Analysis of the Inhibitory Effect of Oestradiol on Functional GABA/5-HT Relationship in the Rat Suprachiasmatic Area

The purpose of this study was to test the capacity of oestradiol to modulate the stimulating effect of a-aminobutyric acid (GABA) on serotonin (5-HT) metabolism, previously described in the Suprachiasmatic area of the male rat. After an in vivo stimulation of GABA transmission by systemic administration of a GABA-transaminase inhibitor (amino-oxyacetic acid) or a GABA_B agonist (RS-baclofen), the 5-HT metabolism was studied in the Suprachiasmatic area of ovariectomized, and ovariectomized oestradiol-treated rats. Amino-oxyacetic acid or RS-baclofen treatment increased the endogenous content of 5-HT in the Suprachiasmatic area of males and ovariectomized rats. These two treatments were without effect in ovariectomized oestradiol-treated rats. GABA transmission stimulation induced by amino-oxyacetic acid treatment failed to affect the release and synthesis of 5-HT in ovariectomized oestradiol-treated rats while it increased these two parameters of 5-HT metabolism in the Suprachiasmatic area of male and ovariectomized rats. To investigate the main target of oestradiol effect, comparative studies of the serotoninergic and GABAergic metabolism in the Suprachiasmatic area were performed in the three experimental groups. Under our experimental conditions the endogenous 5-HT metabolism was similar between ovariectomized and ovariectomized oestradiol-treated rats. Nevertheless, 5-HT metabolism was higher in the two female groups than in the male group. Neither GABA metabolism nor GABAergic response to GABA-related drug treatment differed between ovariectomized, and ovariectomized oestradiol-treated rats. However, the turnover of GABA was higher when compared to the two female groups. It is concluded that the lack of 5-HT responsiveness to GABA transmission stimulation in ovariectomized oestradiol-treated rats was not related to an effect of oestradiol on 5-HT metabolism or to an effect of the steroid on GABA turnover. Furthermore, our results suggest a sex difference in the activity of serotoninergic and GABAergic systems in the Suprachiasmatic area.     

LIPOPROTEIN(α) IN HEALTH AND DISEASE

SUMMARY Elevated plasma levels of Lp(a) do seem to influence the progression of atherosclerosis. Evidence is emerging that certain apo(a) isoforms may be more atherogenic than others, and in transgenic mice free apo(a) has been shown to be associated with accelerated atherosclerosis. Currently it is not known whether treating elevated Lp(a) levels will reduce progression of atherosclerosis and, as therapeutic options are limited, mass screening of Lp(a) levels in populations is not indicated. The presence of raised Lp(a) levels, however, warrants aggressive treatment to reduce other cardiovascular risk factors. Continuing research to investigate the relationship of the apo(a) gene to other genes, including the plasminogen gene and apo(a)-related genes, will add further information pertaining to the evolution, function, regulation and clinical implications of Lp(a).     

Logistic regression in case-control studies: The effect of using independent as dependent variables

In case-control studies, cases are sampled separately from controls. In such studies the primary analysis concerns the estimation of the effect of covariables on being a case or a control. To explore causal pathways, further secondary analysis could concern the relationships among the covariables. In this paper the validity of such secondary analysis is addressed. In particular, the use of multiple logistic regression in case-control studies where the dependent variable is not the case/control indicator is explored. It is shown that only under very restrictive conditions will sample regression coefficients correctly estimate their true value. In many situations, it may be valid to regress one covariable on others in the control group, but not in the case group or the combined sample. This principle is illustrated by a study of sexually transmitted disease in Kenya.     

Thoracoscopic Assisted Pneumonectomy

A lung carcinoma with tumor involving more than one lobe or in close proximity to the mainstem bronchus often requires pneumonectomy for surgical cure. Inflammation, bulky tumors, and dense adhesions limit the operative field of vision and may result in the abandonment of procedures with potential for complete extirpation. This case illustrates the utility of thoracoscopy in visualization of the hilum and other neurovascular structures in a patient with a proximal tumor and dense intrathoracic adhesions. Successful resection was made possible by use of combined open and thoracoscopic modalities.     

Red cell autoantibody production in utero: a case report

BACKGROUND: Autoantibody production by the fetus is thought to be extremely unlikely. Only one possible case of in utero autoantibody production against red cells by the fetus has previously been described. STUDY DESIGN AND METHODS: A case of apparent red cell IgG autoantibody production in utero is reported. RESULTS: This was established by a positive direct antiglobulin test in a newborn infant without evidence of maternal alloantibodies or autoantibodies. There was no evidence of clinically significant hemolysis at the infant's birth. After 6 weeks, his direct antiglobulin test remained strongly positive. The infant thrived without evidence of hemolysis, and after 6 months the direct antiglobulin test was negative. CONCLUSION: The production of autoantibodies to red cells in utero is possible, though rare. This did not result in apparent hemolysis in this patient.     

Sevelamer hydrochloride with or without alphacalcidol or higher dialysate calcium vs calcium carbonate in dialysis patients: an open-label, randomized study.

BACKGROUND: Sevelamer hydrochloride was recently proposed as a phosphate binder to prevent hypercalcaemia in place of calcium alkaline salts in dialysis patients. So far, it has been evaluated only in patients receiving calcitriol, without comparison with CaCO(3) alone, although the latter was found to be as effective as the combination of calcitriol and Al(OH)(3) in suppressing parathyroid hormone (PTH) without inducing hypercalcaemia and to have a better lowering effect on serum phosphate. Moreover, this bile salt binder may decrease serum 25-OH vitamin D. Therefore, we compared for 5 months two strategies for controlling moderate hyperparathyroidism: CaCO(3) alone vs sevelamer in conjunction with measures to increase calcium balance. METHODS: Forty-two patients were randomized: 21 continued their treatment with 4.8 g/day CaCO(3) and 21 were switched to sevelamer (initial dose: 2.4 g/day, increased to 4.4 g/day). Each month, when serum-corrected calcium decreased below 2.30 mmol/l, dialysate calcium was increased or alphacalcidol was given at each dialysis session, according to serum PO(4) levels. The following parameters were monitored: serum Ca, PO(4), bicarbonate and protein, weekly; and serum PTH, 25-OH vitamin D and total, LDL and HDL cholesterol monthly. RESULTS: Except for higher serum phosphate at month 1, lower serum bicarbonate at month 2 and lower LDL cholesterol at month 5 in the sevelamer group, no difference was found between the two groups. Compared with baseline levels, PTH increased and 25-OH vitamin D decreased significantly in both groups, these two parameters being inversely correlated. CONCLUSIONS: Given comparable control of plasma calcium, phosphate and 25-OH vitamin D, PTH control is comparable in both strategies. Sevelamer does not induce greater vitamin D depletion than CaCO(3). The transient decrease of serum bicarbonate after discontinuation of CaCO(3) in the sevelamer group suggests a less optimal prevention of acidosis. The sevelamer-induced decrease in LDL cholesterol gives this drug a potential advantage in cardiovascular prevention.     

Pheochromocytoma and paraganglioma: comparison of MR imaging with CT and I-131 MIBG scintigraphy

To ascertain the magnetic resonance (MR) imaging characteristics of pheochromocytomas and paragangliomas and to compare MR with computed tomography (CT) and iodine-131 metaiodobenzylguanidine (I-131 MIBG), 19 patients (18 with pheochromocytomas, one with a paraganglioma) were studied. The 18 patients with pheochromocytomas had had positive findings with I-131 MIBG scintigraphy. Abdominal pheochromocytomas were generally hypointense compared with normal liver on T1-weighted MR images and extremely hyperintense on T2-weighted MR images. MR imaging was preferable to CT in the evaluation of primary pheochromocytomas due to superior tissue characterization, particularly in the patient with hypertension and borderline catecholamine levels. For patients with recurrent or metastatic disease, the data suggest that I-131 MIBG scintigraphy is the examination of choice.     

A reassessment of the risk of multiple sclerosis developing in patients with optic neuritis after extended follow-up.

One hundred and one of 146 patients presenting with isolated idiopathic optic neuritis, previously reviewed in 1978, were reassessed clinically, and retyped for HLA antigens and Factor B alleles, after a mean follow-up of 11.6 years. Fifty eight patients (57%) had developed multiple sclerosis at the time of reassessment in the present study, of whom 51 (88%) had clinically definite disease. This compared with 40% of the original group, in 1978, of whom 62% then had clinically definite multiple sclerosis. When the life-table method of analysis was used, the probability of developing multiple sclerosis was 75%, 15 years after the initial episode of optic neuritis. The frequencies of HLA-DR2 and the recently defined D-region antigen, DQw1, were significantly increased in patients with isolated optic neuritis and those who subsequently developed multiple sclerosis compared with normal controls, but neither allele appears to influence progression from optic neuritis to multiple sclerosis. Patients with optic neuritis who were HLA-DR3 positive had an increased risk for the development of multiple sclerosis (RR = 2.8) and this risk was further enhanced when DR3 occurred in combination with DR2 (RR = 6.7). The overall increased risk of developing multiple sclerosis for patients with this combination was 26 times that for the normal population. When the patients' original tissue-typing was considered BT 101 no longer influenced conversion of optic neuritis to multiple sclerosis. This may partly be explained by improved methods of tissue-typing, since not all BT 101 patients were subsequently found to be positive for HLA-DR2 or HLA-DQw1 and vice versa and by extended follow-up as multiple sclerosis conversion in HLA-DR2 negative individuals increased with time. All 101 patients were typed for Factor B alleles. No significant differences in frequencies were found between individuals with isolated optic neuritis or those who progressed to multiple sclerosis compared with the control population. Recurrent episodes of optic neuritis were associated with an increased risk for the development of multiple sclerosis in this study.