Improving vaccine storage in general practice refrigerators.
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Biomedical subjects
Publications and source records attributed to H Kelly.
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1. The enteric nervous system is perhaps the most accessible part of the mammalian nervous system in which it is feasible to attempt large scale computer simulation that is based closely on experimentally determined data. Here we summarize the data obtained for simulation of motility reflexes in the guinea-pig small intestine. 2. The chemistry, morphology and connectivity of each type of neuron involved in intrinsic reflexes have been investigated and most classes of neurons are physiologically well characterized. This includes primary sensory neurons, ascending and descending interneurons and motor neurons to circular and longitudinal muscle. 3. The responses of primary sensory neurons and the physiology of synaptic transmission from sensory neurons to interneurons and motor neurons, from interneurons to interneurons and from interneurons to motor neurons have been recorded during reflexes and in some cases the pharmacology of transmission has also been investigated. 4. Computer simulation, in which the activities of up to 30,000 neurons are modelled, produces patterns of activity that closely mimic those recorded in physiological experiments.
OBJECTIVE: To determine the effectiveness of the measles vaccine and to record the morbidity during a measles outbreak. METHODOLOGY: A retrospective cohort study was carried out. It was a community-based study in Bunbury, Western Australia, between February and May 1994, of 53 cases of measles and their household contacts. RESULTS: Of the 53 cases of measles, 24 were from one high school. Only two cases occurred in the high school class that had received the National Health and Medical Research Council of Australia recommended measles, mumps and rubella (MMR) booster 12 months earlier. Neither had been vaccinated. Vaccine effectiveness was 91% (95% confidence interval 67-97%). Ten cases had complications of measles and a further five were admitted to hospital. Doctors prescribed antibiotics to 29 cases and metoclopramide to five cases. One month elapsed between the day the index case became ill and the first notification to the community health centre. CONCLUSIONS: The low herd immunity that led to this high school outbreak can be attributed to low vaccine coverage. There was a significant morbidity associated with this outbreak that may have been averted if earlier notification had occurred. The MMR booster dose should be offered to all 10-16 year olds to prevent high school outbreaks.
In 1994, the Scottish Needs Assessment Programme (SNAP) carried out a stocktaking review of all needs assessment reports in 14 topic areas produced in Scotland on the previous three years. National needs assessment documents from England in the relevant topic areas were also reviewed. The review identified two particular points for comment. First, in respect of content, the definition of need as "the ability to benefit'-while appropriate for NHS purchasing- must be balanced by a greater emphasis on the wider concerns for the public's health. At the same time, relevant economic and costing information should be incorporated. Secondly, the process of information collation for purchasing could be made more efficient. Closer links between clinical experts and public health specialists would ensure assessments based on timely opportunities for change. National reviews should provide generally applicable intelligence and comparative analyses; short local reports can then focus on local quantification and priority setting.
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The health practices and needs of two samples of older individuals with mental retardation were examined and contrasted over a period of 5 years. Their health status varied markedly, but most had poor health maintenance practices, and almost all had difficulty communicating with health care providers. Those who lived in community residential facilities or relatives' homes usually had adequate health care provided for them, whereas individuals who lived more independently had difficulty accessing health care. There is a pressing need for health care advocacy programs to help prevent chronic disability.
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The frequencies of Bgl 11 and BamH1 restriction fragment length polymorphisms (RFLP) of C beta, V beta 8, V beta 11 and V beta 7.2 have been defined in a healthy Australian population. Linkage disequilibrium between alleles of the T cell receptor (TCR) V beta 8 and V beta 11 gene segments has been confirmed. We have also confirmed the lack of linkage disequilibrium between either of these loci and alleles at C beta or V beta 7.2. Using RFLPs at V beta 11 and V beta 8 loci TCR beta haplotypes have been identified in five families in which the probands have insulin-dependent diabetes mellitus (IDDM). An extremely rare haplotype, marked by the higher molecular weight BamH1 allele (H, H) at each of V beta 11 and V beta 8, was found in the DR4+ DR3- probands of two families (P = 0.004). In three families in which the probands had DR3, the more common TCR haplotype LH (V beta 11, V beta 8) was found. Taken together, these data confirm that linkage disequilibrium does exist in the TCR beta locus, at least in some regions, and suggest that detailed analysis of the relationship between TCR V beta haplotypes and HLA is warranted since these RFLPs may be markers for important allelic V gene sequence variations.
PURPOSE: Complications of grafts infected with coagulase-negative staphylococci can be eradicated by antibiotic administration, tissue debridement, and in situ graft replacement, but successful treatment may be diminished in a setting of altered immune function. METHODS: In a canine model of an established aortic graft infection from Staphylococcus epidermidis, outcomes after in situ replacement were compared between normal dogs and animals made immune-deficient by administration of azathioprine (50 mg/day) and prednisone (10 mg/day). In situ replacement of an infected infrarenal aortic graft with either antibiotic-bonded (silver-ciprofloxacin: Ag-cipro) or conventional polytetrafluoroethylene (PTFE) grafts was performed in 17 control and 18 immune-deficient animals. RESULTS: Four weeks after implantation of a Dacron graft colonized with a biofilm of S. epidermidis, all study animals demonstrated a bacterial biofilm infection with perigraft inflammation or abscess, and in immune-suppressed dogs the incidence of perianastomotic aortitis was increased (p < 0.05). Six weeks after in situ replacement both the Ag-cipro and conventional PTFE grafts were healed without signs of infection in controls, but anatomic evidence of persistent infection and increased S. epidermidis recovery was observed in immune-suppressed animals that underwent in situ replacement of a standard (five of seven) versus antibiotic-bonded (one of 11) PTFE graft (p < 0.006). Overall in situ replacement with an antibiotic-bonded graft yielded a lower frequency of S. epidermidis recovery (two of 19 Ag-cipro graft biofilm with positive culture results versus nine of 16 conventional graft biofilm with positive culture results; (p < 0.003). CONCLUSIONS: This study supports the efficacy of in situ replacement for low-grade graft infections caused by S. epidermidis in normal hosts and demonstrates superiority of antibiotic-bonded grafts in immune-deficient hosts.
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Binding of D-Penicillamine (D-Pen) to human monocytes was examined by flow cytometry with fluorescent D-Pen conjugate. Cells from HLA DR1-positive healthy females bound significantly more D-Pen than cells from DR1-negative healthy females (P = 0.015), and DR1 was associated with the highest binding among HLA DR antigens. In contrast, DR4 was associated with the lowest binding in healthy females. A difference in D-Pen binding between healthy females who were DR1-positive, DR4-negative and those who were DR1-negative, DR4-positive was statistically significant (P = 0.026). Neither healthy females nor healthy males showed significant associations of D-Pen binding with HLA A, B, or C antigens, nor did healthy males show an association between strength of D-Pen binding and any DR antigens.
107 patients with insulin-dependent diabetes mellitus (IDDM) were typed for HLA A, B, C-, and DR antigens, and for complement C4A, C4B, and Bf alleles, and the results were compared with those of a combined reference group of 332 appropriately matched healthy subjects. Supratypes (allelic combinations) were identified from the phenotype of each group, and it was shown that the frequency of several supratypes is increased in patients with IDDM, in particular supratypes (A1 Cw7) B8 C4AQ0 C4B1 BfS DR3 (P = 0.0001), (A30 Cw-) B18 C4A3 C4BQ0 BfF1 DR3 (P = 0.0003), (A2 Cw3) B62 C4AR C4B2.9 BfS DR4 (P = 0.0002), and three other supratypes including DR4. It was also shown that increases in the frequency of individual alleles are secondary to increases in supratype frequency. Moreover, supratypes appeared to interact; the presence of two relevant supratypes being particularly important. The absolute risk of IDDM was approximately 0.5 in subjects who were homozygous for B18 C4A3 C4BQ0 BfF1 DR3. We concluded that genetic susceptibility is best recognized by MHC supratypes rather than isolated alleles, and that supratype combinations make the identification of even greater disease risk possible.
HLA antigens, complement allotypes, insulin antibodies and thyrogastric autoantibodies were determined in 69 patients with Type 1 (insulin-dependent) diabetes defined by a tendency to ketosis, non-obesity and insulin requirement within 2 years of diagnosis. Analysis of HLA and C4 allotypes suggested that Type 1 diabetes was associated with only certain DR3- and DR4-containing supratypes. Low antibody response to insulin was associated with all HLA-DR3, being present in 89% of those with DR3 compared with 48% of those without. Thyrogastric autoantibodies were associated with a null allele at the C4A locus, usually with HLA-B8-C4AQO-C4B1-BfS-DR3. These results indicate that, unlike Type 1 diabetes, low insulin antibody response was associated with all HLA-DR3. Thyrogastric autoantibodies, on the other hand, were associated with a null allele at the C4A locus. It is probable that while interaction between certain HLA-DR3 and DR4-containing supratypes is important in conferring susceptibility to Type 1 diabetes, other manifestations of autoimmunity are associated with supratypes containing C4AQ0, and in particular the diabetogenic supratype HLA-B8-C4AQ0-C4B1-BfS-DR3.
The presence of overacting inferior oblique muscles in A-pattern esotropia is a rarely documented finding. During the last three decades, three basic schools of thought have evolved to explain A and V patterns. In certain cases an individualized approach synthesizing these three theories is needed. We saw two patients with paradoxical A-pattern esotropia with inferior oblique muscle overaction. Both cases were treated surgically by weakening both inferior oblique muscles with recession and supraplacement of both medial rectus muscles. The synthesis of these two approaches resulted in good postoperative alignment.
In this simple and rapid "high-performance" liquid-chromatographic method for determining nitrazepam in plasma, serum, or whole blood, the sample at pH 7.4 is extracted into diethyl ether with an internal standard (prazepam), chromatographed, and detected at 280 nm with a fixed-wavelength ultraviolet detector. A specimen, together with standards and a quality control, can be analyzed in duplicate within 90 min. The limit of sensitivity is 5 micrograms/L (nitrazepam and 7-acetamidonitrazepam) and 50 micrograms/L (7-aminonitrazepam), and no interferents have been found. This method has the advantages of a small sample requirement and complete resolution of nitrazepam and the above-mentioned major metabolites. We have used this method for analysis of therapeutic and overdose concentrations of nitrazepam, and to investigate the stability of the drug in blood.
Guinea-pig seminal vesicles reabsorbed Na+ and K+ in vivo from a standard bicarbonate buffer against both electrical and chemical gradients. Water was reabsorbed with the ions. Concentrations of Na+ and K+ in the reabsorbate were greater than in plasma or the initial buffer perfusate. Guinea-pigs castrated for 6 days did not reabsorb water or electrolytes, but daily administration of testosterone or 5 alpha-dihydrotestosterone restored normal reabsorption rates. Addition of prostaglandin E-2 to the perfusate inhibited water and Na+ reabsorption. Section of the hypogastric nerve did not affect reabsorption rates measured 10 days later. We suggest that the guinea-pig seminal vesicle maintains a basal reabsorptive capacity to remove electrolytes and water that diffuse or are secreted into the lumen and that the reabsorptive pump may be coupled to a secretory one activated intermittently and perhaps partly modulated by prostaglandins.
Clonogenic growth (colony-forming efficiency, CFE) of i.v. injected allogeneic W256 tumour cells in the lungs was markedly enhanced by treatment of rats with alpha-naphthyl thiourea (ANTU) injected i.p. from 2 h before to 2 h after the tumour cells. ANTU specifically increases pulmonary vascular permeability in adult rats and causes acute pulmonary oedema and pleural effusion. Inhibition of drug toxicity to the lungs by tachyphylaxis, specific antimetabolites or iodides did not abolish the effect of ANTU on CFE. CFE was not increased when cells were seeded by i.v. injection the lungs affected by advanced pulmonary oedema at 6 to 24 h after treatment with drug. ANTU did not enhance growth of intratracheally injected cells. Although ANTU has no cytotoxic or immunosuppressive action, treatment of tumour-immunized rats with ANTU caused apparent "breakdown" of tumour immunity in 50% of rats, by causing growth of tumour colonies in the lungs. Possible mechanisms for the ANTU-induced decrease in innate resistance to growth of tumour in the lungs are discussed.