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Biomedical subjects

S Nash

Publications and source records attributed to S Nash.

At least 19 recordsLinked to original sources

Social timing, clock genes and autism: a new hypothesis.

BACKGROUND: Timing and social timing deficits are fundamental in autism and may play a developmental role in its manifestation. Sleep problems are associated with this disorder, as is a reduction or loss of Purkinje cells associated with regions of the brain which co-ordinate fine motor movements. Genetic studies suggest that a number of genes of limited effect lead to autism and that the genes are epistatic. CONCLUSIONS: We suggest that anomalies in clock genes operating as timing genes in high frequency oscillator systems may underlie the timing deficits of autism. We outline how anomalies in methylation-related genes may also be implicated.

Animals↗

Are infants with autism socially engaged? A study of recent retrospective parental reports.

The purpose of this study was to identify the specific aspects of social engagement that distinguish infants with autism from infants of similar age and developmental level who do not have autism. Ten parents of preschoolers with autism and 10 parents of matched children without autism were given a semistructured interview, the Detection of Autism by Infant Sociability Interview (DAISI), which elicits reports on whether 19 aspects of social engagement characteristic of typically developing infants were present at some time during the child's first 24 months. The reports of infants with autism differed from those of the control group on 16 items. Findings suggest that infants with autism have marked limitation in both person-to-person and person-person-object social engagement, in keeping with the theory that autism involves impairments in primary as well as secondary intersubjectivity (Hobson, 1993a).

Autistic Disorder↗

Long-term maintenance of therapeutic cyclosporine levels leads to optimal graft survival without evidence of chronic nephrotoxicity.

Since the introduction of cyclosporine into clinical use, a major area of concern within the transplant community has been the fear of chronic nephrotoxicity. Although progressive renal damage does appear to occur in native kidneys of heart and liver transplant patients receiving cyclosporine, it has been our contention that its use is not a major cause of deterioration in renal allografts. We therefore undertook a study of 91 consecutive renal transplants performed over a three-year period with a minimum graft survival of 1 year and a follow-up of 7-9 years. Serial serum creatinine values, iothalamate clearances and cyclosporine levels were obtained at 3 months after transplantation and yearly thereafter. Biopsies were performed on all grafts that had failed as well as on the majority of patients with deteriorating renal function, and were interpreted by two nephropathologists. As measured by iothalamate clearances, 65% of the patients in this series exhibited absolutely stable renal function despite the maintenance of cyclosporine levels of more than 200 ng/ml for 7-9 years. Since these stable patients did not reveal any decline in renal function, it therefore follows that they did not experience chronic cyclosporine nephrotoxicity. Furthermore, none of the patients with declining renal function or with failed grafts showed any evidence of nephrotoxicity on biopsy. Chronic cyclosporine nephrotoxicity may be a cause of declining function or graft loss with renal transplant recipients, but if so, it is exceedingly rare.

Creatine↗

Stability of ceftazidime in a viscous eye drop formulation.

OBJECTIVE: To assess the stability of an extemporaneously prepared ceftazidime eye-drop. METHOD: Ceftazidime was formulated at a concentration of 5% w/v as an eye drop, using Sno Tears, an artificial tear solution containing polyvinyl alcohol, as a vehicle. Two batches of the formulation were stored in 10 ml eye drop bottles at 7 and 25 degrees C for up to 14 days. Ceftazidime and pyridine, its degradation product, were determined at intervals by HPLC. RESULTS: A yellow coloration was evident after 7 days at 7 degrees C and after 24 h at 25 degrees C. Ceftazidime lost approximately 35% after 7 days storage at 25 degrees C. At 7 degrees C, the mean time to 10% degradation, determined by linear regression, was 11 and 8 days for the two batches. However, the lower 95% confidence limits were 8 and 5 days, respectively. Pyridine levels increased during storage. The mass balance between ceftazidime remaining and pyridine formed was close to 100% during the early part of storage. By the end of storage, the balance had reduced to around 95% at 7 degrees C and 80% at 25 degrees C. This discrepancy may be due to sorption of pyridine to the butyl rubber bottle closure. The pH remained in the range 6-7 throughout the storage period. CONCLUSION: The formulation may be stored for 5 days in the refrigerator.

Ceftazidime↗

Endoscopic biopsy pathology of Helicobacter pylori gastritis. Comparison of bacterial detection by immunohistochemistry and Genta stain.

OBJECTIVES: To describe the endoscopic biopsy pathology of Helicobacter pylori gastritis, compare bacterial detection by immunohistochemistry using a specific antibody with the Genta stain, and to compare the relative costs of the 2 techniques. DESIGN: One hundred cases of gastritis identified as positive for H pylori by Genta stain and 100 cases considered negative by the same technique were stained using an anti-H pylori-specific polyclonal antibody. Laboratory reagent and labor costs for the 2 methods were compared. RESULTS: Chronic active gastritis with lymphoid follicles was significantly associated with H pylori infection (P <.0001). The immunohistochemical method had a sensitivity of 97% and a specificity of 98% compared with the Genta stain, with strong agreement for grading density of organisms (kappa = 0.85; P <.001). Reagent costs were similar for both methods, but immunohistochemistry using an autoimmunostainer required less dedicated technical time and hence was less expensive than the Genta stain. CONCLUSIONS: Immunohistochemistry using a specific antibody is an accurate and cost-effective method for H pylori detection in gastric biopsies.

Biopsy↗

Parental autobiographical memory: is this a helpful clinical measure in behavioural child management?

OBJECTIVES: The major hypothesis was that specificity scores on the Parent-Child Autobiographical Memory Test (PCAMT; Hutchings, 1996) would differentiate between mothers of children referred to a child and adolescent mental health service for behavioural management, and those who were not referred. Within the referred sample, the objective was to examine the relationships between the PCAMT, mental health (Beck Depression Inventory; Beck, Ward, Mendelson, Mock & Erbaugh, 1961; General Health Questionnaire; Goldberg, 1972) and socio-economic deprivation (SED5; Hutchings, 1996) and measures of outcome (Eyberg Child Behavior Inventory; Eyberg, 1980). DESIGN: Pre-treatment measures on the PCAMT for the group of mothers whose children were referred were compared with measures on the PCAMT from a group of mothers of non-referred children of similar ages. Within the mothers of the referred sample, correlations of the PCAMT with other measures were examined, pre- and post-treatment. METHODS: Pre-treatment PCAMT scores from 26 mothers of children with behaviour management problems from consecutive referrals to a child and adolescent mental health service were compared with PCAMT scores from 22 mothers of children of a similar age from a local playgroup. Within the referred group, the PCAMT was administered before (N = 26) and after (N = 16) treatment. The 16 treated families received behavioural management advice. RESULTS: The PCAMT distinguished between parents of children referred for behavioural management advice and a non-clinical sample. Within the referred group it also distinguished between those who received treatment and those who did not attend treatment. CONCLUSIONS: The PCAMT is considered to have the potential of being a useful instrument for identifying referred children whose mothers may not attend for treatment and possibly for identifying those mothers who would benefit most from concentrating on attending and observation skills in child management training.

Adult↗

Epilepsy in the accident and emergency department--developing a code of safe practice for adult patients. South East and South West Thames Accident and Emergency Specialty Sub-committees.

OBJECTIVES: To benchmark current practice in the management of adult patients presenting with seizures to the accident and emergency (A&E) departments by performing a comparative interdepartmental audit. To assess the quality and degree of completeness of documentation in A&E records and to develop a proforma for the documentation of any case presenting with a seizure which would incorporate management guidelines for use by A&E doctors. METHODS: This was a retrospective, criterion based audit carried out in 12 A&E departments in the South Thames region. It involved 1200 adult patients who presented to A&E departments after a seizure. The degree of completeness of A&E records was assessed using criteria identified by A&E consultants and neurologists. Guidelines for use in the management of patients with seizures have been produced. RESULTS: Important aspects of the history and examination were frequently unrecorded in patients' notes. The recording of vital signs was particularly poor. A diversity of practice was shown between the departments that were audited and the number of investigations performed in each department varied considerably. Hospital admissions for patients with first seizures varied widely between departments, ranging from between 34.6% to 91.7% of cases. Documentation of advice given to patients about driving was evident in just 0.9% of cases. CONCLUSIONS: Wide interdepartmental variation exists in both the quality of information recorded in A&E records and in the management of patients. Deficiencies could be minimised and potential improvements in the quality of documentation might be achieved by the introduction of a structured proforma incorporating pre-defined management guidelines.

Adolescent↗

Beclomethasone dipropionate 250 µg per dose metered dose inhalers: effect of Volumatic spacer on potentially respirable dose.

The aerodynamic particle size distribution of beclomethasone dipropionate from 250 µg per dose metered dose inhalers tested in conjunction with a Volumatic spacer, was studied using a multistage liquid impinger. The products tested were Becloforte (Allen and Hanburys), Becloforte (parallel import from Spain), Beclazone 250 (Norton Healthcare) and Filair Forte (3M Health Care). Tests were performed with either zero or 3 s time delay between actuation of the inhaler and sampling. Filair Forte gave significantly lower deposition than all the other products in both the <6.8 and <3.1 µm size ranges with both zero and 3 s residence times (49.8% less than Becloforte, UK-origin, at <6.8 µm, zero residence time). This was despite fitting well in the Volumatic. Testing a second batch of Filair Forte confirmed the low deposition results. The only other significant differences were greater depositions from Becloforte (Spanish) compared to Beclazone 250 (<6.8 µm, zero residence time and <3.1 µm, 3 s residence time) and between Becloforte (Spanish) and all the other products (<3.1 µm, zero residence time). The magnitude of these differences were, however, less marked than those shown by Filair Forte. Increasing the residence time of the aerosol in the Volumatic to 3 s, simulating how patients may use the inhaler/spacer combination, gave similar results to those obtained with zero residence time. Filair Forte, used with the Volumatic, delivered a relatively low dose in the potentially respirable size range, compared to Becloforte. No substantial differences were seen at <6.8 µm between Becloforte (UK or Spanish) or Beclazone 250. Further work would be required to determine the importance of the differences observed between the products in the <3.1 µm range.

Journal Article↗

Arousals and nocturnal respiration in symptomatic snorers and nonsnorers.

The purpose of the present investigation was to examine the relationship among upper airway resistance, snoring, and arousals, all measured simultaneously, in nonapneic snorers complaining of excessive daytime sleepiness (EDS). To accomplish this task, we selected a group of nine nonapneic snorers who presented because of snoring, EDS, tiredness, or fatigue. Ten healthy, alert, nonapneic, nonsnoring subjects recruited from among the hospital personnel acted as a comparison group. All subjects had nocturnal polysomnography, which included measurements of snoring, nasal and pharyngeal airway pressure, esophageal pressure, and total respiratory flow. Each polysomnogram was analyzed to identify all arousals and all respiratory events, i.e. apneas, hypopneas, and periods of increased upper airway resistance. Each arousal was examined to determine whether it was associated with a respiratory event, and each respiratory event was examined to determine whether it was associated with an arousal. The results were compared between snorers and nonsnorers. There was no significant difference between the two groups in the total sleep time (182+/-61 minutes in controls vs. 188+/-50 minutes in patients) or the total number of arousals per hour of sleep (24+/-12 in controls vs. 28+/-10 in snorers). However, the distribution of arousals, i.e. electroencephalogram (EEG) vs. respiratory, was different in snorers and nonsnorers. In snorers 55% of arousals were respiratory, whereas in nonsnorers only 17% of arousals were associated with respiratory events. Not unexpectedly, the snorers had significantly more respiratory events during the night (512) than controls (112). However, the relative proportion of these events that was accompanied by arousals was similar in both groups. We conclude that the difference in daytime function between symptomatic snorers and asymptomatic nonsnorers is unlikely to be due strictly to the number of arousals during the night; however, it is possible that respiratory and EEG arousals have different impacts on daytime performance, which may explain the difference in daytime function between our two groups.

Adult↗

Adenocarcinoma of the lung metastatic to the psoas muscle.

Hematogenous metastasis to the psoas muscle is rare, and the resulting clinical symptoms may mimic psoas abscess or hemorrhage. When the clinical history is not specific, CT is important in documenting the presence of a psoas mass and providing biopsy guidance for histologic diagnosis. Only three previously reported cases have been related to a primary carcinoma of the lung.

Adenocarcinoma↗

Gastric perforation in a case of gastric volvulus.

We describe a case of organoaxial gastric volvulus in which the axis was through the body of the stomach. The intraabdominal part of the volvulus was complicated by bleeding from two necrotic ulcers, one of which was perforated by the tip of a nasogastric tube.

Aged↗

Comparing perceptions and measurements of snoring.

The difficulty in measuring and quantifying snoring using objective criteria is that snoring is first and foremost of a subjective perception by a listener. To test the subjective perception of snoring and to compare it with objective measurements, we studied 25 patients referred to our laboratory because of snoring. All had full nocturnal polysomnography including measurements of snoring. Snoring sounds were recorded on paper and simultaneously stored on audiotape. The technologist scoring the polysomnogram counted the number of snores during a 20-minute segment. Two other technologists, unaware of the objective snoring count, listened to the audiotape and also counted the number of events that they perceived as snores. In 11 of 25 patients there was good agreement (within 25%) between the two listeners and the objective snore count. In another 7 of 25 patients there was good agreement between the listeners, but the objective snore count differed > 25%. In the last group of seven of 25 patients the difference in subjective snore counts perceived by both listeners was > 25%. The agreement between both listeners in judging snoring severity was moderate (weighted Cohen's kappa (w) = 0.49). We conclude that perception of snoring is highly subjective. We speculate that investigations studying consequences and treatment of snoring must employ either more sophisticated properly validated methods to measure snoring or alternatively resort to measurements of the underlying physiological abnormalities responsible for snoring, such as elevations in upper airway resistance.

Adult↗

Stability of bupivacaine hydrochloride with diamorphine hydrochloride in an epidural infusion.

The stability of diamorphine (0.02 mg/ml as the hydrochloride) in 250 ml bupivacaine hydrochloride (0.15% wt/vol infusion) was studied by high pressure liquid chromatography at temperatures in the range 7 to 45 degrees C. Diamorphine hydrochloride was degraded by approximately 0.13% per day at 7 degrees C. No bupivacaine hydrochloride degradation was detectable during the study. The storage life of the combination at 7 degrees C, based on the lower 95% confidence limit of the time to 5% diamorphine hydrochloride degradation, was 14 days. The stability at 25 degrees C was adequate to allow transport and administration over 24 h at ambient temperature. Stability was also maintained for at least 24 hr at 32 and 45 degrees C. Infusion of the mixture with an ambulatory infusion pump which uses a standard polyvinyl infusion bag is therefore possible. A study of its compatibility with different infusion pump medication reservoirs was not undertaken. The drugs were also stable on frozen storage at -18 degrees C for up to 6 months.

Analgesia, Epidural↗

A phase II trial of weekly infusional 5-fluorouracil in combination with low-dose leucovorin in patients with advanced colorectal cancer.

Exogenous leucovorin is a source of reduced folate which enhances the inhibition of thymidylate synthase that results from 5-fluorouracil (5-FU) administration. Extracellular reduced folate concentrations of 1 microM have been reported to yield maximal enzyme inhibition in several cell lines treated with 5-FU in vitro. Clinical studies indicate that low doses of leucovorin have equivalent efficacy to higher doses in successfully modulating 5-FU in the treatment of colorectal cancer. Based on pharmacokinetics at higher doses, steady-state total plasma reduced folate concentrations of 1 microM would be expected from the administration of leucovorin 50 mg/m2 by 24 h infusion. This dose was admixed with 5-FU 2300 mg/m2 and administered by 24 h-infusion weekly to 38 patients with advanced colorectal cancer, of whom 32 are evaluable for response. Disease sites included liver (33 patients), lung (12 patients), and bone (4 patients). Toxicity was mild to moderate, except for grade 3 diarrhea in 5 patients, and chest pain in 2 patients. Among the 32 evaluable patients, there were 14 partial remissions for a total response rate of 44% (95% confidence interval 27-61%). The median duration of response was seven (range 1 to 20+) months, and median duration of survival 16 months. These results support the use of low doses of leucovorin to modulate weekly infusional 5-FU in colorectal cancer, and provide a basis for the integration of this regimen with other modulators of 5-FU.

Adult↗