PTSD symptoms and comorbid mental disorders in Israeli war veterans

BACKGROUND: The purpose of this study was to investigate patterns of mental disorders co-morbid with PTSD symptoms in young Israeli men exposed to combat. METHOD: Six hundred and seventeen subjects were selected via a general population sample and evaluated in a two-phase case-identification procedure, culminating in a modified SADS-L interview, administered by psychiatrists. RESULTS: Major depressive disorder (OR = 3.2), substance use disorders (OR = 1.9) and personality disorders (OR = 3.0) occurred more frequently in men reporting symptoms of PTSD than in men who had been under fire who did not report symptoms. With the possible exception of personality disorders, comorbid disorders did not constitute risk factors for PTSD. Comorbid PTSD and RDC disorders were associated with increased help-seeking. CONCLUSIONS: The results suggest similar rates and types of PTSD comorbidity in Israeli war veterans as in veterans in the US assessed in general population studies, and are consistent with shared risk factors for PTSD and comorbid disorders.     

Prostate-specific membrane antigen: a novel folate hydrolase in human prostatic carcinoma cells

A novel monoclonal antibody has been developed that reacts strongly with human prostatic cancer, especially tumors of high grade. This antibody (7E11C-5) is currently in Phase 3 trials as an imaging agent for metastatic disease. We have cloned the gene that encodes the antigen that is recognized by the 7E11C-5 monoclonal antibody and have designated this unique protein prostate-specific membrane (PSM) antigen. PSM antigen is a putative class II transmembranous glycoprotein exhibiting a molecular size of Mr 94,000. Functionally, class II membrane proteins serve as transport or binding proteins or have hydrolytic activity. Preliminary studies have demonstrated binding of pteroylmonoglutamate (folate) to membrane fractions that also cross-reacted with the PSM monoclonal antibody. We observed substantial carboxypeptidase activity as folate hydrolase associated with PSM antigen. The purpose of our study was to demonstrate that human prostatic carcinoma cells expressing PSM antigen exhibit folate hydrolase activity using methotrexate triglutamate (MTXGlu3) and pteroylpentaglutamate (PteGlu5) as substrates. Isolated membrane fractions from four human prostate cancer cell lines (LNCaP, PC-3, TSU-Prl, and Duke-145) were examined for folate hydrolase activity using capillary electrophoresis. After timed incubations at various pH ranges and in the presence and absence of thiol reagents, separation of pteroyl(glutamate)n derivatives was achieved with an electrolyte of sodium borate and SDS, while absorbance was monitored at 300 nm. The results demonstrate clearly that LNCaP cells, which highly express PSM, hydrolyze gamma-glutamyl linkages of MTXGlu3. The membrane-bound enzyme is an exopeptidase, because it progressively liberates glutamates from MTXGlu3 and PteGlu5 with accumulation of MTX and PteGlu1, respectively. The semipurified enzyme has a broad activity from pH 2.5 to 9.5 and exhibits activity maxima at pH 5 and 8. Enzymatic activity is maintained in the presence of reduced glutathione, homocysteine, and p-hydroxymercuribenzoate (0.05-0.5 mm) but was inhibited weakly by DTT (>/=0.2 mm). By contrast to LNCaP cell membranes, membranes isolated from other human prostate adenocarcinoma cells (PC-3, Duke-145, and TSU-Pr1) did not exhibit comparable hydrolase activity, nor did they react with 7E11-C5 monoclonal antibody. After transfection of PC-3 cells with a full-length 2.65-kb PSM cDNA subcloned into a pREP7 eukaryotic expression vector, non-PSM antigen-expressing PC-3 cells developed immunoreactivity to 7E11-C5 monoclonal antibody and demonstrated folate hydrolase activities and optimum pH activity profiles identical to those of LNCaP cells. The membrane-bound enzymes from both LNCaP- and PC-3-transfected cells also have a capacity to hydrolyze an alpha-linked glutamyl moiety from N-acetyl-alpha-aspartylglutamate. We have identified that PSM antigen is a pteroyl poly-gamma-glutamyl carboxypeptidase (folate hydrolase) and is expressed strongly in human prostate cancer. Cancer cells that express this enzyme are resistant to methotrexate therapy. Those developing future therapeutic strategies in the treatment of prostate cancer that utilize folate antagonists need to consider this mechanism of resistance.     

Microtubule depolymerization selectively down-regulates the synthesis of proinflammatory secretory nonpancreatic phospholipase A2

Reports which analyzed the effects of secondary cytoreductive surgery at second-look laparotomy have often included small numbers of patients who have been treated with a variety of first-line chemotherapy regimens and those who may have progressed on first-line therapy. The purpose of this study was to analyze survival following secondary cytoreductive surgery at second-look laparotomy in patients with advanced ovarian cancer. Review of the surgical data of 153 patients allowed classification of tumor size found at second-look laparotomy and tumor size remaining after cytoreduction. Multivariate analysis evaluated multiple risk factors for survival. Of 153 patients, 124 had macroscopic tumor at second-look laparotomy and 29 had microscopic disease only. Fifteen of 69 (22%) patients were found to have tumor > 1 cm in diameter and were cytoreduced to microscopic residual and 18/69 (26%) were left with 1 cm tumor. Twenty-one of 55 (38%) patients with < or = 1 cm tumor were debulked to microscopic residual. The shortest survival relative to patients found to have microscopic disease at second-look laparotomy was observed among patients whose maximum tumor size remained > 1 cm following second-look laparotomy (relative risk = 3.1, P = 0.0004). No difference in survival was seen between patients found to have microscopic disease and those cytoreduced to microscopic disease (P = 0.24). The risk of death was lower among patients debulked to a lower category (< or = 1 cm debulked to microscopic, relative risk = 0.48, P = 0.02; > 1 cm reduced to < or = 1 cm, relative risk = 0.49, P = 0.02; > 1 cm reduced to microscopic, relative risk = 0.44, P = 0.01). Whether this apparent beneficial effect of cytoreductive surgery at second-look laparotomy reflects the biology of the tumor which allows surgical cytoreduction or the effects of cytoreduction can only be addressed in a randomized prospective trial.     

Dose-related reversal of acute lung rejection by aerosolized cyclosporine

This study evaluated the effectiveness of aerosolized cyclosporine as rescue therapy for refractory acute rejection in lung-transplant patients that is unresponsive to conventional therapy. Over 2 yr, nine allograft recipients with histologic evidence of persistent acute rejection and worsening pulmonary function were enrolled. Twenty-two patients with similar degrees of unremitting rejection served as historical controls. Aerosolization of cyclosporin A (300 mg in 4.8 ml propylene glycol) using an AeroTech II jet nebulizer was instituted daily for 12 consecutive days followed by a maintenance regimen of 3 d/wk. Cyclosporine and tacrolimus blood and plasma levels were maintained within therapeutic ranges throughout this trial. Efficacy was assessed by histologic grade of rejection, interleukin-6 (IL-6) mRNA expression by graft bronchoalveolar lavage cells, and pulmonary function testing before and during cyclosporine therapy. In seven patients, results were correlated to deposition of cyclosporine aerosol in the allograft(s) as measured by radioisotopic techniques. At a mean of 37 d after initiation of aerosolized cyclosporine, graft histology improved in eight of the nine patients. Cellular IL-6 mRNA expression decreased significantly in seven patients (mean IL-6/actin +/- SD, 40.96 +/- 118 versus 0.33 +/- 0.57 [p = 0.038]). Pulmonary function (FEV1), which had decreased posttransplant (over a mean of 347 d of observation) from a best value of 1.98 +/- 0.8 L to 1.59 +/- 0.6 L (p = 0.0077), improved over time (152 d) to a posttransplant value of 1.90 +/- 0.8 (p = 0.025). In the control subjects, FEV1 inexorably declined over a comparable period of observation (best posttransplant value 2.36 +/- 0.86 to 1.32 +/- 0.53, p < 0.0001). There was a strong correlation between cyclosporine deposition in the allograft and improvement in FEV1 (r = 0.900, p < 0.01). Fewer cycles of pulsed corticosteroids (1.4 +/- 0.9 versus 0.2 +/- 0.4, p = 0.011) and anti-thymocyte globulin 0.8 +/- 0.4 versus 0, p = 0.018) and reduced doses of oral prednisone (10.8 +/- 3.1 versus 6.1 +/- 4.2 mg/d, p = 0.026) were observed during treatment with aerosolized cyclosporine. Episodes of pneumonia also were reduced significantly during aerosol therapy (2.6 versus 0.95 episodes/100 d, p = 0.029). Nephrotoxicity and hepatotoxicity did not occur, and no patients withdrew from the study. Aerosolized cyclosporine appears to be safe and effective therapy for refractory acute rejection, but confirmation by a larger, randomized trial is necessary. The correlation observed between deposition of cyclosporine aerosol and physiologic improvement of lung function suggests that there is a dose-response relationship between the concentration of cyclosporine in the allograft and immunologic tolerance.     

Inserting and maintaining peripherally inserted central catheters

Peripherally inserted central catheters are a type of vascular access device that has many advantages for patients with longer-term and special infusion needs. Increasingly common in home and hospital settings, nurses should know how to insert, maintain, and educate patients and families about these devices. One hospital's experiences implementing a model program is described.     

Induction of apoptosis of metastatic mammary carcinoma cells in vivo by disruption of tumor cell surface CD44 function

To understand how the hyaluronan receptor CD44 regulates tumor metastasis, the murine mammary carcinoma TA3/St, which constitutively expresses cell surface CD44, was transfected with cDNAs encoding soluble isoforms of CD44 and the transfectants (TA3sCD44) were compared with parental cells (transfected with expression vector only) for growth in vivo and in vitro. Local release of soluble CD44 by the transfectants inhibited the ability of endogenous cell surface CD44 to bind and internalize hyaluronan and to mediate TA3 cell invasion of hyaluronan-producing cell monolayers. Mice intravenously injected with parental TA3/St cells developed massive pulmonary metastases within 21-28 d, whereas animals injected with TA3sCD44 cells developed few or no tumors. Tracing of labeled parental and transfectant tumor cells revealed that both cell types initially adhered to pulmonary endothelium and penetrated the interstitial stroma. However, although parental cells were dividing and forming clusters within lung tissue 48 h following injection, >80% of TA3sCD44 cells underwent apoptosis. Although sCD44 transfectants displayed a marked reduction in their ability to internalize and degrade hyaluronan, they elicited abundant local hyaluronan production within invaded lung tissue, comparable to that induced by parental cells. These observations provide direct evidence that cell surface CD44 function promotes tumor cell survival in invaded tissue and that its suppression can induce apoptosis of the invading tumor cells, possibly as a result of impairing their ability to penetrate the host tissue hyaluronan barrier.     

Management of eye emergencies in the accident and emergency department by senior house officers: a national survey

OBJECTIVE: To assess the training that accident and emergency (A&E) senior house officers (SHOs) receive in dealing with eye emergencies, their own perceived level of confidence and competence in managing such cases, and the availability of appropriate equipment in their departments. METHODS: Prospective telephone survey using a standardised structured questionnaire. One SHO from each United Kingdom A&E department listed in the BAEM directory of 1993 was chosen at random and interviewed. RESULTS: 226 A&E departments were contacted and 192 SHOs were successfully interviewed (response rate 84.9%); 26.0% received no training in the management of eye emergencies, 68.8% had only a little or no confidence in dealing with these cases, and 42.2% worked in A&E departments which had no slit lamp. CONCLUSIONS: There is a lack of adequate basic ophthalmic training for A&E SHOs, leading to a lack of confidence on their part in the management of eye emergencies. In just over 40% of A&E departments in the United Kingdom, the management of these cases may be less than optimal because of the absence of a slit lamp.     

Inhibition of bacterial respiration by a low-molecular weight lectin, scyllin, from Scylla serrata crab hemolymph

Interaction of plant and/or invertebrate lectins with mammalian cells and different microorganisms is well known. In the present study, we have demonstrated that scyllin, a low molecular weight (MW 4000) lectin from the edible crab Scylla serrata hemolymph, purified by GalNAc-Sepharon affinity column followed by Mono-Q ion exchanger in FPLC exhibits antimicrobial activity against Bacillus cereus and Escherichia coli by inhibiting endogenous respiration as well as exogenous glucose oxidation. In both the cases oxygen consumption has been measured in an oxygraph. Scyllin has produced 50% inhibition of endogenous respiration at a concentration of 110 micrograms/ml and 125 micrograms/ml in B. cereus and E. coli respectively. It also reduced the exogenous glucose oxidation by 50% at a concentration of 12 micrograms/ml and 80 micrograms/ml respectively in B. cereus and E. coli. From the above study the mechanism of bacterial growth inhibitory property of scyllin is suggested though the other studies such as inhibition of nucleic acid biosynthesis, cell wall biosynthesis etc. to evaluate its total mode of inhibitory action are not yet obtained.