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Biomedical subjects

S Walker

Publications and source records attributed to S Walker.

At least 199 records · Page 11Linked to original sources
PubMed1996

A clinical and academic outcome study of children attending a day treatment program.

OBJECTIVE: To assess the behavioural and academic improvement of children who attended a day treatment program during a defined period of time. METHOD: Forty-six children admitted consecutively to the project were assessed on admission and discharge using behavioural and academic measures. They also had intelligence and language assessments. The subjects attended the program for one academic year, on the average. The large majority presented with disruptive behaviour disorders and low academic achievement levels. RESULTS: There was a significant improvement reported by the parents in externalizing (P < 0.001) and internalizing (P < 0.05) behaviour. The subjects also gained one academic year, but their levels continued to be low in terms of percentiles. Measures of academic improvement showed significant associations with cognitive measures only (subscales of Wechsler Intelligence Scale for Children-Revised [WISC-R] and Clinical Evaluation of Language Fundamentals-Revised [CELF-R]). CONCLUSION: A day treatment and school program is an effective modality for treatment and remediation of children with severe psychiatric disorders. The academic underachievement may be resistant to remediation within the limited period of attendance in such a program.

Adolescent↗
PubMed1996

The influence of breathhold on peak expiratory flow in normal and asthmatic children.

We have previously demonstrated a 10% reduction in peak expiratory flow (PEF) in healthy adults following a breathhold at total lung capacity (TLC). This fall was attributed to dissipation of airway wall viscoelasticity, increasing airway wall compliance (Caw). To investigate this phenomenon in children and to determine whether the effect of breathhold would be greater in asthmatics than in normal children, 15 asthmatics and 14 normal children (aged 10-15 yrs) performed maximal post expirations (MFE) with and without a 5 s breathhold at TLC. The entire study was repeated following the inhalation of salbutamol (800 micrograms) to relax the airway smooth muscle (and to increase Caw). Breathhold at TLC resulted in a significant decrease in PEF both in the asthmatics (group mean fall 5.8%; p < 0.01) and normal children (group mean fall 10.3%; p < 0.05). Salbutamol diminished this fall, becoming nonsignificant in the normal children. Similar patterns were also seen in forced expiratory volume in one second (FEV1) and in maximal expiratory flow at 50% vital capacity (V'50). These data are consistent with the proposal that breathhold at total lung capacity dissipated viscoelastic energy (increasing airway compliance) and decreased maximal expiratory flows both in normal and asthmatic children. They also demonstrate the need to standardize the forced vital capacity manoeuvre to decrease the variability in the flows recorded during the subsequent forced expiration.

Airway Resistance↗
PubMed1996

A double-blind, placebo-controlled study of vigabatrin three g/day in patients with uncontrolled complex partial seizures. Vigabatrin Protocol 024 Investigative Cohort.

This study compared the efficacy and tolerability of vigabatrin 3/day as add-on therapy with that of placebo in patients with focal epilepsy whose complex partial seizures were difficult to control with established antiepilepsy drug therapy. We enrolled 203 patients; 182 (90 placebo; 92 vigabatrin) received drug therapy under double-blind conditions. We increased the daily dosage to 2.5 g/day during a 4-week titration segment and maintained it at 3 g/day during the 12-week maintenance segment. By analyses we found a statistically significant lower frequency of seizures (complex seizures plus partial seizures secondarily generalized) at the end of the study for patients receiving vigabatrin than for those receiving placebo. The median monthly frequency was reduced by three seizures per 28 days in the placebo group (baseline, 8.3; end of study, 7.5) (p = 0.0002). Therapeutic success (a 50% reduction from baseline in mean monthly seizure frequency) was attained in 40 of the vigabatrin patients (43%) compared with 17 of those treated with placebo (19%) (p < 0.001). Vigabatrin significantly increased the mean number of seizure-free days per 28 days (2.2 days) compared with placebo (0.5 days) (p = 0.0024). Mean trough serum vigabatrin concentration during therapy was 8.6 +/- 7.7 micrograms/ml. The oral clearance of vigabatrin was determined to be 7.8 L/hr, and the elimination half-life was 8.4 hours. No clinically important changes in MRI, evoked potential, or other laboratory tests were noted during vigabatrin treatment. The results of this study indicate that 3 g/day vigabatrin is more effective than placebo as add-on therapy. Vigabatrin was well tolerated, compliance was high with twice-daily administration, and therapy did not result in clinically relevant drug interactions.

Adolescent↗
PubMed1996

A comparison of the effects of oral cetirizine and inhaled beclomethasone on early and late asthmatic responses to allergen and the associated increase in airways hyperresponsiveness.

BACKGROUND: Cetirizine is a non-sedating H1 antihistamine which is effective in the treatment of allergic rhinitis and urticaria. It inhibits eosinophil and basophil chemotaxis in late cutaneous allergic reactions in skin windows. Its effect on early (EAR) and late asthmatic reactions (LAR) is less certain. METHODS: We examined the effect on EAR and LAR of 3 days treatment with oral cetirizine (15 mg twice daily) compared with a single dose of inhaled beclomethasone 10 min prior to allergen challenge in a placebo-controlled (oral and inhaled) double-blind cross-over design with three treatment arms separated by 14 days. RESULTS: Cetirizine did not significantly inhibit either the EAR or LAR documented by maximum percentage fall in FEV1 (0-3 and 6-9 h) or as area under the curve (AUC between 0 and 3 and 6-9 h). Beclomethasone inhibited the LAR compared with placebo (P = 0.02) when expressed as AUC (6-9 h). This did not quite reach statistical significance (P = 0.06) when expressed as maximal percentage late fall in FEV1 between 6 and 9 h. A greater than twofold increase in airways responsiveness to methacholine was observed 3 h after challenge which was significantly reduced by beclomethasone compared with placebo (P < 0.02) and cetirizine (P < 0.05). The data suggest that oral cetirizine does not significantly inhibit either the EAR or LAR. Beclomethasone inhibited both the early increase in airways responsiveness and the subsequent LAR. Our study also confirms the view that early increases in airway responsiveness precede the late response and suggests that these associated events are not dissociable by the pharmacological treatments employed in this study.

Administration, Inhalation↗
PubMed1996

Terlipressin (glypressin) versus somatostatin in the treatment of bleeding esophageal varices--final report of a placebo-controlled, double-blind study.

One hundred and six episodes of bleeding from esophageal or gastric varices in 72 patients with cirrhosis of the liver were randomized to treatment either with intravenous terlipressin 2 mg initially and 1 mg every four hours for 24 hours together with bolus injection and continuous infusion of placebo, or with somatostatin 250 micrograms as a bolus and continuous infusion of 250 micrograms/h somatostatin for 24 hours and placebo injections. Standard treatment with transfusions, fluid and electrolyte correction, and lactulose was administered in both groups. In the terlipressin group, 48 out of 53 bleeding episodes (91%) and in the somatostatin group 43 out of 53 bleeds (81%) were initially stopped by the vasoactive drugs. Four of the five bleeds not arrested by terlipressin, and nine of the ten bleeds not arrested by somatostatin, were stopped by balloon tamponade. In one patient in each group variceal bleeding could not be stopped initially, and both patients died. The failure rate of the vasoactive treatment alone, including rebleeds within the study period, was 17% in the terlipressin, and 28% in the somatostatin, group. The initial hemostasis, including balloon tamponade, were 98%, and the definitive bleeding control rates were 89% in both groups. The hospital mortality rate was 21% (11/53) in the terlipressin, and 21% (11/53) in the somatostatin, group. Blood transfusions and duration of bleeding did not differ significantly. The study indicates that a large proportion of bleeds from esophageal and fundic varices can be stopped initially (86%) and definitively controlled (77%) by vasoactive drugs alone.

Adult↗
PubMed1995

Stimulation of human papillomavirus type 1a DNA replication by a multimerized AT-rich palindromic sequence.

Replication of most papillomaviruses requires the viral E1 and E2 proteins and an origin of replication containing the E1 and E2 binding sites. In the case of human papillomavirus type 1a (HPV-1a), the E1 protein alone is sufficient for DNA replication although the E2 protein significantly stimulates replication. We have further analyzed the role of cis-acting sequences and the E1 and E2 proteins in HPV-1a replication. Previous studies have shown that a 60-bp region lacking the E2 binding sites but containing an imperfect 16-bp AT-rich palindrome corresponding to the putative E1 binding site contains the minimal origin of replication (ori). Using a transient replication assay, we demonstrate that duplication of this 60-bp region causes a severalfold increase in replication. Synthetic oligonucleotides containing a 39-bp region centered around the above palindromic sequence supported only low-level replication in the presence of either E1 alone or both E1 and E2, but replication was significantly increased in the presence of multiple copies of this sequence. Plasmids containing a 19-bp sequence which includes the AT-rich palindrome failed to replicate, but multiple copies of this region supported replication in the presence of both E1 and E2 to significant levels. The results presented indicate that the HPV-1a E1 protein is capable of recruiting all the cellular factors required for replication. Our results also suggest that multimerization of the AT-rich palindromic sequence may result in a significant increase in the recruitment of the E1 protein to the origin, thereby stimulating replication. This increased targeting of the E1 protein to the origin containing multiple copies of the putative E1 binding site may be functionally similar to the targeting of E1 to the origin by E2.

Adenine↗
PubMed1995

The treatment of colorectal liver metastases with conformal radiation therapy and regional chemotherapy.

PURPOSE: Whole-liver radiation, with or without chemotherapy, has been of modest benefit in the treatment of unresectable hepatic metastases from colorectal cancer. A Phase I/II study combining escalating doses of conformally planned radiation therapy (RT) with intraarterial hepatic (IAH) fluorodeoxyuridine (FdUrd) was performed. METHODS AND MATERIALS: Twenty-two patients with unresectable hepatic metastases from colorectal cancer, 14 of whom had progressed after previous chemotherapy (2 with prior IAH FdUrd), were treated with concurrent IAH FdUrd (0.2 mg/kg/day) and conformal hepatic radiation therapy (1.5-1.65 Gy/fraction twice a day). The total dose of radiation given to the tumor (48-72.6 Gy) depended on the fraction of normal liver excluded from the high-dose volume. All patients were assessed for response, toxicity, hepatobiliary relapse, and survival. Median potential follow-up was 42 months. RESULTS: Eleven of 22 patients demonstrated an objective response, with the remainder showing stable disease. Actuarial freedom from hepatic progression was 25% at 1 years. The most common acute toxicity was mild to moderate nausea and transient liver function test abnormalities. There were three patients with gastrointestinal bleeding (none requiring surgical intervention) after the completion of treatment. Overall median survival was 20 months. The presence of extrahepatic disease was associated with decreased survival (p < 0.01). CONCLUSIONS: Combined conformal radiation therapy and IAH FdUrd can produce an objective response in 50% of patients with hepatic metastases from colorectal cancer. However, response was not durable, and hepatic progression was frequent. Improvements in hepatic tumor control for patients with metastatic colorectal cancer may require higher doses of conformal radiation and/or improved radiosensitization. In an effort to increase radiosensitization, we have recently initiated a clinical trial combining IAH bromode-oxyuridine, a thymidine analog radiosensitizer, with conformal high dose radiation therapy.

Adult↗
PubMed1995

Mutagenicity testing of nine herbicides and pesticides currently used in agriculture.

Nine herbicides and pesticides were tested for their mutagenicity using the Drosophila sex-linked recessive lethal mutation assay. These are Ambush, Treflan, Blazer, Roundup, 2,4-D Amine, Crossbow, Galecron, Pramitol, and Pondmaster. All of these are in wide use at present. Unlike adult feeding and injection assays, the larvae were allowed to grow in medium with the test chemical, thereby providing long and chronic exposure to the sensitive and dividing diploid cells, i.e., mitotically active spermatogonia and sensitive spermatocytes. All chemicals induced significant numbers of mutations in at least one of the cell types tested. Some of these compounds were found to be negative in earlier studies. An explanation for the difference in results is provided. It is probable that different germ cell stages and treatment regimens are suitable for different types of chemicals. larval treatment may still be valuable and can complement adult treatment in environmental mutagen testing.

2,4,5-Trichlorophenoxyacetic Acid↗
PubMed1995

Inadequate response to H2-receptor antagonists. Absence of parietal cell cAMP-stimulating autoantibodies.

In peptic ulcer patients with adequate (AR; N = 16) and inadequate response (IR; N = 20) to H2-receptor antagonists, the presence of parietal cell cAMP-stimulating autoantibodies was studied. Serum Ig fractions from these patients and 10 control subjects were examined to test whether they could stimulate cAMP production in a gastric cell line model. The human cell line HGT-1 was found to be a sensitive in vitro model for the cAMP stimulation assay as histamine (10 microM) increased by 11-fold the production of cAMP. Neither IgG (4 mg/ml) nor IgG-free Ig fractions (1 mg/ml) isolated from the blood of AR or IR affected cAMP production in the HGT-1 cells. The results obtained with the cAMP stimulation assay were confirmed by indirect immunofluorescence measurements based on frozen sections of rat stomach and kidney. No specific staining of rat parietal cells could be observed with patient sera. In addition, human gastric biopsies of the oxyntic mucosa from the same patients were studied for immunoreactive cell populations to assess organ-specific autoimmune processes. Biopsy specimens from AR and IR showed increased lymphocytic infiltrates, usually associated with gastritis. However, no significant differences in location of various cell populations between AR and IR could be observed. Our findings do not support a recent hypothesis that poor response to treatment with H2-receptor antagonists is due to the presence of autoantibodies.

Animals↗
PubMed1995

Sleep complaints are common in a dialysis unit.

Sleep disturbance among uremic patients is reported to be high, but data on the actual prevalence, clinical significance, and causative factors is limited. A sleep questionnaire was distributed to an entire hemodialysis unit of 64 patients. Of the 54 patients who completed the survey, 83.3% had sleep-wake complaints. Disturbed sleep was reported by 28 patients (51.8%), and causes were secondary to delayed sleep onset in 25 patients (46.3%), frequent awakening in 19 patients (35.2%), restless legs syndrome (RLS) in 18 patients (33.3%), and generalized restlessness in six patients (11.1%). Daytime sleepiness was the most frequent complaint, reported by 36 patients (66.7%), and RLS was the second most frequent specific complaint, reported by 31 patients (57.4%). Symptoms of sleep apnea were described by seven patients (13.0%). Male gender, age more than 60 years, RLS, and caffeine intake were associated with more sleep-wake complaints (P = 0.009, P = 0.002, P = 0.028, and P = 0.008, respectively). Urea and creatinine levels were higher in patients with RLS (P = 0.04 and P = 0.08, respectively); otherwise, no other metabolic or demographic variable was associated with specific sleep disorders or disturbance. Sleep problems are very common in dialysis patients and likely contribute to the impaired quality of life experienced by many of these patients.

Adult↗
PubMed1995

Integration of free pulses in electrical self-stimulation of the rat brain.

Frequency thresholds for electrical self-stimulation of the medial forebrain bundle were estimated in rats while low frequencies of pulses were applied continuously. When continuous pulses were delivered to the same electrode that received the 0.5-s trains of response-initiated stimulation, thresholds decreased by the free-pulse frequency (Experiment 1), consistently across current (Experiment 2). Estimates of the reward added by concurrent, response-contingent stimulation of the opposite electrode of a bilateral pair predicted the drop in threshold caused by the noncontingent pulses applied to the opposite hemisphere (Experiment 3), again, robustly across test current (Experiment 4). Continuous pulses restricted to times between self-initiated trains lost their effect (Experiment 5). The perception of reward was invariant despite changes in the overall activity of the self-stimulation substrate.

Animals↗
PubMed1995

Distribution of leukocyte subtypes in the sheep ovary after laser drilling.

The distribution of leukocyte subtypes in the sheep ovary following laser drilling of the ovarian capsule was examined to understand a possible mechanism by which this treatment promotes ovulation in polycystic ovarian syndrome. Ovaries were removed from sheep at different time-points following laparoscopic laser drilling and immunohistochemical detection of leukocyte subtypes, using specific monoclonal antibodies; standard histological staining was performed. Migration of leukocytes into the laser-drilled site was observed as early as 6 h after laser drilling and the total number of leukocytes in the site was found to increase up to the 12th day after surgery. In the earlier period, polymorphonuclear leukocytes were the dominant leukocyte subtypes, while macrophages and lymphocytes were the major cellular components on the 12th day and later. These results show that the tissue changes in the ovary following laser drilling are consistent with a local inflammatory reaction. The prolonged appearance of numerous macrophages following the acute inflammatory phase could lead to the secretion of cytokines and other substances suggested to be important in promoting ovulation. These data indicate that part of the effectiveness of the laser drilling in polycystic ovarian syndrome may be attributable to the secretory products of these leukocytes.

Animals↗