Is familial hyperparathyroidism a unique disease?

BACKGROUND: Familial hyperparathyroidism is a rare condition reported to behave more aggressively than sporadic hyperparathyroidism. METHODS: A retrospective (1975 to 1995) analysis was performed on 30 such patients. All patients had at least one first-degree relative with surgically treated hyperparathyroidism and no personal or family history of multiple endocrine neoplasia. RESULTS: There were 19 women and 11 men with a mean age of 39 years (range, 13 to 78 years). Fourteen patients (47%) had nephrolithiasis. The mean serum calcium level was 11.6 mg/dl (range, 10.5 to 15.3 mg/dl). Twenty-three primary and 15 repeat explorations (eight recurrent and seven persistent disease) were performed during the study period. Follow-up was obtained on all patients and ranged from 1 to 21 years (mean, 12 years). At the conclusion of the study, hypercalcemia (five recurrent and one persistent) was present in six patients (20%). CONCLUSIONS: Familial hyperparathyroidism is a distinct and unique entity. Patients are diagnosed at a young age and have a high incidence of nephrolithiasis. Long-term follow-up is mandatory because of the high incidence of both recurrent and persistent hyperparathyroidism. Surgical treatment should include subtotal parathyroidectomy and routine transcervical thymectomy performed in centers with experience in the management of multiple-gland parathyroid disease.     

Accelerated lung function decline in swine confinement workers

We conducted a longitudinal study to determine the annual rate decline in pulmonary function measurements in male swine confinement workers. For comparison, a grain farming group and a nonfarming rural-dwelling control group were also chosen for the longitudinal study. Two hundred seventeen swine confinement workers, 218 grain farmers, and 179 nonfarming control subjects had valid pulmonary function measurements at the baseline observation conducted in 1990 to 1991 and at the second observation conducted in 1994 to 1995. The swine confinement workers were younger (mean age=38.3+/-11.7 [SD] years) than the nonfarming control subjects (42.6+/-10.4 years) and the grain farmers (44.5+/-11.9 years). When stratified by age, nonfarming control subjects had the lowest mean annual rate decline in FEV1 and FVC in all age categories. The swine confinement workers had the largest annual rate decline in FEV1 and FVC, and this was most obvious in the middle age categories. After controlling for age, height, smoking, and baseline pulmonary function, swine confinement workers had excess annual decline of 26.1 mL in FEV1 (p=0.0005), 33.5 mL in FVC (p=0.0002), and 42.0 mL/s in forced expiratory flow between 25% and 75% of FVC (FEF[25-75%]) (p=0.02) over nonfarming control subjects. Grain farmers had excess annual decline of 16.4 mL in FEV1 (p=0.03), 26.7 mL in FVC (p=0.002), and 11.2 mL/s in FEF(25-75%) (p=0.38) over control subjects. These findings suggest that workers engaged in the swine industry and grain farmers appear prone to accelerated yearly losses in lung function and may therefore be at risk for the future development of chronic airflow limitation.     

Role of metabolism in ethyl carbamate-induced suppression of antibody response to sheep erythrocytes in female Balb/C mice

A possible role of metabolism by cytochrome P450 (P450) in ethyl carbamate-induced suppression of the antibody response to a T-cell-dependent antigen, sheep erythrocytes (SRBCs), was investigated in female Balb/C mice. When mice were treated with ethyl carbamate intraperitoneally for 14 consecutive days at 25, 50, 100, 200 and 400 mg/kg, the antibody response was significantly suppressed from 200 mg/kg. These doses also caused a decrease in thymus weight. An acute dosing of ethyl carbamate at 1 g/kg also caused not only a significant suppression of the antibody response, but also a decrease in thymus weight. The antibody response was most likely to be the IgM antibody response, which was demonstrated in a haemagglutination study. When mice were pretreated with phenobarbital (80 mg/kg) for 3 days to induce P450 enzymes, followed by administration of ethyl carbamate intraperitoneally for 7 consecutive days, the antibody response was more suppressed than in saline-pretreated controls. Moreover, a study using aminoacetonitrile, a P450 inhibitor, showed that the antibody response suppressed by ethyl carbamate was completely recovered by the inhibitor. The present results suggest that metabolism of ethyl carbamate by P450 may be the critical pathway to produce metabolites capable of suppressing the antibody response.     

Increased levels of plasma cholesteryl ester hydroperoxides in patients with subarachnoid hemorrhage

The pathophysiology of subarachnoid hemorrhage (SAH) may involve free radical production and lipid peroxidation. We examined plasma levels of cholesteryl ester hydroperoxides (CEOOH) and antioxidants in 25 patients with SAH, and 10 neurologic controls with lacunar stroke. Patients with SAH had significantly increased plasma levels of CEOOH, which peaked on day 5 after the ictus. Concentrations of CEOOH were significantly increased, and ascorbic acid concentrations were significantly decreased in patients who developed vasospasm compared with patients without vasospasm. Increased levels of CEOOH were associated with increased mortality and correlated with clinical outcome scales. These results implicate oxidative stress in the pathogenesis of SAH and suggest that measurements of CEOOH in plasma may be useful both prognostically as well as in monitoring therapeutic interventions.     

Obesity, eating disorders and restrained eating: is leptin the missing link?

Prior to the general availability of Haemophilus influenzae type b vaccine in the Republic of Ireland, a two-year study of the epidemiology of invasive Haemophilus influenzae disease was carried out. Of 137 invasive strains of Haemophilus influenzae examined in a central laboratory, 94.2% were serotype b and 90.5% were biotype I. Seventeen percent of serotype b strains produced beta-lactamase, and 2.3% were resistant to both ampicillin and chloramphenicol. The majority of serotype b strains were electrophoretic types of the electrophoretic 12 clone family, principally 12.5. Meningitis was the most common infection caused by serotype b. The study data extend the current knowledge of strains of Haemophilus influenzae causing invasive disease in the Republic of Ireland.     

Diagnostic value of p53 protein and flow cytometric DNA analysis in the study of serous effusions

OBJECTIVE: To investigate the diagnostic value of p53 protein and DNA analysis in the study of serous effusions. STUDY DESIGN: A total of 76 samples of serous effusions were studied by immunohistochemistry for p53 protein and flow cytometric (FCM) DNA analysis. The results were correlated with final cytologic diagnoses, which were confirmed by immunohistochemistry using antibodies against cytokeratin, carcinoembryonic antigen, epithelial membrane antigen and fibronectin. RESULTS: Final cytologic diagnoses included 28 malignant effusions and 48 benign effusions. No expression of p53 protein was seen in benign effusions. In contrast, p53 protein expression was seen in 19/28 (sensitivity 68%) malignant effusions. FCM detected aneuploid cells in 12/28 (43% sensitivity) of malignant and 0/46 of benign effusions. Immunohistochemical determination of p53 protein combined with FCM DNA analysis increased sensitivity to 79%. CONCLUSION: Immunohistochemical determination of p53 protein and FCM DNA analysis can aid in making an accurate and specific diagnosis of serous effusions, but the principal limitation of these tests is their relatively low sensitivity.