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Biomedical subjects

S Berry

Publications and source records attributed to S Berry.

At least 55 records · Page 3Linked to original sources

Improved method to create the common ostium variant of the distal arteriovenous fistula for enhancing crural prosthetic graft patency.

PURPOSE: Successful use of the distal adjunctive arteriovenous fistula (dAVF) for the enhancement of prosthetic graft patency rates in the crural position is critically dependent on the qualitative and quantitative aspects of the arterial and venous runoff. Precise technical performance of the fistula is equally vital to secure optimal results. The purpose of this study was to determine current prosthetic graft patency and limb salvage rates using a modified version of the common ostium dAVF. METHODS: The standard method to create the common ostium variant of dAVF has been modified to improve apposition of the "otomy" sites of the artery and vein, avoid twisting and stenosis by terminating the fistula suture line at the artery-vein junctures, reshaping the ovoid ostium to a rectangular shape, and finally, use of multiple interrupted heel-toe sutures. RESULTS: Since 1979 we have created 290 fistulas in 281 patients who required leg revascularization procedures. In different time periods we have documented improving graft patency and limb salvage rates. Fistula patency, reflected by annual attrition rates of 13% to 26% per year, continues as a challenge for long-term results. Current 3-year secondary cumulative graft patency and limb salvage rates by life table analysis are 61% and 74%, respectively. The conduit material may play a role with regard to steal phenomena and the need for banding techniques. CONCLUSION: Configuration of the adjunctive dAVF may impact on prosthetic graft patency in the crural position. In addition, the type of graft material used for bypass may be instrumental in preventing or precipitating the steal phenomenon. These issues require further study to better understand flow dynamics, patterns of intimal hyperplasia, and blood distribution as a function of conduit material and impedance of the arterial and venous runoff.

Adult↗

The complete BRCA2 gene and mutations in chromosome 13q-linked kindreds.

Breast carcinoma is the most common malignancy among women in developed countries. Because family history remains the strongest single predictor of breast cancer risk, attention has focused on the role of highly penetrant, dominantly inherited genes in cancer-prone kindreds (1). BRCA1 was localized to chromosome 17 through analysis of a set of high-risk kindreds (2), and then identified four years later by a positional cloning strategy (3). BRCA2 was mapped to chromosomal 13q at about the same time (4). Just fifteen months later, Wooster et al. (5) reported a partial BRCA2 sequence and six mutations predicted to cause truncation of the BRCA2 protein. While these findings provide strong evidence that the identified gene corresponds to BRCA2, only two thirds of the coding sequence and 8 out of 27 exons were isolated and screened; consequently, several questions remained unanswered regarding the nature of BRCA2 and the frequency of mutations in 13q-linked families. We have now determined the complete coding sequence and exonic structure of BRCA2 (GenBank accession #U43746), and examined its pattern of expression. Here, we provide sequences for a set of PCR primers sufficient to screen the entire coding sequence of BRCA2 using genomic DNA. We also report a mutational analysis of BRCA2 in families selected on the basis of linkage analysis and/or the presence of one or more cases of male breast cancer. Together with the specific mutations described previously, our data provide preliminary insight into the BRCA2 mutation profile.

BRCA2 Protein↗

Low incidence of BRCA2 mutations in breast carcinoma and other cancers.

Inherited mutant alleles of familial tumour suppressor genes predispose individuals to particular types of cancer. In addition to an involvement in inherited susceptibility to cancer, these tumour suppressor genes are targets for somatic mutations in sporadic cancers of the same type found in the familial forms. An exception is BRCA1, which contributes to a significant fraction of familial breast and ovarian cancer, but undergoes mutation at very low rates in sporadic breast and ovarian cancers. This finding suggests that other genes may be the principal targets for somatic mutation in breast carcinoma. A second, recently identified familial breast cancer gene, BRCA2 (refs 5-8), accounts for a proportion of breast cancer roughly equal to BRCA1. Like BRCA1, BRCA2 behaves as a dominantly inherited tumour suppressor gene. Individuals who inherit one mutant allele are at increased risk for breast cancer, and the tumours they develop lose the wild-type allele by heterozygous deletion. The BRCA2 coding sequence is huge, composed of 26 exons that span 10,443 bp. Here we investigate the rate of BRCA2 mutation in sporadic breast cancers and in a set of cell lines that represent twelve other tumour types. Surprisingly, mutations in BRCA2 are infrequent in cancers including breast carcinoma. However, a probable germline mutation in a pancreatic tumour cell line suggests a role for BRCA2 in susceptibility to pancreatic cancer.

BRCA2 Protein↗

The impact of zidovudine compared with didanosine on health status and functioning in persons with advanced HIV infection and a varying duration of prior zidovudine therapy. AIDS Clinical Trials Group 116/117 Study Group.

The objective of this study was to compare the effects of zidovudine and didanosine on health-related quality of life in persons with advanced HIV infection and varying duration of prior zidovudine exposure. It was designed as a substudy nested in two similar placebo-controlled active-control-arm randomized trials, using sites of the AIDS Clinical Trials Group participating in the randomized trials of zidovudine versus didanosine (ACTG 116 and 117). The patients comprised 356 participants enrolled in ACTG 116 and 117. All had HIV infection and either a CD4 count of <200 cells/mm3, or a CD4 count of <300 cells/mm3 plus symptoms of HIV disease. Participants were randomized equally within strata defined by duration of prior zidovudine therapy, to receive didanosine sachets at a dose of 500 mg daily (334 mg in subjects weighing <60 kg) or 750 mg daily (500 mg in subjects weighting <60 kg) plus inactive capsules resembling zidovudine, or to receive zidovudine capsules at a dose of 600 mg daily plus inactive sachets resembling didanosine. The main outcome measures were self-reported health-related quality of life, healthcare utilization, disability, work and symptom impact. The results showed no differences in reported symptom impact or healthcare utilization, and most measures of disability were similar. In the group with more than 8 weeks of prior zidovudine therapy, several of the health status scale scores for ongoing participants were significantly better for didanosine recipients, but average differences were small. Use of several different approaches to combining health status and survival showed no differences in the overall quality-time experiences between the treatment groups. Individuals taking zidovudine, low-dose didanosine and high-dose didanosine experienced 33, 34 and 35 weeks, respectively, in at least the typical health state if they had fewer than 8 weeks of previous zidovudine therapy, and had 23, 23 and 26 weeks, respectively, if they had more than 8 weeks previous use of zidovudine. Results did not differ when data were analysed within strata ofpatients who had any versus no prior exposure to zidovudine, or AIDS versus non-AIDS status. In conclusion, functional status and health-related quality of life were substantially similar among persons receiving either zidovudine or didanosine, regardless of the duration of prior zidovudine treatment.

Adult↗

Entropy, irreversibility and evolution.

The Second Law of Thermodynamics is investigated with respect to its value as an indicator of the direction of the evolutionary process. Non-thermodynamic entropy concepts and possible errors in the use of thermodynamic entropy are discussed. The importance of genuine thermodynamic potentials and their correct application for understanding processes is emphasized. There is no direct connection between evolutionary events such as speciation and thermodynamic entropy changes; the irreversibility of evolution is not a consequence of thermodynamic irreversibility.

Animals↗

Health status and function with zidovudine or zalcitabine as initial therapy for AIDS. A randomized controlled trial. Roche 3300/ACTG 114 Study Group.

OBJECTIVE: To evaluate the functional and health status implications of prescribing zalcitabine or zidovudine for initial therapy of acquired immunodeficiency syndrome (AIDS). DESIGN: A substudy of a randomized controlled trial. SETTING: Private and public clinics and referral centers. PATIENTS: Had human immunodeficiency virus (HIV) infection, less than 0.20 x 10(9)/L (200 microliters) CD4+ cells, and either a history of Pneumocystis carinii pneumonia or symptoms of HIV infection. Fifty-eight percent (338/668) of main study enrollees representing 90% of enrollees at participating sites were included in this substudy. INTERVENTIONS: Either zalcitabine at 0.75 mg every 8 hours plus inactive capsules identical in appearance to zidovudine or zidovudine at 200 mg (later 100 mg) every 4 hours plus inactive tablets identical in appearance to zalcitabine. MAIN OUTCOME MEASURES: Results of a periodically completed self-report survey instrument containing specific questions about symptom impact, disability, work, functioning, and utilization as well as nine health and functioning scales adapted from the Medical Outcomes Study (MOS). RESULTS: Zalcitabine recipients were twice as likely to undergo an invasive procedure (P = .004) or be admitted to hospital (P = .01). Zalcitabine recipients reported greater than 40% more symptoms that interfered with activity (P = .001) and greater than 50% more disability days (P < .01). They also had a 7% lower employment rate and a 35% lower monthly income. Average observed health status scores were lower in zalcitabine recipients overall, but especially in the early portion of the study. New methods for combining survival and health status data showed that, over 76 weeks of study, a typical zidovudine recipient spent about 4 (10%) more weeks with at least the typical health state than did a typical zalcitabine recipient. CONCLUSIONS: Zidovudine has substantial advantages over zalcitabine in initial monotherapy of AIDS in terms of functional outcomes such as symptoms impact, disability, work, utilization, and health status. In this case, the differences in functional outcomes presaged differences in physiological and clinical measures. The inclusion of functional outcomes can greatly improve the information available from a clinical trial.

Acquired Immunodeficiency Syndrome↗

A comparison between detailed and simple histories in the diagnosis of genital herpes complicating pregnancy.

OBJECTIVE: All women seropositive for herpes simplex virus-2 are at risk for asymptomatic viral shedding at the onset of labor and neonatal transmission of the virus. Unfortunately, only 20% to 35% of seropositive adults give a history consistent with genital herpes. We evaluated whether more detailed questioning during pregnancy might elucidate symptoms predictive of seropositivity and therefore better identify women at risk for herpes simplex virus shedding at delivery. STUDY DESIGN: During pregnancy 201 randomly selected women were asked in-depth questions about recurrent genital symptoms and whether they "currently have or have ever had genital herpes." An assessment was made whether the patient had a history compatible with genital herpes. This assessment and the "yes/no" history of genital herpes obtained by physicians at the initial prenatal visit were both compared with herpes simplex virus serologic studies by Western blot. RESULTS: Of 201 patients interviewed, 177 gave no history of genital herpes. Of these, 30.4% were seropositive for herpes simplex virus-2. Detailed histories on these 177 patients indicated that among the 159 subjects without suggestive symptoms or with somewhat suggestive symptoms the corresponding rates of seropositivity were 28% and 30%. Among the 18 (10.2%) subjects with highly suggestive symptoms, only 50% were seropositive. The positive predictive values for recurrent genital symptoms to predict herpes simplex virus-2 seropositivity ranged from 30% to 57%. CONCLUSION: A detailed history of genital symptoms is no better at identifying an herpes simplex virus-2 seropositive patient than is simply asking if she has ever had genital herpes. Serologic screening is a more accurate method of identifying women with past genital herpes or those who are at risk for acquiring genital herpes during pregnancy.

Adolescent↗

5-Hydroxytryptamine2A (5-HT2A) receptor desensitization can occur without down-regulation.

The connection between agonist-induced desensitization and down-regulation of 5-hydroxytryptamine2A (5-HT2A) receptors was examined in a clonal cell line that stably expresses the 5-HT2A receptor. Brief (2-hr) and prolonged (24-hr) exposure to the agonist quipazine or the agonist 4-iodo-(2,5-dimethoxy)- phenylisopropylamine (DOI) diminished 5-HT2A receptor-mediated phosphoinositide hydrolysis; no change in 5-HT2A receptor number or affinity was measured after 24 hr of exposure to DOI or quipazine. Immunohistochemical studies demonstrated that a 24-hr exposure to DOI did not alter surface 5-HT2A receptor immunoreactivity. Western blot analysis with G alpha q- and G alpha 11-selective antibodies indicate that a 24-hr agonist exposure did not alter the levels of phospholipase C-dependent G proteins. These results suggest that desensitization after prolonged DOI exposure can occur via a process independent of the levels of phospholipase C-coupled G proteins. Studies with a mutant 5-HT2A receptor (F340L) indicated that binding per se is not sufficient for desensitization. Down-regulation of the protein kinase C isozymes alpha and epsilon by overnight exposure to phorbol-12,13-dibutyrate attenuated the intermediate phase (i.e., after 2-6 hr of agonist exposure) of DOI- and quipazine-induced desensitization. These results indicate that the intermediate phase of DOI-induced desensitization is mediated by the alpha- and/or epsilon-protein kinase C isozymes but that neither is involved in the later phase (i.e., after 24 hr of agonist exposure) of desensitization.(ABSTRACT TRUNCATED AT 250 WORDS)

3T3 Cells↗

Frequent detection of genital herpes simplex virus DNA by polymerase chain reaction among pregnant women.

OBJECTIVE: To investigate the prevalence and level of genital herpes simplex virus (HSV) among women at delivery. DESIGN, PATIENTS, AND SETTING: A prospective analysis of HSV by culture and by polymerase chain reaction (PCR) of genital specimens and by HSV serologic studies in 100 asymptomatic women in labor; prospective analysis of HSV by PCR among 50 seronegative nonpregnant women at a student health center; and retrospective analysis of genital specimens for HSV by PCR from 17 HSV culture-positive women with uninfected neonates and from two HSV culture-negative women with HSV-infected neonates. All pregnant women were at a university hospital. MAIN OUTCOME MEASURES: Presence of HSV by culture and levels of HSV by quantitative, type-specific PCR in cervical and vulvar specimens; HSV serologic testing by Western blot. RESULTS: All of the 100 asymptomatic women in labor who were studied prospectively were HSV culture negative. In nine HSV was recovered by PCR. Herpes simplex virus was recovered by PCR in one of the 50 seronegative nonpregnant women; she soon became seropositive. All 17 culture-positive women had HSV recovered by PCR. High levels of HSV DNA were obtained by PCR from the two culture-negative women with infected neonates. Among those from whom HSV was recovered by PCR, HSV DNA levels were 250 times higher from culture-positive samples than from culture-negative samples (11,571 genome equivalents vs 46 genome equivalents; P < .001). CONCLUSIONS: The frequency of infant exposure to HSV DNA-containing secretions from HSV-seropositive mothers is about eight times higher than previously reported using HSV culture methods. High maternal levels of HSV DNA may be associated with an increased frequency of transmission of HSV to the infant.

Base Sequence↗

Long-term outcome in children with opsoclonus-myoclonus and ataxia and coincident neuroblastoma.

We reviewed the neurologic and developmental courses in 10 children with opsoclonus-myoclonus ("dancing eyes syndrome") and neuroblastoma. All patients are alive without evidence of neoplastic disease after 8+ to 111+ months of follow-up. All had localized disease and 50% had extraabdominal tumors. Neuroblastomas of nine children had favorable Shimada histologic characteristics, and all tumors had single copies of the N-myc oncogene. After neuroblastoma resection, all patients had persistent opsoclonus-myoclonus or ataxia that responded to therapy with adrenocorticotropic hormone. Nine children had relapses of neurologic symptoms. Three years after resection, six of seven patients with sufficient follow-up were free of symptoms and had discontinued therapy. However, nine children had chronic neurologic deficits, including cognitive and motor delays, language deficits, and behavioral abnormalities. All six patients in educational programs required special assistance. Five children required physical, occupational, or speech therapy. Long-term developmental and cognitive problems should be anticipated in patients with neuroblastoma who have opsoclonus-myoclonus or ataxia or both, and early intervention should be instituted to try to minimize these deficits.

Abdominal Neoplasms↗

Immunologic parameters 2 years after high-titer measles immunization in Peruvian children.

Immunization with high-titer measles vaccines has been associated with excess mortality in children 2-4 years after vaccination. In this study, immunologic parameters in 64 Peruvian children who had been immunized an average of 27 months earlier with high-titer vaccines were compared with parameters in 76 recipients of low-titer vaccines. Delayed-type hypersensitivity, lymphocyte phenotype distributions by flow cytometry, and lymphoproliferation after phytohemagglutinin (PHA) stimulation were assessed. High-titer recipients had smaller indurations to tetanus, diphtheria, and Proteus (P < .05) antigens, decreased PHA stimulation (P = .04), and a lower percentage of CD4+ lymphocytes (P = .04) than low-titer recipients. After adjustment for sex, concurrent illnesses, and other variables in regression analyses, high-titer recipients had a lower percentage of CD4+ lymphocytes (P = .025) and decreased lymphocyte proliferation to PHA (P = .058). These results may provide a clue to the pathogenesis of delayed excess mortality after high-titer measles vaccination in some developing countries.

Cell Division↗

Physical properties and repair bond strength of direct and indirect composite resins.

Use of composite resins now includes indirect curing methods. Surface chemistry, repair bond strength, plus location of failure and five physical properties of two direct and three indirect composite resins were determined. There were statistically significant differences in flexural strength of materials and in hardness values. Repair bond strength failures were not significantly different; failures occurred primarily at the interface. Multiple internal reflection spectroscopy confirmed the presence of unpolymerized material after cure in all products. Indirect cure of the direct composite resin increased the degree of cure.

Absorption↗

Comparison of high titer Edmonston-Zagreb, Biken-CAM and Schwarz measles vaccines in Peruvian infants.

In an effort to identify the optimal dose and strain of measles vaccination for early immunization, Peruvian infants were randomly assigned to receive one of three measles vaccines in varying doses at 5 to 6 or 8 to 9 months of age. Edmonston-Zagreb vaccines were significantly (P < 0.001) more immunogenic than equivalent or higher titers of Schwarz or Biken-CAM vaccines as determined by neutralization antibody response 3 months after vaccination. Eighty-two percent of infants who received high titer Edmonston-Zagreb vaccine at 5 to 6 months of age developed protective concentrations of measles antibody, a response rate similar to that observed after standard titer Schwarz (81%) or high titer Biken-CAM vaccine (81%) at 8 to 9 months of age. No significant differences in the rates of fever, rash or other adverse events were noted by vaccine group 10 to 14 days after vaccination. Although the high titer vaccines are more immunogenic in young infants than standard vaccines, long term safety must be assured before these vaccines can be put into widespread use.

Antibodies, Viral↗

Herpes simplex virus-2 (HSV-2) type-specific antibody correlates of protection in infants exposed to HSV-2 at birth.

Western blot analysis was used to compare the herpes simplex virus (HSV)-2 antibody profiles of 40 infants less than 2 wk of age who had been exposed to maternal genital HSV-2 at birth. 4 mothers were HSV seronegative at delivery and seroconverted to HSV-2 ("primary infection"), 9 had HSV-1 antibodies and seroconverted to HSV-2 ("nonprimary first episode infection"), and 27 were HSV-2 seropositive ("recurrent infection"). Neonatal herpes infections developed in 1 of 4 infants of women with primary infection, in 3 of 9 infants of women with nonprimary first episode infection, and in none of the 27 infants of women with recurrent HSV-2. Antibodies to HSV-2 proteins gG-2, VP5, and ICP35 were detected in 83, 89, and 72% of the 36 uninfected infants, respectively. None of the four infected infants had detectable antibodies to gG-2 and only one (25%) had antibodies to VP5 or ICP35. The more limited profiles of the 13 infants born to mothers with first episodes of HSV-2 were then analyzed separately; these profiles were similar among infected and uninfected infants except for gG-2, which elicits antibodies that are type specific for HSV-2. None of the infected infants versus seven of nine (78%) uninfected infants were gG-2 seropositive. These comparisons suggest that maternal type-specific antibodies may play a role in preventing neonatal infection after exposure to HSV-2.

Antibodies, Viral↗