR imaging to detect a lesion within 6 hours of stroke onset was approximately 90%. The false negative results were usually small lesions (1 ml), were seen early, and were usually located in the brain stem. The specificity of this technique was nearly 100% when it was used correctly. The volume and the value of the apparent diffusion coefficient of the detected lesions provided prognostic information. After injection of a contrast agent (perfusion imaging), a time series of volumes were obtained using a T2* sensitive gradient echo EPI sequence. Hemodynamic perturbations of the cerebral parenchyma could be detected as well as the type of perturbation in the lesion. A map representing the mean transit time for each voxel was used to define the maximum volume of the perturbation. A hemodynamic penumbra was defined to be when this volume was larger than the volume detected on the diffusion images. The quantitative measure of cerebral blood flow could predict the irreversibility of the lesions when the value was below 18 ml/min/100g, and the extension of the ischemia in the penumbra zone when the value was below a threshold of 30 ml/min/100g.

Aged↗

Anticonvulsant and adverse effects of avermectin analogs in mice are mediated through the gamma-aminobutyric acid(A) receptor.

Twenty-five avermectin analogs were assessed in a mouse seizure model. The ED(50) against pentylenetetrazole-induced tonic seizures ranged from 0.48 mg/kg (L-676,893) to >160 mg/kg (L-685,869) cf. 0. 26 mg/kg for diazepam. Although avermectins are without acute toxic effects, they have been historically shown to have relative low LD(50) values in mammals. The mechanisms involved in the anticonvulsant effect and the toxicity were investigated. A series of avermectin analogs displaced [(3)H]ivermectin binding to rat brain membranes and recombinant GABA(A) receptors (alpha1beta3gamma2-subtype) with the same affinities, strongly suggesting that [(3)H]ivermectin labels the GABA(A) receptor in rodent brain. Avermectins, which were anticonvulsant, were also potent inhibitors of [(3)H]ivermectin binding in rat brain. However, the rank order for anticonvulsant activity did not parallel the rank order for affinity at the [(3)H]ivermectin site and it was reasoned that avermectins may have differential affinity or efficacy at subtypes of the GABA(A) receptor. All the active compounds tested potentiated the effects of GABA at recombinant GABA(A) receptors in oocytes and at native cortical GABA(A) receptors and the efficacy of avermectins at the GABA(A) receptor correlated best with their anticonvulsant potency. Although avermectins weakly inhibited [(3)H]strychnine binding in rat spinal cord, and inhibited glycine responses on primary cultured cortical neurons, activity at glycine receptors did not correlate with either anticonvulsant activity or toxicity. Because both anticonvulsant activity and toxicity correlated best with activity at GABA(A) receptors, it is unlikely that these effects can be separated, which may contraindicate the potential use of avermectins as anticonvulsants.

Animals↗

Gastric cancer in Iceland. What is the current status? Survival of 193 patients operated on for cure, 1980-1995.

OBJECTIVE: The incidence of gastric cancer has been decreasing in the last decades. Nevertheless, gastric cancer is still a substantial health problem in Iceland. The aim of this study was to analyze the survival of patients with gastric cancer operated on for cure. MATERIAL AND METHODS: We reviewed all medical files for above-mentioned patients, operated on at the National University Hospital in Reykjavik and the Quarter District Hospital of Akureyri during 1980-1995. The study was divided into three periods: 1980-1985, 1986-1990 and 1991-1995. The five-year survival for each study period and for the whole group was evaluated. RESULTS: The study group included 193 patients between the ages of 21-96 (median 71). The five-year survival for the whole group was 28% (26% 1980-1985, 22% 1986-1990, 35% 1991-1995). Despite longer survival during the last period, it was not statistically significant (p = 0.16). The major survival factor of gastric cancer was the stage of the disease at diagnosis. A greater number of patients were at stage IA during 1991-1995. The complication rate was rather high or 31% and the hospital mortality was 6.7%. CONCLUSION: The survival of patients with gastric cancer operated on for cure was low in Iceland but comparable to that in other countries. During the last years, the survival has been rising, and fortunately, more were diagnosed at a lower stage of the disease. These operations have a considerable risk and the hospital mortality was substantial.

Adenocarcinoma↗

Outcome of medical screening of Kosovan refugees in Ireland: 1999.

In March 1999 armed conflict broke out in Kosova and about 900,000 ethnic Albanians were displaced. We reviewed the health care offered to the 945 Kosovan refugees who arrived in Ireland in 1999, which included screening for tuberculosis (TB) and hepatitis B. On arrival in Ireland 540 refugees had already received oral polio vaccine (57%), 512 diphtheria, tetanus, and acellular pertussis or diphtheria and tetanus vaccine (54%), 310 BCG (33%), 207 measles, mumps, and rubella vaccine (22%) and 60 Haemophilus influenzae type b (6%). Twelve refugees were diagnosed with TB. Twenty-six refugees were HBsAg positive (3%) and 168 were anti-HBcAg positive (18%). Organised screening of Kosovan refugees on a voluntary basis (uptake > 95%) revealed low percentages who had been immunised and relatively high rates of TB and hepatitis B. The provision of optimum immunisation, screening, and treatment services to address these issues requires substantial staffing and financial resources.

Albania↗

Percutaneous endoscopic gastrostomy for patients undergoing resection of oral tumours.

Ablation and reconstruction for oral tumours often has a deleterious effect on the ability of patients to maintain an adequate dietary intake. It is well recognized that malnutrition complicates surgery and recovery. Nutritional support can be provided in a variety of ways. This paper reports on the use of percutaneous endoscopic gastrostomy (PEG) in a series of 33 patients undergoing maxillofacial surgery. The results suggest that PEG feeding has a low complication rate and reduces the weight loss suffered by patients undergoing resection and reconstruction procedures.

Adult↗

The 1999 Helene Fuld Health Trust Fellowship. Promoting leadership development in undergraduate nursing students.

In 1999, based on the recommendation of The Conservation Company. The Helene Fuld Health Trust selected New York University's Robert F. Wagner Graduate School of Public Service, in partnership with the Division of Nursing in the School of Education, to restructure its fellowship program for undergraduate nursing students. Bringing together an interdisciplinary team with experience in leadership development, nursing and health policy, and health care administration, NYU designed and delivered an innovative and state-of-the-art leadership development program for the 1999 Fuld Fellowship program. The new program started in June 1999 with 21 nursing students from all over the country. This article describes the goals and methods of the program; it also discusses early observations of the program's success that could be relevant to nursing education.

Education, Nursing, Baccalaureate↗

Non-invasive transgenic mouse genotyping using stool analysis.

Commonly applied genotyping of transgenic mice involves using tail or ear biopsies which may cause discomfort to the animal. We tested the possibility of polymerase chain reaction (PCR)-based mouse genotyping using stool specimens from three transgenic mouse lines that overexpress 10-18 transgene copies of human keratin polypeptide 18, as compared to genotyping using tail biopsies. Stool specimens were obtained with ease and provided easy detection of the human transgene product. The method was also able to detect endogenous mouse actin and keratin genes which presumably are present at two copies each. Nested PCR was not necessary for genotyping using stool-derived genomic material but did increase the relative magnitude of the signal obtained. The non-invasive genotyping method described herein offers a reproducible, sensitive and effective modality that could replace invasive tissue sampling procedures currently used to test thousands of genetically altered mice.

Animals↗

MKP5, a new member of the MAP kinase phosphatase family, which selectively dephosphorylates stress-activated kinases.

Dual-specificity protein tyrosine phosphatases are a burgeoning family of enzymes, some of which, the MKPs, are implicated in the regulation of mitogen-activated protein (MAP) kinases. MKPs have been shown to reverse the activation of the MAP kinases by hydrolyzing phosphothreonine and phosphotyrosine residues present in the substrates. Here we describe the characterization of a novel member of the MKP family, MKP5. The MKP5 gene, which maps to human chromosome 1q32, is expressed tissue-specifically as two transcripts of approximately 3.4 and 2.4 kb in human liver and skeletal muscle. When expressed in mammalian cells, MKP5 blocks the enzymatic activation of MAP kinases with the selectivity p38 approximately JNK/SAPK >> ERK. Immunoprecipitation of endogenous MAP kinases by the catalytically inactive transfected MKP5 demonstrates that it preferentially binds to the p38 and JNK/SAPK kinases. These findings suggest that the selectivity of this phosphatase may be determined at least in part at the level of substrate binding.

Amino Acid Sequence↗

Defective thymocyte maturation in p44 MAP kinase (Erk 1) knockout mice.

The p42 and p44 mitogen-activated protein kinases (MAPKs), also called Erk2 and Erk1, respectively, have been implicated in proliferation as well as in differentiation programs. The specific role of the p44 MAPK isoform in the whole animal was evaluated by generation of p44 MAPK-deficient mice by homologous recombination in embryonic stem cells. The p44 MAPK-/- mice were viable, fertile, and of normal size. Thus, p44 MAPK is apparently dispensable and p42 MAPK (Erk2) may compensate for its loss. However, in p44 MAPK-/- mice, thymocyte maturation beyond the CD4+CD8+ stage was reduced by half, with a similar diminution in the thymocyte subpopulation expressing high levels of T cell receptor (CD3high). In p44 MAPK-/- thymocytes, proliferation in response to activation with a monoclonal antibody to the T cell receptor in the presence of phorbol myristate acetate was severely reduced even though activation of p42 MAPK was more sustained in these cells. The p44 MAPK apparently has a specific role in thymocyte development.

Animals↗

Alternative splicing of the Drosophila PTEN gene.

Mutations in the human PTEN gene have been identified in a number of different tumour types, and in the hamartomatous polyposis syndromes Cowden disease and Bannayan-Zonana syndrome. The PTEN gene encodes a phosphatase that antagonises phosphoinositide 3-kinase (PI3K) signalling by removing the 3' phosphate from phosphatidylinositol 3, 4,5-trisphosphate (PtdIns (3,4,5)P(3)). Here we show that the PTEN gene is conserved in the invertebrate Drosophila melanogaster and demonstrate that the gene undergoes alternative splicing.

Alternative Splicing↗

The orienting response in schizophrenia and mania.

We examined skin conductance (SCR) and finger pulse amplitude response (PULSE) in 53 schizophrenic, 30 manic, and 28 control subjects to provide information on orienting response (OR) dysfunction in severe psychiatric disorders. SCR and PULSE to neutral and task-relevant tones were measured in acutely ill inpatients and normal control subjects on two occasions separated by a 3-week interval. There were no significant group differences in proportions of SCR and PULSE non-responders to neutral tones. PULSE frequency to task-relevant tones in both the schizophrenic and manic patients was lower than that for the control subjects in both OR sessions, but did not differ significantly between patient groups. Although PULSE frequency was inversely related to neuroleptic dose in the schizophrenia sample, reanalysis of unmedicated patients did not change our results. OR frequency to task-relevant but not to neutral tones exhibited test-retest reliability. Certain aspects of OR dysfunction may overlap in schizophrenia and bipolar disorder. Our failure to demonstrate excessive OR non-responding to neutral tones in schizophrenia patients is inconsistent with many previous studies but may be due to a high proportion of OR non-responders among the control subjects.

Acoustic Stimulation↗

Frequency of trisomy 15 and loss of the Y chromosome in adult leukemia.

In the interpretation of the varied and complex cytogenetic counts obtained in analysis of bone marrow (BM) samples for leukemia, loss or gain of certain chromosomes may or may not be significant for prognosis. Loss of the Y chromosome in elderly males is a benign finding. Trisomy 15 is rare and may represent another age-related abnormality, particularly in males, together with -Y. We reviewed 3,242 routine referrals sent to our laboratory for BM cytogenetics, over a period of 34 months. We detected 5 cases with uncomplicated trisomy 15, 3 in males and 2 in females. Three of these patients had the diagnosis of myelodysplastic syndrome (MDS). All 3 males showed a -Y cell line, although the 2 females did not have an X chromosome loss. All 5 patients were alive and well at times varying from 12 months to 4 years post-diagnosis. In the further analysis of our referral cohort, there were 62 males with loss of the Y chromosome as the sole abnormality, and of these 47 (76%), were referred with myeloid disease. The frequency of trisomy 15 in our laboratory was 1/475 referrals, but 1/292 in successful cultures from new patients. This is the first report providing frequency data for trisomy 15. Further data with longer term follow-up is required to establish the significance of trisomy 15 in elderly leukemic patients.

Adult↗

Two children with acute lymphoblastic leukemia and "jumping" translocations: both involve 1q23 as the donor breakpoint.

"Jumping" translocations (JT) are relatively rare and are associated with poor prognosis. We report two male patients with childhood acute lymphoblastic leukemia (ALL) and abnormal cell lines detected on bone marrow cytogenetics. Diagnostic marrow cytogenetics were not available for either patient. In patient 1, approximately 11 years after diagnosis, cytogenetics revealed a single translocation, t(1;2)(q23;q32), which was followed by translocations t(1;22)(q23;p11) and t(1;1)(q23;q21.3). In patient 2, two translocations were present together, t(1;6)(q23;p21.3) and t(1;11)(q23;q21), 12 years after diagnosis. The unbalanced JTs in both patients resulted in partial trisomy for (1)(q23-->qter). Both died within 1-2 years after the appearance of the JT. Our patients provide additional support for chromosome 1q preferential involvement in JTs, and that their appearance is associated with a poor prognosis.

Child, Preschool↗

Safety, tolerability and efficacy of cyclosporine microemulsion in heart transplant recipients: a randomized, multicenter, double-blind comparison with the oil based formulation of cyclosporine--results at six months after transplantation.

BACKGROUND: The introduction of cyclosporine has resulted in significant improvement in the survival of cardiac allograft recipients due to decreased mortality from infection and rejection. The original oil-based cyclosporine formulation exhibits variable and unpredictable bioavailability that correlates with an increased incidence of acute and chronic rejection in those patients in whom this is most pronounced. The primary objectives of this prospective, multicenter, randomized, double-blind study in cardiac transplant patients were: to compare the efficacy of cyclosporine microemulsion (CsA-NL) with oil-based cyclosporine (CsA-SM) as measured by cardiac allograft and recipient survival and the incidence and severity of acute rejection episodes; and to assess the safety and tolerability of CsA-NL compared with CsA-SM in this population. This report represents the analysis of results 6 months after transplantation. METHODS: A total of 380 patients undergoing their first cardiac transplant at 24 centers in the United States, Canada, and Europe were enrolled in this double-blind, randomized trial examining the safety and efficacy of CsA-NL versus CsA-SM. Rejection was diagnosed using endomyocardial biopsy and were graded according to standardized criteria of the International Society of Heart and Lung Transplantation (ISHLT). Clinical parameters were monitored during the study. Survival and freedom from were used for analysis as was Fisher's exact test for comparisons between groups. RESULTS: At 6 months after transplantation, allograft and patient survival were the same for both groups. The frequency of ISHLT grade 3A or greater episodes in the two groups was identical. Fewer CsA-NL patients (5.9%) required antilymphocyte antibody (ATG or OKT-3) therapy for rejection compared with the CsA-SM-treated patients (14.1%, P=0.01). Females with ISHLT rejection grade > or = 3A treated with CsA-NL had a 46% lower incidence of rejection compared with the CsA-SM-treated group (31.3% vs. 57.6%, P=0.032). Fewer infections were seen in the CsA-NL. With the exception of baseline and 1 week posttransplant creatinines which were higher in the CsA-NL group, the overall creatinine was not significantly different between the two groups. CONCLUSIONS: This multicenter, randomized study of cardiac transplant recipients documented less severe rejection (in particular those requiring antibody therapy) and a lower incidence of infection in CsA-NL-treated patients. Results from the female subgroup analysis suggest that the improved bioavailability of CsA-NL might reduce the frequency of rejection episodes in female patients. The use of CsA-NL was not associated with an increased risk of adverse events.

Adolescent↗