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Biomedical subjects

Y Barak

Publications and source records attributed to Y Barak.

At least 37 records · Page 2Linked to original sources

A physiological replacement for polyvinylpyrrolidone (PVP) in assisted reproductive technology.

The technique of intracytoplasmic sperm injection (ICSI) requires mechanical immobilization of the sperm that are to be injected; damage thus caused to the sperm membrane is considered to be necessary to activate the sperm for fertilization. Mechanical immobilization and the injection procedure are facilitated by introducing the sperm into a viscous medium that will hinder motility: a solution of polyvinylpyrrolidone (PVP) has been used successfully for this purpose. PVP is an artificial polymer, which has been regarded as chemically inert, although adverse effects have been reported as a result of its use both in vivo and in vitro. Therefore, the use of hyaluronate, the natural component of the extracellular matrix of the cumulus-oocyte complex, was investigated as a replacement for PVP during ICSI. A solution of hyaluronate was found to be as effective as PVP in facilitating the injection procedure, its effect on sperm motility was readily reversible, and its use did not affect the outcome of the treatment cycles in terms of fertilization, pregnancy and live birth rates. Every attempt should be made to eliminate artificial factors in assisted reproductive procedures. Hyaluronate, a natural and readily degradable glycosaminoglycan can be used as a substitute for the artificial PVP polymer without jeopardising the outcome of the treatment cycle.

Adult↗

Autonomic response to hypobaric hypoxia assessed by time-dependent frequency decomposition of heart rate.

BACKGROUND: Acute hypoxia tolerance varies substantially among healthy individuals. We hypothesized that this variability results from a difference in autonomic (ANS) response to hypoxic stress. METHODS: Peripheral oxygen saturation, respiration and ECG were recorded from 21 healthy subjects (age, 29 +/- 7 yr) in an altitude chamber during normoxia, severe hypoxia (282 mm Hg), and mild hypoxia (360 mm Hg). Cardiovascular control was assessed by time-frequency decomposition of the heart rate signal applying the Selective Discrete Transform Algorithm (SDA). This procedure uses a variable time window, thus providing reliable physiological data even during transient states. Autonomic activity was quantified by power spectral density integrals over a 3-dimensional time-dependent spectral distribution of heart rate fluctuations. RESULTS: Subjects who had slower peripheral oxygen desaturation during severe hypoxia onset (mean 92.9 vs. 58.4 s) were those who displayed higher ANS activity in all ambient states, namely normoxia and hypoxia. These same subjects withstood hypoxia for significantly longer time periods (mean 313 vs. 244 s). CONCLUSION: Improved hypoxia tolerance is linked to enhanced autonomic activity, involving a better management of peripheral blood flow.

Adult↗

Animal-assisted therapy for elderly schizophrenic patients: a one-year controlled trial.

Animal-assisted therapy (AAT) has been used as a therapeutic tool in various psychiatric populations, but there have been no published studies with elderly schizophrenic patients. The authors evaluated, in a blinded, controlled manner, the effects of AAT in a closed psychogeriatric ward over 12 months. Subjects were 10 elderly schizophrenic patients and 10 matched patients (mean age: 79.1+/-6.7 years). The outcome measure was the Scale for Social Adaptive Functioning Evaluation (SAFE). AAT was conducted in weekly 4-hour sessions. Treatment encouraged mobility, interpersonal contact, and communication and reinforced activities of daily living (ADLs), including personal hygiene and independent self-care, through the use of cats and dogs as "modeling companions." The SAFE scores at termination showed significant improvement compared with baseline scores and were significantly more positive for the AAT group on both Total SAFE score and on the Social Functions subscale. AAT proved a successful tool for enhancing socialization, ADLs, and general well-being.

Activities of Daily Living↗

Stem cell transplantation in patients with severe congenital neutropenia without evidence of leukemic transformation.

Severe congenital neutropenia (CN) (Kostmann syndrome) is a hematologic disorder characterized by a maturation arrest of myelopoiesis at the promyelocyte/myelocyte stage of development. This arrest results in severe neutropenia leading to absolute neutrophil counts (ANC) below 0.2 x 10(9)/L associated with severe bacterial infections from early infancy. Data on over 300 patients with CN collected by the Severe Chronic Neutropenia International Registry (SCNIR) beginning in 1994 indicate that more than 90% of these patients respond to recombinant human granulocyte-colony stimulating factor (r-HuG-CSF) treatment with an ANC greater than 1. 0 x 10(9)/L. For patients who are refractory to r-HuG-CSF treatment and continue to have severe and often life-threatening bacterial infections, hematopoietic stem cell transplantation is the only currently available treatment. We report on a total of 11 patients with CN reported to the SCNIR who underwent transplantation for reasons other than malignant transformation between 1976 and 1998. Of these patients, 8 were nonresponders or showed only partial response to r-HuG-CSF treatment with ongoing infections. Results from these patients suggest that transplantation of stem cells from an HLA-identical sibling is beneficial for patients refractory to r-HuG-CSF. (Blood. 2000;95:1195-1198)

Adolescent↗

Multiple sclerosis-from probable to definite diagnosis: a 7-year prospective study.

OBJECTIVES: To investigate the rate of progression from probable to clinically definite multiple sclerosis (MS) and to define patients who had rapidly (within 1 year) progressed to a definite diagnosis. DESIGN: A 7-year prospective study. PATIENTS: A group of 163 patients experiencing their first episode of neurologic symptoms suggestive of MS. All patients had brain magnetic resonance imaging that demonstrated at least 3 demyelinating lesions at onset. RESULTS: Within the follow-up period (mean, 42 months; range, 13-84 months), 136 patients (83.4%) had an additional relapse and were thus defined as having clinically definite MS, whereas 27 patients (16.6%) were defined as having clinically probable MS. Most of the 136 patients with clinically definite MS (57.6%, 94 patients) experienced the additional relapse within 1 year. Demographic and clinical parameters at presentation were analyzed to identify variables predictive of rapid progression (within 1 year) to clinical definite MS. Motor involvement at onset was the only clinical parameter associated with rapid progression to a definite diagnosis. Survival curves demonstrated that polysymptomatic involvement and higher Extended Disability Status Scale score at presentation correlated with rapid progression to definite diagnosis. CONCLUSION: Most patients with a diagnosis of probable MS and positive brain magnetic resonance imaging will progress rapidly to clinically definite MS.

Adolescent↗

Immunoglobulin treatment in refractory Myasthenia gravis.

Failure to induce and maintain remission in severe exacerbations of myasthenia gravis (MG), despite optimal care, is a common problem. We evaluated the efficacy and safety of high-dose intravenous immunoglobulin (IVIg) therapy in an open-label study of 10 patients with severe generalized myasthenia and an acute deterioration unresponsive to conventional therapy including high-dose corticosteroids, cyclosporine, and azathioprine. Intravenous Ig at a loading dose of 400 mg/kg was administered daily for 5 consecutive days, with maintenance IVIg treatment at a dose of 400 mg/kg, once every 6 weeks. Significant improvement occurred in all patients, beginning at 6 +/- 2 days of treatment as measured by the Osserman scale, fatigue variables, muscle strength, and respiratory function tests. No side effects were observed during induction of remission. Further IVIg treatments were highly efficacious in maintaining the remission. The severity of the disease decreased by 2.5 +/- 0.8 grades of the Osserman scale over a period of 1 year (P <0.001), in parallel with reduction of immunosuppressive therapy as well as a decrease in acetylcholine receptor antibody titers (P < 0.01). Intravenous Ig therapy seems to be highly potent for inducing rapid improvement in refractory myasthenia during acute deterioration as well as for maintaining remission.

Adult↗

A long-term, multicenter, open-label study of risperidone in elderly patients with psychosis. On behalf of the Risperidone Working Group.

RATIONALE: Studies have shown that risperidone is safe and efficacious in young and middle-aged adults with chronic schizophrenia, but considerably fewer data are available on the treatment of elderly patients with schizophrenia or other psychotic disorders, particularly long-term outcomes. OBJECTIVE: A 12-month, open-label study was conducted to assess the effects of risperidone in elderly, chronically ill, psychotic patients. METHODS: This study enrolled 180 elderly, chronically ill, psychotic patients (median age, 72 years [range 54-89]), 97 of whom completed the 12-month study. At endpoint, the mean dose of risperidone was 3.7 mg/day. RESULTS: Clinical improvement (> or =20% reduction in Positive and Negative Syndrome Score [PANSS] total score) was achieved by 54% of patients at endpoint. There were significant reductions in PANSS total, subscale (positive, negative, and general psychopathology), and cognition cluster scores at endpoint (p<0.001). Clinical Global Impressions severity of illness scores showed continued improvement through month 12 (p<0.001). In contrast, PANSS data from a historical comparable control group of patients receiving conventional antipsychotic agents showed no symptom improvement over a 12-month treatment period. The severity of preexisting extrapyramidal symptoms (EPS) in patients treated with risperidone decreased significantly from baseline to endpoint (p<0.001), and the use of antiparkinsonian medication decreased from 41.1% of patients before the trial to 25.6% during the trial. There were no spontaneous reports of tardive dyskinesia (TD) and the incidence of assessed TD was 4.3% in contrast to the expected 26% reported in middle-aged and elderly patients receiving conventional antipsychotic agents for 1 year. CONCLUSIONS: Long-term treatment with risperidone was associated with continued symptom improvement, a decrease in the severity of preexising EPS, and a low incidence of TD in elderly psychotic patients.

Adult↗

A new exon 9 glucose-6-phosphate dehydrogenase mutation (G6PD "Rehovot") in a Jewish Ethiopian family with variable phenotypes.

Hereditary nonspherocytic hemolytic anemia (HNSHA) is a rare manifestation of glucose-6-phosphate dehydrogenase (G6PD) gene mutations, caused mainly by mutations located in exon 10 of the G6PD gene and less commonly by mutations in other parts of the gene. A new, exon 9, single-base mutation representing a T --> C transition at cDNA nucleotide 964 was found in three brothers and their carrier mother of Jewish Ethiopian descent. Biochemical characterization of the resultant protein was not performed. Though clinical manifestations included HNSHA in all cases, the severity of hemolysis and the transfusion requirement differed markedly. Severe congenital neutropenia (Kostmann's syndrome)--a disorder never reported before in conjunction with G6PD deficiency--was observed in one case. Levels of white blood cell G6PD activity of the three patients were 0-5% of normal controls. Neutrophil oxidative and bactericidal activities were inherently impaired in the patient with Kostmann's syndrome, but were well preserved in his two siblings.

Anemia, Hemolytic, Congenital Nonspherocytic↗

Is fatigue in patients with multiple sclerosis related to autonomic dysfunction?

Time-dependent frequency decomposition of fluctuations in cardiovascular signals (heart rate [HR], blood pressure, and blood flow) provides noninvasive and quantitative evaluation of autonomic activity during transient and steady-state conditions. This method was applied during a change of position from supine to standing in patients with multiple sclerosis (MS) who experienced unexplained fatigue and in age-matched control subjects. No difference in response to standing, as reflected in the time domain parameters (mean HR, mean blood pressure, and mean blood flow), was observed between patients with MS and control subjects. Moreover, no difference was observed in very-low-frequency and low-frequency (related to sympathetic activity) content of HR, blood pressure, blood flow, or high-frequency content of HR (related to parasympathetic activity). The only spectral estimates that showed a significant difference between groups were the ratio of low-frequency to high-frequency content of HR and low-frequency content of HR normalized to total power. Both these parameters provide an estimate of the sympathovagal balance. A significant increase in these two estimates on standing was observed in control subjects only, indicating possible impairment of the sympathovagal balance response to standing in patients with MS who experienced fatigue. The authors observed a significant age dependence between close age subgroups, which occurred in the MS group only and was observed in some of the investigated spectral estimates that reflect vagal activity. Therefore, the authors assumed that age-related reduction in vagal activity occurred earlier in patients with MS who experienced fatigue. This reduction could also explain the lack of increase in the sympathovagal balance on standing. To validate this enhanced age dependence, further investigation should be performed in a larger group of subjects with a wider age range.

Adult↗

Anxiety among Israeli soldiers during the Gulf War.

The impact of stress was investigated among Israeli soldiers during the Gulf War. The study included 40 healthy young adults in active service. Their scores on the Hamilton Anxiety Rating Scale were evaluated during the first week of the war. Our subjects were divided into two equal sub-groups (N=20); combatants and auxiliary personnel. Higher levels of anxiety were found among the combatants. Factor analysis revealed three differing factors: arousal symptoms, numbing and distraction. We discuss the possible explanations for these differences.

Adolescent↗

Treating depression in Alzheimer's disease: integration of differing guidelines.

BACKGROUND: The developments in the understanding of Alzheimer's disease (AD) have led to genetic testing, expansion of research centers, and emergence of novel treatment modalities. However, behavioral symptoms and disturbances remain the leading cause of distress to families and patients. The management of these disturbances is not fully elucidated and not without controversies. AIM: To review and integrate the two important approaches to management and treatment of depression in AD as published in the American Psychiatric Association's guidelines for the treatment of patients with AD versus the American Academy of Neurology's official publication on managing AD. METHOD: Both publications are analyzed focusing on the pharmacological treatment of depression. The analysis includes sources of data, generalization, and common and conflicting recommendations. CONCLUSION: Selective serotonin reuptake inhibitors are the drugs of choice for the treatment of depression in AD patients.

Aged↗

Fanconi anaemia group A (FANCA) mutations in Israeli non-Ashkenazi Jewish patients.

Fanconi anaemia (FA) is a genetically heterogeneous disease with at least eight complementation groups (A-H). In the present study, we investigated the molecular basis of the disease in 13 unrelated Israeli Jewish (non-Ashkenazi) patients with FA. All 43 exons of the Fanconi anaemia A (FANCA) gene were amplified from genomic DNA and screened for mutations by single-strand conformation polymorphism and DNA sequencing. We identified four ethnic-specific mutations: (1) 2172-2173insG (exon 24), the first 'Moroccan mutation': (2) 4275delT (exon 43), the second 'Moroccan mutation'; (3) 890-893del (exon 10), the 'Tunisian mutation'; and (4) 2574C > G (S858R), the 'Indian mutation'. The tetranucleotide CCTG motif, previously identified as a mutation hotspot in FANCA and other human genes, was found in the vicinity of 2172-2173insG and 890-893del. According to our study, the four mutations account for the majority (88%) of the FANCA alleles in the Israeli Jewish (non-Ashkenazi) FA population. A screening of 300 Moroccan Jews identified three carriers of the first 'Moroccan mutation', but we did not find any carrier of the second 'Moroccan mutation' among 140 Moroccan Jews, nor any carrier of the 'Tunisian mutation' among 50 Tunisian Jews. Two 'Indian mutation' carriers were identified among 53 Indian Jews. All carriers within each ethnic group had the same haplotype, suggesting a common founder for each mutation.

Adolescent↗

Comparison between day-2 embryos obtained either from ICSI or resulting from short insemination IVF: influence of maternal age.

Short incubation time prevents deleterious effects of cumulus cell degeneration and excess spermatozoa in IVF embryos. We performed a short incubation (3 h) protocol in 328 IVF cycles, in order to compare the developmental potential of regular IVF embryos with those originating from 316 cycles entered our intracytoplasmic sperm injection (ICSI) programme over the same period. Embryo transfers were performed in all patients on day 2. The mean number of embryos transferred was 1.92 for the ICSI group and 1.73 for the IVF group (P < 0.007). This was related only to the wishes of patients. However, the policy of the centre is to transfer a low number of embryos in young patients in order to avoid multiple pregnancies. All spare embryos were permitted to grow to the blastocyst stage for freezing. Shortening incubation time did not decrease fertilization rates. In our overall population, no difference was observed in the implantation rates per embryo for IVF (19%) or for ICSI (20%). An age-related decrease in embryo production was observed for both groups of patients (P < 0.01 for ICSI and P < 0.001 for IVF). The age-related decrease in embryo implantation was only significant for the IVF group (P < 0.03 for patients <30 and >35 years of age). A significant overall decrease in blastocyst formation was observed for spare embryos after ICSI versus IVF (34.2 versus 43.8%; P < 0. 05). The significance of this observation is discussed.

Adult↗

Quality of life in multiple sclerosis: development and validation of the 'RAYS' scale and comparison with the SF-36.

OBJECTIVE: To develop a self-administered rating scale for quantifying quality of life (QoL) in multiple sclerosis (MS) patients. METHODS: The RAYS scale items were derived from a source of 600 questions composed by our Centre's experts from commonly used instruments that assess physical, psychological, and social-familial dimensions. Prior to finalization of the RAYS QoL, candidate items were administered to 15 health rehabilitation professionals. Clarity, importance, relevance and specificity were graded for each item by every professional independently. Items chosen for the final version were graded as good or excellent on all these aspects. The Medical Outcome Study Short Form-36 (SF-36) was used to compare health appraisal with the RAYS scale. RESULTS: Each of the three subscales of the RAYS covers a different dimension (physical, psychological, and social-familial) and each includes 15 self-report items scored from 1 (best) to 4 (worse), focusing on the preceding week. Validation was achieved through administration of the scale to 50 randomly selected MS patients and to 50 age, sex-, education- and family status-matched healthy controls. All RAYS dimensions among MS patients reached a Cronbach's coefficient alpha > 0.8. Mean values for all dimensions were greater in patients than in controls (P < 0.002). Patients scored below norms for the general population in the majority of the SF-36 subscales (on average 32% lower). Significant correlation was found between the two scales especially in the physical and social functioning subscales. CONCLUSION: The RAYS scale demonstrated high internal consistency and significant discriminative value, and is thus a suitable disease-specific tool for measuring QoL in MS.

Activities of Daily Living↗

Is selectivity for serotonin uptake associated with a reduced emergence of manic episodes in depressed patients?

To determine whether selectivity for serotonin reuptake plays a role in antidepressant-associated mania (AAM), we evaluated the frequency of treatment-emergent mania in patients with unipolar depression who received either citalopram, a highly selective serotonin uptake inhibitor, or the adrenergic tetracyclic antidepressants (TTCAs) maproriline and mianserin, or placebo. Data were collected from post-marketing reports of adverse events, three placebo-controlled trials and four double-blind comparative trials. Of the total 4,004 depressed patients treated with citalopram (2482 from postmarketing data, 840 from placebo-controlled studies and 682 from TTCAs comparative studies), 25 (0.62%) had manic episodes. The rate of AAM in the comparative trials was significantly lower in the citalopram-treated patients (1/682, 0.15%) than in the TTCA-treated patients (5/389, 1.29%) (P = 0.03). In the placebo-controlled studies, no manic episodes were reported in the patients given placebo, but one manic episode occurred in a citalopram-treated patient (1/840, 0.12%). The citalopram-treated patients in whom AAM developed were significantly older than those in whom it did not (about 10 years, P < 0.001); gender distribution was similar. In conclusion, despite its limitations, our study apparently indicates that citalopram, a highly selective serotonin reuptake inhibitor, is associated with a significantly lower rate of treatment-emergent manic episodes than TTCAs, which have noradrenergic activity, but a similar rate to that reported for less selective SSRIs.

Adult↗

Relationship between nitrite reduction and active phosphate uptake in the phosphate-accumulating denitrifier Pseudomonas sp. strain JR 12.

Phosphate uptake by the phosphate-accumulating denitrifier Pseudomonas sp. JR12 was examined with different combinations of electron and carbon donors and electron acceptors. Phosphate uptake in acetate-supplemented cells took place with either oxygen or nitrate but did not take place when nitrite served as the final electron acceptor. Furthermore, nitrite reduction rates by this denitrifier were shown to be significantly reduced in the presence of phosphate. Phosphate uptake assays in the presence of the H(+)-ATPase inhibitor N,N'-dicyclohexylcarbodiimide (DCCD), in the presence of the uncoupler carbonyl cyanide 3-chlorophenylhydrazone (CCCP), or with osmotic shock-treated cells indicated that phosphate transport over the cytoplasmic membrane of this bacterium was mediated by primary and secondary transport systems. By examining the redox transitions of whole cells at 553 nm we found that phosphate addition caused a significant oxidation of a c-type cytochrome. Based on these findings, we propose that this c-type cytochrome serves as an intermediate in the electron transfer to both nitrite reductase and the site responsible for active phosphate transport. In previous studies with this bacterium we found that the oxidation state of this c-type cytochrome was significantly higher in acetate-supplemented, nitrite-respiring cells (incapable of phosphate uptake) than in phosphate-accumulating cells incubated with different combinations of electron donors and acceptors. Based on the latter finding and results obtained in the present study it is suggested that phosphate uptake in this bacterium is subjected to a redox control of the active phosphate transport site. By means of this mechanism an explanation is provided for the observed absence of phosphate uptake in the presence of nitrite and inhibition of nitrite reduction by phosphate in this organism. The implications of these findings regarding denitrifying, phosphate removal wastewater plants is discussed.

Biological Transport, Active↗

Atypical polyphosphate accumulation by the denitrifying bacterium Paracoccus denitrificans.

Polyphosphate accumulation by Paracoccus denitrificans was examined under aerobic, anoxic, and anaerobic conditions. Polyphosphate synthesis by this denitrifier took place with either oxygen or nitrate as the electron acceptor and in the presence of an external carbon source. Cells were capable of poly-beta-hydroxybutyrate (PHB) synthesis, but no polyphosphate was produced when PHB-rich cells were incubated under anoxic conditions in the absence of an external carbon source. By comparison of these findings to those with polyphosphate-accumulating organisms thought to be responsible for phosphate removal in activated sludge systems, it is concluded that P. denitrificans is capable of combined phosphate and nitrate removal without the need for alternating anaerobic/aerobic or anaerobic/anoxic switches. Studies on additional denitrifying isolates from a denitrifying fluidized bed reactor suggested that polyphosphate accumulation is widespread among denitrifiers.

Acetates↗