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Biomedical subjects

A Cohen

Publications and source records attributed to A Cohen.

At least 181 records · Page 10Linked to original sources

[Diphtheria in a highly immunized population].

Although diphtheria vaccination is routine world-wide, outbreaks of the disease continue to occur in supposedly vaccinated populations. The incidence of diphtheria in Israel is very low, with only 3 cases reported in the past 24 years (all in unvaccinated children). In 2 of the 3 an asymptomatic carrier was identified among the patients' close contacts, presumable the source of the infection. We describe a recent case of diphtheria. It is important for physicians to be aware of the possibility of diphtheria occurring despite the high rate of vaccination in our population.

Child↗

Supraorbital burr hole via a glabellar incision: a simple approach to anterior skull base.

A left subfrontopolar lesion with marked edema was totally resected utilizing a minimally invasive approach. It was possible to expose and resect the lesion, which turned out to be a tuberculoma, through a burr hole placed supraorbitally through a glabellar incision. The development and significance of minimalization techniques for surgery in the skull base region are discussed.

Female↗

[The subcranial approach to the anterior skull base. Retrospective study of 75 cases].

We reviewed the cases of 75 patients who underwent an extended subcranial approach to the anterior skull base for treatment of various tumors (35 patients), repair of craniofacial trauma injury (33 patients), or cerebrospinal fluid leakage (10 patients). Preoperative evaluation and surgical procedures were reassessed. Significant complications in the oncology group consisted of one hematoma requiring aspiration, 2 cases of transient pneumocephalus, 2 osteocutaneous fistulae and 2 epiphoras. In the trauma group, one patient died from intracerebral damage, 2 presented with transient pneumocephalus, 5 with telecanthus and 5 with enophthalmy. The most frequent late complication in all three groups was anosmia. Based on this review, we feel that this technique is a safe and effective procedure for the surgical treatment of various pathological conditions involving the anterior skull base.

Adolescent↗

Yeast SMF1 mediates H(+)-coupled iron uptake with concomitant uncoupled cation currents.

Yeast membrane proteins SMF1, SMF2, and SMF3 are homologues of the DCT1 metal ion transporter family. Their functional characteristics and the implications of these characteristics in vivo have not yet been reported. Here we show that SMF1 expressed in Xenopus oocytes mediates H(+)-dependent Fe(2+) transport and uncoupled Na(+) flux. SMF1-mediated Fe(2+) transport exhibited saturation kinetics (K(m) = 2.2 microM), whereas the Na(+) flux did not, although both processes were electrogenic. SMF1 is also permeable to Li(+), Rb(+), K(+), and Ca(2+), which likely share the same uncoupled pathway. SMF2 (but not SMF3) mediated significant increases in both Fe(2+) and Na(+) transport compared with control oocytes. These data are consistent with the concept that uptake of divalent metal ions by SMF1 and SMF2 is essential to yeast cell growth. Na(+) inhibited metal ion uptake mediated by SMF1 and SMF2 expressed in oocytes. Consistent with this, we found that increased sensitivity of yeast to EGTA in the high Na(+) medium is due to inhibition of SMF1- and SMF2-mediated metal ion transport by uncoupled Na(+) pathway. Interestingly, DCT1 also mediates Fe(2+)-activated uncoupled currents. We propose that uncoupled ion permeabilities in metal ion transporters protect cells from metal ion overload.

Animals↗

A novel family of yeast chaperons involved in the distribution of V-ATPase and other membrane proteins.

Null mutations in genes encoding V-ATPase subunits in Saccharomyces cerevisiae result in a phenotype that is unable to grow at high pH and is sensitive to high and low metal-ion concentrations. Treatment of these null mutants with ethylmethanesulfonate causes mutations that suppress the V-ATPase null phenotype, and the mutant cells are able to grow at pH 7.5. The suppressor mutants were denoted as svf (suppressor of V-ATPase function). The frequency of svf is relatively high, suggesting a large target containing several genes for the ethylmethanesulfonate mutagenesis. The suppressors' frequency is dependent on the individual genes that were inactivated to manifest the V-ATPase null mutation. The svf mutations are recessive, because crossing the svf mutants with their corresponding V-ATPase null mutants resulted in diploid strains that are unable to grow at pH 7.5. A novel gene family in which null mutations cause pleiotropic effects on metal-ion resistance or sensitivity and distribution of membrane proteins in different targets was discovered. The family was defined as VTC (Vacuolar Transporter Chaperon) and it contains four genes in the S. cerevisiae genome. Inactivation of one of them, VTC1, in the background of V-ATPase null mutations resulted in svf phenotype manifested by growth at pH 7.5. Deletion of the VTC1 gene (DeltaVTC1) results in a reduced amount of V-ATPase in the vacuolar membrane. These mutant cells fail to accumulate quinacrine into their vacuoles, but they are able to grow at pH 7.5. The VTC1 null mutant also results in a reduced amount of the plasma membrane H(+)-ATPase (Pma1p) in membrane preparations and possibly mis-targeting. This observation may provide an explanation for the svf phenotype in the double disruptant mutants of DeltaVTC1 and DeltaVMA subunits.

Amino Acid Sequence↗

Structures of a histone deacetylase homologue bound to the TSA and SAHA inhibitors.

Histone deacetylases (HDACs) mediate changes in nucleosome conformation and are important in the regulation of gene expression. HDACs are involved in cell-cycle progression and differentiation, and their deregulation is associated with several cancers. HDAC inhibitors, such as trichostatin A (TSA) and suberoylanilide hydroxamic acid (SAHA), have anti-tumour effects, as they can inhibit cell growth, induce terminal differentiation and prevent the formation of tumours in mice models, and they are effective in the treatment of promyelocytic leukemia. Here we describe the structure of the histone deacetylase catalytic core, as revealed by the crystal structure of a homologue from the hyperthermophilic bacterium Aquifex aeolicus, that shares 35.2% identity with human HDAC1 over 375 residues, deacetylates histones in vitro and is inhibited by TSA and SAHA. The deacetylase, deacetylase-TSA and deacetylase-SAHA structures reveal an active site consisting of a tubular pocket, a zinc-binding site and two Asp-His charge-relay systems, and establish the mechanism of HDAC inhibition. The residues that make up the active site and contact the inhibitors are conserved across the HDAC family. These structures also suggest a mechanism for the deacetylation reaction and provide a framework for the further development of HDAC inhibitors as antitumour agents.

Amino Acid Sequence↗

Final height of patients who underwent bone marrow transplantation for hematological disorders during childhood: a study by the Working Party for Late Effects-EBMT.

Few data are available on the long-term effect of bone marrow transplantation (BMT) on growth. This study examines those factors that play a role in the final height outcome of patients who underwent BMT during childhood. Data on 181 of 230 patients with aplastic anemia, leukemias, and lymphomas who had BMT before puberty (mean age, 9.8 +/- 2.6 years) and who had reached their final height were analyzed. An overall decrease in final height standard deviation score (SDS) value was found compared with the height at BMT (P < 10(7)) and with the genetic height (P < 10(7)). Girls did better than boys, and the younger in age the person was at time of BMT, the greater the loss in height. Previous cranial irradiation + single-dose total body irradiation (TBI) caused the greatest negative effect on final height achievement (P < 10(4)). Fractionation of TBI reduces this effect significantly and conditioning with busulfan and cyclophosphamide seems to eliminate it. The type of transplantation, graft-versus-host disease, growth hormone, or steroid treatment did not influence final height. Irradiation, male gender and young age at BMT were found to be major factors for long-term height loss. Nevertheless, the majority of patients (140/181) have reached adult height within the normal range of the general population.

Adolescent↗

Severe tumor lysis syndrome following splenic irradiation.

A 72-year-old man suffering from non-Hodgkin's lymphoma is described. After failing to respond to chlorambucil-prednisone regimen for three months, he was treated by splenic irradiation (total dose 500 cGY) in 10 consecutive daily doses. Two days after the last irradiation, the patient developed acute tumor lysis syndrome (TLS) with extreme blood levels of uric acid (33.7 mg/dl), phosphorus (13.7 mg/dl), potassium (6.08 mEq/l), and calcium (6.8 mg/dl). It should be remembered that the acute TLS, which usually occurs following chemotherapy, can also be radiation-induced.

Aged↗

The role of bacterial vaginosis in infection after major gynecologic surgery.

PURPOSE: Previous studies have reported an association between bacterial vaginosis (BV) and postoperative fever and infection. This prospective study investigated whether the intermediate or definite stages of BV are risk factors for postoperative infection after major gynecologic surgery. METHODS: Vaginal cultures were obtained preoperatively from 175 women undergoing gynecologic surgery. The diagnostic criteria for BV were based on Nugent's standardized method of Gram stain interpretation. Postoperative fever was defined as at least one temperature equal to 101.0 degrees F or greater, or two or more temperatures more than 6 hours apart equal to 100.4 degrees F or greater. RESULTS: Thirty-six percent of the positive-BV group developed a postoperative fever, compared with 20% of the Lactobacillus-predominant group and 12% of the intermediate-BV group (P = 0.017). The differences between the positive-BV group and the Lactobacillus-predominant group, and between the positive-BV group and the intermediate-BV group, with respect to postoperative fever, were statistically significant (P = 0.045 and P = 0.007, respectively). The difference between the intermediate-BV group and the Lactobacillus-predominant group was not statistically significant (P = 0.28). CONCLUSIONS: Although the association between BV and postoperative febrile morbidity could be a spurious result of confounding with other variables, it may be prudent for the surgeon to identify patients with BV and treat them preoperatively.

Bacterial Infections↗

Evaluation of the Strep B OIA test compared to standard culture methods for detection of group B streptococci.

OBJECTIVE: This study evaluated the accuracy of the commercial product Strep B OIA (optical immunoassay) compared to the standard agar and broth culture methods for detecting vaginal colonization with group B streptococcus (GBS). METHODS: Preoperative vaginal cultures were obtained from 141 nonpregnant gynecological patients undergoing major gynecologic surgery. Major gynecologic surgery was defined as benign gynecologic, gyne-oncology, and urogynecologic procedures. The results of the Strep B OIA test were compared to the results obtained from SXT agar (selective for GBS), colistin-nalidixic acid ((CNA) agar, and Todd-Hewitt broth cultures. RESULTS: The prevalence of vaginal GBS colonization in this population was 20.6%. The sample sensitivity and specificity of the OIA method were 58.6% and 85.7%, respectively. These values are lower than the sensitivity and specificity of 85.4% and 91.5%, respectively, given in the OIA package insert. Although the sample negative predictive value was fairly high (88.9%), the positive predictive value was low (51.5%). CONCLUSION: Although a previous study stated that the product Strep B OIA reduces the time required to obtain results (30 minutes versus days) and can, therefore, function as a useful diagnostic tool in the management of early-onset GBS disease, the present study's finding of low sensitivity and low positive predictive value indicates that this test may have very limited clinical value.

Adult↗

Outcome of idiopathic apparent life-threatening events: infant and mother perspectives.

The objective of this study was to determine the neurodevelopmental and temperamental outcome of infants who suffered an idiopathic apparent life-threatening event (IALTE) and their mothers' perceptions of such an event, and to compare such infants with a matched group of babies hospitalized for nonthreatening events. Infants (N = 19) who were hospitalized at a mean age of 2.8 months for an IALTE with no underlying disease and matched controls hospitalized for an acute nonthreatening illness were sequentially recruited to the study at a mean age of 24 months (SD, 14 months). Physical, neurological, developmental, and temperamental status were assessed. Mothers' stress was assessed by their salivary cortisol response to the physical examination of their infants and completion of appropriate questionnaires assessing their infants' temperament. The investigators were not blinded to the assignment of the infants to each of the study groups. Infants' perceived "difficultness" was positively correlated with the time interval following the event (r = 0.5, P = 0.001), mothers' stress as related to their child (r = 0.4, P = 0.004), and mothers' cortisol response (r = 0.5, P = 0.01) among the study group mothers only. IALTE during early infancy was associated with developmentally and neurologically normal outcome in infancy. We conclude that mothers of infants with IALTE differed in the way they perceived their infants' temperament over time, and in their stress response compared to mothers of a control group of hospitalized children who had not experienced an IALTE.

Adult↗

Enhancement of cellular immune response in HIV-1 seropositive individuals: A DNA-based trial.

A DNA-based vaccine containing HIV-1 Env and Rev genes was tested for safety and host immune response in 15 HIV-infected asymptomatic patients with CD4-positive lymphocyte counts >/=500/microl of blood and receiving no antiviral therapy. Successive groups of patients received three doses of vaccine at 30, 100, or 300 microg at 10-week intervals in a dose-escalation trial. Some changes were noted in cytotoxic T-lymphocyte activity against gp160-bearing targets. Importantly, enhanced specific lymphocyte proliferative activity against HIV-1 envelope was observed in multiple patients. Three of three patients in the 300-microg dose group also developed increased MIP-1alpha levels which were detectable in their serum. Interestingly patients in the lowest dose group showed no overall changes in the immune parameters measured. The majority of patients who exhibited increases in any immune parameters were contained within the 300 microg, which was the highest dose group. These studies support further investigation of this technology for the production of antigen-specific immune responses in humans.

AIDS Vaccines↗

Rate of uterine rupture during a trial of labor in women with one or two prior cesarean deliveries.

OBJECTIVE: We sought to determine whether there is a difference in the rate of symptomatic uterine rupture after a trial of labor in women who have had 1 versus 2 prior cesarean deliveries. STUDY DESIGN: The medical records of all women with a history of either 1 or 2 prior cesarean deliveries who elected to undergo a trial of labor during a 12-year period (July 1984-June 1996) at the Brigham and Women's Hospital were reviewed. Rates of uterine rupture were compared for these 2 groups. Potential confounding variables were controlled by using logistic regression analyses. RESULTS: Women with 1 prior cesarean delivery (n = 3757) had a rate of uterine rupture of 0.8%, whereas women with 2 prior cesarean deliveries (n = 134) had a rate of uterine rupture of 3.7% (P =.001). In a logistic regression analysis that was controlled for maternal age, use of epidural analgesia, oxytocin induction, oxytocin augmentation, the use of prostaglandin E(2) gel, birth weight, gestational age, type of prior hysterotomy, year of trial of labor, and prior vaginal delivery, the odds ratio for uterine rupture in those patients with 2 prior cesarean deliveries was 4.8 (95% confidence interval, 1.8-13. 2) CONCLUSIONS: Women with a history of 2 prior cesarean deliveries have an almost 5-fold greater risk of uterine rupture than those with only 1 prior cesarean delivery.

Adult↗

Uterine rupture during induced or augmented labor in gravid women with one prior cesarean delivery.

OBJECTIVE: Our purpose was to examine the risk of uterine rupture during induction or augmentation of labor in gravid women with 1 prior cesarean delivery. STUDY DESIGN: The medical records of all gravid women with history of cesarean delivery who attempted a trial of labor during a 12-year period at a single center were reviewed. The current analysis was limited to women at term with 1 prior cesarean delivery and no other deliveries. The rate of uterine rupture in gravid women within that group undergoing induction was compared with that in spontaneously laboring women. The association of oxytocin induction, oxytocin augmentation, and use of prostaglandin E(2) gel with uterine rupture was determined. Logistic regression analysis was used to examine these associations, with control for confounding factors. RESULTS: Of 2774 women in the analysis, 2214 had spontaneous onset of labor and 560 women had labor induced with oxytocin or prostaglandin E(2) gel. The overall rate of rupture among all patients with induction of labor was 2.3%, in comparison with 0.7% among women with spontaneous labor (P =.001). Among 1072 patients receiving oxytocin augmentation, the rate of uterine rupture was 1.0%, in comparison with 0.4% in nonaugmented, spontaneously laboring patients (P =.1). In a logistic regression model with control for birth weight, use of epidural, duration of labor, maternal age, year of delivery, and years since last birth, induction with oxytocin was associated with a 4.6-fold increased risk of uterine rupture compared with no oxytocin use (95% confidence interval, 1.5-14.1). In that model, augmentation with oxytocin was associated with an odds ratio of 2.3 (95% confidence interval, 0.8-7.0), and use of prostaglandin E(2) gel was associated with an odds ratio of 3.2 (95% confidence interval, 0.9-10.9). These differences were not statistically significant. CONCLUSION: Induction of labor with oxytocin is associated with an increased rate of uterine rupture in gravid women with 1 prior uterine scar in comparison with the rate in spontaneously laboring women. Although the rate of uterine rupture was not statistically increased during oxytocin augmentation, use of oxytocin in such cases should proceed with caution.

Cesarean Section↗

The impact of patient delay and physician delay on the outcome of laparoscopic cholecystectomy for acute cholecystitis.

BACKGROUND: Laparoscopic cholecystectomy is now used in the management of acute cholecystitis. Under these circumstances unfavorable conditions may result in conversion and complications. Information about these conditions may help in planning the laparoscopic approach or in proceeding directly to open cholecystectomy. This study was initiated to evaluate perioperative factors associated with conversion and complications of laparoscopic cholecystectomy in acute cholecystitis. Special attention was paid to the duration of complaints until surgery, to the delay on the part of the patient, and to the delay on the part of the physician. METHODS: Between January 1994 and December 1997, we attempted to perform laparoscopic cholecystectomy on 348 patients with acute cholecystitis. All perioperative data were collected on standardized forms. RESULTS: There were 182 cases (52%) of acute uncomplicated cholecystitis, 90 (26%) of gangrenous cholecystitis, 33 of hydrops (9.5%), and 43 of empyema of the gallbladder (12.5%). Seventy six patients (22%) needed conversion to open cholecystectomy and complications occurred in 57 cases. Advanced cholecystitis was associated with significant patient delay (P = 0.01), and it had a significantly higher conversion rate (39%) compared with early cholecystitis (14.5%); (P <0.00001). Conversion rates were also associated with male gender (P = 0.0017), a history of biliary disease (P = 0.0085), and a patient delay of >48 hours (P = 0.028). The total and infectious complication rates were associated with an age older than 60 years (P = 0.023 and 0.007, respectively) and male gender (P = 0.026 and 0.014, respectively). CONCLUSIONS: In acute cholecystitis, patient delay is associated with a high conversion rate. Early timing of laparoscopic cholecystectomy tends to reduce the conversion rate, as well as the total and the infectious complication rates. Male gender, a history of biliary disease, and advanced cholecystitis are associated with conversion. Male and older patients are associated with a high total and infectious complication rates.

Acute Disease↗

Utility of 18F-FDG positron emission tomography scanning on selection of patients for resection of hepatic colorectal metastases.

BACKGROUND: Hepatectomy represents a standard and potentially curative therapy for hepatic colorectal metastases. However, up to two thirds of patients explored for resection are found to have unsuspected disease, which precludes resection. METHODS: In order to determine if 18F-FDG positron emission tomography (PET) scanning may prevent unnecessary surgery, a group of 40 patients being considered for hepatic resection but at high risk for unresectable disease by clinical criteria were subjected to whole body 18F-FDG-PET scanning. Effect on clinical outcome was evaluated. In addition, PET findings in the 25 patients who underwent resection of hepatic metastases were directly compared with the resected specimen to determine the sensitivity of 18F-FDG PET scanning in the liver. RESULTS: Findings on 18F-FDG-PET scanning influenced the clinical management in 16 patients (40%) and directly altered management in 9 cases (23%). Six patients were spared laparotomy, and 3 others had PET-directed surgery that found extrahepatic tumor and spared the patient unwarranted liver resection. In 3 cases PET missed peritoneal metastases found on laparotomy. In these cases all missed tumors were less than 1 cm in size. Out of 52 resected hepatic lesions, 18F-FDG-PET detected 37. Within the liver, sensitivity of detection was also related to size. Only 25% of hepatic lesions smaller than 1 cm were detected by PET, while 85% of lesions larger than 1 cm were detected. CONCLUSIONS: FDG-PET is best for detecting extrahepatic disease. There are few false positives, and surgeons should carefully evaluate and biopsy extrahepatic positive sites. This test should be used for patients at high risk for extrahepatic disease and should be evaluated prospectively for all patients under consideration for liver resection.

Adult↗