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Biomedical subjects

D Cohen

Publications and source records attributed to D Cohen.

At least 37 records · Page 2Linked to original sources

Locomotion and nightwaking.

OBJECTIVE: In this study we addressed the association between two major achievements of infancy: independent locomotion and 'sleeping through the night'. METHODS: Mothers of 107 healthy infants aged between five and eight months completed a sleep questionnaire and a motor checklist. RESULTS AND CONCLUSIONS: Infants who were already crawling had more bedtime difficulties and nightwaking than did pre-crawlers. Among 7- and 8-month-old infants, locomotion predicted 17% of nightwaking variance, after controlling for age and gender. In discussing the developmental implications of locomotion we suggest that crawling may not only 'broaden the mind' but also 'cost' sleep. More studies, across time, on how motor development and sleep-wake regulation interrelate are recommended.

Age Factors↗

Mycobacterium avium complex infection in kidney transplant patients.

Mycobacterium avium complex (MAC) infections have been reported rarely in renal transplant patients. Consequently the clinical course and optimal treatment of these patients are not well understood. We present 3 patients with MAC infections after receiving a renal transplant (2 with generalized and 1 with localized infection). All patients were treated with combination antibiotic therapy and reduction of immunosuppression. One patient experienced clinical control of disease but a mild cellular rejection that was successfully treated with high-dose corticosteroids. One patient died of disseminated MAC infection. The patient with localized infection died of unrelated causes. In summary, MAC infection, although rare in renal transplant patients, may respond to combination antimicrobial therapy and reduction of immunosuppression.

Adult↗

Efflux transporters and their clinical relevance.

It is increasingly recognized that efflux transporters play an important role, not only in chemo protection e.g. multi-drug resistance, but also in the absorption, distribution, and elimination of drugs. The modulation of drug transporters through inhibition or induction can lead to significant drug-drug interactions by affecting intestinal absorption, renal secretion, and biliary excretion, thereby changing the systemic or target tissue exposure of the drug. Few clinically significant drug interactions that affect efficacy and safety are due to a single mechanism and there is considerable overlap of substrates, inhibitors, and inducers of efflux transporters and drug metabolizing enzymes, such as CYP3A. As well, genetic polymorphisms of efflux transporters have been correlated with human disease and variability of drug exposure. Accordingly, this review will discuss drug interactions and suitable probe substrates, as well as, the clinical relevance of the variability and modulation of efflux transporters and the exploitation of substrates as diagnostic tools. An update is given on inhibitors, which clinically reverse drug resistance and minimize the risk of metabolic interactions.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

DC magnetic fields from the human body generally: a historical overview.

A review is presented of the earliest dc magnetic field (dcMF) measurements, made between 1969 and 1983, due to natural currents in the body. The measurements were essentially a mapping over the whole body, except for the brain (dcMEG), which was omitted because of interfering non-neural sources in the head. This mapping can be useful today in interpreting new measurements over the body, especially dcMEG data, where the new authors assume only a neural source in the head; our mapping suggests that this assumption may be in error. Briefly, in our mapping, dcMFs were found over almost the entire body; they were larger over the limbs and head than over the torso proper except over the abdomen, where it was usually the largest in the body Some of the sources were: 1. A strong and complicated reflex in the abdomen due to drinking cold water, suggesting that other dcMF reflexes might be common in the body. 2. Long muscle fibers in the limbs, suggesting sources also in scalp muscles. 3. Hair follicles due to touching the scalp; these sources could also exist, unrecognized, in recent dcMEG whole-head measurements. 4. Injury currents from the ischemic human heart, suggesting dcMFs could arise from injured muscle in the body generally. One major mechanism for producing dcMFs appeared to be a change in the potassium ion concentration in the vicinity of long excitable fibers. Overall, we concluded that the dcMFs were complicated, and it may be difficult to identify each source, especially in the head.

Body Weights and Measures↗

An outbreak of norovirus gastroenteritis on an Israeli military base.

BACKGROUND: Noroviruses (NVs) are a predominant cause of viral gastroenteritis outbreaks, but they are difficult to identify because they cannot be cultivated in cell culture. Therefore, reverse-transcriptase polymerase chain reaction (RT-PCR) assays are widely used in the testing of clinical stool specimens for NV. However, testing of perianal swabs in the context of an outbreak is considered to be an insensitive method for identification of NV using the RT-PCR technique. An outbreak of acute gastroenteritis involving 159 soldiers on a training base of the Israel Defense Force in December 1999 allowed us to evaluate this identification method. PATIENTS AND METHODS: An epidemiologic investigation, a sanitation survey and a case-control study of exposure to different food items served up to 48 h preceding the outbreak were conducted. Stool samples in the form of post-defecation perianal swabs were collected from 24 ill personnel and three non-ill food handlers. Swabs were tested for the presence of NV by RT-PCR assay. RESULTS: Epidemiologic data were consistent with a pointsource food-borne outbreak which was associated with consumption of fresh vegetable salad in the base mess hall (OR = 4.38, 95% CI 1.51-13.35). Both epidemiologic and clinical features were suggestive of gastroenteritis caused by NV, and upon laboratory analysis perianal swabs from four of 24 cases were positive for NV. CONCLUSION: The combination of practical specimen collection with perianal post-defecation swabs, and the utilization of a molecular epidemiology approach, can simplify the rapid identification of outbreaks caused by NVs.

Adult↗

Ganciclovir prophylaxis delays but does not prevent cytomegalovirus infection in renal transplant recipients.

Cytomegalovirus (CMV) infection is associated with reduced graft and patient survival among renal transplant recipients. The purpose of this study was to examine the effect of routine prophylaxis with 12 weeks of oral ganciclovir on the incidence of CMV infection in a center that predominantly uses antibody induction together with tacrolimus/mycophenolate mofetil-based maintenance immunosuppressive therapy. The control group consisted of a historical patient cohort transplanted immediately prior to the use of oral ganciclovir prophylaxis. The use of tacrolimus (88% vs 77%, P=.02) and cytolytic therapy (81% vs 46%, P <.0001) was likewise greater among patients who received ganciclovir prophylaxis. CMV infection occurred in 20 (9%) patients in the ganciclovir era and 4 (3%) patients in the preganciclovir era (P=.003). The mean time to CMV infection was longer in patients who received ganciclovir prophylaxis than in patients in the preganciclovir era (23.4 +/- 10.9 weeks vs 9.8 +/- 5.6 weeks, P=.03). We conclude that 12 weeks of ganciclovir prophylaxis delays but does not prevent CMV infection from occurring in renal transplant recipients. These results suggest that with the use of 12 weeks of ganciclovir prophylaxis, vigilance for CMV infection is needed well beyond 24 weeks posttransplant.

Adult↗

A novel mutation in the SLC17A5 gene causing both severe and mild phenotypes of free sialic acid storage disease in one inbred Bedouin kindred.

Four members of an extended consanguineous Bedouin family presented with different phenotypic variants of an autosomal recessive lysosomal free sialic acid storage disease. One affected individual had congenital ascites followed by rapid clinical deterioration and death, a presentation concordant with the clinical course of infantile free sialic acid storage disorder. His three first cousins had a more slowly progressive neurodegenerative disease, in line with the clinical phenotype of the milder form (Salla type) of this lysosomal disorder. Diagnosis of free sialic acid storage disease was based on clinical findings, histology, and biochemical assays of sialic acid. Molecular studies showed that all four affected individuals were homozygous for the same novel 983G > A mutation in exon 8 of the SLC17A5 gene, replacing glycine with glutamic acid at position 328 of the sialin protein. This family demonstrates the significant phenotypic variability of the disease in affected members of a single inbred kindred with precisely the same mutation, suggesting a role for modifier genes or environmental factors. It also highlights the need to consider this rare disorder in the differential diagnosis of congenital ascites and of unexplained psychomotor retardation, ataxia, and hypomyelination in infancy.

Adult↗

Blood invasiveness of Salmonella enterica as a function of age and serotype.

We explored the dual influence of the patient's age and the infecting serotype on the blood invasiveness patterns of non-Typhi Salmonella enterica (NTS). Blood invasiveness ratio (BIR) was calculated as the ratio between the number of blood and blood + stool isolates. Analysis of 14,951 NTS isolates showed that the BIR increased drastically above the age of 60 years, reaching levels 3.5-7 times higher compared to age group < 2 years. Different patterns of age-related invasiveness were observed for the five most common NTS serotypes (Enteritidis, Typhimurium, Virchow, Hadar, Infantis). Among children < 2 years, the BIR was highest for serotype Virchow and lowest for serotype Hadar, while in persons > or = 60 years it was highest for serotypes Enteritidis and lowest for serotype Infantis. The tendency of NTS serotypes to invade the bloodstream was significantly influenced by the patient's age, however the impact of age differed for various NTS serotypes.

Adolescent↗

Atypical antipsychotics and new onset diabetes mellitus. An overview of the literature.

During the last few years, several case reports and studies have been published on the potential diabetes mellitus (DM)-inducing effect of some atypical antipsychotics, especially clozapine and olanzapine. The purpose of our study was to evaluate diabetogenic effects of atypical antipsychotics in the literature. In order to give a full-scale overview, both peer-reviewed publications and oral and poster presentations on this subject were screened. We found 27 case reports of new-onset DM for clozapine, 39 for olanzapine, 4 for risperidone, and 3 for quetiapine. Related to the year of introduction of these drugs on the market and the number of treatment days of each drug during the last 6 years in 13 western countries, Brazil, and Japan, the cases show an over-representation of cases related to olanzapine and clozapine. In the majority of cases, risk factors (DM family history, obesity, Negroid ethnicity) were present. Eighty-four percent of the cases arose in patients < 50 years, in contrast to the general population (most cases, > 50 years). Comparative epidemiological studies point in the same direction, with two studies showing no differences between the atypical drugs. Antipsychotic agents are used often for treatment of schizophrenia, a condition that appears to be associated with DM also in untreated subjects. Some antipsychotics appear to induce new-onset diabetes mellitus. In view of the health risks of DM and the predisposition in patients with schizophrenia, it is advised to be cautious with prescription of antipsychotics that are associated with new-onset DM. Especially in predisposed patients (family history of DM, obese, Negroid ethnicity), reticence in this respect is required. Moreover, careful monitoring of weight, BMI, and glucose levels is advised both before these antipsychotics are prescribed and during treatment.

Adult↗

Consistent cytotoxic-T-lymphocyte targeting of immunodominant regions in human immunodeficiency virus across multiple ethnicities.

Although there is increasing evidence that virus-specific cytotoxic-T-lymphocyte (CTL) responses play an important role in the control of human immunodeficiency virus (HIV) replication in vivo, only scarce CTL data are available for the ethnic populations currently most affected by the epidemic. In this study, we examined the CD8(+)-T-cell responses in African-American, Caucasian, Hispanic, and Caribbean populations in which clade B virus dominates and analyzed the potential factors influencing immune recognition. Total HIV-specific CD8(+)-T-cell responses were determined by enzyme-linked immunospot assays in 150 HIV-infected individuals by using a clade B consensus sequence peptide set spanning all HIV proteins. A total of 88% of the 410 tested peptides were recognized, and Nef- and Gag-specific responses dominated the total response for each ethnicity in terms of both breadth and magnitude. Three dominantly targeted regions within these proteins that were recognized by >90% of individuals in each ethnicity were identified. Overall, the total breadth and magnitude of CD8(+)-T-cell responses correlated with individuals' CD4 counts but not with viral loads. The frequency of recognition for each peptide was highly correlated with the relative conservation of the peptide sequence, the presence of predicted immunoproteasomal cleavage sites within the C-terminal half of the peptide, and a reduced frequency of amino acids that impair binding of optimal epitopes to the restricting class I molecules. The present study thus identifies factors that contribute to the immunogenicity of these highly targeted and relatively conserved sequences in HIV that may represent promising vaccine candidates for ethnically heterogeneous populations.

AIDS Vaccines↗

Family physicians are an important source of newborn care: the case of the state of Maine.

Family physicians (FPs) provided 30 percent of inpatient newborn care in Maine in the year 2000. FPs cared for a large proportion of newborns, especially those insured by Medicaid and in smaller, rural hospitals where FPs also delivered babies. Family medicine's commitment to serve vulnerable populations of newborns requires continued federal, state, and institutional support for training and development of future FPs.

Family Practice↗

Family physicians make a substantial contribution to maternity care: the case of the state of Maine.

Family physicians provided nearly 20 percent of labor and delivery care in Maine in the year 2000. A substantial proportion of this care was provided to women insured by Medicaid and those delivering in smaller, rural hospitals and residency-affiliated hospitals. As family medicine explores its future scope, research identifying regional variations in the maternity care workforce may clarify the need for maternity care training in residency and labor and delivery services in practice.

Delivery, Obstetric↗

[Schizophrenia and diabetes mellitus: not an improbable combination].

Three male schizophrenia patients, aged 41, 40 and 61 years respectively, who had undergone treatment without a satisfactory result, were treated with the antipsychotic clozapine. Diabetes mellitus developed within a period of several months to several years. The antipsychotic medication could be continued once the patients had been started on blood-glucose lowering medication. There seems to be an increased incidence of type-2 diabetes mellitus in patients with schizophrenia. It has been suggested that treatment with neuroleptics, especially atypical neuroleptics, provokes the onset of diabetes mellitus. The relatively young age (often < 50 years) at onset is a cause for concern. From a pathophysiological viewpoint, an increased prevalence of diabetic risk factors has been suggested for schizophrenia in addition to the toxic effect of neuroleptics in general. The possible consequences for the general health of this vulnerable group of patients warrant recommendations concerning the regular monitoring of these patients during treatment.

Adult↗

An outbreak of pertussis among young Israeli soldiers.

In winter 2001, an outbreak of pertussis involving an estimated 75 people occurred among soldiers serving in an infantry regiment of the Israeli Defense Forces (IDF). Nasopharyngeal swabs were obtained from patients and contacts for culture and PCR. Serum samples were obtained and assayed by ELISA for the presence of IgA, IgM and IgG antibodies to a lysate antigen of Bordetella pertussis. The calculated attack rate was 21% based on clinical signs alone (cough lasting 30 days or longer) and 9.5% based on clinical signs with laboratory confirmation (by PCR, IgA or IgM). A high carriage rate was observed; 20% of the asymptomatic and previously symptomatic subjects were PCR-positive for B. pertussis. These findings emphasize the importance of B. pertussis as a causative agent of epidemic respiratory infections in young adults and reveal the occurrence of a significant proportion of pertussis transient carriers during an outbreak of the disease.

Adult↗

Clinical and laboratory presentation of EBV positive infectious mononucleosis in young adults.

Clinical descriptions of Epstein-Barr virus (EBV) positive infectious mononucleosis (IM) are rare and their results are inconsistent. Over a 4-year period, we prospectively studied 590 young adults with clinically suspected IM, all of whom were tested for the presence of EBV IgM antibodies. We investigated the demographical, clinical and laboratory features of subjects with positive EBV IgM serology and heterophile antibodies. Contrary to previous studies, we found a seasonal disease pattern with a peak incidence during summer months, and a lower-than-expected prevalence of lymphadenopathy (88.9%), leucocytosis (46.2%), atypical lymphocytosis (89.2%) and elevated liver enzymes (57.9%). The prevalence of hyperbilirubinemia was relatively high (14.9%). The classic triad of fever, sore throat and lymph-adenopathy had relatively low sensitivity (68.2%) and specificity (41.9%) for EBV infection. Our study provides a complete and updated description of the clinical and laboratory presentation of laboratory confirmed IM, which is important for both clinicians and epidemiologists.

Adolescent↗

IGF-1 and insulin receptor expression in the minor salivary gland tissues of Sjögren's syndrome and mucoceles--immunohistochemical study.

OBJECTIVE: To investigate the expression of IGF-1 receptors and insulin receptors on the minor salivary gland (MSG) tissues of patients diagnosed with Sjögren's syndrome (SS) and normal salivary gland tissue surrounding mucoceles. SUBJECTS AND METHODS: Five MSG tissue sections from SS and seven from mucocele patients were stained immunohistochemically using antibody to IGF-1 receptor and insulin receptor in a horse radish peroxidase and DAB system. RESULTS: The expression of the insulin receptor was increased in the SS sections compared with controls, while the insulin-like growth factor-1 receptor was more intensely expressed in the controls. CONCLUSION: The presence of differential expression of receptors for IGF and insulin might suggest a possible role of these growth factors in the pathogenesis of SS.

Aged↗

Comprehensive epitope analysis of human immunodeficiency virus type 1 (HIV-1)-specific T-cell responses directed against the entire expressed HIV-1 genome demonstrate broadly directed responses, but no correlation to viral load.

Cellular immune responses play a critical role in the control of human immunodeficiency virus type 1 (HIV-1); however, the breadth of these responses at the single-epitope level has not been comprehensively assessed. We therefore screened peripheral blood mononuclear cells (PBMC) from 57 individuals at different stages of HIV-1 infection for virus-specific T-cell responses using a matrix of 504 overlapping peptides spanning all expressed HIV-1 proteins in a gamma interferon-enzyme-linked immunospot (Elispot) assay. HIV-1-specific T-cell responses were detectable in all study subjects, with a median of 14 individual epitopic regions targeted per person (range, 2 to 42), and all 14 HIV-1 protein subunits were recognized. HIV-1 p24-Gag and Nef contained the highest epitope density and were also the most frequently recognized HIV-1 proteins. The total magnitude of the HIV-1-specific response ranged from 280 to 25,860 spot-forming cells (SFC)/10(6) PBMC (median, 4,245) among all study participants. However, the number of epitopic regions targeted, the protein subunits recognized, and the total magnitude of HIV-1-specific responses varied significantly among the tested individuals, with the strongest and broadest responses detectable in individuals with untreated chronic HIV-1 infection. Neither the breadth nor the magnitude of the total HIV-1-specific CD8+-T-cell responses correlated with plasma viral load. We conclude that a peptide matrix-based Elispot assay allows for rapid, sensitive, specific, and efficient assessment of cellular immune responses directed against the entire expressed HIV-1 genome. These data also suggest that the impact of T-cell responses on control of viral replication cannot be explained by the mere quantification of the magnitude and breadth of the CD8+-T-cell response, even if a comprehensive pan-genome screening approach is applied.

Acquired Immunodeficiency Syndrome↗

Retrospective analysis of the first clonal outbreak of nalidixic acid-resistant Shigella sonnei shigellosis in Israel.

Reported here is a retrospective molecular analysis of the isolates recovered from the first outbreak of nalidixic acid (NA)-resistant Shigella sonnei shigellosis to occur in Israel. The outbreak affected 94 children. In the retrospective analysis, a total of 13 NA-resistant isolates and five NA-susceptible isolates recovered during the outbreak period were examined. Restriction fragment length polymorphism profiles obtained by digestion with BamHI, PvuI, HinfI or SmaI yielded identical profiles for all 18 isolates. All NA-resistant strains had an identical plasmid profile, but this profile differed from that displayed by the susceptible strains. In all of the NA-resistant strains a 304 bp fragment in the gyrA gene coding for a region associated with NA resistance was sequenced and showed a single point mutation, Ser83-->Phe. In this outbreak, the isolates of NA-resistant Shigella sonnei belonged to a single clone and NA resistance was associated with a point mutation in the gyrA gene.

Adolescent↗