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Biomedical subjects

E Wilkinson

Publications and source records attributed to E Wilkinson.

At least 19 recordsLinked to original sources

The epidemiology of burns in secondary care, in a population of 2.6 million people.

The numbers of residents of the four counties in the west of Anglia and Oxford Region (UK) who were treated for burns (including scalds) in accident and emergency (A&E) departments or admitted to hospital in 1994-95 were obtained from A&E departments and district health authority records. Burns comprised about 1 per cent of the workload in the A&E departments. Using the data from district health authorities, the rate of admission with a main diagnosis of burns to any hospital was 0.14 per thousand population per year. Children under five had the highest rate of admission. Approximately half the patients admitted to hospital with burns were admitted to burns units, a quarter to plastic surgery wards and the rest to different specialties including trauma and orthopaedics, paediatrics, and ophthalmology. The median length of stay was 6 days for burns units and 3 days for plastic surgery units.

Adolescent

Inherited somatic mosaicism caused by an intracisternal A particle insertion in the mouse tyrosinase gene.

A recessive, fully penetrant mutation (c(m1OR)) at the mouse albino locus that results in coat-color mottling has been characterized at the molecular level. Restriction mapping and DNA sequencing analyses provide evidence that mutants carry a 5.4-kb intracisternal A particle (IAP) element insertion upstream of the tyrosinase (Tyr) promoter. Northern blot analysis and reverse transcription-PCR results show that the tyrosinase gene is expressed at much lower levels in mutant than in wild-type mice. The mutant Tyr gene still retains the tissue-specific expression pattern, and the Tyr transcript is not initiated from the IAP long terminal repeat promoter. We propose that the IAP insertion isolates the promoter of the tyrosinase gene from upstream cis-acting regulatory elements, leading to a substantially decreased level of Tyr gene expression in mutants.

Animals

Trial of two bandaging systems for chronic venous leg ulcers.

A four-layer bandaging system developed at Charing Cross Hospital has been found to be effective in healing chronic venous ulcers but is not available on the Drug Tariff. An alternative system was devised from bandages available on the Drug Tariff and a community-based randomised controlled trial was undertaken to compare the two systems. Twenty-nine patients with a total of 35 ulcerated legs were recruited. Equal numbers of ulcerated legs healed using the two compression systems. Nineteen ulcerated legs did not heal, of which six were withdrawn from the trial-two in the trial system and four in the Charing Cross system. Of the 13 remaining ulcerated legs, for which treatment was completed, the mean reduction in ulcer area was 34% with the trial system and 39% with the Charing Cross system. The change in ulcer area was not statistically significant. However, a much larger trial is required in order to demonstrate definitively that the two bandaging systems are equivalent.

Bandages

Lack of effect of thyroxine in patients with Graves' hyperthyroidism who are treated with an antithyroid drug.

BACKGROUND: Antithyroid drugs are effective in patients with hyperthyroidism due to Graves' disease, but the rate of recurrence after treatment is high. In a recent Japanese study, adjunctive treatment with thyroxine (T4) was associated with a recurrence rate 20 times lower than that among patients who received only an antithyroid drug. If these results are confirmed, combined therapy with an antithyroid drug and T4 might become the treatment of choice for all patients with Graves' hyperthyroidism. METHODS: We treated 111 patients (89 women and 22 men) who had Graves' hyperthyroidism. All patients initially received 40 mg of carbimazole daily for one month. Then one group received carbimazole alone for 17 months (52 patients), and the other group received carbimazole plus T4 for 17 months and T4 alone for 18 months (59 patients). In the carbimazole group, the dose was adjusted after one month to maintain a normal serum thyrotropin concentration. In the carbimazole-T4 group, the dose of carbimazole was not changed, but 100 micrograms of T4 per day was added to the regimen and the dose was adjusted to maintain an undetectable serum thyrotropin concentration (< 0.04 microU per milliliter). RESULTS: At the time of our analysis, 53 of the 111 patients had completed at least 3 months of follow-up (median, 12 months) after carbimazole was withdrawn. Hyperthyroidism recurred in eight patients in each group after a mean (+/- SD) of 6 +/- 4 months in the carbimazole group and 7 +/- 4 months in the carbimazole-T4 group. There was no difference between the recurrence rates in the two groups, despite the fact that serum thyrotropin concentrations were undetectable in 73 percent of patients in the carbimazole-T4 group on at least 75 percent of their visits. CONCLUSIONS: The administration of T4 to patients with Graves' disease during carbimazole treatment and after its withdrawal neither delays nor prevents the recurrence of hyperthyroidism.

Adult

Disease in the scurfy (sf) mouse is associated with overexpression of cytokine genes.

The murine X-linked lymphoproliferative disease scurfy is similar to the Wiskott-Aldrich syndrome in humans. Disease in scurfy (sf) mice is mediated by CD4+ T cells. Based on similarities in scurfy mice and transgenic mice that overexpress specific cytokine genes, we evaluated the expression of cytokines in the lesions of sf mice by Northern blotting, quantitative reverse-transcription polymerase chain reaction (RT-PCR) and by hybridization in situ. Overall, the phenotypic characteristics of scurfy disease correlated well with increased interleukin (IL)-4 (lymphadenopathy), IL-6 (B cell proliferation, hypergammaglobulinemia), IL-7 (dermal inflammatory cell infiltration), and high levels of tumor necrosis factor-alpha (wasting).

Animals

Relationship of admission thyroid function tests to outcome in critical illness.

One hundred and eighty patients had serum thyrotropin, total triiodothyronine and free thyroxine concentrations measured within 3 h of admission to the Intensive Therapy Unit to assess whether thyroid function tests could predict outcome in critical illness. Overall mortality was 30.6%. Nonsurvivors were older (p = 0.001), and had higher APACHE II scores (p < 0.001) and predicted mortalities (p < 0.001). There was no difference in the median values of thyrotropin, total triiodothyronine and free thyroxine concentrations between survivors and nonsurvivors. Thyrotropin concentration was subnormal in 15 patients, normal in 152 and elevated in 13 patients. In contrast, 80 patients had subnormal triiodothyronine concentration. Free thyroxine was subnormal in five patients. Thyrotropin, total triiodothyronine and free thyroxine concentrations were not related to outcome (p = 0.360, p = 0.622, p = 0.726, respectively). No variable independently predicted death. Total triiodothyronine concentrations were lower in patients who received dopamine before admission to the intensive therapy unit than those who did not (p = 0.008); thyrotropin and free thyroxine concentrations were not influenced by dopamine administration. Serum concentrations of thyrotropin, total triiodothyronine and free thyroxine measured within 3 h of admission to the intensive therapy unit are not predictive of outcome.

Adolescent

Interlaboratory/intermethod differences in functional sensitivity of immunometric assays of thyrotropin (TSH) and impact on reliability of measurement of subnormal concentrations of TSH.

Clinically relevant interassay precision profiles for thyrotropin (thyroid-stimulating hormone; TSH) were constructed with human serum pools measured over 4-8 weeks by six immunometric assays, in at least two different reagent lots. Functional sensitivities (the concentration at which the interassay CV is < or = 20%) were determined in four to eight clinical laboratories plus the respective manufacturer's laboratory. These studies revealed that the manufacturer's stated functional sensitivity limit is rarely duplicated in clinical practice. Loss of specificity (indicated by artifactually high values) was seen with some methods when used to measure certain unrefrigerated low-TSH sera. Measurement of TSH in four human serum pools (TSH < 0.05-0.25 mIU/L) by 16 different methods (each in at least eight UK or US laboratories) showed that some methods could not reliably distinguish subnormal from normal TSH values. Better pool rankings and fewer misclassifications of low-TSH sera as "normal" were seen with use of assays capable of "third-generation" functional sensitivity (0.01-0.02 mIU/L) than with assays with "second-generation" functional sensitivity (0.1-0.2 mIU/L). Because inter- and intramethod differences in functional sensitivity negatively impact the diagnostic accuracy and cost-effectiveness of a TSH-centered thyroid-testing strategy, laboratories should independently establish an assay's functional sensitivity by a clinically relevant protocol. Moreover, manufacturers should assess functional sensitivity more realistically and improve the robustness of assays to ensure that their performance potential is consistently met in clinical practice.

Drug Stability

Chemiluminescent third-generation assay (Amerlite TSH-30) of thyroid-stimulating hormone in serum or plasma assessed.

We assessed the laboratory performance and clinical utility of a new commercial third-generation assay of thyroid-stimulating hormone (TSH), Amerlite TSH-30. The interassay CV was 6% at TSH concentrations of approximately 0.08 mIU/L, and the analytical and functional detection limits of the assay were 0.005 and 0.0125 mIU/L, respectively. Although the assay recovered approximately 96% of TSH International Reference Preparation (TSH-IRP) 80/558 added to serum samples, the endogenous TSH concentrations in basal samples were significantly lower than those found by using two other TSH assays; bias data obtained from thyroliberin stimulation tests suggested that the negative bias found with TSH-30 may be due to the heterogeneity of TSH in basal samples. TSH-30 completely discriminated hyperthyroid and hypothyroid patients from euthyroid ambulatory patients but also detected TSH (> 0.0125 mIU/L) in 3 of 46 untreated hyperthyroid patients. Compared with two second-generation assays, TSH-30 better discriminated between patients with subnormal TSH due to hyperthyroidism, thyroxine overreplacement, and nonthyroidal illness but there was still significant overlap between results for these groups.

Bias

Expression of the whey acidic protein in transgenic pigs impairs mammary development.

The whey acidic protein has been found in milk of mice, rats, rabbits and camels, and its gene is expressed specifically in mammary tissue at late pregnancy and throughout lactation. A characteristic of whey acidic protein is the 'four-disulfide-core' signature which is also present in proteins involved in organ development. We have generated six lines of transgenic pigs which carry a mouse whey acidic protein transgene and express it at high levels in their mammary glands. Transgenic sows from three lines could not produce sufficient quantities of milk to support normal development of healthy offspring. This phenotype appears to be similar, if not identical, to the milchlos phenotype exhibited by mice expressing whey acidic protein transgenes. Mammary tissue from post-partum milchlos sows had an immature histological appearance, which was distinct from that observed during normal development or involution. Expression of the whey acidic protein transgene was found in mammary tissue from sexually immature pigs from milchlos lines, but not in sows from lines that appeared to lactate normally. We suggest that precocious synthesis of whey acidic protein impairs mammary development and function. Impaired mammary development due to inappropriate timing of whey acidic protein expression is consistent with the notion that proteins with the 'four-disulfide-core' signature participate in tissue formation.

Aging

Fluid, blood, and blood product management in the craniofacial patient.

This report is a retrospective review of the perioperative management of 56 children who underwent craniofacial surgical procedures. The use of a combination of 5% dextrose in normal saline or 5% dextrose in Ringer's lactate and normal saline resulted in postoperative sodium values in a normal range. In patients receiving a combination of 5% dextrose and electrolyte No. 48 and normal saline, the mean postoperative sodium level was 130 mEq/l with 9 of 18 patients below 130 mEq/l. Two patients in the series suffered clinical seizures on postoperative day 1 as a result of serum sodium levels of 122 and 121 mEq/l, respectively. We recommend that only solutions with a sodium content between 77 and 154 mEq/l be used routinely in the perioperative management of craniofacial patients.

Adolescent

The clinical utility of a non-isotopic two-step assay (DELFIA) and an analogue radioimmunoassay (SimulTRAC) for free thyroxine compared.

The analytical and diagnostic performance of a new non-isotopic, two-step immunoassay (DELFIA) for the measurement of free thyroxine (free T4) in plasma or serum has been compared with an established second generation analogue radioimmunoassay (SimulTRAC). Both methods had a good diagnostic specificity in pregnancy, thyroid clinic patients, and patients taking anticonvulsant drugs. In patients presenting to a general medical ward the diagnostic specificity of both methods was poor. Two samples appeared to contain substances which produced assay interference by DELFIA but not by SimulTRAC assays. When free T4 was measured by equilibrium dialysis a clear association between sample dilution and free T4 concentration was demonstrated in sick euthyroid patients. In contrast, using samples obtained from patients with known thyroid disease, free T4 was little influenced by sample dilution. The effects of sample dilution on free T4 measured by DELFIA were similar to those found using equilibrium dialysis. It would appear that free T4 measurements have a relatively poor diagnostic specificity in non-thyroidal illness irrespective of the method used.

Anticonvulsants

Unrecognized invasive carcinoma in vulvar intraepithelial neoplasia (VIN).

Sixty-nine patients having had pretreatment biopsy diagnosis of vulvar intraepithelial neoplasia were treated with surgical excision of all visible lesions. Complete surgical specimens were submitted for pathological study in an attempt to identify occult invasive vulvar carcinoma. Unsuspected invasion was noted in 13 patients (18.8%). Superficial invasion (less than 1 mm) was seen in 8 patients, 4 had greater than 1 mm of invasion, and one verrucous carcinoma was identified. Patients of advancing age with disease that had a raised and irregular surface pattern were more likely to have lesions with occult invasion. Treatment that utilizes ablative techniques cannot be recommended based on the use of preoperative representative biopsies.

Adult

Aneurysms of the basilar artery treated with circulatory arrest, hypothermia, and barbiturate cerebral protection.

Complete circulatory arrest, deep hypothermia, and barbiturate cerebral protection are efficacious adjuncts in the surgical treatment of selected giant intracranial aneurysms. These techniques were utilized in seven patients, one with a large and six with giant basilar artery aneurysms; four had excellent results, one had a good result, one had a fair outcome, and one died. The rationale for the use of complete cardiac arrest with extracorporeal circulation, hypothermia, and barbiturate cerebral protection is outlined. The surgical and anesthetic considerations are reviewed. The perioperative morbidity and long-term results support the use of these techniques in selected patients with complex intracranial vascular lesions.

Aged

Pressure care.

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Aged

Colposcopic findings in women with vulvar pain syndromes. A preliminary report.

Of 105 women referred for vulvar discomfort, 77 had idiopathic vulvodynia (pain, dyspareunia, burning or pruritus not explicable by a standard diagnosis). Physical examination showed that patients with those complaints fell into one of two categories: (1) diffuse, irritative acetowhitening of both the cutaneous and mucosal surfaces (42 patients), and (2) painful vestibular erythema, with or without acetowhitening (35 patients). The physical findings appeared to be predictive of therapeutic response. Among women with only diffuse, irritative acetowhitening, low-dose topical 5 fluorouracil was about 75% effective in milder cases, while CO2 laser photovaporization controlled 77% of cases with moderate and severe symptomatology. In contrast, medical regimens succeeded in just 8% of women with painful vestibular erythema, and only 59% were cured by hymenal resection. Several of the remaining cases have responded to selective argon laser photocoagulation of the hyperemic blood vessels within symptomatic areas.

Adolescent

Clinicopathologic, renal immunofluorescent, and light microscopic features of glomerulonephritis in the dog: 41 cases (1975-1985).

In a 10-year retrospective study, we evaluated the clinicopathologic features and renal immunofluorescence patterns of glomerulonephritis in 41 dogs. On the basis of results of histologic examinations, the dogs were segregated into 3 groups, including membranous (n = 12), mesangioproliferative (n = 15), or membranoproliferative glomerulonephritis (n = 14). No significant differences existed among groups in regard to age or duration of illness. Most dogs had been ill for one month or longer. The proportion of dogs with azotemia, anemia, and hyperphosphatemia were not different among the disease groups. Proportion of dogs with hypoalbuminemia and the severity of hypoalbuminemia were not different among groups. Highest urine protein losses and 24-hour urine protein/creatinine ratios developed in dogs with membranous glomerulonephritis. Although hypoalbuminemia and hypercholesterolemia were common (49%), the formation of edema or ascites was not (15%) and, therefore, few dogs had all of the classic features of the nephrotic syndrome. Few dogs suffered thromboembolic complications. Antinuclear antibody titers developed in 11 dogs, the highest titers developing in dogs with polyarthritis and systemic lupus erythematosis. Cellulose acetate electrophoresis detected alpha 2 and beta 1 globulin spikes in most dogs (87%). Results of renal immunofluorescence testing were positive in 36 dogs, using polyvalent antisera for immunoglobulins (Ig)G, IgA, IgM, and/or antisera for complement factor C3. When monovalent antisera for IgG, IgA, and IgM, and fibrinogen were used, immunofluorescence was not observed as often. The major fluorescent pattern was discrete multifocal segmental granular glomerular fluorescence, consistent with immune-complex deposition. Two dogs had linear glomerular staining patterns; however, antibodies directed against normal glomerular basement membrane were not found via elution studies. A high prevalence of glucocorticoid excess (treatment with glucocorticoids and spontaneous hyperadrenocorticism) (34%), chronic inflammatory skin disease (27%), neoplasia (17%), polyarthritis (12%), and systemic lupus erythematosis (7%) were observed as clinical problems concurrent with glomerulonephritis. In 5 dogs, treatment of glomerulonephritis with prednisolone (0.5 to 1.1 mg/kg) did not result in beneficial effects and in fact appeared to be detrimental, leading to azotemia and worsening proteinuria and physical condition in some of the dogs.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals

Surgical management of large AVM's by staged embolization and operative excision.

A series of 20 patients with giant arteriovenous malformations (AVM's) managed with staged embolization and surgical resection is presented. Complete excision was accomplished in 18 of these patients. There were no deaths and only three complications, of which one was disabling. Further evidence for the presence of low perfusion surrounding the AVM, emphasizing the risk of normal perfusion pressure breakthrough, is provided by cortical perfusion pressure, cortical cerebral blood flow (CBF), and stable xenon computerized tomography CBF measurements. The staged approach to giant AVM management is a proposed method to render AVM's that were previously considered inoperable or marginally operable into totally excisable lesions, while maintaining an acceptable level of morbidity and mortality.

Adolescent