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Biomedical subjects

S Cohen

Publications and source records attributed to S Cohen.

At least 19 recordsLinked to original sources

Rasagiline is neuroprotective in an experimental model of brain ischemia in the rat.

The neuroprotective effects of intravenous rasagiline were investigated in a rat model of stroke. Middle cerebral artery (MCA) occlusion was performed in male rats and the short- (neurological severity score [NSS], infarct size), intermediate- (cognition) and long-term (necrotic area) effects were assessed. A bolus (3 mg/kg) of rasagiline followed by a 3-h infusion (3 mg/kg/h), initiated immediately after MCA occlusion, reduced infarct size by 48.6% and NSS by 32.7% relative to saline treatment. Cognitive function, tested in a water maze 2-3 weeks after occlusion, also significantly improved compared with saline-treated controls. Necrotic brain area was 35-50% smaller with rasagiline than with saline following a single bolus dose. The single bolus rasagiline dose was as effective as a rasagiline bolus followed by rasagiline infusion in short-term outcomes. The neuroprotective effect of rasagiline was fully reproducible when administered at 2 h following occlusion but not after 4 h.

Animals↗

Molecular and imaging correlates of the fragile X-associated tremor/ataxia syndrome.

OBJECTIVES: To assess changes in regional brain volumes associated with the fragile X-associated tremor/ataxia syndrome (FXTAS) and the molecular correlates of these changes. METHODS: We administered molecular, MRI, and neurocognitive tests to 36 male premutation carriers (ages 51 to 79), 25 affected and 11 unaffected with FXTAS, and to 21 control subjects of similar age and education. RESULTS: We found differences among the three groups in whole brain, cerebrum, cerebellum, ventricular volume, and whole-brain white matter hyperintensity, with the affected group showing significantly more pathology than the control and unaffected groups. Brainstem volume was significantly smaller in the unaffected group vs controls but did not differ from the affected group. Within the premutation sample, CGG repeat length correlated with reductions in IQ and cerebellar volume and increased ventricular volume and whole-brain white matter hyperintensity. CONCLUSIONS: The current findings, coupled with recent evidence linking the degree of neuropathology (numbers of intranuclear inclusions) to the size of the premutation allele, provide evidence that the neurodegenerative phenotype in the fragile X-associated tremor/ataxia syndrome is a consequence of the CGG repeat expansion.

Aged↗

Does sodium hyaluronate- and carboxymethylcellulose-based bioresorbable membrane (Seprafilm) decrease operative time for loop ileostomy closure?

BACKGROUND: Adhesions can result in serious clinical complications and make ileostomy closure, which is relatively simple procedure into a complicated and prolonged one. The use of sodium hyaluronate and carboxymethyl cellulose membrane (Seprafilm) was proven to significantly reduce the postoperative adhesions at the site of application. The aim of this study was to assess the incidence and severity of adhesions around a loop ileostomy and to analyze the length of time and morbidity for mobilization at the time of ileostomy closure with and without the use of Seprafilm. METHODS: Twenty-nine surgeons from 15 institutions participated in this multicenter prospective randomized study. 191 patients with loop ileostomy construction were randomly assigned to either receive Seprafilm under the midline incision and around the stoma (Group I), only under the midline incision (Group II), or not to receive Seprafilm (Group III). At ileostomy closure, adhesions were quantified and graded; operative morbidity was also measured. RESULTS: All 3 groups were comparable relative to gender, mean age and number of patients with prior operations (26, 25 and 19, respectively). Group II patients were significantly more likely to have pre-existing adhesions than Group III patients (30.6% vs. 14.1%, p = 0.025). At stoma mobilization, significantly more patients in Group III than in Group I had adhesions around the stoma (95.2% vs. 82.3%, p = 0.021). Mean operative times were 27, 25, and 28 minutes, respectively (p = 0.38), with significant differences among sites. There was no significant difference in the number of patients needing myotomy or enterotomy (29, 27 and 24 patients, respectively), nor in the number of postoperative complications (7, 9 and 7 patients, respectively). CONCLUSIONS: When consistently applied, Seprafilm significantly decreased adhesion formation around the stoma but not operative times without any increase in the need for myotomy or enterotomy. These findings were not seen in the overall study population possibly due to the large number of surgeons using a variety of application techniques.

Adjuvants, Immunologic↗

Use of thermal and visible imagery for estimating crop water status of irrigated grapevine.

Achieving high quality wine grapes depends on the ability to maintain mild to moderate levels of water stress in the crop during the growing season. This study investigates the use of thermal imaging for monitoring water stress. Experiments were conducted on a wine-grape (Vitis vinifera cv. Merlot) vineyard in northern Israel. Irrigation treatments included mild, moderate, and severe stress. Thermal and visible (RGB) images of the crop were taken on four days at midday with a FLIR thermal imaging system and a digital camera, respectively, both mounted on a truck-crane 15 m above the canopy. Aluminium crosses were used to match visible and thermal images in post-processing and an artificial wet surface was used to estimate the reference wet temperature (T(wet)). Monitored crop parameters included stem water potential (Psi(stem)), leaf conductance (g(L)), and leaf area index (LAI). Meteorological parameters were measured at 2 m height. CWSI was highly correlated with g(L) and moderately correlated with Psi(stem). The CWSI-g(L) relationship was very stable throughout the season, but for that of CWSI-Psi(stem) both intercept and slope varied considerably. The latter presumably reflects the non-direct nature of the physiological relationship between CWSI and Psi(stem). The highest R(2) for the CWSI to g(L) relationship, 0.91 (n=12), was obtained when CWSI was computed using temperatures from the centre of the canopy, T(wet) from the artificial wet surface, and reference dry temperature from air temperature plus 5 degrees C. Using T(wet) calculated from the inverted Penman-Monteith equation and estimated from an artificially wetted part of the canopy also yielded crop water-stress estimates highly correlated with g(L) (R(2)=0.89 and 0.82, respectively), while a crop water-stress index using 'theoretical' reference temperatures computed from climate data showed significant deviations in the late season. Parameter variability and robustness of the different CWSI estimates are discussed. Future research should aim at developing thermal imaging into an irrigation scheduling tool applicable to different crops.

Air↗

Angry breathing: A prospective study of hostility and lung function in the Normative Aging Study.

BACKGROUND: Hostility and anger are risk factors for, or co-occur with, many health problems of older adults such as cardiovascular diseases, all-cause mortality, and asthma. Evidence that negative emotions are associated with chronic airways obstruction suggests a possible role for hostility in the maintenance and decline of pulmonary function. This study tests the hypothesis that hostility contributes to a faster rate of decline in lung function in older adults. METHODS: A prospective examination was undertaken of the effect of hostility on change in lung function over time. Data are from the VA Normative Aging Study, an ongoing cohort of older men. Hostility was measured in 1986 in 670 men who also had an average of three pulmonary function examinations obtained over an average of 8.2 years of follow up. Hostility was ascertained using the 50-item MMPI based Cook-Medley Hostility Scale. Pulmonary function was assessed using spirometric tests to obtain measures of forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC). RESULTS: Baseline pulmonary function differed between high and medium/low hostility groups (mean (SE) percent predicted FEV(1) 88.9 (18.5) v 95.3 (16.9) and FVC 92.5 (16.5) v 98.9 (15.9), respectively; p < 0.01 for both). This overall association between higher hostility and reduced lung function remained significant after adjusting for smoking and education, although the effect size was attenuated for both FEV1 and FVC. Higher hostility was associated with a more rapid decline in lung function, and this effect was unchanged and remained significant for FEV1)in multivariate models but was attenuated for FVC. Each standard deviation increase in hostility was associated with a loss in FEV1 of approximately 9 ml/year. CONCLUSIONS: This study is one of the first to show prospectively that hostility is associated with poorer pulmonary function and more rapid rates of decline among older men.

Age Factors↗

Numerical solution of Dalgarno-Lewis equations by a mapped Fourier grid method.

Inhomogeneous radial differential equations emerging in applications of standard perturbation theory are numerically solved by a novel approach making use of Fourier grid methods in conjunction with a simple mapping scheme. The proposed algorithm is applied along the lines of the Dalgarno-Lewis method [Proc. R. Soc. London, Ser. A 223, 70 (1955)] to the calculation of the static dipole polarizabilities and hyperpolarizabilities of 1s, 2s, and 2p states of hydrogen atom and their frequency dependent dynamic dipole polarizabilities. The high efficiency and accuracy of the algorithm are demonstrated for the above test cases, where exact values are available. Then, the frequency dependent dipole polarizability of the ground state of lithium atom is computed by a variationally stable method combining an effective local potential approach with a second-order energy correction. The obtained results are in perfect agreement with other elaborate theoretical approaches.

Journal Article↗

A survey of oesophageal cancer: pathology, stage and clinical presentation.

BACKGROUND: Oesophageal adenocarcinoma is the sixth leading cause of cancer-related mortality worldwide. Previously, oesophageal cancer was mainly squamous cell, presenting late with dysphagia and weight loss. AIMS: To examine the distribution of oesophageal cancer histopathology at a large, urban hospital; to determine the tumour stage and symptoms at presentation; and to evaluate the impact of endoscopic surveillance in Barrett's oesophagus. METHODS: From 1999 to 2004, all patients diagnosed with oesophageal cancer were evaluated retrospectively for demographics and tumour stage at presentation using endoscopic ultrasonography and computerized tomography. RESULTS: A total of 131 patients were included. 81% of tumours were adenocarcinomas; most localized to the distal oesophagus (97%). Patients presented with dysphagia (56%), pain (30%) and/or weight loss (16%). Irrespective of histology, locally advanced lesions accounted for most cases. Thirteen patients had lesions detected in Barrett's surveillance; these were early or intermediate stage in nine patients, but late stage in four patients. CONCLUSIONS: Adenocarcinoma has become the dominant histologic subtype, comprising 81% of proven malignancies. Despite a change in histopathology, most cancers are diagnosed at an advanced stage, presenting with dysphagia, pain and/or weight loss. Endoscopic surveillance of Barrett's oesophagus allows earlier diagnosis of cancer in most, but not all, patients.

Adenocarcinoma↗

Retrospective follow-up of transplantation of kidneys from 'marginal' donors.

The organ shortage has led to extend the procurement to kidneys from 'marginal' donors. As a result, an increasing number of kidneys are discarded, but an extended analysis of the validity of the clinical decision to accept or decline a marginal graft remains to be determined. We have retrospectively analyzed the outcome of 170 kidney transplantations, performed in eight renal transplantation centers between 1992 and 1998. Study group included transplantation from donors accepted after refusal for poor donor or graft quality by at least two centers. Control group included 170 paired recipients from kidneys unanimously accepted by all centers. Main causes of kidney refusal included impaired donor hemodynamics (28%), abnormal pre-harvesting serum creatinine (22%), advanced age in donors (15%), and donor atheroma (14%). The 5-year patient survival (88.2% in the study group and 88.9% in controls) and graft survival (70.4% in the study group and 76.7% in controls, P=0.129) were not significantly different. Delayed graft function occurred significantly more often in the study group patients than in controls patients (63 vs 32%, P<0.0001). Primary non-functioning kidneys were significantly more frequently observed in study patients than in controls (7.7 vs 1.8%, P=0.01). Mean creatinine clearance was significantly lower in the study group patients compared with controls during the post-transplant course. Our results suggest that these initially discarded kidneys provide satisfactory survival rates despite their impaired early functional recovery and poorer long-term renal function, and therefore might be considered acceptable for transplantation in the context of organ shortage.

Adult↗

[Blood screening of benzodiazepines and tricyclic antidepressants. Results of 5 years of interhospital controls].

Pro bio Qual Association of Lyon have proposed a control which include the control for detecting benzodiazepines (BZD) and tricyclic antidepressants (ADT) since 2000. With this control, we have evaluated the specificity and the sensitivity of techniques used. We have tested the maprotiline reactivity too (tetracyclic antidepressant). We report results achieved with different immunoassay methods and their performances: specificity and sensitivity. The number of laboratories which realize these analyses is constant: these laboratories are hospital laboratories. Two methods are most common used: the fluorescence polarization immunoassay (FPIA) and the enzyme multiplied immunoassay test (EMIT). The evolution of these techniques does square with the evolution of chemistry analysers used in hospital laboratories. For the BZD, the specificity is good. For the ADT, carbamazepine at low concentration (5 mg/L) gives a positive result with FPIA Abbott assay; carbamazepine at high concentration (25 mg/L) gives a negative result with EMIT assay; phenothiazines give a positive response. For the BZD, the analyser Integra gives best results of sensitivity. Results of sensitivity obtained with the kit EMIT DAU are better than results obtained with the kit EMIT Serum. For the ADT, results of sensitivity obtained with FPIA Abbott assay seem better; the adaptation of EMIT assay on Integra analyser gives less good results. The reactivity for the BZD is very different: we can ignore a severe intoxication with alprazolam or lorazepam (response << cut off) but we can give a positive result for a therapeutic concentration of diazepam for example. With ADT, we haven't the same problem. But the reactivity for nortriptyline is less good than the reactivity for amitriptyline. So we should use a "cut off" concentration which corresponds to the best sensitivity and the best specificity.

Antidepressive Agents, Tricyclic↗

Adolescents anticipated experience of screening for genital herpes.

Screening asymptomatic adolescents for genital herpes will require sensitivity to adolescents' developmental needs. Twenty-four adolescents (age range 1619 years) were interviewed to explore their perceptions of screening. In general, adolescents thought screening for genital herpes would be viewed as taking care of themselves, although there were concerns that their peers might view getting screened as implying that the adolescent was infected or sexually promiscuous. Most adolescents expected their parents to respond positively, but typically thought that younger adolescents should obtain parental consent for screening, and that adolescents should inform their parents of positive test results. Adolescents wanted to be screened in settings that provided confidentiality and by non-judgemental care providers, but they differed on the setting which they believed would accomplish this. Some recommended mass screening (for example, screening all of those in a certain year at school), presumably as a way to reduce embarrassment and/or stigma. Screening programmes that are adolescent-friendly and accessible, and address adolescents' specific concerns regarding managing the information, can be created.

Adolescent↗

Fulminant neurological deterioration in a neonate with Leigh syndrome due to a maternally transmitted missense mutation in the mitochondrial ND3 gene.

Leigh syndrome can result from both nuclear and mitochondrial DNA defects. Mutations in complex V genes of the respiratory chain were considered until recently as the most frequent cause for mitochondrial inherited Leigh syndrome, while gene defects in complex I were related to recessive Leigh syndrome. Recently few reports of mutations in the mitochondrial-encoded complex I subunit genes causing Leigh syndrome have been reported. We describe a 1-month-old baby who acutely deteriorated, with abrupt onset of brainstem dysfunction, due to basal ganglia lesions extending to the brainstem. A muscle biopsy demonstrated complex I deficiency. Subsequent analysis of the mitochondrial genome revealed a homoplastic T10191C mutation in the ND3 gene (in blood and muscle), resulting in a substitution of serine to proline. Hair root analysis revealed a 50% mutant load, reflecting heteroplasmy in early embryonic stages. The mutation was also detected in his mother (5%). Western blot analysis revealed a decrease of the 20 kDa subunit (likely ND6) and of the 30 kDa subunit (NDUFA9), which is probably due to instability attributed to the inability to form subcomplexes with ND3. This is the first description of infantile Leigh syndrome due to a maternally transmitted T10191C substitution in ND3 and not due to a de novo mutation. This mutation is age and tissue dependent and therefore may not be amenable to prenatal testing.

DNA, Mitochondrial↗

The effect of gastro-oesophageal reflux and omeprazole on key sleep parameters.

BACKGROUND: The effect of gastro-oesophageal reflux on sleep and sleep quality is highly controversial. AIM: To determine the temporal relationship of abnormal objective sleep parameters to gastro-oesophageal reflux during acid suppression in patients with self diagnosed sleep disorders. METHODS: Polysomnography during oesophageal pH monitoring was conducted in 16 subjects with and without gastro-oesophageal reflux as determined by a standardized questionnaire. Subjects were studied before and after omeprazole. RESULTS: All reflux events were followed by a sleep arousal or awakening. Nocturnal acid reflux events were not predicted by the Carlsson score. Omeprazole reduced acid reflux-associated arousals from 11.6 +/- 3.8 to 1.5 +/- 0.8 (P < 0.01) and awakenings from 7.7 +/- 1.2 to 3.7 +/- 0.5 (P < 0.05). Sleep efficiency improved from 70.2% to 81.6% in a small subset of subjects with decreased sleep (P < 0.05); rapid eye movement sleep increased from 55.0 +/- 4.5 to 94.5 +/- 18.9 min (P < 0.05); total sleep time increased from 294.0 +/- 15.9 to 345.6 +/- 55.6 min (P < 0.05). Apnoea, hypopnoea and hypoxaemia were not associated with reflux. CONCLUSIONS: In subjects with gastro-oesophageal reflux, sleep arousals and awakenings are closely related to acid reflux events. Reflux-related arousals and awakenings are decreased by acid suppression. Acid suppression in selected subjects with reflux events and reduced sleep efficiency is associated with increased total sleep time, rapid eye movement sleep and sleep efficiency.

Adolescent↗

A retrospective analysis of medical or surgical therapy in young patients with diverticulitis.

BACKGROUND: Acute diverticulitis is increasingly being recognized in younger patients, but its management remains controversial. AIM: To compare long-term outcomes of young patients treated with surgery vs. medical therapy for their first episode of diverticulitis. METHODS: A retrospective chart analysis at a university and an affiliated community hospital between 1991 and 2002 revealed 149 patients < or = 40 years of age with confirmed diverticulitis. Forty-nine patients (38 males, 11 females) were contacted at least 1 year after their first episode of diverticulitis. Outcomes were compared based on initial therapy--antibiotics or surgical resection. The groups were compared by outcomes, gender, age, white blood cell count, temperature and diet. RESULTS: Three (15%) of 20 surgical patients (mean follow-up 6.89 years), and 16 (55%) of 29 medical patients had a recurrence of diverticulitis (mean follow-up 5.72 years; P = 0.01). The treatment groups did not differ in age, white blood cell count, or temperature. CONCLUSIONS: (i) Surgical treatment is effective initial therapy but disease may recur in a minority of patients; (ii) medical treatment is less effective initial therapy, with recurrence in half of the patients; (iii) initial presentation is not a strong predictor of disease recurrence.

Acute Disease↗

Failure of dietary oligofructose to prevent antibiotic-associated diarrhoea.

BACKGROUND: Oligofructose is metabolized by bifidobacteria, increasing their numbers in the colon. High bifidobacteria concentrations are important in providing 'colonization resistance' against pathogenic bacteria. AIM: To reduce the incidence of antibiotic-associated diarrhoea in elderly patients. METHODS: Patients over the age of 65 taking broad-spectrum antibiotics received either oligofructose or placebo. A baseline stool sample was cultured for Clostridium difficile and tested for C. difficile toxin. A further stool sample was analysed for C. difficile if diarrhoea developed. RESULTS: No difference was seen in the baseline characteristics, incidence of diarrhoea, C. difficile infection or hospital stay between the two groups (n = 435). Oligofructose increased bifidobacterial concentrations (P < 0.001, 95% CI: 0.69-1.72). A total of 116 (27%) patients developed diarrhoea of which 49 (11%) were C. difficile-positive and were more likely to be taking a cephalosporin (P = 0.006), be female (P < 0.001), to have lost more weight (P < 0.001, 95% CI: 0.99-2.00) and stayed longer in hospital (P < 0.001, 95% CI: 0.10-1.40). Amoxicillin (amoxycillin) and clavulanic acid increased diarrhoea not caused by C. difficile (P = 0.006). CONCLUSION: Oligofructose does not protect elderly patients receiving broad-spectrum antibiotics from antibiotic-associated diarrhoea whether caused by C. difficile or not. Oligofructose was well-tolerated and increased faecal bifidobacterial concentrations.

Aged↗

Manometric evaluation of achalasia in the elderly.

BACKGROUND: The effect of ageing on oesophageal motility in patients with achalasia is not well described. Oesophageal contraction amplitude is decreased in otherwise healthy elderly subjects. AIM: To evaluate whether ageing influences the motor function of the oesophagus in achalasia. METHODS: Initial manometry studies of patients with achalasia were reviewed and findings (lower oesophageal sphincter basal and residual pressures and oesophageal body contraction amplitudes) were compared between two groups of patients, those 65 years of age or older (49 patients) and those younger than 65 years (68 patients). The older group was further divided into those > or =70 years and those <70 years. RESULTS: Patients 65 years and older had significantly higher lower oesophageal sphincter basal pressures compared with younger patients (65.6 +/- 4.9 vs. 52.3 +/- 2.7, P = 0.02). At an age cut-off of 70 years, older patients had significantly higher basal (70.7 +/- 1.6 vs. 53.0 +/- 2.4, P = 0.02) and residual (19.7 +/- 1.6 vs. 15.9 +/- 0.7, P = 0.03) lower oesophageal sphincter pressures compared with younger patients. Amplitude of oesophageal contractions was not different between the groups. Across all age groups, there was no linear correlation between age and basal or residual lower oesophageal sphincter pressures (r = 0.28 and 0.12, respectively). CONCLUSIONS: Older patients with achalasia have higher lower oesophageal sphincter pressures, however there is no linear correlation between age and lower oesophageal sphincter pressures. Unlike healthy subjects, advanced age is not associated with a decrease in oesophageal contraction amplitude in patients with achalasia.

Adult↗

Efficacious, nontoxigenic Bacillus anthracis spore vaccines based on strains expressing mutant variants of lethal toxin components.

We reported previously on the development of a Bacillus anthracis vaccine strain expressing high levels of recombinant protective antigen (rPA) [Cohen et al., Infec Immun 2000;68(8):4549-58]. To further explore the potential of the B. anthracis platform, we generated several attenuated strains expressing lethal toxin components PA and LF, which are biologically inactive, yet retain their antigenic properties. A single injection of 5 x 10(7) spores of one of these strains, carrying PA mutation at a site involved in effector translocation (residues 313-314) was shown to resemble wild type PA in inducing production of high levels of anti-PA neutralizing antibodies and producing effective protective immunity for 12 months. Long-term protection and persistence of functional antibody titers was observed after the gradual elimination of spores from guinea pig tissues 3 months after injection and in the measurable absence of bacteria in tissues. The mutant toxin components could, thus be an effective alternatives to their native counterparts when presented to the immune system in context of a live B. anthracis strain. These live vaccine prototypes may serve as a platform for future multi-component vaccines.

Animals↗

Quantification of docetaxel and its main metabolites in human plasma by liquid chromatography/tandem mass spectrometry.

Docetaxel is an antineoplastic agent widely used in therapeutics. The objective of this study was to develop and validate a routine assay, using liquid chromatography coupled to tandem mass spectrometry (LC/MS/MS), for the simultaneous quantification of docetaxel and its main hydroxylated metabolites in human plasma. A structural analogue, paclitaxel, was used as the internal standard. Determination of docetaxel and four metabolites (M1, M2, M3 and M4) was achieved using only 100 microL of plasma. Liquid-liquid extraction was used for sample preparation, with extraction efficiency of at least 90% for all analytes. Detection used positive-mode electrospray ionization in selected reaction monitoring mode. The lower limit of quantification (LLOQ) was 0.5 ng/mL for all analytes. The assay was linear in the calibration curve range 0.5-1000 ng/mL and acceptable precision and accuracy (<15%) were obtained with concentrations above the LLOQ. This method was sufficiently selective and sensitive for quantification of metabolites in plasma from cancer patients receiving docetaxel chemotherapy, and is suitable for routine analyses during pharmacokinetic studies.

Antineoplastic Agents↗