Cerebrospinal fluid calcium, parathyroid hormone, and monoamine and purine metabolites and the blood-brain barrier function in primary hyperparathyroidism.

Psychiatric disturbances are common in primary hyperparathyroidism (HPT), but their pathogenesis is essentially unknown. This study deals with cerebrospinal fluid (CSF) calcium homeostasis and its connection with parathyroid hormone (PTH), blood-brain barrier (BBB) function, and central monoamine and purine metabolites in patients with primary HPT. In 22 patients with primary HPT (serum calcium 2.85 +/- 0.21 mmol/l), the CSF concentrations of total and ionized calcium were higher (1.21 +/- 0.08 mmol/l, p less than 0.01, and 1.09 +/- 0.05 mmol/l, p less than 0.001, respectively) than in 11 normocalcemic reference subjects. The values correlated with serum calcium concentration (p less than 0.001) and CSF/serum albumin ratio, a measure of BBB permeability. The latter ratio was elevated in one-third of the patients with HPT, indicating BBB damage. CSF immunoreactive intact PTH was higher in the HPT patients than in the reference group (p less than 0.05), and serum and CSF PTH were positively correlated (p less than 0.05). The CSF levels of the monoamine metabolites 5-hydroxyindoleacetic acid (5HIAA) and homovanillic acid (HVA) were lower, and the level of urate in CSF was higher, in the HPT patients than in the reference subjects, while there were no consistent differences in CSF hypoxanthine or xanthine. CSF 5HIAA correlated inversely with CSF ionized calcium (r = -0.42, p = 0.02). After parathyroid surgery, CSF calcium and urate decreased significantly and CSF monoamine metabolites increased slightly. The decrease in CSF ionized calcium correlated with the alleviation of psychiatric symptoms. The results indicate the importance of increased CSF calcium concentrations in patients with primary HPT and suggest a relation between central calcium regulation and central turnover of monoamines.     

Electromechanical properties of perfusion/metabolism mismatch: comparison of nonfluoroscopic electroanatomic mapping with 18F-FDG PET.

The aim of this study was to compare nonfluoroscopic electroanatomic mapping (NOGA), SPECT perfusion imaging, and PET metabolic imaging for assessment of myocardial viability. In particular, we sought to elucidate differences of electromechanical properties between the perfusion/metabolism mismatch as an indicator of a potentially reversible ischemic injury and the perfusion/metabolism match indicating irreversibly damaged myocardial tissue. METHODS: Twenty-one patients with coronary artery disease underwent NOGA mapping of endocardial unipolar voltage, cardiac 18F-FDG PET of glucose utilization, and resting 201Tl SPECT of myocardial perfusion. RESULTS: Electrical activity was 10.8 +/- 4.6 mV (mean +/- SD) in normal myocardium and was unchanged in hypoperfused segments with maintained glucose metabolism (perfusion/metabolism mismatch), 9.3 +/- 3.4 mV (P = not significant). In contrast, hypoperfused segments with a perfusion/metabolism match and nonviable segments showed significantly lower voltage (6.9 +/- 3.1 mV, P < 0.0001 and 4.1 +/- 1.1 mV, P < 0.0001 vs. normal). In hypoperfused segments, metabolic activity was more closely related to endocardial voltage than was myocardial perfusion (201Tl vs. voltage: r = 0.38, SEE = 3.2, P < 0.001; 18F-FDG PET vs. voltage: r = 0.6, SEE = 2.8, P < 0.0001). CONCLUSION: In hypoperfused myocardium, electrical activity by NOGA mapping is more closely related to PET metabolic activity than to SPECT myocardial perfusion. As NOGA mapping does not differentiate hypoperfused myocardium with enhanced glucose utilization from normal myocardium, results from NOGA mapping need to be correlated with results from perfusion imaging to identify hypoperfused, yet viable, myocardium and to stratify patients for revascularization procedures.     

A novel frame shift mutation in the HMG box of the SRY gene in a patient with complete 46,XY pure gonadal dysgenesis.

Pure gonadal dysgenesis or Swyer syndrome is a sex-reversal disorder resulting from embryonic testicular regression sequences especially during the first few weeks of fetal life and is induced by mutations in the SRY gene. In the present report, we describe a nonmosaic XY sex-reversed female with pure gonadal dysgenesis. Molecular analysis using sequential PCR to detect Y chromosomal microdeletions showed the presence of SRY, ZFY and AZFa, b and c regions. Automated sequencing of the SRY region revealed a new mutation (deletion of A (adenine) in codon 82 at position +244), leading to a frame shift mutation within the helix I of the HMG-box domain. This mutation generates a truncated protein and is very likely to produce an impairment of SRY DNA binding activity. The present findings further support the functional importance of the putative DNA binding activity of the SRY HMG-box domain.     

P53 overexpression as an indicator of overall survival and response to treatment in osteosarcomas

The p53 gene located at chromosome 17pl3 is found to be altered (allelic loss or other mutation) in multiple human cancers, including osteosarcomas. The mutated gene produces a protein with a prolonged half-life thus rendering it detectable by conventional immunohistochemistry. We examined the correlation between p53 expression and clinical prognosis as well as response to therapy. Twentyone patients with previously untreated and histologically verified highly malignant osteosarcoma were used for this study. Biopsy material taken both prior to the start of COSS 91 protocol and at the time of surgery (ten weeks later) was examined for alterations in p53 protein expression and drug resistance. Two patients who had strong (+++) p53 protein expression and three others who became positive during the chemotherapy had significantly worse prognosis (all of them died within one year) than those who showed no p53 expression both at biopsy and after chemotherapy (all 11 patients are alive, average follow-up time: 3.5 years). All patients who showed any kind of positive p53 protein expression on initial biopsy were non-respon-ders to chemotherapy. In contrast, 69% (9 out of 13) of those who exhibited no p53 expression on initial biopsy were responders or intermediate responders to chemotherapy. We concluded that p53 expression may be a useful prognostic factor in osteosarcomas. The direct correlation between p53 positive expression and resistance to therapy can help in identifying patients who are in need of a more vigorous or different chemotherapeutical protocol.     

Electron microscopy and X-ray microanalyses of uterine epithelium from lead-injected mice in an experimental delay of implantation

Mice in experimental delay of implantation were injected intravenously with 75 g · g^–1 body weight of lead chloride, corresponding to a dose of lead of about 56 g · g^–1 body weight. Delay of implantation was obtained by ovariectomy 3 days after mating followed by a depot dose of progesterone every fifth day. Electron microscopy showed that the uterine lumen, which was closed in control mice, was opened in lead-injected mice. This morphology suggested that lead caused an increase in uterine secretion. X-ray microanalysis of pyroantimonate precipitates in the uterine epithelium of injected mice demonstrated lead in the precipitates, suggesting that lead could have a direct effect on the function of the uterine epithelium and that lead also could be secreted into the uterine lumen and affect the blastocysts.     

Impaired glucose handling in active rheumatoid arthritis: relationship to the secretion of insulin and counter-regulatory hormones

An intravenous glucose tolerance test was performed in 45 untreated patients with active inflammatory rheumatoid arthritis and in age- and sex-matched healthy subjects. The mean k value in the patients, which correlated to the inflammatory activity, was 1.0 +/- 0.05 (SEM), which was significantly lower (P less than .001) than in the controls (1.8 +/- 0.09). The basal serum insulin concentration and the maximum insulin response to glucose loading were significantly higher (P less than .001 and P less than .01, respectively) in the patient group. The patients had a normal basal concentration of growth hormone in the serum, but during glucose infusion the concentration increased. The plasma glucagon level was significantly lower than in the controls (P less than .001). The urinary output of cortisol and catecholamines was normal. It is concluded that impaired glucose handling in active chronic inflammatory disease cannot be explained as a stress reaction but may be due to peripheral insulin resistance mediated by the inflammatory process. A paradoxical increase in growth hormone secretion during glucose infusion may suggest that this hormone is one factor that influences glucose handling in chronic inflammation. The pathophysiologic relevance of altered glucose metabolism and enhanced insulin secretion is uncertain but may reflect a possible link with the proposedly increased risk of atherosclerotic cardiovascular disease in rheumatoid arthritis.     

Alcohol and heart failure

BACKGROUND: Current heart failure (HF) guidelines note that alcohol use should be discouraged or restricted in patients with HF resulting from left ventricular systolic dysfunction. Existing knowledge is limited in the area of HF and alcohol. METHODS AND RESULTS: The purpose of this article is to review the evidence regarding the acute and long-term use of alcohol in the setting of HF. In addition, general aspects about alcohol and alcoholic beverages that are important for understanding and interpreting alcohol-related literature are reviewed and that can be used when discussing alcoholic beverage use with patients with HF. CONCLUSIONS: There is some emerging evidence that suggests light drinking (1 to 14 drinks per week) is safe and even beneficial in HF patients with ischemic left ventricular dysfunction (LVD). However, there are no effects of light drinking in HF patients with nonischemic LVD. Clinicians should reinforce the importance of evidence based pharmacologic and nonpharmacologic therapies in HF.     

Relationship of the sex of the foetus to the amount of human chorionic gonadotrophin in placentae; single and dizygotic twin placentae compared.

Human chorionic gonadotrophin (HCG) was assayed by biological and radioimmunological methods in placentae from 16 women with a normal twin pregnancy. When the concentration and total amount of HCG in placentae was related to the sex of the twin foetus, no significant difference between 'male' and 'female' placentae was found. This is contrary to findings that there is a significant (P less than 0-005) difference in the concentration of HCG per g and per placenta of singletons at term. A comparison between the grouped geometric mean data from bioassays shows that the amount of HCG per g and per placenta falls between the geometric mean values for 'male' and 'female' singleton placentae.