Paget's disease of the breast in a man without underlying breast carcinoma

A case of histologically confirmed Paget's disease of the breast in a 72 year old man, without underlying breast carcinoma, is reported. This report raises questions about the pathogenesis of this condition and suggests that Paget's disease is an independent, intraepidermal carcinoma rather than a direct extension of intraductal carcinoma of the breast to the nipple and areola.     

Association of symptoms of depression with diagnostic test charges among older adults

BACKGROUND: Previous studies have documented greater use of health services by depressed persons and have postulated that health care costs could be reduced overall through better recognition and treatment of depression. OBJECTIVE: To determine whether a greater burden of medical illness contributes to excess charges for diagnostic tests among older adults with symptoms of depression. DESIGN: Prospective cohort study. SETTING: A primary care group practice at an academic institution. PATIENTS: 3767 patients 60 years of age and older who completed testing on the Centers for Epidemiologic Studies Depression Scale (CES-D) during routine office visits. MEASUREMENTS: Charges for all inpatient and ambulatory diagnostic testing for 2 years, including clinical pathology, diagnostic imaging, and special procedures; number of visits to the ambulatory care center or emergency department; and number of hospitalizations. The Ambulatory Care Group case-mix approach, which is based on ambulatory diagnoses, was used as a measure of health status and expected resource consumption. RESULTS: Patients with symptoms of depression (CES-D scores > or = 16) were significantly younger (66.6 compared with 68.1 years; P < 0.001), more likely to be white (50.5% compared with 33.9%; P = 0.001), and more likely to be female (75.8% compared with 67.6%; P = 0.001) than were those without these symptoms (CES-D scores < 16). They also had more nonpsychiatric comorbid conditions, had more visits to the ambulatory care center (9.2 compared with 7.8; P < 0.001), were more likely to use the emergency department (52.3% compared with 40%; P = 0.001), were more likely to be hospitalized (22.4% compared with 17%; P = 0.002), and had greater median total diagnostic test charges for a period of 1 year ($583 compared with $387; P < 0.001). The difference in charges, most of which were clinical pathology charges (54.2%), persisted into the second year. Ambulatory Care Group assignment was independently associated with diagnostic test charges. The CES-D summary score was not independently associated with diagnostic test charges when controlling for Ambulatory Care Group assignment. CONCLUSIONS: Patients with symptoms of depression accrue greater average diagnostic test charges. However, these data suggest that such patients also have a greater burden of comorbid nonpsychiatric illness. Efforts to improve outcome and decrease cost for patients who have late-life depression must target interventions to improve the care of psychiatric and medical illness concurrently.     

Adverse effects of dental local anaesthesia

This paper considers the adverse effects that a patient may suffer as a result of anticipating an injection of dental local anaesthetic. Although most of these are extremely rare (a testimony to good technique), the dental practitioner should be aware of the possibility of their occurrence and of ways to deal with them.     

Ascorbic acid is a stimulatory cofactor for mitochondrial glycerol-3-phosphate dehydrogenase

We describe in this report a sensitive and direct method for the analysis of tamoxifen (TAM) in microsamples of plasma. The drug and internal standard (quinine bisulfate, I.S.) were separated on a 10-microm particle, 10 cm X 8 mm CN cartridge in conjunction with a radial compression system. The mobile phase was a mixture of 0.1 M sodium acetate in 0.001 M tetrabutylammonium phosphate solution (pH 6) and methanol (30:70, v/v) at a flow-rate of 4 ml/min. After addition of I.S. and o-phosphoric acid in acetonitrile (0.6 M) to the plasma (30 microl), the mixture was placed in an ultraviolet shortwave transluminator for 2 min prior to injection into the chromatograph. The compounds were detected in the effluent fluorometrically at excitation and emission wavelengths of 258 and 378 nm, respectively. Under these conditions, no interference in the assay from any endogenous substance or other concurrently used drugs was observed and the retention times of I.S. and TAM were 4.4 and 10.15 min, respectively. The concentration of TAM in plasma was linearly (r>0.9983) related to the peak height ratio (TAM/I.S.) in the range 0.01-2.0 microg ml(-1) and C.V. at 0.075, 0.4 and 1.2 microg ml(-1) was < or = 4.96%. We are currently using this assay for monitoring TAM in plasma and investigating its pharmacokinetics in cancer patients receiving cytotoxic drugs in addition to TAM as a multi-drug resistance modifier.     

Circulating angiotensin II and renal sodium handling in man: a dose-response study

1. Animal studies have shown that angiotensin II has a biphasic effect on urinary sodium excretion. To examine whether this is also true in man, we studied seven salt-replete male subjects in a single-blind placebo-controlled manner. 2. While undergoing maximum diuresis, subjects were infused with 0, 1, 2, 5 or 10 ng of angiotensin II min-1 kg-1 over 80 min. Subjects were studied while seated, and stood every 20 min for urine collection. 3. Angiotensin II produced a dose-dependent antidiuretic effect. The urine flow rate, in ml/min expressed as the change from baseline with increasing dose of angiotensin, was: +3.4 +/- 1.77, -1.26 +/- 0.49 (P < 0.05), -2.75 +/- 1.23 (P < 0.05), -4.21 +/- 0.82 (P < 0.05) and -6.51 +/- 1.07 (P < 0.01). 4. In contrast, the effect of angiotensin II on sodium excretion showed a flat dose-response curve beyond 5 ng min-1 kg-1. The urinary sodium excretion, in mumol/min expressed as the change from baseline with increasing dose of angiotensin, was: 9.5 +/- 21.2, -18.9 +/- 29.6, -37.0 +/- 11.6 (P < 0.05), -67.7 +/- 19.6 (P < 0.01) and -63.8 +/- 14.3 (P < 0.01). 5. The fractional distal reabsorption of sodium, determined by using the lithium clearance technique, showed a rise with all doses of angiotensin II used and reached statistical significance with the top two doses. 6. Unlike antidiuresis, antinatriuresis after graded doses of angiotensin II in human subjects showed a flat dose-response curve beyond 5 ng min-1 kg-1. Pressor doses of angiotensin II also have a significant effect on the distal tubule in promoting sodium reabsorption.     

Cardiovascular effects of conventional sulfonylureas and glimepiride

Sulfonylureas have, in the past, been reported to have adverse cardiovascular effects. Glimepiride is a new sulfonylurea. In spite of stimulating less insulin secretion, it has, depending on the species, equal or higher blood glucose decreasing activity and according to preliminary studies less cardiovascular activity than glibenclamide. Further studies were performed to confirm the lower cardiovascular activity of glimepiride. The IC50 for inhibition of rilmakalim-activated KATP channel currents in isolated ventricular myocytes was 31.6 nM for glimepiride and 6.8 nM for glibenclamide. In endotoxin shock-rats at a dose of 1 x 2 mg/kg i.v., glibenclamide induced a significantly higher blood pressure increase than glimepiride. At two i.v. doses of 20 mg/kg 4 min apart, in normal rats, glibenclamide produced signs of ischemia in the ECG in nearly all animals, glimepiride almost none, in diabetic rats, glibenclamide produced in all animals a lethal cardiogenic shock preceeded by serious ECG changes, glimepiride only in one fifth of the animals. In open-chest dogs, on intracoronary infusion of equieffective blood glucose-lowering doses, glibenclamide, gliclazide and glimepiride all reduced coronary blood flow, increased coronary resistance, depressed the mechanical activity of the heart, enhanced myocardial O2-extraction, reduced the serum potassium level and induced a moderate endocardial ST-segment elevation, but glimepiride to a significantly less extent than glibenclamide and gliclazide. The presented data confirm that glimepiride at equivalent blood glucose decreasing doses has less cardiovascular activity than conventional sulfonylureas.     

Intestinal metaplasia with adherent Helicobacter pylori: a hybrid epithelium with both gastric and intestinal features

Helicobacter pylori seem to avoid areas of intestinal metaplasia in the gastric mucosa, but attachment of these bacteria to epithelium with the appearance of incomplete intestinal metaplasia has been documented. To characterize the nature of the epithelium to which H pylori was attached, we carried out an immunohistochemical study using monoclonal antibodies against gastric surface mucous cell mucins (M1), blood group-related carbohydrates antigens (Le(a), sialyl Le(a), Le(b), type 1H, and type 2H) and sialyl Tn antigen. The results of this study suggest that these areas of H pylori attachment represent a hybrid epithelium whose cells share characteristics of both gastric surface mucous cells and intestinal metaplastic cells. Whether all areas of incomplete intestinal metaplasia represent an intermediate stage between the normal gastric epithelium and the fully developed complete type of metaplasia remains to be determined.     

Study of the beta -delayed neutron decay of 18N

The shortage of suitable liver donors for children has motivated the use of ABO-incompatible (ABO-I) grafts for transplantation in urgent situations. However, survival after ABO-I liver grafts has been reported at about 30% as compared with 80% in cases of ABO-identical or -compatible liver grafts. This difference has been attributed to antibody-mediated, hyperacute or chronic liver rejection, due to preformed ABO antibodies (alloantibodies). In this study, we report our results with ABO-I livers in children without alloantibodies at the time of transplantation. From January 1988 to June 1993, 143 OLT were performed in 122 children. Eight children received 8 ABO-I liver grafts. Of these, 7 patients were included in the study. All 7 were alloantibody free before OLT. Five children were spontaneously alloantibody free, while in 2 children, the plasma alloantibodies were eliminated before and after transplantation using intravenous infusion of specific blood group antigens of the donor blood group (soluble antigens). Immunosuppression consisted of a triple-drug treatment combining CsA, AZA, and steroids. The follow-up period was between 10 and 48 months. One child died from a surgical complication. Six children survived, but 1 died 10 months later from intestinal obstruction. There were no graft losses and no episodes of hyperacute or chronic rejection. The graft and patient survival rate was 71%. There was a 28% incidence of rejection, but all were mild (requiring steroid boluses only). Our results suggest that the absence of ABO alloantibodies at the time of and after transplantation can protect ABO-I liver grafts against antibody-mediated rejection, whether hyperacute or chronic, and that soluble antigens are effective in eliminating alloantibodies in children.