Differences in the Course of Alcohol Withdrawal in Women and Men: A Polish Sample

A retrospective study compared the course of alcohol withdrawal, including delirium tremens, in women and men hospitalized in the Nowowiejski Hospital in Warsaw from 1973 to 1987. Medical records pertaining to 1179 patients were analyzed; 13.8% of these patients were women and 86.2% were men. The study showed that women began intensive alcohol drinking later than men ( p < 0.0001), but the period between the onset of alcohol abuse and the first occurrence of alcohol withdrawal was shorter in women than in men ( p < 0.0001). In the period of heavy drinking before hospitalization, women consumed significantly less alcohol then men ( p < 0.0001); moreover, women drank nonbeverage alcohol less frequently than men ( p < 0.05). Women were hospitalized substantially longer than men ( p < 0.0001), whereas the duration of alcohol withdrawal symptoms at the time of hospitalization was comparable in both groups. Withdrawal seizures were significantly more frequent among men than among women ( p < 0.001). Significant differences in the patients'somatic conditions were not noted between the groups, with the exception of anemia and decreased potassium concentration, which were more frequently observed in women (both p < 0.0001), and of increased concentration of ALT and hypoproteinemia, which were more frequent in men (respectively, p < 0.05 and p < 0.01). Co-existing personality disorders, depressive disorders, and anxiety disorders—as well as abuse of benzodiazepines and barbiturates—were more frequently observed in women ( p < 0.0001). The period between the first hospitalization due to alcohol withdrawal and the time of death was significantly shorter in men than in women ( p < 0.05). The results point to differences in the conditions and the course of alcohol dependence and alcohol withdrawal between women and men.     

Modified algorithm in treatment of patients with chronic low back pain with neuroradiological diagnostic techniques]

The most difficult in proper qualification of the patient with chronic low back pain for an operative treatment is determination of the chance for satisfactory result. The diversity of the pain eliciting structure in the spine influence the decision. In the paper we have analyzed patient where the operative treatment was considered. In 149 patients divided in two groups the (not being previously operated on the spine--group 1 and after spine surgery--group 2) the neuroradiological procedures were performed (sacral epidural block, facet injections, root injections of the lumbar spine). As the result of this procedure in 108 patients (72%) surgical intervention at that time was abandoned. Conclusion. In our opinion the neuroradiological diagnostic procedures should be mandatory in back pain management of the patient were operative treatment is considered. We present the modified algorithm in diagnostic procedure preceding the operation.     

Immunization with a combination of merozoite surface proteins 4/5 and 1 enhances protection against lethal challenge with Plasmodium yoelii

It is widely believed that subunit vaccines composed of multiple components will offer greater protection against challenge by malaria, and yet there is little experimental evidence to support this view. We set out to test this proposition in the Plasmodium yoelii challenge system in rodents by comparing the degree of protection conferred by immunization with a mixture of merozoite surface proteins to that conferred by single proteins. We therefore examined a defined protein mixture made of the epidermal growth factor-like domains of P. yoelli merozoite surface protein 1 (MSP1) and MSP4/5, the homologue of P. falciparum MSP4 and MSP5. In the present study we demonstrate that this combination of recombinant proteins dramatically enhances protection against lethal malaria challenge compared to either protein administered alone. Many mice immunized with the MSP4/5 plus MSP1(19) combination did not develop detectable parasitemia after challenge. Combined immunization with MSP1(19) and yMSP4/5, a product characterized by lower protective efficacy, also greatly enhanced protection by reducing peak parasitemias and increasing the numbers of survivors. In some combination trials, levels of antibodies to MSP1(19) were elevated compared to the MSP1(19) alone group; however, improved protection occurred regardless of whether boosting of the anti-MSP1(19) response was observed. Boosting of anti-MSP1(19) did not appear to be due to contaminating endotoxin in the EcMSP4/5 material since enhanced protection was observed in C3H/HeJ mice, which are endotoxin insensitive. Collectively, these experiments show that multiantigen combinations offer enhanced levels of protection against asexual stage infection and suggest that combinations of MSP1, MSP4, and MSP5 should be evaluated further for use in humans.     

TCRs with high affinity for foreign pMHC show self-reactivity

T cells with high-affinity T cell receptors (TCRs) for a foreign peptide-major histocompatibility complex (pMHC) appear to be negatively selected, even though they have never seen the foreign antigen. To examine how this process operates, we used in vitro yeast display to isolate high-affinity TCRs from the T cell clone 2C. The TCRs showed fast on-rates, which were consistent with reduced CDR (complementarity determining region) flexibility, and cross-reactivity with other cognate pMHCs. T cell hybridomas transfected with a high-affinity TCR were stimulated by endogenous self-pMHC, which suggested that T cells bearing the TCR would be negatively selected. The immune system appears to maintain a repertoire of flexible, low-affinity TCRs at the expense of more effective high-affinity TCRs.     

Effects of tryptophan depletion on central and peripheral chemoreflexes in man

Klein (Arch. Gen. Psychiatry 50, 306-317, 1993) suggests that panic attacks are the result of a defective 'suffocation alarm' threshold that presents with carbon dioxide (CO(2)) hypersensitivity, exaggerated ventilatory response and panic in panic disorder (PD) patients. Serotonergic deficiencies enhance this ventilatory response in PD patients, as per 'suffocation alarm' theory predictions, suggesting that serotonin (5-HT) normalizes the ventilatory response. Other research supports a serotonin system-mediated stimulation of ventilation. Knowledge of 5-HT's role on ventilatory output and its neurophysiological sources impacts on the 'suffocation alarm' theory validity and predictive value. We used tryptophan depletion (TRP-) in concert with a modified Read rebreathing test to determine the effect of deficient serotonergic modulation on the central and peripheral chemoreflex threshold and sensitivity of response to CO(2) in 11 healthy men. TRP- did not affect central or peripheral chemoreflex threshold or sensitivity of response to CO(2). However, basal ventilation was significantly elevated during TRP-. In contrast to 'suffocation alarm' theory predictions, decreased 5-HT neurotransmission does not significantly affect the respiratory chemoreflex response to CO(2), impacting on non-chemoreflex drives to breathe. Panic associated respiratory abnormalities may be related to defective 5-HT modulation of non-chemoreflex drives to breathe, unrelated to any respiratory chemoreflex abnormality.     

Variable MHC class I engagement by Ly49 natural killer cell receptors demonstrated by the crystal structure of Ly49C bound to H-2K(b)

The Ly49 family of natural killer (NK) receptors regulates NK cell function by sensing major histocompatibility complex (MHC) class I. Ly49 receptors show complex patterns of MHC class I cross-reactivity and, in certain cases, peptide selectivity. To investigate whether specificity differences result from topological differences in MHC class I engagement, we determined the structure of the peptide-selective receptor Ly49C in complex with H-2K(b). The Ly49C homodimer binds two MHC class I molecules in symmetrical way, a mode distinct from that of Ly49A, which binds MHC class I asymmetrically. Ly49C does not directly contact the MHC-bound peptide. In addition, MHC crosslinking by Ly49C was demonstrated in solution. We propose a dynamic model for Ly49-MHC class I interactions involving conformational changes in the receptor, whereby variations in Ly49 dimerization mediate different MHC-binding modes.     

P-glycoprotein expression influences the result of 99mTc-MIBI scintigraphy in tertiary hyperparathyroidism

Precise localization of parathyroid glands using 99mTc-labeled hexakis-2-methoxyisobutylisonitrile (99mTc-MIBI) scintigraphy could be affected by various biological factors. There is increasing evidence that radiotracer retention could be controlled by members of multidrug resistance (MDR) system, especially P-glycoprotein (P-gp). Since the role of P-gp in tertiary hyperparathyroidism (T-HPTH) scintigraphic studies is poorly recognized, the aim of the study was to compare the correlation between parathyroid P-gp expression and results of their scintigraphy in T-HPTH versus primary hyperparathyroidism (P-HPTH). P-HPTH (n = 19) and T-HPTH (n = 18) patients were subjected to 99mTc-MIBI scintigraphy followed by surgical treatment. The parathyroid glands were assessed in routine hematoxylin-eosin staining and P-gp expression was analyzed using immunohistochemistry. Parathyroids collected during cadaver donor multi-organ harvesting were used as a control. It has been found that P-HPTH-derived parathyroid glands with predominating adenoma morphology expressed less P-gp, as compared to P-gp-rich T-HPTH glands, mainly displaying nodular or diffused hyperplasia phenotype. This finding reversely correlated with results of 99mTc-MIBI scintigraphy. However, we did not observe any difference in P-gp expression nor scintigraphy result between nodular or diffused hyperplasia. Altogether, these data suggest that P-gp overexpression in T-HPTH could be responsible for decreased sensitivity of 99mTc-MIBI scintigraphy in those patients. Therefore, the recently proposed reduced neck exploration or limited parathyroid resection on the basis of scintigraphy could create the risk of persisted/recurrent hyperparathyroidism. However, this problem requires further study.     

Analysis of Serum Fatty Acids Profile in Kidney Transplant Recipients

Patients with end-stage kidney disease, treated with renal transplantation, are at increased risk of cardio-vascular disease (CVD) and cardio-vascular mortality. They are also characterized by an atherogenic dyslipidemia. Alterations of the fatty acids (FA) profile contribute to increased cardio-vascular risk in the general population. In the current study we test the hypothesis that kidney transplantation is associated with ab-normalities in FA profile. FA profile was analysed by gas chromatography–mass spectrometry in 198 renal transplant recipients, and 48 control subjects. The most profound differences between renal transplant patients and controls were related to the content of branched chain FA, monounsaturated FA, and n-6 polyunsaturated FA, respectively. The FA profile significantly separated the patients from the controls in the principal component analysis (PCA). The abnormalities of FA profile showed a tendency for normalization in long-term kidney recipients, as compared to patients with recent transplants. The n-3 PUFA content demonstrated a strong inverse association with the presence of inflammation. Most profound alterations of the FA profile were observed in patients with impaired graft function (glomerular filtration rate < 45 mL/min). The study demonstrated significant disorders of the FA profile in kidney transplant recipients, that might contribute to cardio-vascular risk in this vulnerable patient population.     

Maspin expression is characteristic for cisplatin-sensitive ovarian cancer cells and for ovarian cancer cases of longer survival rates.

High cytoplasmic expression of maspin was described in ovarian cancers of shorter survival rates. Until now, no relationship has been described between expression of maspin and sensitivity to cisplatin in ovarian cancers. This study aimed at examining the relationship between expression of maspin, detected by immunohistochemistry and clinical response to cisplatin in ovarian cancer cases as well as the in vitro sensitivity to cisplatin of 11 ovarian cancer cell lines. The analyzes were performed on 73 samples of ovarian cancer and on A2780P, A2780RCIS, CAOV-3, EFO 21, EFO 27, ES-2, Mdah 2774, OAW 42, OVCAR-3, PA-1, and SKOV-3 ovarian cancer cells. Cytoplasmic maspin expression in studied cells significantly correlated with cisplatin sensitivity. A significantly shorter overall survival and progression-free survival was associated with lower cytoplasmic maspin expression at first-look laparotomies and nuclear maspin expression and secondary cytoreductions. Higher nuclear maspin at first-look laparotomies expression was specific for cases of complete response. In the study, the elevated expression of maspin was shown to be typical for cisplatin-sensitive ovarian cancers.