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Biomedical subjects

W Andrews

Publications and source records attributed to W Andrews.

At least 19 recordsLinked to original sources

The international infections in pregnancy study: group B streptococcal colonization in pregnant women.

BACKGROUND: Heavy colonization with group B streptococcus (GBS) has been associated with increased risk of preterm birth and neonatal sepsis; the burden of neonatal GBS disease varies geographically. To determine whether variation in heavy colonization and GBS serotypes could contribute to geographic differences in disease burden, we assessed the prevalence of heavy colonization and the distribution of serotypes in asymptomatic pregnant women in multiple countries. METHODS: Cervical, lower vaginal and urine samples were collected from women attending seven prenatal clinics in six countries. Light colonization was defined as GBS isolation from Lim broth only; heavy colonization was isolation from urine or sheep blood agar plates. Isolates were serotyped using capillary precipitation. RESULTS: GBS was present in 11.3% of 1308 participants (range 7.1-21.7%); 5.0% were heavily colonized (0.4-18.8%) and 6.4% were lightly colonized (2.9-8.0%). Serotypes III and V were most common (both 17.2%). Serotypes VII and VIII were found in one study center. CONCLUSIONS: The prevalence of heavy colonization and GBS serotypes varied significantly among our study centers. Whether this variation could in part explain geographic differences in neonatal morbidity and mortality is a hypothesis that needs further study.

Adult↗

The influence of age, gender and ethnicity on cadaveric organ recovery rate.

In view of the influence of donor factors such as age on graft outcome and the performance standards that measure OPO productivity by the number of organs recovered and transplanted, it is important to understand the relationship of certain donor factors on organ recovery for transplantation from cadaveric donors. We examined the influence of donor age, gender and ethnicity on the number and type of transplanted organs recovered from 598 consecutive cadaveric donors in our OPO between 1994 and July 1999. The highest number of organs/donor ocurs in the 11-20 donor age range and declines significantly with each age range. The type of organ recovered is also influenced by age, but the least effect is on liver recovery. No difference was seen in the number of organs recovered/donor by race. When the data were re-analyzed with regard to renal and extra-renal organs transplanted/million donor population, 78% of the kidneys (n=781/1006) were from the 11-50 age range and 81% of the extra-renal organs (n=822/1,192) were from that age range. Stepwise regression yielded a model where donor age significantly influenced (P=0.001) the number of organs recovered. Finally, the incidence of recovered and transplanted organs was significantly higher in males compared with females for hearts [51% (187/360) vs. 40% (86/214); P<0.006] and pancreata [18% (66/360) vs. 11% (24/214); P<0.02]. The number of organs recovered and transplanted from cadaveric organ donors is influenced predominantly by the age of the donor, with the exception being liver donors. Increasing organ recovery and transplantation of organs from donors from the two age extremes results in less gain in the number of organs/million population than recovery from the 11-50 age range.

Adolescent↗

The effectiveness of tonsillectomy in diagnosing lymphoproliferative disease in pediatric patients after liver transplantation.

OBJECTIVE: To determine the effectiveness of diagnosing forms of lymphoproliferative disease by performing tonsillectomy in pediatric patients who develop symptomatic or asymptomatic tonsillar hypertrophy during immunosuppressive therapy after liver transplantation. DESIGN: Retrospective chart and pathological review. SETTING: Urban tertiary referral children's hospital. MAIN OUTCOME MEASURES: The presence of a pathological stage of lymphoproliferative disease or Epstein-Barr virus (EBV) diagnosed using tonsillar specimens, resulting in a change in therapy. RESULTS: Of 275 pediatric patients who underwent liver transplantation, 13 had tonsillectomy performed with histopathological review of the tonsillar specimens. The specimens from 5 patients (39%) demonstrated pathological changes thought to be consistent with EBV-related changes or a form of lymphoproliferative disease. Histological changes ranged from tonsillar hyperplasia associated with EBV infection to large cell lymphoma. Immunosuppressive therapy was reduced or discontinued, and antiviral therapy was initiated. CONCLUSION: Children who have undergone liver transplantation and develop tonsillar hypertrophy should undergo a diagnostic tonsillectomy, regardless of the clinical presentation, to rule out a form of posttransplant lymphoproliferative disease. Arch Otolaryngol Head Neck Surg. 2000;126:1444-1447

Antiviral Agents↗

A bench-top method for evaluating modular total hip component combinations.

A modular total hip prosthesis allows the surgeon to vary head size, neck length, and acetabular coverage. Different combinations, however, may increase the risk of impingement of the prosthesis neck on the acetabular liner, leading to dislocation. We developed a bench-top model to test different modular component combinations to determine how far the femoral component could travel within the acetabular liner before impingement led to dislocation. We tested two hip systems, each from a different manufacturer. Certain components increased the risk of impingement and dislocation: skirted necks, smaller heads, and lipped liners. While the contribution of each component was small, the risk was additive, so that the combination of a small head with a skirted neck in a lipped liner actually reduced the available range of motion by 18 degrees, from 146 degrees to 128 degrees, in the first system, and by 13 degrees, from 156 degrees to 143 degrees in the other. This method could be adapted to test a wide range of component configurations, from a number of manufacturers. These findings may be useful in avoiding potentially unstable configurations when given a choice of modular components.

Hip Prosthesis↗

The epidemiology of clinical neonatal seizures in Newfoundland: a population-based study.

OBJECTIVE: To study the incidence, clinical features, etiologic distribution, and day of seizure onset by etiology in neonates with seizures. DESIGN: Prospective, population-based study involving all the obstetric and neonatal units across the province of Newfoundland, Canada. All units were given educational sessions on neonatal seizure symptomatology. SUBJECTS: Detailed questionnaires were prospectively collected for all infants with probable neonatal seizures for a period of 5 years. RESULTS: The incidence rate was 2. 6 per 1000 live births, 2.00 for term neonates, 11.1 for preterm neonates, and 13.5 for infants weighing <2500 g at birth. Seizures lasting 30 minutes or longer were present in 5%, and the neonatal death rate among infants with seizures was 9%. Hypoxic-ischemic encephalopathy was the presumed cause in 40%, infections in 20%, and metabolic abnormalities in 19%. CONCLUSIONS: Clinical neonatal seizures occur 6 times more often in preterm infants than in term infants. Hypoxic-ischemic encephalopathy continues to be a major marker of the likelihood of seizures.

Apgar Score↗

The SSRI antidepressants: exploring their "other" possible properties.

BACKGROUND: Anecdotal reports suggest that the SSRIs may have important properties in addition to their antidepressant effects, possibly modifying mediating variables that dispose to and maintain depression. This preliminary study seeks to identify any such potential variables. METHODS: Fifty three subjects who had reported substantial general benefit to their clinician after treatment with an SSRI were requested to retrospectively rate change across a range of constructs assessed by questionnaire. RESULTS: Differential effects were identified. Irritability, trait depression, worry and neuroticism scores showed the most marked improvement, with cognitive style components also showing significant positive change. Equally importantly, there was no evidence of a positive response bias across all constructs. CONCLUSION: We suggest that the SSRIs may act as "antiworry" agents and reduce irritability, neuroticism and dysfunctional attributions. LIMITATIONS: Our study was retrospective and relied on self-report by volunteer patients who had been previously depressed. The study design cannot exclude the possibility that improvement reported on a number of measures may have been due to the amelioration of residual depression. CLINICAL RELEVANCE: The SSRIs, recognised as having antidepressant and anti-obsessional properties, may also have the capacity to lower irritability, worrying and neuroticism. This capacity could be useful per se but may, in addition, reduce the occurrence and duration of depressive episodes, particularly by reducing "anxious worrying".

1-Naphthylamine↗

Randomized comparison of ganciclovir plus intravenous immune globulin (IVIG) with IVIG alone for prevention of primary cytomegalovirus disease in children receiving liver transplants.

A randomized placebo-controlled trial was conducted to determine the benefit of ganciclovir (5 mg/[kg x d]) for 30 days in addition to intravenous immune globulin (IVIG) for 16 weeks for prevention of primary cytomegalovirus (CMV) disease in children receiving liver transplants. Patients were monitored for 6 months after transplantation. The two groups of patients (recipients of 29 ganciclovir plus IVIG and 27 recipients of IVIG alone) were similar in terms of age, sex, and underlying disease. The incidence of CMV disease among the ganciclovir plus IVIG recipients and the IVIG alone recipients was 17% and 26%, respectively, and the time to disease in these recipients was 46 days and 32 days, respectively. There was no difference between groups in terms of survival; episodes of rejection, bacteremia, or fungemia; use of immunosuppressive agents; and incidence of leukopenia or thrombocytopenia. These results suggest that a 4-week course of ganciclovir with IVIG is not more effective than IVIG alone for prevention of primary CMV disease. Since short-term prophylaxis with ganciclovir may delay the onset of CMV disease, further studies with a longer course of ganciclovir prophylaxis are warranted.

Adolescent↗

10 years of pediatric liver transplantation.

PURPOSE: Pediatric liver transplantation is an accepted therapy for end-stage liver disease, but little long-term data exist. METHODS: From October 1984 to October 1994, 202 patients underwent a total of 225 liver transplantations. There were 98 boys and 104 girls, the average age was 5.1 +/- 4.9 (range, 0.2 to 19.1) years. Thirty (16%) were under 1 year of age. The diseases that required transplantation included biliary atresia (BA) (45%), metabolic liver disease (MLD) (9.9%), acute hepatic failure (6.9%), and Alagille's syndrome (AS) (5.4%). Originally the immunosuppression was cyclosporine- and steroid-based; the later regimens also included azathioprine and antilymphocyte preparations. All reported survival rates were derived from life-table analysis. RESULTS: The patient survival rates at 1, 5, and 10 years were 76%, 70%, and 61%; the retransplantation rate was 11%. The respective graft survival rates were 71%, 63%, and 59%. There were 60 deaths; 48 (81%) occurred in the first year. These first-year deaths were from sepsis (20; 42%), central nervous system problems (5; 11%), intraoperative complications (4; 8%), lymphoproliferative disease (LPD) (2; 4%), rejection (2; 4%), primary nonfunction (2; 4%), and miscellaneous other causes (7; 15%). There were 12 deaths after the first year, from LPD (3; 25%), sepsis (1; 8%), rejection (2; 18%), cancer (1; 9%), secondary hepatic failure (1; 9%), cerebral vascular accident (1; 9%), or pre- or postoperative complications (3; 25%). Compared with the overall survival rate, patients with MLD had a better chance of survival (83%; P <.012) than did those with AS (45%; P < .001). The 5- and 10-year survival rates for patients with BA were 61% and 58%. Over the past 2 years, the survival rate has increased (87% v 72%; P < .05) as early septic deaths have decreased (from 2.6 to 1.0 per year). CONCLUSION: Liver transplantation is effective treatment for end-stage liver disease. Decreasing the number of early septic deaths has improved the chance of survival, and better diagnosis and treatment of LPD would improve the late survival rate.

Adolescent↗

From pseudocholinesterase to human immunodeficiency virus.

Pseudocholinesterase is a protein for which no function exists in mammals including human beings. To date, no substrate has been identified for this 'enzyme'. Involvement of this protein in the aetiopathogenesis of many diseases, such as hyperlipoproteinaemia, is still actively debated. Here, we propose a theoretical method to immobilize pseudocholinesterase in hepatocytes using antibody bound to liposomes. Conceptually, this approach will have widespread application, especially in blocking human immunodeficiency virus replication in vivo.

Animals↗

The construction and characterization of poliovirus antigen chimeras presenting defined regions of the human T lymphocyte marker CD4.

Defined regions of the CDR2-like region of the T cell antigen CD4 that are implicated in the binding of the surface glycoprotein (gp120) of human immunodeficiency virus type 1 (HIV-1) to CD4+ T lymphocytes have been engineered in place of antigenic site 1 of Sabin type 1 poliovirus. The antigenic properties of the recovered chimeric virus particles were investigated using monoclonal antibodies (MAbs) and polyclonal serum to CD4. None of the MAbs tested neutralized the chimeras, presumably because they are directed against conformational determinants of the V1 domain of CD4. In contrast, the three antigen chimeras were neutralized by polyclonal serum to CD4, which suggested that the CD4-derived sequences were presented in a relevant conformation. A panel of six MAbs were raised against one of the chimeras, and the epitopes were mapped by the selection of neutralization-resistant mutants and cross-neutralization studies. Five of the six MAbs reacted with soluble CD4 (sCD4) in ELISA, and one (MAb 1686) bound to CD4 expressed at the surface of HeLa cells. The high affinity interaction between gp120 and sCD4 was not blocked by MAb 1686, and the poliovirus-CD4 chimeras did not interact with gp120. These results demonstrate that poliovirus can be used as an epitope expression vector for the presentation of sequences in an immunodominant location on the virus particle which adopt a native or near-native conformation, and supports the findings of previous studies involving the presentation of epitopes derived from pathogens.

Amino Acid Sequence↗

Comparison of two kits for measuring ferritin in blood.

Ferritin concentrations in blood are a good indicator of iron stores and can be measured in plasma or serum with commercial kits. We have measured plasma ferritin content in infants ranging from 3 to 15 months of age. During the first three years of a four-year study, plasma samples drawn from these infants were shipped to Abbott Laboratories in Chicago and assayed using the Ferrizyme immunoassay technique (Abbott Laboratories, Chicago, Illinois). For the last year of the study, we analyzed the remaining samples in St. John's using the radioimmunoassay GammaDab125 I Kit (Baxter Travenol Diagnostics, Inc., Cambridge, Massachusetts). Both kit manufacturers report inter- and intra-assay variability of < or = 5%. Results for samples analyzed by the second method were higher than earlier results from infants of the same age with the same intakes of iron; thus, we decided to analyze subsequent samples with both kits.

Ferritins↗

New-generation RIBA hepatitis C strip immunoblot assays.

Second-generation hepatitis C virus (HCV) ELISAs are currently in use in Europe and have been submitted for approval in the United States. These new assays contain additional antigens from the putative nucleocapsid and NS-3 regions of the HCV genome in addition to the c100-3 antigen present in first-generation ELISAs. A supplementary test, the second-generation RIBA HCV strip immunoblot assay (2-RIBA HCV SIA) has also been developed. The strip immunoblot assay uses four recombinant HCV antigens [5-1-1 (NS-4), c100-3 (NS-4), c33c (NS-3), and c22-3 (NS-3) (nucleocapsid)] slot blotted on nitrocellulose. Screening of random volunteer blood donors with the Ortho second-generation HCV ELISA (ORTHO HCV 2.0 ELISA) indicates that a substantial change in the repeat reactive donor population is observed with the new test. Two notable features of this change are: (1) A large number of samples reactive in the 2-RIBA HCV SIA for the second-generation antigens, c33c and c22-3, are detected by the ORTHO HCV 2.0 ELISA; (2) the percentage of ORTHO HCV 2.0 ELISA reactive specimens found indeterminate (reactive for only one HCV antigen) by the 2-RIBA HCV SIA is higher than in first-generation HCV ELISAs (approximately 25 vs. 5%). In addition, ORTHO HCV 2.0 ELISA repeat reactive, 2-RIBA HCV SIA indeterminate samples are dominated by reactivity to c22-3 instead of c100-3, which is the case for first-generation HCV ELISA repeat reactive samples. Resolution of 2-RIBA HCV SIA indeterminate samples as either containing anti-HCV antibodies or not, is important in both diagnostic and blood screening environments, especially where donor notification is required. Our approach to resolution of these troublesome samples evolved from initial work with HCV peptides. Early studies with an experimental strip immunoblot assay containing 5 peptides from the nucleocapsid, E2 (NS-1), NS-4, and NS-5 regions of the viral genome indicated that peptides from the nucleocapsid and NS-4 regions of the genome could provide additional evidence for the presence of anti-HCV antibodies with good specificity, but other peptides suffered from poor specificity. In addition, no immunoreactive peptide from the NS-3 (c33c) region of the virus is available, presumably because the major epitope(s) of this key second-generation antigen is a conformational determinant.(ABSTRACT TRUNCATED AT 400 WORDS)

Blood Transfusion↗

Expectant management of preterm ruptured membranes: effects of antimicrobial therapy.

OBJECTIVE: To determine whether the addition of broad-spectrum antimicrobial therapy to traditional expectant management improves pregnancy outcome in patients with premature rupture of membranes (PROM) remote from term. METHODS: Patients with preterm PROM before 34 weeks' gestation who were not in labor and had no signs of infection or fetal distress were randomized to one of two study groups: 1) expectant management alone and 2) expectant management plus antimicrobial therapy. Women in the latter group received intravenous ampicillin, gentamicin, and clindamycin for 24 hours, followed by amoxicillin plus clavulanic acid orally for 7 days. Other than antibiotic use, management of the two groups was identical. RESULTS: Significantly more women (P < .01) treated with antibiotics (20 of 48, 42%) remained undelivered 7 days after admission compared with those managed expectantly without antibiotics (seven of 46, 15%). In addition, more neonates in the group managed with antibiotics were admitted to the routine nursery (nine of 48 versus two of 45; P = .03). However, there was no difference between the groups in the frequency of serious maternal or neonatal morbidity. CONCLUSIONS: The addition of broad-spectrum antimicrobial therapy to traditional expectant management of pregnancy complicated by preterm PROM may increase the number of gestations undelivered 7 days after admission. It may also decrease the proportion of infants admitted to special care nurseries. Whether these effects result in significant short- or long-term maternal or neonatal benefit remains to be determined.

Anti-Bacterial Agents↗

New generation RIBA hepatitis C strip immunoblot assays.

Second generation hepatitis C virus (HCV) Elisas are currently in use in Europe and have been submitted for approval in the United States. These new assays contain additional antigens from the putative nucleocapsid and NS-3 regions of the HCV genome in addition to the c100-3 antigen present in first generation Elisas. A supplementary test, the second generation RIBA (Chiron Co trademark) HCV strip immunoblot assay (2-RIBA HCV SIA) has also been developed. The strip immuno-blot assay uses four recombinant HCV antigens (5-1-1 [NS-4], c100-3 [NS-4], c33c [NS-3], and c22-3 [NS-3 [nucleocapsid]) slot blotted on nitrocellulose. Screening of random volunteer blood donors with the Ortho (Ortho Diagnostic Systems trademark) second generation HCV Elisa (2-Ortho HCV Elisa) indicates that a substantial change in the repeat reactive donor population is observed with the new test. Two notable features of this change are: i) a large number of samples reactive in the 2-RIBA HCV SIA for the second generation antigens, c33c and c22-3, are detected by the 2-Ortho HCV Elisa; ii) the percentage of 2-Ortho HCV Elisa reactive specimens found indeterminate (reactive for only one HCV antigen) by the 2-RIBA HCV SIA is higher than in first generation HCV Elisas (approximately 25 versus 5%). In addition, 2-ortho HCV Elisa repeat reactive, 2-RIBA HCV SIA indeterminate samples are dominated by reactivity to c22-3 instead of c100-3 which is the case for first generation HCV Elisa repeat reactive samples.(ABSTRACT TRUNCATED AT 250 WORDS)

Enzyme-Linked Immunosorbent Assay↗

Schistosoma mansoni tropomyosin: production and purification of the recombinant protein and studies on its immunodiagnostic potential.

A cDNA that encodes Schistosoma mansoni tropomyosin, except for 10 amino acids at the amino terminus, has been cloned into a pOTSNCO plasmid vector. Induced expression resulted in a constant level of recombinant protein production. The recombinant S. mansoni tropomyosin was purified from preparative SDS-PAGE gel and by a combination of 20% ammonium sulfate fractionation and fast protein liquid chromatography-ion-exchange chromatography. The purified recombinant S. mansoni tropomyosin was tested as an immunodiagnostic reagent in Western blot and enzyme-linked immunosorbent assays. Sera from individual patients with chronic S. mansoni infection, but not S. haematobium, S. japonicum, parasitic infections other than schistosomiasis, and without infection reacted with the recombinant tropomyosin. The species specificity of S. mansoni tropomyosin suggests that further study of its potential as an immunodiagnostic reagent is warranted.

Animals↗