Audit of an anticoagulant clinic: doctor and patient knowledge.

Oral anti-coagulation with warfarin is increasingly required in the prophylaxis and treatment of vascular thrombosis and embolism. Unless the degree of anti-coagulation is maintained in the narrow therapeutic range either serious bleeding or failure to prevent thromboembolism may occur. Complications may occur in up to 31% of patients. We randomly sampled 50 patients attending an anticoagulant clinic and interviewed them. We found the PTR between 2.0-4.0 in 70% patients. Their records indicated that they attended 0.9 +/- 0.5 times per month, but the patients themselves said that they had 2.4 +/- 1.7 visits per month, lasting on average 1.9 +/- 0.7 hours per visit. The mean duration of therapy was 4.3 +/- 5.4 years [range 1 month to 26 years]. Many patients perceived that they had received no education about warfarin (23%) while the majority 67% of the remainder said their doctor had educated them. Concomitant aspirin was avoided by 74% patients but 14% considered it safe in combination with warfarin; 49% patients believed that alcohol was safe in combination with warfarin. When asked about the colours and strengths of warfarin tablets, 37% of our sample were completely correct, 9% were completely incorrect and 54% were partly correct. In 16% patients they could not describe their current therapy. As doctors may adjust warfarin dosage for patients in terms of tablet colour, we asked a sample of junior doctors about the colours or strengths of warfarin tablets: 10% were completely correct, one doctor knew none of the colours or strengths and the remainder had a partial knowledge. These studies suggest that the majority of patients on warfarin are cautious about therapy and are safe in their practices. However, we feel that a significant minority may be at risk from complications because of inadequate knowledge. We suggest that improving patient understanding by education may reduce complications and lead to more stable control of anticoagulant therapy.

Acetaminophen or ketorolac for post myringotomy pain in children? A prospective, double-blinded comparison.

Myringotomy with tube placement (BMT) is the most frequent surgical procedure performed in children. The purpose of this prospective, double-blinded study was to determine if 15 mg.kg-1 of acetaminophen (paracetamol) provides analgesia similar to that provided by ketorolac, 1 mg.kg-1, at a lower cost. One-hundred-and-thirty-two children, ages six months to nine years, scheduled for elective BMT were randomized to receive oral acetaminophen or ketorolac 30 min preoperatively. An Objective Pain Scale score was assessed upon arrival to the PACU and at five, ten and 20 min. Time of awakening, time of PACU and day surgery discharge and incidence of vomiting were recorded. Groups were comparable in demographics, side effects and time to discharge. Median pain scores were lower in the ketorolac group at five and ten min but no differences were seen at discharge nor in postdischarge analgesic requirements. Is ten min of better analgesia worth the cost of ketorolac? We conclude that the slight analgesic benefit from ketorolac does not justify its cost in this setting.

Use of 24 h ambulatory ECG recordings in the assessment of new chemical entities in healthy volunteers.

1. Ambulatory (24 h) cardiac monitoring (ACM) is frequently used to screen healthy volunteers before inclusion in trials of new chemical entities in man. We analysed 156 consecutive ACM recordings in 'healthy' volunteers (on no medication). 2. Only 20 (13%) of the recordings showed normal sinus rhythm throughout. 3. Supraventricular ectopics were the commonest abnormality (83%). Ventricular ectopics occurred in 11%; ventricular tachycardia (unsustained) in 2% and sinus pauses in 6.5%. One volunteer was found to be in atrial fibrillation throughout. 4. The data indicate that when ACM recordings are performed in the assessment of the effects of experimental drugs, guidelines are needed to assess 'normality' to suggest when cardiological investigation is needed and to assign causality of the arrhythmia to the new chemical entity. 5. Proposed guidelines are presented.

Hyperinsulinaemia is associated with stimulation of cholesterol synthesis in both type 1 and type 2 diabetes.

The effect of hyperinsulinaemia and hyperglycaemia on cholesterol synthesis was examined in lymphocytes from diabetic subjects. The first part of the study involved the provocation of hyperinsulinaemia by consumption of a carbohydrate-rich meal, in obese patients with Type 2 diabetes mellitus. Cholesterol synthesis was measured before and 4 h after completing the meal. Results were compared to groups of obese non-diabetic patients and to control subjects. Analysis of the three groups demonstrated that the percentage change in cholesterol synthesis was directly proportional to the percentage rise in serum insulin (r = 0.49, p < 0.05). This physiological study demonstrated that postprandial hyperinsulinaemia promoted cholesterol synthesis; however, we could not estimate the effect of the meal on cholesterologenesis. To study hyperinsulinaemia in isolation, we examined the effects of varying insulin infusion rates for 4 h at either low or high levels of serum glucose using the glucose clamp technique in young Type 1 diabetic patients. Cholesterol synthesis in lymphocytes was again measured before and after the study period. Hyperinsulinaemia stimulated cholesterol synthesis (+28.6%, p < 0.05) but hyperglycaemia alone did not exhibit this effect (-1.7% NS). The combination of hyperinsulinaemia and hyperglycaemia produced the greatest increase in cholesterol synthesis (+51.4%, p < 0.05) but this increase was not significantly different from hyperinsulinaemia alone. The percentage increase in serum insulin levels was again proportional to the percentage change in cholesterol synthesis (r = 0.46, p < 0.05).

The regulation of post-prandial cellular cholesterol metabolism in type 2 diabetic and non-diabetic subjects.

The purpose of the study was to determine the effect of diabetes on the regulation of postprandial cholesterol metabolism. Four groups of patients (n = 8 for each group) were examined: Type 2 diabetic patients with and without hypercholesterolaemia and non-diabetic subjects with and without hypercholesterolaemia. Serum lipoproteins, lipoprotein composition, cellular cholesterol, and cellular cholesterol synthesis were measured before and 4 h after a high calorie meal. The BMI for the hypercholesterolaemic diabetic patients of 31.5 +/- 0.95 (SEM) was significantly higher than that for the control group of 26.2 +/- 1.0 (p < 0.01). Fasting triglyceride levels were significantly higher in the normocholesterolaemic and hypercholesterolaemic diabetic patients and in the hypercholesterolaemic non-diabetic subjects (1.45 +/- 0.22, 2.27 +/- 0.34, and 1.58 +/- 0.18 mmol l-1, respectively) compared with normocholesterolaemic non-diabetic subjects (0.75 +/- 0.12 mmol l-1: p < 0.01). The normocholesterolaemic and hypercholesterolaemic diabetic subjects had significantly lower fasting serum high density lipoprotein (HDL) (1.06 +/- 0.08 and 1.04 +/- 0.06 mmol l-1) compared to the corresponding non-diabetic groups (1.29 +/- 0.11 and 1.45 +/- 0.17 mmol l-1, p < 0.05). The esterified/free cholesterol ratio of very low density lipoprotein (including chylomicrons VLDL-C) decreased postprandially in all groups with an overall decrease of 1.33 to 0.83 (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Shooting off fireworks: the successes and failures of an intensive, broad-based AIDS awareness campaign.

Broad-based AIDS awareness campaigns often involve media advertisements, posters and/or pamphlets intended to address a specific concern related to HIV/AIDS. They focus on safer sex, prevention for young adults, women's issues in relation to HIV, etc. During the autumn of 1991 a group of Manitoba AIDS organizations came together to organize, promote and deliver an eight-week AIDS Awareness Campaign that would address a broad spectrum of HIV/AIDS-related issues. Instead of attempting to solidify one prevention message, this campaign attempted to satisfy a variety of organizational agendas. Although it achieved its goals and was a very visible, but short-lived exercise in AIDS awareness, this campaign proved to be taxing on local community-based resources.

An assessment of the thermogenic effects of fluoxetine in obese subjects.

Fluoxetine is an antidepressant drug with weight reducing properties. To assess whether fluoxetine has an ability to promote diet induced thermogenesis (DIT), 30 obese subjects (BMI 30-45 kg/m2) underwent a double blind, randomized, cross-over trial of 60 mg fluoxetine versus placebo. A two week single blind, run-in period on placebo was incorporated into the study to allow for placebo responders. The first stage of the study lasted for 14 days followed by a six week cross-over wash-out phase and concluded with the second 14 day stage of the study. An estimate of resting metabolic rate (RMR) was measured by continuous indirect calorimetry using the ventilated hood technique. Metabolic measurements were performed on six occasions, immediately before the first tablet was taken in the first stage, 24 hours after the first tablet was consumed and on the last day of the first stage; these three recordings were repeated on the second stage of the study. On each occasion a control reading of RMR was taken for 30 minutes then DIT was measured for 90 minutes following a lemon and glucose drink (1 g/kg body weight). Whilst a significant weight reduction (1.16 kg, P less than 0.05) occurred in the active stage, no such effect was achieved in the placebo phase. No differences were found between the two stages with regard to RMR, total DIT, peak DIT and time taken to reach peak DIT. We conclude that fluoxetine does not stimulate metabolism and that the weight reduction after 14 days therapy is due to other mechanisms.

Familial cryptogenic fibrosing alveolitis: a case report.

A family of seven siblings is described, all of whom, developed finger clubbing during their third decade. Three of the seven developed cryptogenic fibrosing alveolitis (CFA). Of the remaining four siblings, two have died prematurely from conditions possibly associated with cryptogenic fibrosing alveolitis. The youngest two siblings remain asymptomatic at present. This paper reports one of the most concentrated incidences of the rare familial form of CFA.

Intranuclear helioid inclusions.

We have coined the term 'helioid inclusion' to describe a new type of single-membrane-bound intranuclear inclusion which contains one or more rounded bodies with radiating filaments (helioid bodies). Helioid bodies were not found in the rough endoplasmic reticulum in the cytoplasm, or in the cytoplasmic matrix, but a helioid body was seen in dilated rough endoplasmic reticulum included in a double-membrane-bound intranuclear pseudoinclusion. No firm conclusion regarding the genesis of helioid inclusions has emerged from our studies, but two possibilities exist: 1) that helioid bodies derive from modification of serous secretory granules sequestrated in an intranuclear inclusion; or 2) that they develop by condensation of the contents of the perinuclear cistern or rough endoplasmic reticulum subsequent to its sequestration in an intranuclear inclusion.

Rod-shaped organism in the liver of a patient with Whipple's disease.

Histological review of a liver biopsy from a patient with known Whipple's disease revealed a prominence of Kupffer cells containing PAS-positive granules. Electron microscopy revealed rod-shaped organisms in the Kupffer cells but the presence of these structures were not associated with overt liver injury. This is thought to be the first reported demonstration of these bacillary bodies in this location.

Mucinous (adenocystic) carcinoma of sweat glands with widespread metastasis. Case report with ultrastructural study.

An unusual case of mucinous adenocarcinoma of the sweat glands originating from the right axilla is described. Despite complete control of the primary tumor after local excision, diffuse metastatic lesions continued to appear in the scalp, face, upper and lower extremities, sacral and pelvic bones, and left posterior iliac bone marrow space. The tumors were radioresistant. Multiple trials of various chemotherapeutic regimens, including alkylating agents, antifolates, antipyrimidines, vinca alkaloids, and antineoplastic antibiotics, were ineffective. The cutaneous neoplasms were grossly round, smooth, red, glistening, and cystic and were filled with a gelatinous mucinous material. Microscopic and ultrastructural findings are described.

Morphologic and immunologic studies of a human colon tumor cell line (SW-48).

A permanent human tissue culture cell line (SW-48) has been established from an adenocarcinoma of the transverse colon. Cells in the center of early colonies were cuboidal and loosely bound; cells on the periphery of the same colonies were more columnar, the nuclei were displaced toward the basal region, and the free surface formed stunted microvilli. These columnar cells ofter aligned themselves to resemble normal absorptive tissue. Carcinoembryonic antigen (CEA) was identified by immunofluorescent microscopy on the surface membrane of the tumor cells. Significantly more CEA could be isolated from the culture medium than from the whole cells. On agar gel diffusion analysis with a monospecific anti-CEA serum (G.P. 32), SW-48 CEA and CEA preparations from solid tumors demonstrated complete identity.

Classification of human colorectal adenocarcinoma cell lines.

Eleven human colorectal adenocarcinoma cell lines established in this laboratory were classified into three groups based on morphological features (light and electron microscopy), modal chromosome number, and ability to synthesize carcinoembryonic antigen (CEA). Group 1 cell lines contained both dedifferentiated and differentiating cells growing in tight clusters or islands of epithelium-like cells; their modal chromosome number was about 47, and they synthesized small to moderate amounts of CEA. Group 2 cell lines were more dedifferentiated, were hyperdiploid, and synthesized small amounts of CEA. Group 3 cell lines were morphologically similar to those of Group 1 by light microscopy. They differed ultrastructurally by containing microvesicular bodies; the modal chromosome number varied from hyperdiploid to hypertriploid or they had bimodal populations of hypodiploid and hypertriploid cells, and they synthesized relatively large amounts of CEA. No correlation could be found between Broder's grade or Duke's classification of the original tumor and modal chromosome number or ability to synthesize CEA. These findings support Nowell's hypothesis that the stem line is different for each solid tumor, which makes it difficult to relate chromosomal changes to the initiation of the neoplastic state.