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Biomedical subjects

S Walker

Publications and source records attributed to S Walker.

At least 235 records · Page 13Linked to original sources
PubMed1994

The long-term follow-up of severely malnourished children who participated in an intervention program.

18 severely malnourished children (IM) who participated in a 3-year home-visiting program were compared with 2 other comparison groups comprising 17 severely malnourished (NIM) and 19 adequately nourished children (controls). On enrollment, all the groups were in the same hospital, and both malnourished groups had lower developmental levels than the controls. The IM group received intervention for 3 years after hospitalization, consisting of weekly or 2 weekly home visits with toy demonstrations. At 7, 8, 9, and 14 years after leaving the hospital, the 3 groups were compared on tests of school achievement and IQ. The NIM group showed no sign of reducing their deficits, and at the 14-year follow-up they had markedly lower scores on the WISC verbal and performance scales, the Wide Range Achievement Test (WRAT), and the Peabody Picture Vocabulary Test (PPVT), than the controls. Throughout the follow-up the IM group's scores were intermediate between the NIM and the controls in every test. At the 14-year follow-up, their scores were significantly higher than those of the NIM group in the WISC verbal scale, and the difference approached significance in the WRAT. We conclude that psychosocial intervention should be an integral part of treatment for severely malnourished children.

Adolescent↗
PubMed1994

Serum lipid profile determines platelet reactivity to native and modified LDL-cholesterol in humans.

The effects of thrombin (0.2 U/ml) and native (n-LDL), malondialdehyde-modified (MDA-LDL) and auto-oxidized (ox-LDL) low-density lipoproteins (20 micrograms of protein/ml) on platelet activation were evaluated in seven hyperlipidemic patients and compared to seven controls (fasting serum cholesterol 8.49 +/- 0.5 and 4.61 +/- 0.4 mM, respectively). Basal and thrombin-induced increases in platelet intracellular free calcium ion concentration ([Ca2+]i; fura-2) were similar in hyperlipidemic patients and controls (45 +/- 5 vs 42 +/- 3 and 635 +/- 51 vs 599 +/- 69 mM, respectively). n-LDL, MDA-LDL and ox-LDL increased basal [Ca2+]i (16, 36 and 81 percent, p < 0.01 between LDL-types), increases were consistently smaller in patients. There was an inverse relationship between LDL-induced responses and fasting serum LDL cholesterol as well as LDL/HDL ratio. In conclusion, modified LDL activated platelets to a greater extent than n-LDL, suggesting different types of LDL-receptors. Their agonistic effect was inversely related to the fasting serum lipid profile, suggesting that blunting of platelet responses to LDL could represent a protective mechanism in hyperlipidemic patients.

Adult↗
PubMed1993

Phase I pharmacokinetic study of cyclosporin A combined with doxorubicin.

We performed a phase I trial of cyclosporin A (CsA) in combination with doxorubicin (dox) to determine the maximally tolerated dose (MTD) of the combination in man, to define the quantitative and qualitative toxicities of the combination, and to determine the pharmacokinetics of the two drugs when used together. CsA was administered as a continuous infusion for 6 days, and dox was administered as a single 10-min infusion 24 h after the initiation of CsA. The starting CsA infusion rate was 5 micrograms/kg/min, and the dox starting dose was 30 mg/m2. Courses were administered every 4 weeks with first CsA and then dox being escalated in consecutive cohorts of patients until the MTD was determined. Twenty-three patients and 40 courses were evaluable for toxicity. Pharmacokinetic analysis was performed in 23 patients on the first course for whole blood CsA and plasma dox and doxorubicinol. The MTD of CsA was 6 micrograms/kg/min, and for dox it was 45 mg/m2. Dose-limiting toxicity was neutropenia. Serum creatinine and creatinine clearance did not change over the infusion period. Bilirubin increased from a median of 10 mumol/liter at the initiation of the infusion to a median of 40.4 mumol/liter at the end of the infusion but returned to normal before the next cycle of therapy. Nausea and vomiting were common and marked, whereas thrombocytopenia was mild. Two patients, one with small cell lung cancer and one with breast cancer, had stable disease while receiving treatment for 5 and 6 months, respectively. Mean whole blood steady state concentrations of CsA were 2210 ng/ml during the infusion with total body clearance of 0.177 liter/h/kg. The area under the concentration x time curve (AUC) increased linearly with dose of dox, and total body clearance was independent of dose. The mean total body clearance was 2.46 liters/h/m2, and terminal half-life was 49.6 h. The AUC for dox was greater and clearance was less than has been previously reported at the doses administered in this study. The ratio of AUC for doxorubicinol to AUC for dox was less than expected, suggesting that the metabolism and/or excretion of dox was decreased when administered with CsA. We conclude that dox can be combined with infusioned CsA but at a lower dose than when given alone. This may be due to altered metabolism and/or excretion of dox or increased bone marrow stem cell sensitivity to dox.

Adult↗
PubMed1993

Genomic structure and chromosomal localization of the human deoxycytidine kinase gene.

Deoxycytidine kinase (NTP:deoxycytidine 5'-phosphotransferase, EC 2.7.1.74) is an enzyme that catalyzes phosphorylation of deoxyribonucleosides and a number of nucleoside analogs that are important in antiviral and cancer chemotherapy. Deficiency of this enzyme activity is associated with resistance to these agents, whereas increased enzyme activity is associated with increased activation of such compounds to cytotoxic nucleoside triphosphate derivatives. To characterize the regulation of expression of this gene, we have isolated genomic clones encompassing its entire coding and 5' flanking regions and delineated all the exon/intron boundaries. The gene extends over more than 34 kilobases on chromosome 4 and the coding region is composed of 7 exons ranging in size from 90 to 1544 base pairs (bp). The 5' flanking region is highly G+C-rich and contains four regions that are potential Sp1 binding sites. A 697-bp fragment encompassing 386 bp of 5' upstream region, the 250-bp first exon, and 61 bp of the first intron was demonstrated to promote chloramphenicol acetyltransferase activity in a T-lymphoblast cell line and to have > 6-fold greater activity in a Jurkat T-lymphoblast than in a Raji B-lymphoblast cell line. Our data suggest that these 5' sequences may contain elements that are important for the tissue-specific differences in deoxycytidine kinase expression.

Base Sequence↗
PubMed1993

The safety of ranitidine in elderly versus non-elderly patients.

The authors conducted a retrospective review of 21 United States trials of ranitidine in acid peptic diseases and compared the adverse events in elderly (> or = 65 years) and nonelderly (< 65 years) patients. Ranitidine dosages ranged from 150 mg/day to 300 mg twice daily for treatment periods of 4 to 52 weeks. Of the 4041 patients included in this review, 402 elderly and 2188 nonelderly patients received ranitidine and 245 elderly and 1206 nonelderly patients received placebo; 29%, 29%, 32%, and 26% of these patients, respectively, reported some type of adverse event. When only drug-related adverse events (as judged by the investigators under blinded conditions) were evaluated, these percentages dropped to 2%, 2%, and 1% and 2%, respectively. Gastrointestinal adverse events (e.g., nausea and diarrhea) and central nervous system adverse events (e.g., headache and dizziness) were the most common (0.7% and 0.8%, respectively), with comparable incidence rates in the elderly and nonelderly patients. The authors conclude that ranitidine is as safe in elderly patients as it is in nonelderly patients. No difference in the incidence of adverse events was found between older and younger patients who received ranitidine or placebo.

Adult↗
PubMed1993

Physical and genetic mapping of a human apical epithelial Na+/H+ exchanger (NHE3) isoform to chromosome 5p15.3.

A gene family of Na+/H+ exchanger isoforms has been identified. Characterization of rabbit NHE3 suggests that it is the apical epithelial Na+/H+ exchanger isoform responsible for transepithelial, electroneutral Na+ absorption in intestinal and renal epithelial cells. We have previously isolated from a human kidney cortex library a partial human NHE3 cDNA, clone HKC-3. Using HKC-3 to probe human/rodent somatic cell hybrid mapping panels, the human NHE3 gene was physically mapped to the distal portion of chromosome 5p15.3. Southern analysis of EcoRI-digested human genomic DNAs of CEPH pedigrees probed with HKC-3 detected three polymorphic sites containing a total of nine alleles that segregate in a Mendelian fashion. The observed heterozygosity for the NHE3 locus in unrelated individuals was 71%. Linkage analysis between NHE3 and other markers known to map at 5p15 confirmed the localization of NHE3 to chromosome 5p15.3, making NHE3 the most telomeric gene identified on the short arm of chromosome 5.

Animals↗
PubMed1993

[Condylomata acuminata in pregnancy. Is there an indication for Cesarean section?].

Condylomata acuminata are very rare in children, although the prevalence of clinically or cytologically visible human papilloma virus infections is high. We report on a 28-year old G IV, P II with genital warts at the time of delivery, who had a baby boy without any signs of HPV-infection. The condylomata of the mother persisted, and subsequently laser vaporisation was performed one year after delivery. One year after laser therapy, a recurrent HPV-infection in the mother was detected. At this time, her two year old son had condylomata on his scrotum. The same serotypes, HPV 6 and 11, could be identified in the mother and child. With this case report, we discuss the possible ways of transmission and consequent clinical management of HPV infections in pregnancy.

Adult↗
PubMed1993

MEG and EEG in epilepsy: is there a difference?

Interictal epileptiform activity recorded by scalp EEG, foramen ovale electrodes and MEG is discussed. Gross differences in waveform between the electric and magnetic records are discussed in the light of intracranial depth recordings.

Electroencephalography↗
PubMed1993

Enoxacin relieves symptoms of recurrent urinary infections more rapidly than cefuroxime axetil.

In patients with a history of recurrent infections, treatment with enoxacin (200 mg/12 h for 3 days) relieved symptoms of acute urinary infection significantly more rapidly than treatment with cefuroxime axetil (125 mg/12 h for 7 days). Other parameters, including clinical and bacteriological cure rates and patients' overall opinion of their treatment, did not differ significantly between the treatments.

Adult↗
PubMed1993

Transcriptional activation by the acidic domain of Vmw65 requires the integrity of the domain and involves additional determinants distinct from those necessary for TFIIB binding.

In this work we have examined the requirements for activity of the acidic domain of Vmw65 (VP16) by deletion and site-directed mutagenesis of the region in the context of GAL4 fusion proteins. The results indicate that the present interpretation of what actually constitutes the activation domain is not correct. We demonstrate, using a promoter with one target site which is efficiently activated by the wild-type (wt) fusion protein, that amino acids distal to residue 453 are critical for activity. Truncation of the domain or substitution of residues in the distal region almost completely abrogate activity. However, inactivating mutations within the distal region are complemented by using a promoter containing multiple target sites. Moreover, duplication of the proximal region, but not the distal region, restores the ability to activate a promoter with a single target site. These results indicate some distinct qualitative difference between the proximal and distal regions. We have also examined the binding of nuclear proteins to the wt domain and to a variant with the distal region inactivated by mutation. The lack of activity of this variant is not explained by a lack of binding of TFIIB, a protein previously reported to be the likely target of the acidic domain. Therefore some additional function is involved in transcriptional activation by the acid domain, and determinants distinct from those involved in TFIIB binding are required for this function. Analysis of the total protein profiles binding to the wt and mutant domains has demonstrated the selective binding to the wt domain of a 135-kDa polypeptide, which is therefore a candidate component involved in this additional function. This is the first report to provide evidence for the proposal of a multiplicity of interactions within the acidic domain, by uncoupling requirements for one function from those for another.

Amino Acid Sequence↗
PubMed1993

A psychiatric follow-up study of adoptees.

This is a five year follow-up study of adopted children and adolescents. Thirty-five adoptees and 23 control subjects were assessed. Five years earlier, the initial sample consisted of 57 pairs of adoptees and controls. The study showed that both adopted and control subjects were improved at the follow-up assessment and that there were no significant differences in clinical diagnoses and social adaptation between the groups. Compared with the controls, the adoptees were scored higher on a behaviour scale (Revised Behavior Problem Checklist) by parents. Adoption by the sixth month of age was associated with better overall psychosocial functioning. Significantly more adoptees were not living with their adoptive families. Factors associated with outcome are discussed.

Adaptation, Psychological↗
PubMed1993

Treatment of primary hepatobiliary cancers with conformal radiation therapy and regional chemotherapy.

PURPOSE: To develop more effective regional therapy for patients with unresectable primary hepatobiliary cancer using concurrent conformal radiation therapy and intraarterial hepatic (IAH) fluorodeoxyuridine (FdUrd). PATIENTS AND METHODS: Twenty-six patients with unresectable, nonmetastatic primary hepatobiliary cancer were treated with concurrent IAH FdUrd (0.2 mg/kg/d) and conformal hepatic radiation therapy (1.5 to 1.65 Gy per fraction twice per day). The total dose of radiation administered to the tumor depended on the fraction of normal liver excluded from the high-dose volume. All patients were assessed for toxicity, hepatobiliary relapse, and survival; 17 patients were assessable for response (eight had cholangiocarcinoma not assessable by computed tomographic [CT] scan and one progressed distantly during treatment). The median potential follow-up duration was 27 months. RESULTS: Whole-liver radiation was administered to six patients with diffuse hepatocellular carcinoma (HCC). Eleven patients with localized HCC and nine with cholangiocarcinoma received focal radiation to a dose of 48 to 72.6 Gy. An objective response for assessable patients was observed in 11 of 11 patients treated with focal radiation, but only one of six patients treated with whole-liver radiation. Whole-liver radiation accounted for five of seven patients with > or = grade 3 toxicity and four of six local treatment failures. Two patients had nonfatal radiation hepatitis. The median survival duration for patients with localized hepatobiliary cancer was 19 months, while patients with diffuse HCC had a median survival duration of 4 months. The rate of actuarial freedom from hepatobiliary progression in patients with localized disease was 72% at 24 months. CONCLUSION: These findings suggest that three-dimensional planned focal liver radiation and IAH FdUrd can produce a high, durable response rate and an encouraging median survival duration in patients with nondiffuse, unresectable primary hepatobiliary cancer.

Actuarial Analysis↗