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Biomedical subjects

R G Jones

Publications and source records attributed to R G Jones.

At least 55 records · Page 3Linked to original sources

Experimental evaluation of ovine antisera to Thai cobra (Naja kaouthia) venom and its alpha-neurotoxin.

Conventional treatment of Naja kaouthia (Thai cobra) envenoming requires large volumes (up to 600 ml) of equine antivenom, which results in a high incidence of serum reactions. The inefficiency of the antivenom is assumed to be related to the high percentage (approx. 20%) of alpha-neurotoxin, a relatively weak and highly toxic immunogen, present in the native venom. First, antibodies to N. kaouthia venom were raised in sheep, which protected mice against challenge with whole venom. Second, ovine antibodies to the purified neurotoxin and to three different neurotoxin conjugates were developed and their neutralising abilities against either whole venom or neurotoxin were compared using murine ED50 tests. High titre antibodies, assessed by enzyme immunoassay and Western blot, were obtained from all four neurotoxin immunisation regimens. Neurotoxin conjugated to rabbit anti-sheep IgG produced the highest titres against both neurotoxin and whole venom. This antiserum provided protection against neurotoxin challenge but failed to protect against whole venom. Furthermore, the addition of neurotoxin antibodies to whole venom antiserum did not enhance the neutralisation efficacy of the latter. These findings raise the possibility that in mice other toxins apart from the neurotoxin may significantly contribute to the lethal effect of N. kaouthia venom.

Animals↗

Commercial assays for serum osteocalcin give clinically discordant results.

Serum samples from 9 healthy controls and from subjects with primary hyperparathyroidism (n = 5), Paget disease (n = 3), pregnancy (n = 5), glucocorticoid therapy (n = 5), postmenopausal osteoporosis (n = 10), and renal failure (n = 10) were used to assess the clinical agreement among eight commercially available assay kits for osteocalcin (OC). These kits differ in their assay configurations (six radioimmunoassays, two immunoradiometric assays), standards (five bovine, three human), and antibodies (six polyclonal, two monoclonal). Individual results were divided by the mean OC of the control subjects for each assay and expressed as percentage deviations. The expected wide variation in absolute OC concentrations between kits was only partially reduced by this transformation. Agreement was equally poor when absolute OC concentrations were compared with the reference ranges quoted by the manufacturers. The discordance was particularly marked in renal failure, presumably because of immunoreactive fragments, and in osteoporosis. Systematic differences could not be attributed to assay format, species source of standard, or antibody specificity. We conclude that results cannot be compared between assays even when normalized against healthy subjects, and that standardization is needed.

Adult↗

Superoxide formation preceding flight muscle histolysis in Solenopsis: fine structural cytochemistry and biochemistry.

In Solenopsis spp., muscle histolysis or breakdown is a normal process in females and is initiated in the flight muscles only immediately after a mating flight. Information regarding the presence of the oxyradical scavenging enzyme superoxide dismutase (SOD) and the formation of the radical oxygen intermediate superoxide (SO) during the early stages of flight muscle histolysis in this insect was investigated. In normal fibrillar flight muscles from control animals, SOD was immunolocalized to vesicular and tubular components of the sarcotubular system. Lanthanum tracer studies indicated that some of these SOD-positive structures might be tubulovesicles continuous with the extracellular space. Following the injection of virgin alates with experimental haemolymph obtained from artificially inseminated females, the membrane delimited elements of the sarcotubular system became increasingly swollen and dilated with time (from 60 to 120 minutes postinjection) with a concomitant decrease in SOD activity and an increase in oxyradical formation. Many similar vesicles were lanthanum-positive. SO was not seen in the sarcoplasmic vesicles and tubules of control insects. The biochemical quantification of SO release over a 2-hour period showed a marked increase in oxyradical formation following treatment with the experimental haemolymph in comparison to control insects. Also, the addition of superoxide dismutase depressed SO formation under these conditions. Despite the histochemical and biochemical changes seen in the muscles of experimental insects, by 2 hours post-treatment there was no evidence of muscle necrosis. From these studies on flight muscle histolysis/necrosis in Solenopsis it appears that the formation of oxyradicals might represent an early event in myopathogenesis and subsequent tissue involution. The generation of SO is more than likely to be associated with alterations in the normal structure, biochemistry and permeability of the biomembranes which delimit the sarcotubular system.

Animals↗

Febrile children with no focus of infection: a survey of their management by primary care physicians.

We mailed a checklist survey to 1600 randomly selected pediatricians, family practice physicians (FPPs) and emergency medicine physicians (EMPs) in the United States regarding their management of children with high fever and no focus of infection at various ages: 3 weeks; 7 weeks; 4 months; and 16 months. Completed questionnaires were returned by 211 of 600 (35.2%) pediatricians, 145 of 500 (29%) FPPs and 141 of 500 (28.2%) EMPs. Most pediatricians, FPPs and EMPs would hospitalize a 3- or 7-week-old infant with fever and most pediatricians and FPPs would treat infants of this age group empirically with antibiotics. Most pediatricians, FPPs and EMPs would not hospitalize a 4-month-old or a 16-month-old with high fever with no focus of infection but 44 and 25% of pediatricians, 38 and 24% of FPPs and 41 and 34% of EMPs, respectively, would treat a 4- and 16-month-old child with high fever and no focus of infection with antibiotics. The preferred antibiotic treatment for hospitalized 3- and 7-week-old infants was ampicillin plus gentamicin or ampicillin plus cefotaxime; for older outpatients preferred treatment was amoxicillin or ceftriaxone. We conclude that hospitalization and empiric antibiotic treatment of very young infants (< 2 months of age) with high fever and no focus of infection are preferred by most of the pediatricians, FPPs and EMPs surveyed. Nearly one-half of these physicians would treat 4-month-olds and a fourth would treat 16-month-olds with high fever and no focus of infection with antibiotics as outpatients.

Anti-Bacterial Agents↗

Isotretinoin therapy for acne vulgaris: a re-evaluation of the need for measurements of plasma lipids and liver function tests.

A retrospective analysis of patients receiving isotretinoin for acne was performed, in order to determine the necessity for routine testing of lipid profiles and liver function tests during therapy. Data were analysed from 209 individuals, 113 (69 males, 44 females) of whom had been treated with 1 mg/kg/day, and 96 (67 males, 29 females) with 0.5 mg/kg/day. There were no significant changes in any of the tests of liver function. There were significant elevations in both plasma cholesterol and triglycerides at 8 and 16 weeks (P < 0.01) for both dose schedules, which were significant in both male and female subjects (P < 0.001). All the individuals with elevated cholesterol (> 6.5 mmol/l) at 16 weeks had elevated cholesterol at the onset of therapy. Triglyceride concentrations were elevated at 8 weeks, but there was no further increase thereafter. It was not possible to predict which subjects would become hypertriglyceridaemic from pretreatment lipid estimations. In conclusion, there appears to be little evidence to support the previously recommended regular biochemical monitoring of liver function and lipid profiles in patients who are treated with isotretinoin for 16 weeks. It would appear prudent to ensure that there is neither liver disease nor hyperlipidaemia prior to the onset of therapy, and to determine the triglyceride response to therapy on one occasion after 4 weeks' treatment. This change in patient management should result in considerable savings both in patient time and in blood collection and analysis.

Acne Vulgaris↗

Trends in causes and treatment of infertility at Flinders Medical Centre, Adelaide, 1976-1989.

OBJECTIVE: To describe the causes of infertility among couples presenting to a fertility clinic over a period of 14 years. Changes in treatment methods over the same period are described. DESIGN: A retrospective analysis of records of patient age, date of first visit, duration and cause of infertility, treatment and outcome. SETTING: A fertility clinic set in a large public hospital. Patients are referred by both general gynaecologists and general practitioners. PATIENTS: From 1976 to 1989 (inclusive) 2895 couples who had engaged in unprotected intercourse for at least 12 months without conceiving attended the clinic. RESULTS: Three major diagnostic categories were considered; these embraced aetiological factors relating to semen, ovulation, and pelvic anatomy. Investigation of the causes of infertility after a couple's first visit showed these to be a semen defect in 22%, irregular cycles or anovulation in 29%, and a pelvic disorder in 57%. The incidence of semen defects as the cause remained constant between 1976 and 1989 while that of ovulation "problems" declined from 42% in 1976 to 13% in 1989. In contrast, the incidence of pelvic dysfunction increased from 40% in 1976 to 68% in 1989, predominantly due to an increased diagnosis of endometriosis. The principal treatments were ovulation induction/cycle regulation (51%), in-vitro fertilisation/gamete intrafallopian transfer (42%), and donor insemination (18%). CONCLUSIONS: Provided patient information is accurately and consistently recorded a Fertility Audit is a useful window on the activates of a Fertility Clinic and serves to highlight areas which warrant further investigation.

Adult↗

Use of the urinary protein creatinine index to assess proteinuria in renal transplant patients.

The use of 24-h urine protein collections for the assessment of proteinuria in renal transplant patients has been compared with the protein creatinine index (PCI) obtained from spot urine samples. Paired data from 148 patients showed a correlation of 0.77 (P less than 0.001) between 24-h protein excretion and the PCI. A PCI of 750 identified proteinuria of greater than 1.0 g/24 h with a sensitivity of 89% and a specificity of 93%. The predictive value of a positive test was 81% and that of a negative test 96%. Similar performance was observed for the detection of proteinuria of differing severities ranging from 0.5 g/24 h to 2.0 g/24 h. The use of spot testing was popular with both patients and staff, and reduced the sample handling cost to 15% of that of 24-h urine collection. We recommend that PCI be adopted as the standard outpatient test for the assessment of proteinuria following renal transplantation.

Adolescent↗

A nursing guide for patient care after percutaneous cardiopulmonary support.

Information is presented about a relatively new procedure being used in the critical care area. The percutaneous insertion technique for the initiation of cardiopulmonary bypass support (PCPS) has given new hope for patients who are considered high risk for elective coronary angioplasty and to those who suffer cardiopulmonary arrest in the cardiac catheterization laboratory or critical care unit. The initiation process of cardiopulmonary bypass support and the criteria for elective cases are reviewed and two case studies follow. Specific attention is given to the immediate postprocedural phase, where nursing responsibilities and prioritization of patient care are addressed. A nursing care guide is included.

Aged↗

Cryofixation, ultracryomicrotomy, and X-ray microanalysis of enterocytes from chick duodenum: vitamin-D-induced formation of an apical tubulovesicular system.

New methods of tissue preparation were developed to study the morphology and distribution of calcium ions in duodenal enterocytes from normal, rachitic, and vitamin D-replete (either cholecalciferol [CC] or 1,25-dihydroxycholecalciferol [1,25-DHCC] treated) chicks. Frozen hydrated sections were prepared from cryofixed tissues by ultracryomicrotomy at -125 degrees C. Sections were subsequently freeze-dried by increasing the temperature to -100 degrees C. The latter temperature was maintained throughout both the structural and elemental analyses. In cells from normal, rachitic, and vitamin D-treated [CC] animals the brush border from lanthanum-infused tissues was electron dense and calcium-lanthanum positive by x-ray analysis. In the absence of lanthanum, i.e., sucrose-infused duodena, the microvilli were still calcium positive. In the terminal web region of normal and CC-treated enterocytes, numerous, apparently interconnected, tubules and vesicles were seen. Vacuole-like structures were also seen. Such structures were especially prominent in the enterocytes from the vitamin-treated [CC] animals. Except for the vacuoles, the tubules and vesicles were electron dense in the lanthanum-infused duodena, and clear in sucrose-infused tissues. In both instances, the structures were calcium positive. Similar, but even larger structures were seen below the terminal web. Here however, the tubules and vesicles seemed to be organized into multiple complex interconnecting networks, i.e., tubulo-vesicular complexes. Both the tubules and the vesicles seemed to be interconnected via smaller channel-like entities. The extensiveness of this structure was better appreciated in the enterocytes from lanthanum-infused tissues, where it appeared similar in structure and complexity to an en face view of the sarcoplasmic reticulum of skeletal muscle. These intestinal complexes were less well developed, decreased in number, and quite often absent, in the apical cytoplasm of absorptive cells from rachitic chicks. In the enterocytes from animals treated for 24 hours with 1,25-DHCC, the same highly developed tubulo-vesicular networks were again seen in the enterocyte apical cytoplasm. They were even more developed in the 1,25-DHCC-treated animals. All structures were intensely calcium positive in enterocytes from both the lanthanum- and the sucrose-infused preparations. Numerous endocytotic (pinocytotic) vesicles were seen at the lumenal plasmalemma. Similar structures were also apparent in the terminal web region of the 1,25-DHCC-treated enterocytes. Exocytotic vesicles were seen at the apical aspect of the lateral cell membrane, below the level of the junctional complex. All components of this unique system contained high concentrations of calcium.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Antigenuria after immunization with Haemophilus influenzae oligosaccharide CRM197 conjugate (HbOC) vaccine.

We tested the urine of 30 infants 6 weeks to 7 months of age after they received standard 10-micrograms (0.5-ml) doses of HbOC (HibTITER) Haemophilus influenzae b (Hib) conjugate vaccine for the presence of Hib antigenuria using a commercially available latex particle agglutination assay (Directigen). Urines were collected within 1 hour, from 1 to 3 hours, at 24 hours and at 3, 6 and 9 days after vaccine administration and reactions were quantitated from 0 to 3+. In contrast to previous studies in older children which showed little or no antigenuria following HbOC vaccination, our study shows that in infants intense Hib antigenuria is evident within 2 to 3 hours and persists 3 days after vaccine administration and that less intense antigenuria may be detected in some infants for several days. With efficacious vaccines now being used in 2- to 6-month-old infants, invasive Hib disease may soon be limited to infants of this age just before their seroconversion. It should be recognized that antigenuria occurs for several days after vaccination with Hib conjugate vaccines and that it could be erroneously interpreted as evidence of invasive Hib infection.

Antigens, Bacterial↗

Mnemonic coding system for clinical data entry into laboratory computers: its effect on quality and efficiency.

A simplified coding method for entering the clinical details found on pathology request cards was developed. The method uses a basic four letter code, derived from the initial character of the first four words in a clinical detail, being expanded to four characters with letters from the final word if the number of words is less than four. Rules were devised to cope with common medical terminology. In excess of 90% of clinical details on request cards are readily input by clerical staff using our coding system, and 8% of clinical details are used intelligently by the computer in scheduling further tests or automatically commenting on results. A carefully designed coding system such as the one outlined above could greatly facilitate input of clinical detail without the penalty of reduced throughput.

Clinical Laboratory Information Systems↗

Use of immunoglobulin heavy-chain and light-chain measurements in a multicenter trial to investigate monoclonal components: I. Detection.

We assessed the combined use of serum protein electrophoresis (SPE) and nephelometric measurement of immunoglobulin heavy- and light-chain components for detecting serum monoclonal immunoglobulins (monoclonal components, MC) in 4788 unselected samples from 4173 patients. MC were detected in 514 samples from 390 patients. In 356 these were detected by SPE; the other 34 had a normal SPE pattern but an abnormal kappa:lambda light-chain ratio (KLR). Only 208 of the 356 (58%) samples with bands by SPE had abnormal KLRs. Samples with MC concentrations greater than 5 g/L had a higher proportion of abnormal KLRs (75%) than those with concentrations less than 5 g/L (42%). The KLR was abnormal in 13% of samples in which no MC were visible by SPE or immunofixation electrophoresis (IFE). Compared with quantitative measurements of immunoglobulin heavy and light chains, high-quality SPE remains the method of choice for the detection of MC. Quantitative methods, however, are able to detect additional MC, especially those containing free light chains, and in the absence of SPE and IFE will detect about 75% of MC present at greater than 5 g/L.

Antibodies, Monoclonal↗

Use of immunoglobulin heavy-chain and light-chain measurements in a multicenter trial to investigate monoclonal components: II. Classification by use of computer-based algorithms.

We describe a computer algorithm for classifying serum monoclonal proteins (MC) based on serum protein electrophoresis (SPE) and the automated measurement of kappa and lambda light chains and IgG, IgA, and IgM. We developed the algorithm by using a large database of unselected samples containing MC collected in a multicenter study. The performance of the algorithm was optimized by using iterative computational procedures and was tested on both the development database and on an independent set of MC-containing samples. With the development database, the algorithm correctly classified 50% and misassigned 2.5% of the MC. Where the MC were present in concentrations greater than 10 g/L, the rate of successful classification increased to 72% with 3% misclassification. When the algorithm was tested on a group of 101 MC-containing samples from an independent source, 67% were correctly classified and 8% misclassified, half of the latter being unusual IgD myelomas. We discuss the scope for the application of the algorithm in routine laboratory practice involving personal computer software.

Algorithms↗