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Biomedical subjects

S D Smith

Publications and source records attributed to S D Smith.

At least 73 records · Page 4Linked to original sources

In-vitro maturation of human oocytes from regularly menstruating women may be successful without follicle stimulating hormone priming.

This prospective randomized study investigated whether the developmental potential of in-vitro matured (IVM) human oocytes is improved by follicle stimulating hormone (FSH) priming before aspiration. Normally cycling women were recruited among couples referred for in-vitro fertilization or intracytoplasmic sperm injection because of male factor and/or tubal disease. In the first experiment, 20 women were randomly allocated to either no stimulation (n = 10) or stimulation for 3 days with rec-FSH (Gonal-F, Serono) at a fixed dose of 150 IU/day from day 3 (n = 10). The oocytes were aspirated when the follicle(s) was observed to be 10 mm and matured in vitro for 36 h. In experiment 2, 12 women received rec-FSH (150 IU/daily) from day 3. In five patients stimulation was given for 3 days and aspiration performed as in the first experiment; the remaining seven patients continued stimulation until follicles were 10 mm in diameter and aspiration was performed 72 h later. All the oocytes were cultured for 48 h. FSH priming did not increase the number of oocytes obtained per aspiration and did not improve on maturation to metaphase II, cleavage rate or embryo development. The implantation potential of IVM embryos may be improved by maturation for 36 h compared to 48 h. In the first experiment, five out of 20 patients (25%) obtained a clinical pregnancy with an implantation rate of 15% (5/33). One has delivered a healthy boy and three pregnancies are ongoing beyond 32 gestational weeks. In the second experiment, an implantation rate of 7% and a single pregnancy (8%) was obtained, with delivery of a healthy girl.

Cytoplasm↗

Evolution of the modified Rossetti fundoplication in children: surgical technique and results.

OBJECTIVE: To compare the modified Rossetti fundoplication with the classic Nissen. SUMMARY BACKGROUND DATA: The traditional surgical treatment of gastroesophageal reflux in children has been the classic Nissen fundoplication, defined by liver mobilization, crural repair, takedown of short gastric vessels, and floppy wrap. The authors have progressed in our technique of fundoplication and now perform a modified Rossetti fundoplication, defined by liver retraction without mobilization, no crural repair, short gastric vessels left intact, and 2-cm floppy wrap. METHODS: A retrospective chart review was performed on 407 pediatric patients who had open fundoplications (Jan. 13, 1993, to Feb. 25, 1998). Two groups were analyzed: the Nissen group (171 patients) and the Rossetti group (236 patients). Groups were compared for incidence of recurrent reflux, dysphagia, hiatal hernia, need for esophageal dilation, revision of fundoplication, time to discharge, and operative time. RESULTS: Incidence of dysphagia (3.7% vs. 3.3%), postoperative hiatal hernia (1.9% vs. 1.4%), need for esophageal dilation (1.2% vs. 0.5%), and need for fundoplication revision (2.5% vs. 2.3%) were similar between the groups. The mean operative time was significantly decreased in the Rossetti group (65 +/- 25 minutes) versus the Nissen group (73 +/- 33 minutes). Recurrent reflux occurred significantly more often in the Nissen group (11.2%) than in the Rossetti group (5.1 %). CONCLUSION: The modified Rossetti fundoplication has a low complication rate and is the authors' preferred method for the surgical treatment of gastroesophageal reflux in children.

Child, Preschool↗

Encounters with doctors: quantity and quality.

Continuity of care and the large numbers of health care professionals who deliver that care are issues that frequently concern patients and their families. This study examined the number of doctors encountered by 50 patients, during the period of their cancer care. This ranged from 4 months to 26 years, with a median time of 2 years and 4 months. The doctors included in this number were general practitioners, doctors met during hospital inpatient admissions and when attending outpatient appointments, and doctors at the hospice. Descriptive statistics are included detailing the total number of doctors encountered by patients; the number met by patients within the first year of their cancer care; and the average number of new doctors met each year. The minimum number of doctors met was 13, maximum 97 and median 32. Notable examples include one patient who met 31 doctors during a 6-month period, and one patient who met 73 doctors during a period of 2 years and 1 month. Patients in this study with a history of less than 1 year met 28 doctors on average. Semi-structured interviews with these patients were conducted adopting a qualitative approach. Patients were asked about their recollections of the doctors they had met during their cancer care and what value they attributed to these encounters. Interviews were subject to thematic analysis. The major themes to emerge were: continuity of care, the provision of information and explanations and honesty in that process, breaking of bad news, the manner adopted by the doctor and issues relating to specialist referral. The large number of health care professionals, including the doctors quantified in this study, involved in the care of each patient represents a major challenge to 'seamless' and consistent communication between those involved.

Aged↗

Early video-assisted thoracic surgery in the management of empyema.

OBJECTIVE: The appropriate timing, as well as the type of intervention, for the treatment of empyema in children is controversial. The advent of video-assisted thoracic surgery (VATS) has changed the way we treat these children. Therefore, we reviewed our experience with the early use of VATS in the treatment of empyema and formulated a treatment algorithm. METHODS: We retrospectively reviewed medical records of all patients undergoing VATS for empyema at Arkansas Children's Hospital from December 1994 to February 1997. All patients were treated by the pediatric surgical service and had the diagnosis of empyema confirmed at surgery. Results are reported as means, unless otherwise noted. RESULTS: Twenty-five children with empyema were treated with VATS during the review period. Their age was 48.3 months, and the duration of symptoms was 7.4 days. All the patients had parapneumonic empyemas and had received preoperative antibiotics for 10.1 days. Preoperative imaging included chest radiography in 25 (100%), ultrasonography in 20 (80%), and computed tomography in 10 (40%). All patients with documented loculated parapneumonic fluid collections underwent VATS within a mean of 2 days of hospitalization. Chest tubes were removed in 3.2 days, resulting in a postoperative length of stay of 4.9 days. Total length of stay was 7.3 days. One patient required conversion to minithoracotomy and required a transfusion. There were no other complications or deaths. Follow-up was available for 22 (88%) children, and there was resolution of symptoms in all children with no recurrences. CONCLUSIONS: Earlier intervention with VATS in the treatment of empyema in children is safe and may reduce hospital charges by shortening hospital stay. A treatment algorithm based on early use of VATS is also described.

Adolescent↗

A new economic benchmark for surgical treatment of appendicitis.

Cost reduction in the management of common surgical diseases such as appendicitis has become paramount for the survival of children's hospitals. We designed a clinical pathway to treat appendicitis with the goal of reducing cost and hospital length of stay (LOS) while maintaining quality of care. From September 1995 through December 1996, patients with nonperforated appendicitis (NPApp) and perforated appendicitis with peritonitis (PApp) were enrolled into a clinical pathway. NPApp patients were discharged when tolerating a regular diet. PApp patients were discharged if the following criteria were met: temperature < 38.5 degrees C for 24 hours, WBC < 14,000 on postoperative day 3, tolerating diet, and transition to oral analgesics accomplished. Hospital LOS and actual hospital costs in pathway patients were compared with those of historic controls. Patients with appendicitis from the Pediatric Health Information Systems (PHIS) database, a consortium of 20 children's hospitals in the United States, served as concurrent controls. Hospital LOS and hospital charges in PHIS NPApp and PApp patients from our institution were compared with national PHIS database patients. Mean LOS and hospital costs for both NPApp and PApp pathway patients were significantly decreased compared with historic controls (P < 0.05). Mean LOS and hospital charges in our institution's PHIS NPApp and PApp patients were also significantly decreased compared with the national PHIS database (P < 0.05). Innovative approaches such as these are necessary for the survival of children's hospitals in an increasingly cost competitive healthcare market.

Anti-Infective Agents↗

A randomized double-blind trial of oral L-arginine for treatment of interstitial cystitis.

PURPOSE: Nitric oxide synthase activity is decreased in the urine of patients with interstitial cystitis compared to the urine of controls. In a preliminary trial oral L-arginine, the substrate for nitric oxide synthase, increased urinary nitric oxide synthase activity and improved interstitial cystitis symptoms. This randomized, double-blind, placebo controlled study further investigates the efficacy of L-arginine treatment for interstitial cystitis. MATERIALS AND METHODS: A total of 53 interstitial cystitis patients were assigned to receive daily 1,500 mg. L-arginine or placebo orally for 3 months. Interstitial cystitis symptoms were assessed by interviews at 2 weeks, and 1, 2 and 3 months. RESULTS: The trial was completed by 21 of 27 patients in the L-arginine group and 25 of 26 in the placebo group. Using per protocol analysis 29% (6 of 21 patients) in the L-arginine group and 8% (2 of 25) in the placebo group were clinically improved by the end of the trial (p = 0.07). A Likert scale showed greater global improvement in the L-arginine group (48%, 10 of 21) compared to the placebo group (24%, 6 of 25) at 3 months (p = 0.05) with a decrease in pain intensity (p = 0.04), and tendency toward improvement in urgency (p = 0.06) and frequency of pain (p = 0.09). Using an intention to treat approach to analysis there were no differences between groups. CONCLUSIONS: Oral L-arginine (1,500 mg. daily) may decrease pain and urgency in a subset of interstitial cystitis patients.

Administration, Oral↗

Inducible nitric oxide synthase with transitional cell carcinoma of the bladder.

PURPOSE: Nitric oxide (NO) plays a critical role as both a cell signaling molecule and as a cytotoxic/cytostatic mediator. Nitric oxide synthase (NOS) present in macrophages and neutrophils produces NO in response to immune stimulation. We evaluated NO production in both bladder tissue and urine from patients with transitional cell carcinoma (TCC) of the bladder. MATERIALS AND METHODS: Inducible NOS (iNOS) RNA and protein were evaluated in bladder tissue from patients with and without TCC. Human iNOS-RNA products were identified with the reverse transcriptase-polymerase chain reaction (RT-PCR). Western blot analysis using a polyclonal antibody directed against iNOS recognized immunoreactive iNOS protein. Using the same iNOS antibody, the distribution of iNOS was examined in formalin-fixed, paraffin embedded samples of various grades of TCC. NOS activity was measured in the urine particulate fraction from patients with TCC and from controls by the conversion of [14C]-L-arginine to [14C]-L-citrulline. RESULTS: Inducible NOS-RNA products and iNOS specific proteins were found in bladder tissue that contained TCC but not in control bladder tissue. Inducible NOS was uniformly localized in inflammatory cells within the carcinomas. Scattered tumor cells expressed iNOS in 8 of 12 specimens. There was no clear relationship between tumor immunoreactivity and tumor grade. NOS activity in urine from patients with TCC was not significantly elevated or decreased in comparison with control urine. CONCLUSIONS: Inducible NOS is expressed by cells comprising and surrounding human bladder tumors. It is primarily localized to inflammatory cells, but also is demonstrated within individual tumor cells.

Carcinoma, Transitional Cell↗

Minimally invasive surgery: the pediatric surgery experience.

BACKGROUND: Minimally invasive surgery (MIS) has become an important aspect of general surgery. The degree to which pediatric surgeons have incorporated MIS into their practice is not known. STUDY DESIGN: An MIS survey was sent to all members of the American Pediatric Surgical Association. Respondents were separated into two groups: nonperformers and performers of MIS. Performers were asked how they were trained in MIS and the total number and types of minimally invasive procedures they have performed. RESULTS: Eighty-two percent of surveyed pediatric surgeons perform MIS. Eighty-seven percent received some or all of their training in a postgraduate course. Two percent received their only training during their general surgery residency. Forty-seven percent of performers reported 50 or fewer total procedures. A wide variety of procedures were reported, but laparoscopic cholecystectomy (95%) was the procedure most frequently reported. Thoracoscopic procedures (71%) were also reported at high rates. CONCLUSIONS: Most pediatric surgeons in our survey perform MIS. The high rate of laparoscopic cholecystectomies reported suggests that the initial MIS experience of pediatric surgeons in our survey is similar to adult general surgeons. The frequency, however, of thoracic cases reported indicates that MIS techniques are being applied to all areas of pediatric surgery. The total minimally invasive procedure experience of our respondents also suggests that pediatric surgeons are early in their learning curve.

Adult↗

Establishment and characterization of a megakaryoblast cell line with amplification of MLL.

A new cell line with megakaryoblastic features, designated UoC-M1, was established from the malignant cells of a 68-year-old patient with acute myeloid leukemia. The patient's leukemic cells reacted with alpha-naphthyl acetate esterase and acid phosphatase and expressed CD7, CD24, CD34, CD38, CD45, HLA-DR and CD61. Cytogenetic analysis of the patient's malignant cells (and of the UoC-M1 cells) showed a human, male hypodiploid karyotype with many chromosome rearrangements and marker chromosomes. Spectral karyotyping (SKY) analysis complemented the G-banded karyotyping and clarified several chromosomal translocations and identified the marker chromosomes. Fluorescence in situ hybridization (FISH) and SKY analysis demonstrated that one marker chromosome contained three segments of chromosome 9 interspersed with three segments of chromosome 11, as well as a portion of chromosome 19. FISH analysis with a probe for MLL revealed that the UoC-M1 cells contained four copies of the MLL gene. Southern blot analysis determined that the MLL gene had a germline profile while Northern and Western analyses showed that the MLL mRNAs and protein were of the appropriate sizes. This is the first report of amplification of the MLL gene which may be an additional mechanism of leukemogenesis or disease progression.

Aged↗

Detection of urinary tract infections by reduction of nitroblue tetrazolium.

BACKGROUND: Nitroblue tetrazolium (NBT) reduction to formazan has been used as a marker for nitric oxide synthase (NOS). Since inducible NOS activity is elevated in urine from patients with urinary tract infections (UTIs), we investigated the accuracy of NBT reduction as an early predictor of UTIs and quantified the relationship between inducible NOS and NBT. METHODS: Urine samples from 434 patients were screened for the presence of UTIs with leukocyte-esterase and nitrite dipsticks and with NBT reduction. The rapid screening results from each test were compared to urine culture results. In addition, NBT reduction parameters were measured in urine pellet at 595 nm after incubation with one of four factors: NOS cofactors, NOS inhibitors, NADH, or superoxide dismutase/catalase. RESULTS: As a urine screening test for UTIs, NBT reduction was more sensitive with a higher negative predictive accuracy than the nitrite dipstick. NBT reduction also was more specific with a higher positive predictive accuracy and negative predictive accuracy than the leukocyte-esterase dipstick. In infected urine pellet, both NADPH, a NOS cofactor, and NADH increased NBT reduction. Superoxide dismutase/catalase decreased NBT reduction. CONCLUSIONS: Although NOS may not be the only NBT reducing enzyme, rapid, visible reduction of NBT is induced in urine from patients with UTIs.

Adolescent↗

Novel mutations in the connexin 26 gene (GJB2) that cause autosomal recessive (DFNB1) hearing loss.

Mutations in the connexin 26 (Cx26) gene (GJB2) are associated with the type of autosomal recessive nonsyndromic neurosensory deafness known as "DFNB1." Studies indicate that DFNB1 (13q11-12) causes 20% of all childhood deafness and may have a carrier rate as high as 2. 8%. This study describes the analysis of 58 multiplex families each having at least two affected children diagnosed with autosomal recessive nonsyndromic deafness. Twenty of the 58 families were observed to have mutations in both alleles of Cx26. Thirty-three of 116 chromosomes contained a 30delG allele, for a frequency of .284. This mutation was observed in 2 of 192 control chromosomes, for an estimated gene frequency of .01+/-.007. The homozygous frequency of the 30delG allele is then estimated at .0001, or 1/10,000. Given that the frequency of all childhood hearing impairment is 1/1,000 and that half of that is genetic, the specific mutation 30delG is responsible for 10% of all childhood hearing loss and for 20% of all childhood hereditary hearing loss. Six novel mutations were also observed in the affected population. The deletions detected cause frameshifts that would severely disrupt the protein structure. Three novel missense mutations, Val84Met, Val95Met, and Ser113Pro, were observed. The missense mutation 101T-->C has been reported to be a dominant allele of DFNA3, a dominant nonsyndromic hearing loss. Data further supporting the finding that this mutation does not cause dominant hearing loss are presented. This allele was found in a recessive family segregating independently from the hearing-loss phenotype and in 3 of 192 control chromosomes. These results indicate that 101T-->C is not sufficient to cause hearing loss.

Alleles↗

Infection control in the outpatient setting.

This article discusses aspects of ambulatory care that increase the difficulty of practicing infection control in this setting or that require infection control staff to use different methods than they would use in the inpatient setting. The article reviews basic infection control precautions that apply to the outpatient setting in general and specific precautions that apply to dialysis centers and physical therapy programs. The article also describes outbreaks that have occurred in the outpatient setting, defines the deficiencies in infection control practice that caused the outbreaks, and discusses methods to prevent transmission of pathogens in the outpatient setting.

Ambulatory Care Facilities↗

Effects of familiarity and temporal organization on memory for event schemas in aged and Alzheimer subjects: implications for clinical management.

Individuals with Alzheimer disease (AD) often forget how to perform everyday activities. To understand better this type of memory loss, the effects of familiarity and temporal organization on memory for event schemas was investigated in college students, elderly controls, and individuals with AD. Participants were asked to read short stories describing common activities. Both recall and recognition memory were assessed immediately after reading the story. The number of items correctly remembered and the error types were recorded and analyzed. Both familiarity and temporal organization were found to play a role in memory for event schemas. All groups remembered the most information when the stories were familiar and sequentially organized. Elderly participants were more likely to remember items associated with, but included in, the stories than were the other groups. The AD group was the only group to recall or recognize items not associated with the story. It was concluded that event schema memory in AD participants is moderated by the same factors that influence memory in healthy young and elderly participants. These results suggest that individuals with AD will be best able to perform common everyday activities when they are familiar and when daily activities follow a predictable sequential pattern.

Activities of Daily Living↗

Transmucosal passage of bacteria across rat intestinal epithelium in the Ussing chamber: effect of nutritional factors and bacterial virulence.

Transmucosal passage of bacteria across the intestine, the essential and prerequisite step for bacterial translocation, cannot be effectively studied using in vivo models of translocation. We have adapted the Ussing chamber into a fresh, sterile organ culture system that can facilitate the study of bacterial-epithelial interactions. Intestinal membranes were mounted in the Ussing chamber and perfused with a solution rich in putative mucosal micronutrients. The transmembrane potential difference was constantly monitored as a marker of intestinal integrity. Transmucosal passage of various bacteria across the normal intestinal epithelium was quantitated, and the mucosal membrane was examined by light and transmission electron microscopy. The addition of potassium cyanide to the mucosal perfusate resulted in an irreversible loss of potential difference. Oxygen deprivation also led to a precipitous drop in potential difference, but it was reversible with prompt reoxygenation. In contrast, intestinal membranes perfused with a solution consisting of Dulbecco's modified Eagle's medium + 20 mM glutamine maintained their potential difference for a sustained period (>180 min). Both the viability and structural integrity of the ileal intestinal membrane were maintained in culture ex vivo using this perfusate. Qualitative differences were observed in the mechanism of transmucosal passage of mild to moderately virulent bacteria such as Escherichia coli C-25 and Proteus mirabilis M-13, which pass through the intestinal epithelium without causing overt damage to the mucosa, and more virulent organisms such as Salmonella typhimurium, which cause extensive mucosal damage by light and transmission electron microscopy. The Ussing system should provide a useful model of intact organ culture for the study of the mechanisms of bacterial translocation and the pathogenesis of enteric infections.

Animals↗

Molecular approaches to the genetic analysis of specific reading disability.

Specific reading disability is a complex phenotype that is under both genetic and environmental influences. There is evidence for at least one major gene, which may be detectable by parametric linkage analysis, but detection of other quantitative trait loci may require nonparametric methods. Phenotype definition may also be critical in identifying genes that affect different components of the reading process. Current research from two separate laboratories supports the localization of one gene influencing reading disability to the histocompatibility region of chromosome 6p and suggests that another gene may be located on chromosome 15. Actual identification of these and similar genes is complicated by reduced penetrance and phenocopies in families, so that delineation of the critical region using crossover analysis is problematic. This difficulty can result in the identification of many candidate genes that need to be evaluated through combinations of association analysis, functional analysis, and mutation assays.

Dyslexia↗

The efficacy of the dicon screening field to detect eyes with glaucomatous field loss by Humphrey threshold testing.

PURPOSE: The authors compare the results of the Dicon suprathreshold, kinetic fixation perimeter with multiple stimulus presentation to automated threshold perimetry (Humphrey) in the same eye. METHODS: A Dicon screening visual field test and a Humphrey threshold visual field test were performed in 148 eyes of 148 persons with glaucoma or who were suspect for glaucoma. The number and pattern of missed points on the Dicon test were compared with Humphrey global indices in each eye. RESULTS: The median time to complete the 40-point, Dicon suprathreshold test was 2.7 minutes per eye. Regression analyses indicated that Dicon test parameters were modestly correlated with Humphrey corrected pattern standard deviation (CPSD) probability and mean deviation (R2 ranging from 0.21 to 0.46, p = 0.000). With glaucoma defined as a Humphrey Glaucoma Hemifield Test (GHT) result of outside normal limits, the best mix of sensitivity and specificity of Dicon results occurred at 2 or more missed points, with sensitivity of 64% and specificity of 83%. The specificity was maximum (90%) with a Dicon criterion of 3 or more adjacent missed points, but sensitivity at this level was 55%. With glaucoma defined by CPSD probability value less than 1%, sensitivity and specificity for two adjacent missed Dicon points were 69% and 87%, respectively. CONCLUSION: Dicon suprathreshold testing is a practical means to differentiate between some persons with glaucomatous damage and glaucoma suspects.

Adult↗

Linkage analysis of progressive hearing loss in five extended families maps the DFNA2 gene to a 1.25-Mb region on chromosome 1p.

Thus far, 13 genes for autosomal dominant hearing loss have been localized to specific chromosomal regions, but none of the genes has been cloned. Only a single family has been linked to each of these loci, with the exception of DFNA2. DFNA2 was originally mapped in two extended families originating from Indonesia and the United States. In this study we report linkage to DFNA2 in three additional large families with autosomal dominant hearing loss from Belgium and The Netherlands. These five DFNA2 families show a similar progressive sensorineural hearing loss, starting in the high frequencies and also affecting the middle and low frequencies later in life. Combining the information from all linked families, the candidate region that is most likely to contain the DFNA2 gene was reduced to a 1.25-Mb region between markers D1S432 and MYCL1. Different haplotypes segregating with the hearing loss were found in all five families, suggesting that different mutations are present in the same gene. These results indicate that DFNA2 is most likely an important gene for autosomal dominant hearing loss.

Alleles↗

Bacterial infection induces nitric oxide synthase in human neutrophils.

The identification of human inflammatory cells that express inducible nitric oxide synthase and the clarification of the role of inducible nitric oxide synthase in human infectious or inflammatory processes have been elusive. In neutrophil-enriched fractions from urine, we demonstrate a 43-fold increase in nitric oxide synthase activity in patients with urinary tract infections compared with that in neutrophil-enriched fractions from noninfected controls. Partially purified inducible nitric oxide synthase is primarily membrane associated, calcium independent, and inhibited by arginine analogues with a rank order consistent with that of purified human inducible nitric oxide synthase. Molecular, biochemical, and immunocytochemical evidence unequivocally identifies inducible nitric oxide synthase as the major nitric oxide synthase isoform found in neutrophils isolated from urine during urinary tract infections. Elevated inducible nitric oxide synthase activity and elevated nitric oxide synthase protein measured in patients with urinary tract infections and treated with antibiotics does not decrease until 6-10 d of antibiotic treatment. The extended elevation of neutrophil inducible nitric oxide synthase during urinary tract infections may have both antimicrobial and proinflammatory functions.

Adult↗