Physical illness among all discharged psychiatric inpatients in a national case register

Previous studies have found that although psychiatric patients tend to have more physical illness than the rest of the population, it frequently goes unrecognized and untreated in psychiatric settings. This study investigated rates of reported physical illness among hospitalized psychiatric patients in preparation for national reform in mental health services. Data from the Israeli National Psychiatric Case Registry were analyzed on reported physical illness among all 38,714 psychiatric discharges during 1989–1991. Physical illness was reported for 10.62% of patients under age 25, 14.4% of patients 25 to 44, 34.27% of patients 45 to 65, and 61.26% of patients 65 and older. Rates differed among hospitals. Reported physical illness was considerably lower than expected as compared with other studies. Underdiagnosis is suggested as a possible explanation. Study results were used to add differential payment for physical comorbidity under the new National Health Insurance Law. Other corrective measures are discussed.     

Correlation of 99mTc-DTPA SPECT of the blood-brain barrier with neurologic outcome after acute stroke.

We conducted a study on humans to determine whether quantitative evaluation of blood-brain barrier (BBB) breakdown using the (99m)Tc-diethylenetriaminepentaacetic acid ((99m)Tc-DTPA) SPECT technique at the peak time of stroke evolution can predict neurologic outcome. METHODS: Thirty consecutive patients with acute stroke of the middle cerebral artery occurring >24 h and <48 h before admission were included in the study. Each patient underwent a complete neurologic examination according to the Scandinavian stroke score at 72 h after the stroke (S1) and again at 30 d (S2). The difference between initial and late scores was calculated (Delta S) and used to evaluate the change in neurologic status. A CT scan was obtained on all patients to determine the volume of stroke. The integrity of the BBB was evaluated using (99m)Tc-DTPA brain SPECT. A quantitative index of BBB disruption was defined as the ratio of the mean counts/pixel in the infarcted region compared with the mean counts/pixel in the contralateral nonaffected hemisphere. SPECT perfusion imaging was also performed with (99m)Tc-hexamethylpropyleneamine oxime ((99m)Tc-HMPAO) at 24 h after the (99m)Tc-DTPA study. The relative perfusion in the infarct region was expressed as the percentage of contralateral perfusion. RESULTS: The mean (99m)Tc-DTPA disruption index was 6.8 +/- 6.9 (range, 1-26.2). Seven patients (23%) had no BBB disruption. Statistical analysis showed that the disruption index was negatively correlated with Delta S (r = -0.423, P < 0.02). A disruption index of <2.5 was associated with a significantly better neurologic outcome (mean Delta S, 17.5 +/- 9.5) compared with patients with an index of >2.5 (mean Delta S, -0.85 +/- 4.97, P < 0.0001) with a sensitivity of 95% and a specificity of 89%. S2 was significantly correlated with S1 (r = 0.738, P < 0.001) and with Delta S (r = 0.656, P < 0.001). Perfusion abnormalities on the (99m)Tc-HMPAO SPECT studies ranged between 12% and 90% (mean, 37.6% +/- 17.8%) compared with those on the contralateral nonaffected side. No correlation was found between (99m)Tc-HMPAO uptake and Delta S, infarct volume by CT, or disruption index. The CT volume measurements were negatively correlated with S2 (r = -0.560, P < 0.004) but not with Delta S. CONCLUSION: (99m)Tc-DTPA SPECT of the BBB combined with quantitative analysis in patients with acute stroke is significantly related to clinical outcome, with a distinct prognostic cutoff threshold of 2.5. The use of this radionuclide brain SPECT technique represents a unique application of conventional nondiffusible brain agents.     

Halothane Prevents Postischemic Production of Hydroxyl Radicals in the Canine Heart

Background: Recent studies indicate that during regional myocardial ischemia and subsequent reperfusion, volatile anesthetics may provide protection against free radical-related injury. The effect of halothane on free radical production during ischemia and reperfusion, in the canine heart, was investigated. The level of hydroxyl radical ([center dot] OH)-mediated conversion of salicylate to its dehydroxybenzoate derivatives (2,3-DHBA and 2,5-DHBA) was monitored.

Methods: Under general anesthesia, the heart was exposed through median sternotomy. Salicylate (100 mg/kg given intravenously) was administered 30 min before left anterior descending artery occlusion. Six dogs were studied using inhaled halothane (1.6%) 10 min before and during the 10-min ischemic period, followed by 50 min of reperfusion, and then they were compared with seven other dogs used as controls. Blood concentrations of salicylate, 2,3-DHBA and 2,5-DHBA, K+, lactate, oxygen content, and pH were monitored.

Results: An acute increase in the normalized concentrations of 2,3-DHBA and 2,5-DHBA was observed in the control animals during reperfusion. In contrast, halothane inhalation completely inhibited the production of both metabolites (P < 0.02), but 2,5-DHBA concentrations in the halothane-treated group were even less than the basal level (P <0.05).

The increase in lactate concentrations in the experimental animals was significantly less than that of controls (P < 0.05) and followed the same time-dependent pattern as the changes in K+ and pH. Halothane significantly decreased (P < 0.0001) the difference in oxygen content between coronary sinus and aortic root blood, suggesting decreased oxygen utilization during reperfusion.     

Genetic screening for autosomal recessive nonsyndromic mental retardation in an isolated population in Israel

Nonsyndromic mental retardation (NSMR) is the diagnosis of exclusion in mentally retarded individuals without additional abnormalities. We have recently identified a protein-truncating mutation, G408fsX437, in the gene CC2D1A on chromosome 19p13.12 in nine consanguineous Israeli Arab families with severe autosomal recessive NSMR, and have developed a comprehensive prevention program among the at-risk population in the village. The subjects tested were healthy women who were invited to undergo the genetic screening test as a part of their routine pregnancy monitoring. One hundred and seventeen subjects reported a family history positive for mental retardation. We tested 524 pregnant or preconceptional women and found 47 carriers (approximately 1/11), whose spouses were then recommended to undergo testing. We identified eight carrier couples, who were given genetic counseling and offered prenatal diagnosis. Of all the marriages, 28.6% were consanguineous; 16.5% of the total were between first cousins. The high prevalence of the mutation can be explained both by the founder effect owing to the generally high consanguinity rate among the inhabitants of the village, and also because two families with excessive numbers of mentally retarded offspring were unacceptable as marriage partners by the rest of the families. This is the first example of the establishment of a large-scale genetic screening program for autosomal recessive NSMR, which was made possible owing to the high frequency of the specific causative mutation in this isolated population.     

Orbital marginal zone lymphomas: an immunohistochemical, polymerase chain reaction, and fluorescence in situ hybridization study

Many studies have been performed on chromosomal aberrations of extranodal marginal zone lymphomas. However, only a few have been published so far on ocular adnexal marginal zone lymphomas. We studied 18 cases of orbital lymphoid cell infiltrates. Using fluorescence in situ hybridization (FISH), we studied some of the most common chromosomal aberrations found in extranodal marginal zone lymphomas as: trisomies 3, and rearrangements of the 18q21 MALTI gene to detect the translocations t(11;18)(q21;q21) and t(14;18)(q32;q21)MALT1. Our goals were as follows: (1) study those aberrations in our material and compare them with the literature, (2) check their prognostic significance, and (3) check whether studying those aberrations with FISH can be used as a diagnostic tool to differentiate reactive from neoplastic infiltrates, in addition to immunohistochemistry and polymerase chain reaction. We found a high frequency of trisomies 3 (68%) and 18 (56.6%), the highest published so far in orbital lymphomas. On the other hand, no rearrangement was seen in any of our cases. The histologic picture and the clinical course were the same when there was one or more aberrations. As for the diagnostic significance, the presence of a prior, concurrent, or subsequent lymphoma in almost all the positive for aberrations cases suggests that either the orbital infiltrates in these cases are lymphomas, or they have, at least, a malignant potential or a genetic instability. Therefore, the demonstration of these numerical aberrations by FISH may be an additional sensitive, reliable, and relatively simple tool to differentiate reactive from neoplastic orbital lymphoid cell infiltrates when the immunohistochemistry and polymerase chain reaction, performed in a busy and routine-based histopathology laboratory, are unsatisfactory.     

The trans-Golgi network-associated human ubiquitin-protein ligase POSH is essential for HIV type 1 production

HIV type 1 (HIV-1) was shown to assemble either at the plasma membrane or in the membrane of late endosomes. Now, we report an essential role for human ubiquitin ligase POSH (Plenty of SH3s; hPOSH), a trans-Golgi network-associated protein, in the targeting of HIV-1 to the plasma membrane. Small inhibitory RNA-mediated silencing of hPOSH ablates virus secretion and Gag plasma membrane localization. Reintroduction of native, but not a RING finger mutant, hPOSH restores virus release and Gag plasma membrane localization in hPOSH-depleted cells. Furthermore, expression of the RING finger mutant hPOSH inhibits virus release and induces accumulation of intracellular Gag in normal cells. Together, our results identify a previously undescribed step in HIV biogenesis and suggest a direct function for hPOSH-mediated ubiquitination in protein sorting at the trans-Golgi network. Consequently, hPOSH may be a useful host target for therapeutic intervention.     

Sustained elevation of intraocular pressure after intravitreal injections of bevacizumab in eyes with neovascular age-related macular degeneration

Background

The use of intravitreal anti-VEGF agents in general, and of bevacizumab (Avastin) in particular, has become the common first-line treatment of neovascular age-related macular degeneration (AMD). Several reports addressed the possible elevation of intraocular pressure (IOP) following intravitreal injection of anti-VEGF. The aim of this study was to determine the prevalence of sustained IOP elevation following intravitreal bevacizumab injections for neovascular AMD and identify possible risk factors for the development of increased IOP.

Methods

This retrospective cohort study included 174 consecutive patients (201 eyes) receiving intravitreal bevacizumab (1.25?mg/0.05?ml) as treatment for neovascular AMD. The records of the study patients were reviewed for age, gender, history of glaucoma, phakic status, IOP levels, length of follow-up, total number of injections, intervals between injections, and IOP management in eyes that exhibited IOP elevation. Sustained IOP elevation was defined as IOP ≥22?mmHg and a change from baseline of ≥6?mmHg recorded on at least two consecutive visits and lasting ≥30?days. Risk factors for an IOP increase were identified from the association between the studied variables and IOP elevations.

Results

Sustained IOP elevation was found in 22 of 201 eyes (11%). The increased IOP was controlled with topical medications in all eyes. Among the variables studied, only male gender [OR?=?3.1, 95% CI (1.1, 8.5) p?=?0.029] and length of interval between injections <8?weeks [OR?=?3.0, 95%CI (1.1, 7.9), p?=?0.028] emerged as risk factors for IOP elevation in a multivariable model. The prevalence of IOP elevation was significantly higher when the interval between injections was <8?weeks than ≥8?weeks (17.6 and 6%, respectively, p?=?0.009). Pre-existing glaucoma was not associated with IOP elevation (p?=?0.9).

Conclusions

Sustained IOP elevations can occur in normotensive eyes undergoing intravitreal bevacizumab treatment for neovascular AMD. This phenomenon was related to shorter intervals between injections, with 8?weeks being taken as the cut-off point. AMD eyes that receive intravitreal bevacizumab injections need to be monitored for IOP changes, especially those in which the intervals between injections are <8?weeks.     

Staphylolysin is an effective therapeutic agent for <Emphasis Type="Italic">Staphylococcus aureus</Emphasis> experimental keratitis

Background  

Therapy of S. aureus keratitis is increasingly challenging due to emerging resistant strains. Staphylolysin (LasA protease) is a staphylolytic endopeptidase secreted by Pseudomonas aeruginosa. The purpose of the current study was to study the effect of treatment with staphylolysin on experimental keratitis caused by various Staphylococcus aureus strains.