Osteomyelitis of the humerus complicating BCG vaccination.
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BCG Vaccine↗
Biomedical subjects
S Segal
Publications and source records attributed to S Segal.
The flow-cytometry-based evaluation of cellular immunity in cases of cutaneous leishmaniasis and healthy controls from the endemic area in southern Israel.
Only limited data are available on the early immunological events associated with human cutaneous leishmaniasis (CL). In this study, peripheral-blood mononuclear cells were obtained from 66 individuals (34 patients with cutaneous lesions and 32 apparently healthy controls) who had each spent no more than 3 months in the endemic region of Qetzioth, in southern Israel. These cells' responses to Leishmania major antigen were then explored, by the flow-cytometry-based evaluation of blast transformation (BT). The lymphocytes from 17 (50%) of the patients but only one (3%) of the controls displayed BT. When, in an ELISA, most (52) of the subjects were checked for anti-L. major antibodies, none of the 22 controls investigated but 19 (63%) of the 30 patients were found seropositive. Although 14 (47%) of the 30 patients who were checked for antibodies were BT-positive, the seropositive patients were not significantly more or less likely to be BT-positive than the seronegative patients (P<0.919). These data indicate that, in CL, the hosts' cellular and humoral responses develop independently within the first 3 months post-infection, but further investigation is required to confirm this hypothesis.
Animals↗
Hippocampal cerebrospinal fluid spaces on MR imaging: Relationship to aging and Alzheimer disease.
BACKGROUND AND PURPOSE: Perihippocampal fissures (PHFs) and hippocampal sulcus residual cavities (HSCs) are common findings in the MR imaging examination of the hippocampus in aging and Alzheimer disease (AD); however, little is known about how to distinguish them or their relative clinical relevance. We hypothesized that prominence of the HSC, unlike PHF, is not significantly influenced by the hippocampal atrophy related to aging or AD. METHODS: We studied and evaluated these hippocampal CSF spaces on MR imaging scans from 130 normal control (NC) subjects (20-90 years of age) and 27 AD patients. RESULTS: HSC is poorly correlated with age and is not related to the magnitude of hippocampal atrophy. There is no significant difference of HSCs between AD and age-matched NCs, but in the extremely high HSCs group (top 20%), 91% of cases are NC. PHFs, on the other hand, are strongly correlated with age and are valuable in the diagnosis of AD. Location and communication with ambient cistern is the key to distinguish HSC from PHF. CONCLUSION: Identifying hippocampal atrophy (enlarged PHF) may be particularly challenging in the presence of HSC. Distinguishing among the CSF spaces in hippocampus may help in the radiologic evaluation of hippocampal atrophy. Patients with extremely high HSCs (>8.4) can be excluded from AD risk with 93% specificity.
Adult↗
The endoscopic Draf II frontal sinusotomy: non-navigated approach.
OBJECTIVE: Endoscopic endonasal Draf II frontal sinusotomy is indicated for a variety of pathologies such as mucocele and non-responsive chronic frontal sinusitis. However, this approach is challenged and controversial. The objectives were to evaluate the advantages, disadvantages, indications, and rate of complications of this approach, without the use of a navigation system. METHODS: The files and computed tomography (CT) scans of 25 patients who underwent endoscopic endonasal Draf II sinusotomy at Assaf Harofeh Medical Center between 1999 and 2002 were reviewed. RESULTS: Thirty-one frontal sinuses were operated on and follow-up was between 18 and 62 months (average 30.3). Twenty-two sinuses (71%) had previous surgery. The Draf II procedure was used in 3.7% of all cases during the survey period. The most frequent indication for surgery was inflammation (48%) followed by mucocele (28%). In all but 2 sinuses (93%), the frontal floor between the lamina papyracea and the middle concha was drilled out. Twenty-four patients (96%) were successfully ventilated. No major complications were noted. CONCLUSIONS: The Draf II approach can be used safely and successfully without a navigation system, including cases of revision endoscopic sinus surgery. Correct interpretation of the surgical field and a CT scan are crucial for success. Careful patient selection is essential for this procedure.
Adolescent↗
Longitudinal CSF and MRI biomarkers improve the diagnosis of mild cognitive impairment.
The diagnosis of Alzheimer's disease (AD) in patients with mild cognitive impairment (MCI) is limited because it is based on non-specific behavioral and neuroimaging findings. The lesions of Alzheimer's disease: amyloid beta (Abeta) deposits, tau pathology and cellular oxidative damage, affect the hippocampus in the earlier stages causing memory impairment. In a 2-year longitudinal study of MCI patients and normal controls, we examined the hypothesis that cerebrospinal fluid (CSF) markers for these pathological features improve the diagnostic accuracy over memory and magnetic resonance imaging (MRI)-hippocampal volume evaluations. Relative to control, MCI patients showed decreased memory and hippocampal volumes and elevated CSF levels of hyperphosphorylated tau and isoprostane. These two CSF measures consistently improved the diagnostic accuracy over the memory measures and the isoprostane measure incremented the accuracy of the hippocampal volume achieving overall diagnostic accuracies of about 90%. Among MCI patients, over 2 years, longitudinal hippocampal volume losses were closely associated with increasing hyperphosphorylated tau and decreasing amyloid beta-42 levels. These results demonstrate that CSF biomarkers for AD contribute to the characterization of MCI.
Aged↗
Vaccines against bacterial meningitis.
Meningitis remains an important cause of morbidity and mortality among children >5 years of age and is especially prevalent in developing countries. Effective routine immunization against Hib, pneumococcus and serogroupC meningococcus has had a significant impact on both invasive disease and carriage caused by these encapsulated bacteria. The major challenge in prevention of meningitis remains the delivery of vaccines worldwide, especially to resource-poor regions with the greatest disease burden.
Bacterial Proteins↗
Hemodynamic effects of spinal anesthesia and simultaneous intravenous bolus of combined phenylephrine and ephedrine versus ephedrine for cesarean delivery.
BACKGROUND: Hypotension following spinal anesthesia for cesarean delivery can produce adverse maternal symptoms and neonatal acid-base effects. Single-agent prophylaxis, most notably with ephedrine, does not reliably prevent spinal anesthesia-induced hypotension; recently, however, the prophylactic use of phenylephrine with ephedrine as an infusion was observed to be effective. We postulated that this combination, when given as an intravenous bolus for prophylaxis and rescue treatment, could be similarly effective. METHOD: Forty-three term parturients were randomized to receive a bolus of ephedrine 10 mg +/- phenylephrine 40 microg (groups E and EP, respectively) simultaneously with spinal anesthesia. Hypotension was defined as a systolic blood pressure below 100 mmHg or a decrease of 20% from a baseline value. Rescue boluses comprised of ephedrine 5 mg +/- phenylephrine 20 microg. RESULTS: For groups E and EP, respectively, the incidence of hypotension was 80% vs. 95% (P=0.339), with the mean number of rescue boluses being 3.85+/-3.7 and 3.05+/-1.7 and the mean umbilical artery pH being 7.246+/-0.081 vs. 7.244+/-0.106. All comparisons were not significant (NS). CONCLUSION: The combination of ephedrine and phenylephrine given as an intravenous bolus at the doses selected is not superior to ephedrine alone in preventing or treating hypotension in healthy parturients undergoing cesarean delivery.
Adult↗
Treatment policies among Israeli specialists in paediatric dentistry.
AIM: This was to evaluate some suggested diagnostic procedures, treatment policies and professional attitudes of specialists in paediatric dentistry, in light of the periodically published guidelines by The American Academy of Pediatric Dentistry, The European Academy of Paediatric Dentistry and The British Society of Paediatric Dentistry. METHODS: Using a structured questionnaire, 67% of the Israeli specialists in paediatric dentistry, who agreed to participate in this study, were personally interviewed. RESULTS: Only 7.5% of the participants reported that they carry out pulp capping of primary teeth in cases of pulp exposure. Over 50% reported restoring teeth after pulpotomy with preformed crowns. Most indicated sealing pit and fissures after considering depth and morphology of the fissures and correlation with the patient's risk to caries. Cleaning teeth after eruption of the first tooth was suggested by 75.5% of the participants. A striking majority (96%) claimed that they restored permanent anterior teeth with composite resins and most used these materials for occlusal restoration in both primary and permanent posterior teeth. Most specialists advocated the use of amalgam in proximal posterior restorations. The presence of a parent in the operatory/surgery was preferred by 85% of the dentists. CONCLUSIONS: Israeli specialists in paediatric dentistry mostly comply with the mentioned guidelines. Further studies of this nature should also be encouraged in other countries to emphasize the importance of monitoring compliance with established and evidence based guidelines.
Adult↗
Atrophy rate in medial temporal lobe during progression of Alzheimer disease.
OBJECTIVE: To establish the progression of brain atrophy rates in patients with a known date of onset of Alzheimer disease (AD). METHODS: Each of 18 subjects had two high-resolution T1-weighted three-dimensional MRI examinations. The two MRIs were coregistered and the annual rate of brain tissue atrophy was derived both for the entire brain and regionally for the left and right medial temporal lobe (MTL). Time since onset (TSO) of AD, defined as the interval between the date of onset and the midpoint of MRI dates, ranged from -2.9 to 4.2 years. RESULTS: In patients with AD, TSO was a correlate of the atrophy rate for both the left MTL (R2 = 0.58, p = 0.001) and right MTL (R2 = 0.30, p = 0.03). When serial measurements were applied to a control group of 21 cognitively normal elderly subjects, MTL atrophy rate classified the group membership (AD vs normal cognition) with an accuracy of 92.3%. CONCLUSION: Increased annual atrophy rate in the medial temporal lobe is a potential diagnostic marker of the progression of Alzheimer disease.
Aged↗
Long-term safety and tolerability of tadalafil in the treatment of erectile dysfunction.
OBJECTIVE: To assess the long-term safety and tolerability of tadalafil for patients with erectile dysfunction (ED). PATIENTS AND METHODS: This was a multicentre, open-label, 24-month extension trial involving 1173 men with ED. The mean age was 57 (range 23-83) years and 74.8% of patients were taking concomitant medications for comorbid conditions, including diabetes mellitus in 30.5% of men and hypertension in 29.5%. These patients had participated in 1 of 5 previous 8-week or 12-week randomised, double-blind, placebo-controlled tadalafil studies. In the present trial, the starting 10mg dose of tadalafil could be increased to 20mg if the patient could not achieve satisfactory intercourse or reduced to 5mg for an adverse event that was persistent, intolerable and judged by the investigator to be related to tadalafil. RESULTS: Four hundred ninety-three (42.0%) men completed 24 months of treatment. In addition, a further 234 (19.9%) completed 18 months of treatment due to a sponsor decision to reduce the study duration. The total tadalafil exposure was 1676.0 patient-years. Tadalafil was safe and well tolerated. Headache (15.8%), dyspepsia (11.8%), nasopharyngitis (11.4%), and back pain (8.2%) were the most common treatment-emergent adverse events. The rate of discontinuations due to adverse events for this 18-24-month study was 6.3% and the rate for any individual event was <1%. Serious adverse events occurred in 8.6% of patients. No consistent pattern of serious adverse events assessed as causally associated with tadalafil administration was observed. None of the four deaths that occurred during the study was assessed as tadalafil related. There were no clinically significant laboratory or electrocardiographic findings or changes in vital signs in mean baseline-to-endpoint analysis attributable to tadalafil. Tadalafil administration was not causally associated with drug-induced hepatotoxicity, neutropenia, thrombocytopenia, or renal dysfunction. CONCLUSION: Tadalafil at doses of 5, 10, or 20mg taken as needed up to once daily for 18 to 24 months was safe and well tolerated. These findings support the long-term use of tadalafil in the clinical management of erectile dysfunction.
Adult↗
The integrity of cholesterol-enriched microdomains is essential for the constitutive high activity of protein kinase B in tumour cells.
A deregulated activity of PKB/Akt (where PKB stands for protein kinase B) renders tumour cells resistant to a variety of apoptosis-inducing stimuli. Elucidation of the mechanisms responsible for this deregulation is of prime importance for the development of novel anti-cancer drugs. Results of the present study demonstrate that the constitutive activity of PKB/Akt in B16BL6 melanoma cells depends on the integrity of cholesterol-enriched membrane microdomains, since the exposure of cells to cholesterol-depleting agents decreases the phosphorylation of this enzyme, with no change in its total protein level. Inhibitors of Hsp90 (heat-shock protein 90) decreased phosphorylation of PKB/Akt with a similar pattern. Dephosphorylation of the enzyme, as a consequence of raft disintegration, could be precluded by inhibition of serine/threonine (but not tyrosine) phosphatases. Our results imply that destabilization of lipid rafts seemingly affects the association of Hsp90 with the respective serine/threonine phosphatases, thereby increasing the accessibility to PKB/Akt to deactivating phosphatases. We have found recently that reconstituted expression of H-2K class I glycoproteins in class I-deficient B16BL6 cells also decreases the phosphorylation of PKB/Akt. Therefore it is possible that raft-associated regulation of this important enzyme involves both H-2K glycoproteins and Hsp90.
Animals↗
MRI and CSF studies in the early diagnosis of Alzheimer's disease.
The main goal of our studies has been to use MRI, FDG-PET, and CSF biomarkers to identify in cognitively normal elderly (NL) subjects and in patients with mild cognitive impairment (MCI), the earliest clinically detectable evidence for brain changes due to Alzheimer's disease (AD). A second goal has been to describe the cross-sectional and longitudinal interrelationships amongst anatomical, CSF and cognition measures in these patient groups. It is now well known that MRI-determined hippocampal atrophy predicts the conversion from MCI to AD. In our summarized studies, we show that the conversion of NL subjects to MCI can also be predicted by reduced entorhinal cortex (EC) glucose metabolism, and by the rate of medial temporal lobe atrophy as determined by a semi-automated regional boundary shift analysis (BSA-R). However, whilst atrophy rates are predictive under research conditions, they are not specific for AD and cannot be used as primary evidence for AD. Consequently, we will also review our effort to improve the diagnostic specificity by evaluating the use of CSF biomarkers and to evaluate their performance in combination with neuroimaging. Neuropathology studies of normal ageing and MCI identify the hippocampal formation as an early locus of neuronal damage, tau protein pathology, elevated isoprostane levels, and deposition of amyloid beta 1-42 (Abeta42). Many CSF studies of MCI and AD report elevated T-tau levels (a marker of neuronal damage) and reduced Abeta42 levels (possibly due to increased plaque sequestration). However, CSF T-tau and Abeta42 level elevations may not be specific to AD. Elevated isoprostane levels are also reported in AD and MCI but these too are not specific for AD. Importantly, it has been recently observed that CSF levels of P-tau, tau hyperphosphorylated at threonine 231 (P-tau231) are uniquely elevated in AD and elevations found in MCI are useful in predicting the conversion to AD. In our current MCI studies, we are examining the hypothesis that elevations in P-tau231 are accurate and specific indicators of AD-related changes in brain and cognition. In cross-section and longitudinally, our results show that evaluations of the P-tau231 level are highly correlated with reductions in the MRI hippocampal volume and by using CSF and MRI measures together one improves the separation of NL and MCI. The data suggests that by combining MRI and CSF measures, an early (sensitive) and more specific diagnosis of AD is at hand. Numerous studies show that neither T-tau nor P-tauX (X refers to all hyper-phosphorylation site assays) levels are sensitive to the longitudinal progression of AD. The explanation for the failure to observe longitudinal changes is not known. One possibility is that brain-derived proteins are diluted in the CSF compartment. We recently used MRI to estimate ventricular CSF volume and demonstrated that an MRI-based adjustment for CSF volume dilution enables detection of a diagnostically useful longitudinal P-tau231 elevation. Curiously, our most recent data show that the CSF isoprostane level does show significant longitudinal elevations in MCI in the absence of dilution correction. In summary, we conclude that the combined use of MRI and CSF incrementally contributes to the early diagnosis of AD and to monitor the course of AD. The interim results also suggest that a panel of CSF biomarkers can provide measures both sensitive to longitudinal change as well as measures that lend specificity to the AD diagnosis.
Aged↗
Non-immune functions of MHC class I glycoproteins in normal and malignant cells.
MHC class I glycoproteins play a pivotal role in the regulation of immune responses by presenting antigenic peptides to cytotoxic T lymphocytes and by regulating cytolytic activities of natural killer cells. Cells originating in malignant tumours are often characterized by a profound immune escape phenotype. This phenotype is frequently associated with alterations in MHC class I-related antigen processing and presentation that enable tumours to escape immune surveillance. However, it now becomes clear that MHC class I molecules do not only provide a mechanistic framework for the presentation of antigenic peptides but, rather, possess broader biological functions due to their ability to regulate cell-to-cell communication and receptor-mediated trans-membrane signal transduction. In the present review we made an attempt to reevaluate the significance of an altered MHC class I phenotype for tumour progression in view of the current state of knowledge concerning the aforementioned non-immune functions performed by these membrane glycoproteins.
Animals↗
The significance of the degree of myometrial invasion in patients with stage IB endometrial cancer.
OBJECTIVE: To study the validity of the FIGO staging classification of endometrial cancer Stage IB by correlating degree of myometrial invasion depth with outcome measures. STUDY DESIGN: Fifty patients with endometrial adenocarcinoma FIGO Stage IB who underwent hysterectomy between 1989 and 2001 were divided into two groups according to depth of myometrial invasion. The first group comprised of 31 patients with myometrial invasion of less than or equal to one-third. The second group included 19 patients with invasion greater than one-third but less than one-half. The two groups were compared with regard to prognostic factors and outcome measures. RESULTS: The overall 5-year recurrence-free survival, disease specific survival and overall survival rates were 87%, 94% and 77%, respectively. These outcome measures did not vary significantly between the two groups. There were no statistically significant differences between the two groups with regard to the following parameters: duration of follow-up, age, proportion of patients who underwent complete surgical staging and postoperative adjuvant radiotherapy. Histologic parameters of the two groups, such as histological type, grade and proportion of patients with capillary space-like involvement and lower uterine segment involvement were not significantly different. CONCLUSIONS: In patients with Stage IB endometrial cancer the amount of myometrial invasion defined as less than one third compared with invasion greater than one third does not appear to correlate with their outcome, thus validating the FIGO staging system.
Adenocarcinoma↗
The future of meningitis vaccines.
Without effective vaccines meningitis remains a substantial worldwide threat with major health-care implications. A number of advances have been made in vaccine design and implementation over the last decade, with new vaccine initiatives providing substantial promise for the future reduction of global disease burden.
Bacterial Capsules↗
Longitudinal cerebrospinal fluid tau load increases in mild cognitive impairment.
Cross-sectional cerebrospinal fluid (CSF) levels of tau and amyloid (A) beta (beta) are of diagnostic importance for Alzheimer's disease (AD) and mild cognitive impairment (MCI). However, most longitudinal studies of tau fail to demonstrate progression. Because predominantly brain-derived proteins such as tau, have higher ventricle to lumbar ratios, we hypothesized that adjusting for the ventricular enlargement of AD would correct for the dilution of tau, and improve detection of longitudinal change. Abeta which is not exclusively brain derived, shows a ratio <1, and no benefit was expected from adjustment. In a 1 year longitudinal study of eight MCI and ten controls, we examined CSF levels of hyperphosphorylated (P) tau231, Abeta40, and Abeta42. In cross-section, MCI patients showed elevated Ptau231 and Abeta40 levels, and greater ventricular volumes. Longitudinally, only after adjusting for the ventricular volume and only for Ptau231, were increases seen in MCI. Further studies are warranted on mechanisms of tau clearance and on using imaging to interpret CSF studies.
Aged↗
Treatment of obstetric hemorrhage with recombinant activated factor VII (rFVIIa).
Recombinant activated factor VII (rFVIIa, NovoSeven) was used in three patients with massive obstetric hemorrhage due to placenta previa accreta, rupture of the uterus and pre-eclampsia with HELLP. Administration of the drug markedly decreased the bleeding and enabled control of the hemorrhage. rFVIIa seems to be an adjunctive hemostatic measure for the treatment of severe obstetric hemorrhage.
Blood Transfusion↗
Single dermatome analgesia sparing in an obstetric patient following previous radiation to that region.
We present a case of an obstetric patient with prior radiation therapy for Hodgkins lymphoma to the right hip, right flank region and lumbar spine, who suffered persistent right sided L1 dermatone distribution sensory and analgesia sparing after routine epidural placement despite additional boluses of local anesthetic. We postulate that the previous radiation therapy received by our patient left sufficient epidural fibrosis as a barrier to prevent spread of local anesthetic to cover the L1 dermatome. Subsequent replacement, using a combined spinal-epidural technique at a higher lumbar space, overcame this obstruction. In patients who have received substantial radiation therapy to the lumbosacral region in the past, awareness of this potential problem may assist in clinical management.
Journal Article↗