Humoral hypercalcaemia of malignancy: metabolic and histomorphometric studies during surgical management of the primary tumour

Several aspects of calcium metabolism were studied in five patients during the surgical exploration of malignant tumours associated with humorally-mediated hypercalcaemia. Before operation in all patients the renal tubular threshold for calcium reabsorption was raised and the threshold for renal tubular phosphate reabsorption depressed. On removal of the primary tumour in three cases, serum calcium returned to normal, renal calcium threshold fell, renal phosphate threshold rose, but urinary hydroxyproline excretion did not change. In two patients where the tumour proved inoperable, serum calcium remained elevated and no changes in renal calcium threshold or phosphate threshold occurred. Histomorphometry carried out on biopsy specimens from four patients showed normal bone resorption in three, and slightly increased resorption in one, without depression of osteoblastic bone formation. It is suggested that hypercalcaemia in these patients resulted mainly from an alteration in renal calcium threshold caused by a humoral substance released by tumour cells. Correction of hypercalcaemia on removal of the primary tumour was achieved rapidly and could be explained principally by a reduction in renal calcium threshold with increased loss of calcium into the urine. These data contrast with those of many previous studies which have emphasised the predominant role of accelerated osteoclastic bone resorption as the principal cause of hypercalcaemia in malignancy and suggest that a renal effect of the putative humoral agent may predominate in some cases.     

Pharmacokinetics,safety and tolerability of three dosage regimens of buccal adhesive testosterone tablets in healthy men suppressed with leuprorelin

We used a randomised, double-blind, crossover design to evaluate the pharmacokinetics, safety and tolerability of three doses of buccal adhesive testosterone tablets (BATT). Twenty-four healthy men, whose endogenous testosterone was suppressed to 相似文献   

Development of a non-targeted metabolomics method to investigate urine in a rat model of polycystic kidney disease

Aim: The purpose of this research was to use metabolomics to investigate the cystic phenotype in the Lewis polycystic kidney rat. Methods: Spot urine samples were collected from four male Lewis control and five male Lewis polycystic kidney rats aged 5 weeks, before kidney function was significantly impaired. Metabolites were extracted from urine and analysed using gas chromatography–mass spectrometry. Principal component analysis was used to determine key metabolites contributing to the variance observed between sample groups. Results: With the development of a metabolomics method to analyse Lewis and Lewis polycystic kidney rat urine, 2‐ketoglutaric acid, allantoin, uric acid and hippuric acid were identified as potential biomarkers of cystic disease in the rat model. Conclusion: The findings of this study demonstrate the potential of metabolomics to further investigate kidney disease.     

Do people become healthier after being promoted?

This paper examines the hypothesis that greater job status makes a person healthier. It begins by successfully replicating the well-known cross-section association between health and job seniority. Then, however, it turns to longitudinal patterns. Worryingly for the hypothesis, the data-on a large sample of randomly selected British workers through time-suggest that people who start with good health go on later to be promoted. The paper can find relatively little evidence that health improves after promotion. In fact, promoted individuals suffer a significant deterioration in their psychological well-being (on a standard General Health Questionnaire (GHQ) mental ill-health measure).     

Welfare state regimes,health and health inequalities in adolescence: a multilevel study in 32 countries

Comparative research on health and health inequalities has recently started to establish a welfare regime perspective. The objective of this study was to determine whether different welfare regimes are associated with health and health inequalities among adolescents. Data were collected from the ‘Health Behaviour in School‐aged Children’ study in 2006, including 11‐ to 15‐year‐old students from 32 countries (N = 141,091). Prevalence rates and multilevel logistic regression models were calculated for self‐rated health (SRH) and health complaints. The results show that between 4 per cent and 7 per cent of the variation in both health outcomes is attributable to differences between countries. Compared to the Scandinavian regime, the Southern regime had lower odds ratios for SRH, while for health complaints the Southern and Eastern regime showed high odds ratios. The association between subjective health and welfare regime was largely unaffected by adjusting for individual socioeconomic position. After adjustment for the welfare regime typology, the country‐level variations were reduced to 4.6 per cent for SRH and to 2.9 per cent for health complaints. Regarding cross‐level interaction effects between welfare regimes and socioeconomic position, no clear regime‐specific pattern was found. Consistent with research on adults this study shows that welfare regimes are important in explaining variations in adolescent health across countries.     

Granulocyte independence of pulmonary oxygen toxicity in the rat

The role of neutrophils in the mediation of severe normobaric hyperoxic lung injury has been studied by monitoring the effects of neutrophil depletion on a rat model of pulmonary oxygen toxicity. Pulmonary capillary permeability, assessed using an [125I]albumin lung permeability index (LPI), progressively increased with an increased duration of hyperoxia exposure in normal animals (LPI = 0.43 +/- 0.09 at 24 h; 0.95 +/- 0.17 at 48 h; 1.56 +/- 0.21 at 60 h), despite the absence of any significant tissue or bronchoalveolar lavage evidence of neutrophil infiltration until 60 h of hyperoxia exposure. Neutrophil depletion (using cyclophosphamide) blocked this late neutrophil infiltrate but failed to attenuate lung injury (LPI = 0.38 +/- 0.06 at 24 h; 0.89 +/- 0.16 at 48 h; 1.58 +/- 0.10 at 60 h; all p greater than .05 compared with leucocyte-replete/normal animals exposed to hyperoxia). The temporal dissociation of pulmonary neutrophil accumulation and pulmonary injury and the failure of effective neutrophil depletion to abrogate hyperoxic lung injury indicate that neutrophil polymorphs play no substantive role in the mediation of tissue injury in this model of severe pulmonary oxygen toxicity.     

Tolerance and safety of pharmacologic coronary vasodilation with adenosine in association with thallium-201 scintigraphy in patients with suspected coronary artery disease

Adenosine thallium-201 myocardial scintigraphy is a promising test for coronary artery disease detection, but its safety has not been reported in large patient cohorts. Accordingly, the tolerance and safety profile of adenosine infusion were analyzed in 607 patients (351 men, 256 women, mean age 63 +/- 11 years) undergoing this test either because of suspected coronary artery disease (Group I, n = 482) or for risk stratification early (5.2 +/- 2.8 days) after myocardial infarction (Group II, n = 125). Adenosine increased the heart rate from 74.5 +/- 14.0 to 91.8 +/- 15.9 beats/min (p less than 0.001) and decreased systolic blood pressure from 137.8 +/- 26.8 to 120.7 +/- 26.1 mm Hg (p less than 0.001). Side effects were frequent and similar in both groups. Flushing occurred in 35%, chest pain in 34%, headache in 21% and dyspnea in 19% of patients. Only 35.6% of Group I patients with chest pain during adenosine infusion had concomitant transient perfusion abnormalities, compared with 60.7% of Group II patients (p less than 0.05). First- and second-degree AV block occurred in 9.6% and 3.6% of patients, respectively, and ischemic ST changes in 12.5% of cases. Concomitance of chest pain and ischemic ST depression was uncommon (6%) but, when present, predicted perfusion abnormalities in 73% of patients. Most side effects ceased rapidly after stopping the adenosine infusion. The side effects were severe in only 1.6% of patients and in only six patients (1%) was it necessary to discontinue the infusion. No serious adverse reactions such as acute myocardial infarction or death occurred.(ABSTRACT TRUNCATED AT 250 WORDS)     

Implementation of an emergency department triage procedure for the detection and isolation of patients with active pulmonary tuberculosis

STUDY OBJECTIVES: To investigate the ability of an emergency department screening protocol to initiate respiratory isolation of patients with pulmonary tuberculosis at ED triage before chest radiography. METHODS: We conducted a prospective cohort study with retrospective medical record review of adult patients who presented for care to an urban, university-affiliated hospital in Los Angeles County over a 4-month period. Ambulatory patients were administered a triage screening protocol that used patient-reported tuberculosis risk factors and symptoms in combination with selective chest radiography to screen patients at ED triage for active pulmonary tuberculosis. RESULTS: A total of 10,674 patients were screened; 2, 218 were isolated at triage and underwent chest radiography, and 378 were kept in isolation in the ED. The respiratory isolation of pulmonary tuberculosis (RIPT) protocol detected 17 of 27 visits made by patients with unsuspected pulmonary tuberculosis, yielding a sensitivity of 63% (95% confidence interval [CI] 42% to 81%). The estimated specificity was 78%. For each patient with tuberculosis who was detected by the RIPT protocol, 624 patients were screened at triage, 130 chest radiographs were taken, and 22 patients were placed in respiratory isolation in the ED. Patients with undetected pulmonary tuberculosis more commonly had nonpulmonary chief complaints (76% versus 20%; odds ratio [OR] 13, 95% CI 2.1 to 78.3), and only 60% (95% CI 26% to 88%) were ultimately isolated in the hospital. Among RIPT screen-positive patients, radiographic findings predictive of pulmonary tuberculosis were cavitary lesions (OR 84.3, 95% CI 22.6 to 315), upper lobe infiltrates (OR 24.2, 95% CI 9.1 to 64.4), pleural effusions (OR 8.9, 95% CI 2.5 to 31.8), diffuse/interstitial infiltrates (OR 5.7, 95% CI 1.8 to 17.9), and non-upper lobe infiltrates (OR 3.1, 95% CI 1.0 to 9.5). CONCLUSION: The RIPT screening protocol was only moderately sensitive for isolating patients with pulmonary tuberculosis at ED triage. Future studies should evaluate modified and abridged screening protocols, as well as the cost-effectiveness of triage screening.     

Tumor necrosis factor prevents alendronate-induced osteoclast apoptosis in vivo by stimulating Bcl-xL expression through Ets-2

OBJECTIVE: To investigate why bisphosphonates are less effective at preventing focal bone loss in rheumatoid arthritis (RA) patients than in those with generalized osteoporosis, and the mechanisms involved. METHODS: The response of osteoclasts to alendronate (ALN) in tumor necrosis factor-transgenic (TNF-Tg) mice that develop erosive arthritis and in wild-type littermates was studied. TNF-Tg and wild-type mice were given ALN, and the osteoclast numbers in the inflamed joints and in the long bones were compared. The expression levels of Bcl-xL in the osteoclasts of TNF-Tg and wild-type mice were examined by immunostaining. The effect of overexpression of Bcl-xL and Ets-2 proteins on ALN-induced osteoclast apoptosis was determined using an in vitro osteoclast survival assay and retrovirus transfer approach. RESULTS: ALN reduced osteoclast numbers in the metaphyses by 97%, but by only 46% in the adjacent inflamed joints. Bcl-xL expression was markedly higher in osteoclasts in the joints than in those in the metaphyses of TNF-Tg mice. Bcl-xL or Ets-2 overexpression protected osteoclasts from ALN-induced apoptosis, and TNF stimulated Bcl-xL and Ets-2 expression in osteoclasts. Overexpression of Ets-2 increased Bcl-xL messenger RNA in osteoclasts, while a dominant-negative form of the Ets-2 blocked the protective effect of Bcl-xL or TNF on ALN-induced apoptosis. CONCLUSION: The reduced efficacy of bisphosphonates to stop bone erosion in the inflamed joints of RA patients may result from local high levels of TNF up-regulating Ets-2 expression in osteoclasts, which in turn stimulates Bcl-xL expression in them and reduces their susceptibility to bisphosphonate-induced apoptosis.