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Biomedical subjects

D Sherman

Publications and source records attributed to D Sherman.

At least 19 recordsLinked to original sources

Fluid preload before spinal anaesthesia in Caesarean section: the effect on neonatal acid-base status.

BACKGROUND AND OBJECTIVE: We evaluated the effect of two different preload solutions: (i) Ringer's lactate (compound sodium lactate intravenous infusion BP) and (ii) 0.9% sodium chloride solution on the neonatal acid-base status of the newborn infants. The two standard regimens were compared to detect a possible difference. METHODS: A 2 L crystalloid fluid bolus was administered immediately before spinal anaesthesia for elective Caesarean section in two groups of 20 healthy parturients, while rigorously maintaining maternal normotension. RESULTS: No significant differences in the Apgar scores at 1 and 5 min, or infant well-being were demonstrated in either of the two groups. The data show that umbilical artery PCO2 is lower in the Ringer's lactate group and that pH is insignificantly higher by 0.03. CONCLUSIONS: The choice of Ringer's lactate or saline for fluid preload does not have any effect on neonatal well-being.

Acid-Base Equilibrium↗

Characterization of a major Bacillus anthracis spore coat protein and its role in spore inactivation.

A major Bacillus anthracis spore coat protein of 13.4 kDa, designated Cot alpha, was found only in the Bacillus cereus group. A stable ca. 30-kDa dimer of this protein was also present in spore coat extracts. Cot alpha, which is encoded by a monocistronic gene, was first detected late in sporulation, consistent with a sigma(K)-regulated gene. On the basis of immunogold labeling, the protein is in the outer spore coat and absent from the exosporium. In addition, disruption of the gene encoding Cot alpha resulted in spores lacking a dark-staining outer spore coat in thin-section electron micrographs. The mutant spores were stable upon heating or storage, germinated at the same rate as the wild type, and were resistant to lysozyme. They were, however, more sensitive than the wild type to phenol, chloroform, and hypochlorite but more resistant to diethylpyrocarbonate. In all cases, resistance or sensitivity to these reagents was restored by introducing a clone of the cot alpha gene into the mutant. Since Cot alpha is an abundant outer spore coat protein of the B. cereus group with a prominent role in spore resistance and sensitivity, it is a promising target for the inactivation of B. anthracis spores.

Amino Acid Sequence↗

Prevention of genital prolapse following Burch colposuspension: comparison between two surgical procedures.

Our objective was to evaluate the efficacy of cul-de-sac obliteration in preventing pelvic floor anatomical defects formation following Burch colposuspension. We evaluated 441 patients who had undergone Burch colposuspension. The patients were divided into two groups: group A (132 patients) who underwent Burch colposuspension only, and group B (309 patients) who had had a concomitant cul-de-sac obliteration. Cul-de-sac obliteration was performed using two different techniques, the Moschocowitz procedure in 131 patients, and approximation of the sacrouterine ligaments in 178 patients. The follow-up period was 8.6 years (range 3-16). In total we found 43/441 (9.7%) postoperative anatomical defects. Obliteration of the cul de sac significantly (P<0.0001) reduced the formation of anatomical defects compared to Burch colposuspension. In a comparison of the two surgical procedures for cul-de-sac obliteration, the approximation of the sacrouterine ligaments was significantly more effective than either the Moschcowitz procedure (P<0.001) or the Burch colposuspension alone (P<0.001). The Moschcowitz procedure reduced the formation of anatomical defects to 15/131 (11.4%) compared to Burch colposuspension only (25/132; 18.9%), but statistically the difference was insignificant. The time of anatomical defect detection was significantly reduced after cul-de-sac obliteration: 2 years 6/25 (24%) in group A compared to 1/8 (5.5%) in group B (P<0.01). After 5 years the detection rate was 64% (16/25) and 22.2% (4/18) respectively (P<0.01). It was concluded that cul-de-sac obliteration using approximation of the sacrouterine ligaments significantly reduced the incidence of anatomical defect formation following Burch colposuspension. A long follow-up period is needed to evaluate the truce incidence.

Douglas' Pouch↗

Large local deflections of a dynamic crack front induced by intrinsic dislocations in brittle single crystals.

We show that intrinsic dislocations in brittle single crystals can be a source of strong local perturbations along the crack path. A theoretical model was developed which predicts substantial crack front deflections. Investigating the crack surfaces in Si crystals with induced dislocation density of 10(9)-10(10) cm(-2) revealed a significant amount of crack front perturbations in the form of V-shaped grooves, which were completely missing in dislocation-free Si specimens. The measured depths of the perturbations were in the range of 2-20 nm and in excellent agreement with the theoretical model.

Journal Article↗

Maternal serum human chorionic gonadotrophin levels in systemic lupus erythematosus and antiphospholipid syndrome.

Maternal serum human chorionic gonadotrophin (hCG) levels were measured during the second and the third trimesters of pregnancy in patients with either systemic lupus erythematosus (SLE) or primary antiphospholipid syndrome (APS). All results were expressed in multiples of the gestation-specific normal medians (MoM). The median MoM level in 17 samples from SLE patients was 1.48 compared with 0.79 MoM in 99 controls of similar gestation (p < 0.002, Wilcoxon Rank sum test). In contrast the median MoM level in 19 samples from primary APS patients was only 1.14. These preliminary findings should be further studied to evaluate the implications for Down syndrome screening, detection of SLE cases during pregnancy and the prediction of adverse outcome in SLE gestations.

Antiphospholipid Syndrome↗

Long-Term (10-15 years) follow-up after Burch colposuspension for urinary stress incontinence.

The study group comprised 127 patients who underwent a Burch colposuspension for urinary incontinence. All had undergone urodynamic investigation both pre- and postoperatively. All patients had a mean follow-up of 12.4 years (range 10-15); 109 patients had an additional urodynamic investigation at least 10 years after the operation. Following surgery there was an improvement in symptoms of frequency (P<0.001), urgency (P<0.01) and urge incontinence (P<0.001). The cure rate was 93.7%. The only significant changes found on urodynamics were the measurements of the pressure transmission ratio, which were higher postoperatively (P<0.001) and remained so after 10 years. The most frequent postoperative complications were de novo detrusor instability (16.6%) and anatomical defects (18.7%). All failed cases were found during the first postoperative year. De novo detrusor instability appeared in 12/17 patients during the first year of follow-up. Postoperative anatomical defects were found only in 4/24 patients after 5 years. Ten years postoperatively most of the anatomical defects had been detected (20/24), stressing the need for long-term follow-up.

Adult↗

Neuropsychological performance of right- and left-frontotemporal dementia compared to Alzheimer's disease.

The performance of 16 patients with Alzheimer's disease (AD) was compared to 11 patients with right-frontotemporal dementia (FTD) and 11 patients with left-FTD on a comprehensive neuropsychological battery. Standardized scores (i.e., z scores based on normal control data) were analyzed for 5 cognitive domains. The results revealed that the AD group displayed significant impairment in visual-constructional ability relative to the two FTD groups; however, no significant difference was found between the groups on memory scores (verbal and nonverbal). Patients with left-FTD scored significantly below patients with AD on the language measures (e.g., word retrieval, verbal semantic memory), and verbal executive ability (phonemic fluency); AD patients did not differ from patients with right-FTD on these measures. Patients with right-FTD exhibited significantly more perseverative behavior than AD patients; AD patients did not differ from left-FTD patients on this parameter. These results indicate that the pattern of neuropsychological performance of AD patients is distinguishable from patients with left and right frontal frontotemporal dementia.

Alzheimer Disease↗

Transvaginal sonographic assessment of cervical length changes during triplet gestation.

The current study aimed to evaluate the contribution of transvaginal sonography (TVS) for monitoring cervical changes during the second half of triplet gestation. Forty-five pregnant women with triplets pregnancies were prospectively scanned by TVS from approximately 26 weeks gestation and were longitudinally followed-up until delivery. Based on a receiver-operating curve it was found that a cervical length of 25 mm is the most accurate parameter (94% sensitivity and 45% specificity) for predicting premature delivery < or =33 gestational weeks. Thus, a single cervical length measurement of < or =25 mm at 26 weeks gestation correlated well with premature delivery at < or =33 weeks (chi(2); P = 0.002). Using the linear regression model, a mathematical equation [(Week of delivery = 27.4 + 1.6 x cervical length; R(2) = 0.46; P = 0.01)] for predicting the gestational age of delivery (dependent variable) was determined based on mid-gestation cervical measurements (predictors). In parturient women with triplet gestation, TVS assessment of the uterine cervix offers insight into the cervical status and provides valuable information for prenatal care. This includes both monitoring the cervical changes throughout third trimester as well as predicting the likelihood of premature delivery.

Adult↗

Inadvertent diclofenac rechallenge from generic and non-generic prescribing, leading to liver transplantation for fulminant liver failure.

This case report describes fulminant hepatic failure in a 53-year-old female caused by inadvertent rechallenging with diclofenac, treated by orthotopic liver transplantation. The case also illustrates the hazards of using both generic and non-generic drug prescribing, with drugs that are known to be toxic. The literature on non-steroidal anti-inflammatory drugs and hepatoxicity is reviewed.

Anti-Inflammatory Agents, Non-Steroidal↗

Cellular and subcellular localization of S-adenosyl-L-methionine:benzoic acid carboxyl methyltransferase, the enzyme responsible for biosynthesis of the volatile ester methylbenzoate in snapdragon flowers.

The benzenoid ester, methylbenzoate is one of the most abundant scent compounds detected in the majority of snapdragon (Antirrhinum majus) varieties. It is produced in upper and lower lobes of petals by enzymatic methylation of benzoic acid in the reaction catalyzed by S-adenosyl-L-methionine:benzoic acid carboxyl methyltransferase (BAMT). To identify the location of methylbenzoate biosynthesis, we conducted an extensive immunolocalization study by light and electron microscopy at cellular and subcellular levels using antibodies against BAMT protein. BAMT was immunolocalized predominantly in the conical cells of the inner epidermal layer and, to a much lesser extent, in the cells of the outer epidermis of snapdragon flower petal lobes. It was also located in the inner epidermis of the corolla tube with little BAMT protein detected in the outer epidermis and in the yellow hairs within the tube on the bee's way to the nectar. These results strongly suggest that scent biosynthetic genes are expressed almost exclusively in the epidermal cells of floral organs. Immunogold labeling studies reveal that BAMT is a cytosolic enzyme, suggesting cytosolic location of methylbenzoate biosynthesis. The concentration of scent production on flower surfaces that face the pollinators during landing may increase pollination efficiency and also help to minimize the biosynthetic cost of advertising for pollinators.

Benzoates↗

Serum levels of inhibin B, unlike inhibin A and activin A, are not altered in women with preeclampsia.

PROBLEM: To investigate whether inhibin A, inhibin B, and activin A serum levels are altered in women with preeclampsia. METHOD OF STUDY: Serum samples of 20 women with preeclampsia (study group) and 20 normotensive pregnant women, matched for maternal and gestational age and parity, were assayed for inhibin A, inhibin B and activin A by specific enzyme-linked immunosorbent assay. RESULTS: Median serum concentrations of inhibin A and activin A were significantly higher among women with preeclampsia than in women with normotensive pregnancies, while inhibin B levels were comparable in both groups. Activin A levels were positively correlated with those of inhibins A and B, and inhibin A levels were positively correlated with diastolic blood pressure and inhibin B concentration in the study group. CONCLUSIONS: Inhibin A and activin A, but not inhibin B, serum levels are markedly increased in women with preeclampsia. These hormones might serve as an endocrine marker for preeclampsia.

Activins↗

Midodrine prevents orthostatic intolerance associated with simulated spaceflight.

Many astronauts after being weightless in space become hypotensive and presyncopal when they assume an upright position. This phenomenon, known as orthostatic intolerance, may interfere with astronaut function during reentry and after spaceflight and may limit the ability of an astronaut to exit a landed spacecraft unaided during an emergency. Orthostatic intolerance is more pronounced after long-term spaceflight and is a major concern with respect to the extended flights expected aboard the International Space Station and for interplanetary exploration class missions, such as a human mission to Mars. Fully effective countermeasures to this problem have not yet been developed. To test the hypothesis that alpha-adrenergic stimulation might provide an effective countermeasure, we conducted a 16-day head-down-tilt bed-rest study (an analog of weightlessness) using normal human volunteers and administered the alpha(1)-agonist drug midodrine at the end of the bed-rest period. Midodrine was found to significantly ameliorate excessive decreases in blood pressure and presyncope during a provocative tilt test. We conclude that midodrine may be an effective countermeasure for the prevention of orthostatic intolerance following spaceflight.

Adrenergic alpha-Agonists↗

Treatment outcomes of benign paroxysmal positional vertigo.

OBJECTIVE: The purpose of this study was to examine the efficacy of the particle repositioning manoeuvre (PRM) in the treatment of benign paroxysmal positional vertigo (BPPV). DESIGN: A randomized prospective study of patients with BPPV. METHODS: Seventy-one patients were randomized to one of three groups at their first clinic visit. These groups included the PRM, a sham PRM, and a control group. Patients were followed up in clinic at 2 weeks and 3 months. The mean long-term follow-up was 12 months. A telephone questionnaire was also conducted. RESULTS: At 2-week follow-up, 81.8% of patients in the PRM group had a resolution of symptoms and a negative Dix-Hallpike test compared with 15.3% in the sham PRM group and 60% in the control group. This difference was statistically significant between the treatment (PRM) and sham PRM groups and between the sham and control groups. It nearly reached significance between the treatment and control groups (p = .06). The sham treatment group had by far the worst outcome at the 2-week interval. There was no statistically significant difference between the groups after 2 weeks. CONCLUSION: The PRM is side specific. It may help induce remission of the vertiginous symptoms of BPPV in the short term. This cannot be attributable to a placebo effect. The PRM does not seem to affect the natural history of the disorder in the long term. The sham treatment causes a delay in spontaneous recovery, possibly by preventing the particles from falling into the utricle. This study has not compared the frequency or severity of symptoms.

Calculi↗

Laryngectomy clinical pathway: development and review.

OBJECTIVE: The goal of the study is to determine if the implementation of a protocol for the preoperative and postoperative care of patients receiving a laryngectomy for cancer of the larynx or hypopharynx (i.e., laryngectomy clinical pathway) reduced length and cost of hospital stay without increasing complication rates. DESIGN: This study is a comparison of the perioperative course of two groups of laryngectomy patients. Data were collected retrospectively from the records of patients operated on before the implementation of the clinical pathway as the institutional historical control. Comparison was made with data collected prospectively on patients operated on after the implementation of the clinical pathway. SETTING: The study was performed at a mid-sized teaching hospital associated with two regional cancer centres. All surgeries were performed by one of two otolaryngology-head and neck surgeons and residents under their supervision. METHODS: The demographic, patient, tumour, treatment, dietary, and complication data were analyzed. Fisher's exact (two-tailed) statistical test was used for parametric data and Wilcoxon scores for nonparametric data. MAIN OUTCOME MEASURE: The principal outcome measure was the length of postoperative inpatient stay. Secondary outcome measures were readmissions and postoperative complications. RESULTS: There was a statistically significant decrease of 6.7 days in the mean length of hospitalization in the clinical pathway group even when taking postoperative readmissions into account. There was no concomitant increase in surgical complications. The mean reduction in hospital cost per case was calculated to be $3,420 (Can). CONCLUSIONS: Application of a clinical pathway for patients receiving laryngectomy is both feasible and effective.

Case-Control Studies↗

Complete inhibition of rhabdomyosarcoma xenograft growth and neovascularization requires blockade of both tumor and host vascular endothelial growth factor.

Growth of the human rhabdomyosarcoma A673 cell line in nude mice is substantially reduced but not completely suppressed after systemic administration of the antihuman vascular endothelial growth factor (VEGF) monoclonal antibody (Mab) A.4.6.1. Potentially, such escape might be attributable to incomplete local penetration of the antibody because of a diffusion barrier associated with tumor growth. Alternatively, it might reflect a compensatory up-regulation of murine VEGF, produced by the stroma of the host, or of other angiogenic factor genes. To test these potential mechanisms, systemic administration of Mab A.4.6.1, was performed in conjunction with intratumoral administration of an irrelevant antibody, an antihuman VEGF Fab or mFlt(1-3)-IgG that neutralizes both human and murine VEGF. Tumor growth in the systemic-plus-intratumoral anti-VEGF group was not different from that in the systemic anti-VEGF-plus-intratumoral-control antibody group, arguing against the possibility that bioavailability is the factor that limits the antitumor efficacy of Mab A.4.6.1. However, intratumoral mFlt(l-3)-IgG administration dramatically enhanced the activity of systemic anti-VEGF Mab and resulted in complete suppression of tumor growth, which indicated that host VEGF significantly contributes to tumor growth. Systemic administration of mFlt(1-3)-IgG alone replicated these findings. Histological analysis of residual tumor tissues revealed an almost complete absence of host-derived vasculature and massive tumor-cell necrosis in the mFlt(1-3)-IgG groups. Such extensive necrotic areas were not present in the other groups. Real-time reverse transcription-PCR analysis of total RNA derived from tumor tissues indicated strong up-regulation of both human and murine VEGF as well as other genes regulated by hypoxia. Our findings emphasize the need to completely block VEGF for maximal inhibition of tumor growth.

Animals↗

Ion chromatographic determination of acidity.

The practice of determining acid concentrations by titrations has remained unchanged for more than a century. We introduce a new approach to the determination of acid concentrations based on cation exchange chromatography. We demonstrate the ability of sulfonated styrene-divinylbenzene based stationary phases to separate the hydrogen ion from other monovalent cations. The eluent is a dilute solution of a neutral salt, sometimes containing a small concentration of the corresponding acid, e.g., sodium ethanesulfonate, pH adjusted with ethanesulfonic acid. The high equivalent conductance (approximately 350 S.cm2/equiv) of H+ and relatively low eluent concentration allows sensitive conductometric detection of H+, down to the 50 microM level under favorable conditions. The conductometric response to H+ can be linear over a wide range of H+ concentrations, from sub-millimolar to several molar concentrations. The system allows the rapid quantitation of strong acids; weak acids can also be determined depending on pKa and injected concentration. The determinations of several strong and weak acids are presented along with factors that govern their chromatographic analysis.

Carboxylic Acids↗

Antimicrobial effects of novel siderophores linked to beta-lactam antibiotics.

As a strategy to increase the penetration of antibiotic drugs through the outer membrane of gram-negative pathogens, facilitated transport through siderophore receptors has been frequently exploited. Hydroxamic acids, catechols, or very close isosteres of catechols, which are mimics of naturally occurring siderophores, have been used successfully as covalently linked escorting moieties, but a much wider diversity of iron binding motifs exists. This observation, coupled to the relative lack of specificity of siderophore receptors, prompted us to initiate a program to identify novel, noncatechol siderophoric structures. We screened over 300 compounds for their ability to (1) support growth in low iron medium of a Pseudomonas aeruginosa siderophore biosynthesis deletion mutant, or (2) compete with a bactericidal siderophore-antibiotic conjugate for siderophore receptor access. From these assays we identified a set of small molecules that fulfilled one or both of these criteria. We then synthesized these compounds with functional groups suitable for attachment to both monobactam and cephalosporin core structures. Siderophore-beta-lactam conjugates then were tested against a panel of Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus strains. Although several of the resultant chimeric compounds had antimicrobial activity approaching that of ceftazidime, and most compounds demonstrated very potent activity against their cellular targets, only a single compound was obtained that had enhanced, siderophore-mediated antibacterial activity. Results with tonB mutants frequently showed increased rather than decreased susceptibilities. suggesting that multiple factors influenced the intracellular concentration of the drugs.

Anti-Bacterial Agents↗

Double-blind, randomized, controlled trial of atosiban and ritodrine in the treatment of preterm labor: a multicenter effectiveness and safety study.

OBJECTIVE: This study was undertaken to compare the efficacy and safety of intravenous administration of atosiban versus ritodrine for the treatment of preterm labor. STUDY DESIGN: Women with preterm labor and intact membranes diagnosed at 23 to 33 gestational weeks (n = 247) were randomly assigned to treatment arms and received atosiban (6.75 mg intravenous bolus, 300 microg/min for 3 hours, then 100 microg/min intravenously) or ritodrine (0.10-0.35 mg/min intravenously) for as long as 18 hours. Tocolytic effectiveness was assessed in terms of the numbers of women who had not been delivered after 48 hours and after 7 days. Safety was assessed in terms of maternal side effects and neonatal morbidity. Secondary outcomes included mean gestational age at delivery and mean birth weight. An intent-to-treat analysis was performed with the Cochran-Mantel-Haenszel test. RESULTS: The proportion of women who had not been delivered at 48 hours was 84.9% (n = 107) in the atosiban group and 86.8% (n = 105) in the ritodrine group. At 7 days 92 women had still not been delivered in both the atosiban (73.0%) and ritodrine (76.0%) groups. Neither of these differences was statistically significant. The incidence of maternal cardiovascular side effects was substantially lower in the atosiban group (4.0% vs 84.3%, P <.001). In addition, intravenous therapy was terminated more frequently as a result of maternal adverse events in the ritodrine group (29.8%) than in the atosiban group (0.8%). The overall occurrences of fetal adverse events in the two treatment groups were comparable. Neonatal morbidity was similar between the treatment groups after adjustment for unbalanced enrollment of women with multiple pregnancies and for gestational ages within treatment groups. CONCLUSION: Atosiban was comparable in clinical effectiveness to conventional ritodrine therapy but was better tolerated than ritodrine, with no evidence of significant maternal or fetal adverse events. Neonatal morbidity, which was similar between the two treatment arms, was apparently related to the gestational age of the infant rather than to the exposure to either tocolytic agent.

Adult↗