Integration of local and central laboratory functions in a worldwide multicentre study: Experience from the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study.

BACKGROUND: Measurement of glucose in multiple Field Laboratories requires rigorous standardization when patients and caregivers are masked, unless predefined thresholds are met. Local misclassification of participants at the thresholds can introduce recruitment bias and adversely affect the integrity of study findings. PURPOSE: To describe the challenges and the approach to meeting them in measuring glucose, HbA1c, and C-peptide in the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study. HAPO is an observational epidemiologic study of 25 000 pregnant women from 15 centres in 10 countries, designed to clarify unanswered questions on associations of maternal glycemia, less severe than overt diabetes mellitus, with risks of adverse pregnancy outcome. METHODS: Glucose tolerance (75 g two-hour OGTT) is assessed locally at 24-32 weeks' gestation, with results masked if fasting and two-hour plasma glucose are

The use of dextromethorphan to treat repetitive self-directed scratching, biting, or chewing in dogs with allergic dermatitis.

OBJECTIVE: To evaluate the efficacy of oral dextromethorphan in dogs with a repetitive behavior problem (self-licking, self-chewing, and self-biting associated with chronic allergic dermatitis). ANIMALS: Fourteen dogs with chronic allergic dermatitis were enrolled in the study. Twelve dogs completed the study. PROCEDURE: The dogs were treated for 2 weeks each with dextromethorphan (2 mg/kg BID) and placebo in a randomized, double blind, crossover designed study. A dermatology score, including an assessment of affected areas of the integument and the level of self-directed behavior, was generated before and following each 2-week phase of the study. Owners were required to record daily the amount of time they spent with their dog and the amount of time that the dog was observed to be engaged in any of the specified self-directed behaviors. RESULTS: The percent of the observed time that the dogs were reported to be involved in self-directed behaviors was significantly less during the 2-week active drug treatment phase. The pruritus score component of the dermatology score also was significantly less during the active treatment phase. In addition, a dermatologist-rated global assessment was more favorable in 11 of 12 dogs following the active treatment phase. CONCLUSIONS: Dextromethorphan significantly reduces the percentage of time that allergic dogs spend self-licking, self-chewing, and self-biting. CLINICAL RELEVANCE: Dextromethorphan may be a useful adjunct in the management of self-directed behaviors associated with allergic dermatitis and possibly in other repetitive behaviors as well.

Prediction of Recurrent Events by D-Dimer and Inflammatory Markers in Patients with Normal Cardiac Troponin I (PREDICT) Study.

BACKGROUND: The independent predictive value of d-dimer and inflammatory markers for the risk of recurrent adverse events in patients with acute chest pain but normal levels of cardiac troponin I (cTnI) remains unclear. METHODS: We studied 391 patients admitted to the hospital in 1 year with acute ischemic-type chest pain. Creatine kinase-myocardial band isoenzyme (CK-MB) mass and cTnI levels were measured in initial and 12-hour samples. Soluble intercellular adhesion molecule (sICAM)-1, vascular cell adhesion molecule (sVCAM)-1, sP-selectin, sE-selectin, high sensitivity C-reactive protein (hsCRP), interleukin-6 (IL6), fibrinogen, and d-dimer levels were measured in initial samples. A 1-year incidence of death, myocardial infarction (MI), revascularization, or readmission with chest pain was determined (with death/MI as the primary end point). RESULTS: Patients with normal levels of CK-MB(mass) and cTnI (195/391[50%]) were at a lower risk than patients with elevated levels of CK-MB(mass) or cTnI, but still had an important incidence of events (77/195[39%]). Marker elevation was defined as >75th percentile (upper quartile). Elevated d-dimer levels (>580 ng/mL) was predictive of death/MI (odds ratio, 5.4; 95% CI, 1.5-20.2; P =.005). Elevated sP-selectin levels (>152 ng/mL; odds ratio, 3.2; 95% CI, 0.9-11.6; P =.06) trended to increased death/MI rates, with weaker trends for elevated levels of hsCRP (>7.1 mg/L), IL6 (>10.7 pg/mL), and ST depression. Other markers, other electrocardiogram changes, or classic risk factors were not predictive of death/MI. With a multivariate analysis, d-dimer and sP-selectin were found to be of independent significance for death/MI after adjustment for inflammatory, hemostatic, and electrocardiogram markers and d-dimer after adjustment for classic risk factors. CONCLUSION: Normal cTnI levels after acute chest pain does not confer absence of future risk. Concurrent assessment of d-dimer and inflammatory markers may improve risk stratification.

Suspected angina pectoris: a rapid-access chest pain clinic.

We prospectively evaluated a rapid-access chest pain clinic in terms of clinical diagnoses, outcomes, morbidity and mortality at 3 months follow-up in patients, and cost-effectiveness. All patients seen at the clinic from February 1999 to December 2000 were assessed. Referring doctors indicated the management they would have provided had the clinic been unavailable, to allow a cost-effectiveness analysis. Overall, 709 patients were referred, 471 (66%) from General Practitioners, 212 (30%) from Accident and Emergency doctors and 26 (4%) from other sources. All had recent onset, or increasing frequency of ischaemic-type chest pain (excluding those with suspected myocardial infarction or rest chest pain angina). Fifty-one (7%) had acute coronary syndromes, 119 (17%) had stable ischaemic heart disease, 144 (20%) had possible ischaemic heart disease, and 395 (56%) were considered to have non-ischaemic symptoms. Some 70% of patients were seen within 24 h. Only 57 patients (8%) were admitted. Had the clinic been unavailable, 160 patients would have been admitted. Out-patient cardiology appointments were arranged for 116 patients (16%), and 429 patients (60%) were discharged directly. Follow-up data at 3 months were obtained from 565/567 eligible patients (99.6%). No major cardiac events (death/myocardial infarction) occurred in those with non-ischaemic chest pain. There were five deaths (including one due to cancer) and three patients had a myocardial infarction (event rate 1%). There were eleven readmissions for angina: six were in patients with acute coronary syndromes, and four of these six were awaiting revascularization. The estimated net saving was pound 58/patient. A rapid-access chest pain clinic offers a prompt, safe and cost-effective service in a challenging group of patients.

Bedside blood ketone body monitoring.

The use of a reagent strip and reflectance meter for the bedside measurement of 3-hydroxybutyrate during the clinical management of diabetic ketoacidosis is described. Comparison of this method with a laboratory enzymatic assay shows good correlation (r = 0.97, p less than 0.05). Initial use in acute ketoacidosis suggests that knowledge of hourly changes in 3-hydroxybutyrate levels could be helpful in determining the optimum insulin dose.

Erythropoietic protoporphyria. The problem of a suitable screening test.

Erythropoietic protoporphyria (EPP) is characterized by increased red cell protoporphyrins and is included in the differential diagnosis of children presenting with photosensitivity. In the past 20 years, using the traditional solvent extraction qualitative screening test for blood porphyrins, the diagnosis of EPP had been missed in 9 out of 10 patients but recently, using fluorescence microscopy of erythrocytes, no patients with EPP have been missed. All 14 patients in Northern Ireland known to have EPP were recalled and it was found that fluorescence microscopic determination was positive in all cases. We recommend fluorescence microscopy as the screening test of choice for the detection of increased red cell porphyrins.

Suxamethonium induced myalgia and the effect of pre-operative administration of oral aspirin. A comparison with a standard treatment and an untreated group.

Eighty-four fit, unpremedicated patients who presented for routine surgery and received a standard anaesthetic technique were allocated randomly to three equal groups. Group 1 received tubocurarine 0.05 mg/kg before induction of anaesthesia. Group 2 received soluble aspirin 600 mg orally one hour before surgery, while Group 3 received no pretreatment. Aspirin prophylaxis produced a significant reduction in the incidence of subsequent suxamethonium-induced myalgia and the improvement was similar to that achieved with tubocurarine pretreatment. Pre-operative oral administration of aspirin effectively reduces muscle pains and avoids many of the complications associated with pretreatment with non-depolarising agents.

Michel's medium as a preservative for immunofluorescent staining of cutaneous biopsy specimens in dogs and cats.

Paired 3-mm skin biopsy specimens from 24 dogs and 11 cats with suspected autoimmune dermatopathies were stained with fluorescein-conjugated antisera. In each case, 1 specimen was immediately embedded in optimum cutting temperature compound, quick frozen to -30 C, processed, stained, and examined. The other sample was placed in Michel's transport medium, held for 7 days, and then processed, stained, and examined. The location, quality, and intensity of immunofluorescent staining (when positive) were then compared in the 2 specimens. There were no differences in the staining patterns between the specimens processed immediately and those held in Michel's medium, thus demonstrating the validity of preserving canine and feline skin biopsy specimens in Michel's medium for immunofluorescent examination.

Diagnosis and management of concurrent diabetes mellitus and hyperadrenocorticism in thirty dogs.

Concurrent diabetes mellitus and hyperadrenocorticism were diagnosed in 30 dogs over a 2-year period. Clinical signs included polyuria, hepatomegaly, polyphagia, abdominal distension, truncal alopecia, anorexia, and vomiting. Because of the similar clinical and laboratory findings for hyperadrenocorticism and diabetes mellitus, hyperadrenocorticism was initially overlooked in some dogs. Insulin resistance, characterized by high daily insulin requirements, developed in the diabetic dogs with untreated hyperadrenocorticism. Therapy with o,p'-DDD resulted in precipitous declines in insulin requirements. By lowering the dosage of o,p'-DDD and supplementing with glucocorticoids during the o,p'-DDD loading period, serious hypoglycemia was avoided. Control of coexisting hyperadrenocorticism lessened the severity of the diabetes mellitus, but insulin therapy remained a necessity in all dogs.

Canine hypothyroidism: a retrospective study of 108 cases.

Hypothyroidism, defined as a serum concentration of less than 70 ng of triiodothyronine (T3)/dl or less than 1.5 microgram of thyroxine (T4)/dl, or both, was diagnosed in 108 dogs by means of radioimmunoassay techniques. Both T3 and T4 values were determined in 96 dogs. Both values were low in approximately 50% (47/96) of the hypothyroid dogs; 25% (24/96) were T3 hypothyroid (low T3, normal T4), and 26% (25/96) were T4 hypothyroid (normal T3, low T4). The T3 values varied markedly between animals. Common clinical signs were alopecia, changes in coat (dryness, dullness, dandruff, scales, coarseness, and slow regrowth of hair), hyperpigmentation, and pyoderma. Doberman Pinschers, Great Danes, Poodles, Schnauzers, Irish Setters, and Boxers accounted for 50% (54/108) of the hypothyroid dogs. Therapy consisted of T4, T3, or combination T3 and T4 replacement. A good clinical response was observed with T4 replacement in 40.4% (19/47) within 2 months and in 21.3% (10/47) within 5 months. A poor clinical response was observed in 25.5% (12/47) after 6 months of therapy. Posttherapeutic evaluation was based on peak serum concentrations of T3 and T4, pretreatment (basal) thyroid hormone values, type of replacement therapy, dosage and time of sampling after treatment, concurrent clinical problems, and, most important, clinical response to thyroid replacement therapy.

Fleabite allergic dermatitis: a review and survey of 330 cases.

Clinical signs of acute fleabite allergic dermatitis (FAD) in dogs included intense pruritus and erythema. Dogs with chronic FAD had diminished pruritus. The primary lesion of FAD was a papule. Secondary lesions (hyperkeratosis and hyerpigmentation) were common. Diagnosis of FAD was based on history of flea infestation and on type and location of lesions. Intradermal testing with glycerinated flea antigen was of little diagnostic value. Treatment of FAD included (1) breaking the flea life cycle in the indoor and kennel environment by vacuuming and washing bedding as well as by the use of aerosol insecticides for fumigation, (2) minimizing flea infestation on the dogs by using insecticidal dips, baths, and flea collars, and (3) hyposensitization with flea antigen.