Biomedical subjects

B Hollis

Publications and source records attributed to B Hollis.

At least 19 recordsLinked to original sources

PubMed2004

Effect of parity on second-trimester uterine artery Doppler flow velocity and waveforms.

OBJECTIVES: To investigate the relationship between second-trimester uterine artery Doppler findings and parity in a large pregnant population. METHODS: Uterine artery Doppler studies were performed in all singleton pregnancies at 18-23 weeks of gestation. The mean uterine artery resistance index and the presence or absence of protodiastolic notches were recorded. Two groups were identified: pregnancies not complicated by pre-eclampsia, and pregnancies with pre-eclampsia severe enough to require delivery at or before 32 weeks of gestation. RESULTS: In the 4132 pregnancies uncomplicated by pre-eclampsia, parity was shown to be an independent predictor for both mean uterine artery resistance index (beta = 0.073, P < 0.001) and the presence of bilateral protodiastolic notches (odds ratio = 0.67; 95% CI, 0.45-0.98). In the 17 pregnancies complicated with severe pre-eclampsia, uterine artery Doppler indices showed a trend towards being better predictors of disease in nulliparous compared with parous women. CONCLUSION: Parity has a significant effect on the resistance index and the prevalence of protodiastolic notching in the uterine artery flow waveforms. This difference is clinically noticeable in its effect on notching. These findings suggest that some permanent modification may persist in the maternal vessels after a successful pregnancy, altering their impedance in subsequent pregnancies.

Adult↗

PubMed2003

First-trimester uterine artery blood flow and birth weight.

OBJECTIVES: To determine reference values for first-trimester uterine artery resistance index (RI) in healthy pregnant women with uncomplicated pregnancies and to investigate the relationship between uterine artery Doppler indices and birth weight. METHODS: This was a cross-sectional study of 265 consecutive pregnant women attending routine ultrasound examination at 11-14 weeks' gestation. Both uterine arteries were identified using color Doppler ultrasound and the RI was measured. The presence or absence of an early diastolic notch was also noted. Pregnancy outcomes were obtained from the delivery suite database and birth weight was expressed as Z-scores. RESULTS: The 5(th), 50(th) and 95(th) centiles for uterine artery RI between 11 and 14 weeks' gestation were 0.53, 0.71 and 0.85, respectively. Complete pregnancy outcome data were available for 246 fetuses. There was a significant negative correlation between birth-weight Z-scores and first-trimester uterine artery mean RI (r = - 0.219, P = 0.001). The difference in birth weight between fetuses with absent and those with bilateral diastolic notches was also significant (P < 0.001). Multiple regression analysis demonstrated that both mean RI (standardized regression coefficient = - 0.14, P = 0.039) and uterine artery notching (standardized regression coefficient = - 0.17, P = 0.017) contributed independently towards the prediction of birth-weight Z-score. CONCLUSIONS: A significant negative correlation exists between birth weight and first-trimester uterine artery Doppler parameters, a reliable and non-invasive method of examining uteroplacental perfusion. The value of first-trimester uterine artery Doppler as a prognostic screening tool, either in isolation or in conjunction with maternal biochemistry, remains to be determined.

Adolescent↗

PubMed2002

Comparison of feticide carried out by cordocentesis versus cardiac puncture.

OBJECTIVE: Feticide may be achieved by the injection of strong potassium chloride (KCl) into the fetal circulation via the cardiac route, or less frequently, into the umbilical cord. Despite the relative frequency of this procedure, little published information is available on the subject. SUBJECTS AND METHODS: This was a retrospective analysis of all feticide procedures carried out prior to legal pregnancy termination in mid trimester of pregnancy from January 1996 to July 2001, in a tertiary fetal medicine referral center. The effect of gestational age and the route of access to fetal the circulation on the dose of strong KCl required to achieve cardiac asystole was evaluated. RESULTS: A total of 106 women underwent the procedure of feticide during the study period. Gestational age had no effect on the dose of strong KCl. The median dose of KCl administered by cordocentesis (5 mL) was significantly less (P < 0.001) than the dose required when fetal cardiocentesis was performed for administration of the drug (10 mL). CONCLUSION: This is the first comparative study of feticide by the administration of strong KCl by fetal cardiocentesis and cordocentesis. The study demonstrates that both cardiac and umbilical routes can be used to achieve feticide effectively, without compromising maternal safety. A finding of this study is that significantly smaller doses of KCl were required to achieve fetal cardiac asystole when using the umbilical compared to the cardiac route, although this may be explained by differences in technique. Strong 15% KCl can safely be used to achieve feticide in volumes up to 20 mL for cardiocentesis and 8 mL for cordocentesis.

Abortion, Induced↗

PubMed2002

Sensitivity and accuracy of routine antenatal ultrasound screening for isolated facial clefts.

Facial clefts, as a group, represent one of the most frequently occurring congenital abnormalities detectable on prenatal mid-trimester scan. It has been estimated that, at term, approximately 1 in 1000 infants will be diagnosed with an isolated facial cleft. The aim of this study was to determine the sensitivity and accuracy of routine second trimester ultrasound screening for facial clefts. This was a prospective study of isolated fetal facial clefts, detected at 18-23 weeks gestation, in a routine obstetric population. The antenatal detection rate of facial clefts was derived by comparing the number of cases identified antenatally with the number of neonatal cleft surgeries performed in this centre, for the local population only. The accuracy of antenatal diagnosis of facial clefts was calculated by matching data from the ultrasound database to birth registries and neonatal cleft surgeries performed in this centre, including the referred cases. During the study period, 17,551 women underwent a routine anomaly scan at 18-23 weeks of gestation. A total of 30 babies underwent surgery for isolated facial cleft in this centre during that period. There were no false positive diagnoses of facial clefts, and in five cases (all unilateral), the antenatal diagnosis was found to be inaccurate. 12 babies were from the local population, of which 9 had an antenatal diagnosis of facial cleft, giving a sensitivity of 75%. The current study highlights the effectiveness of antenatal screening for facial clefts. Additionally, it highlights the appropriate terminology that needs to be used in the accurate description of antenatally diagnosed facial clefts.

Cleft Lip↗

PubMed2001

Reproducibility and repeatability of transabdominal uterine artery Doppler velocimetry between 10 and 14 weeks of gestation.

OBJECTIVE: To assess the intraobserver repeatability and interobserver reproducibility of Doppler flow velocity measurements of the uterine arteries in pregnant women between 10 and 14 weeks of gestation. METHODS: In this prospective study, Doppler velocimetric indices (maximum peak systolic velocity, end-diastolic velocity, peak systolic velocity/end-diastolic velocity ratio, pulsatility index and resistance index) were measured twice by the same trained observer in each uterine artery of 63 women. In 47 of these women, a second trained observer then repeated the measurements. In addition, both observers classified qualitatively the blood flow with regard to the presence or absence of an early diastolic notch. The coefficient of variation, intraclass correlation coefficients, within observer and between observers repeatability coefficient and Cohen's kappa coefficient were calculated. RESULTS: The best parameter in terms of repeatability and reproducibility in both uterine arteries was the resistance index with a low coefficient of variation and high intraclass correlation coefficient. The other parameters (pulsatility index, peak systolic velocity/end-diastolic velocity ratio, peak systolic velocity and end-diastolic velocity) performed poorly with high coefficients of variation on both sides. Agreement between the repeated observations (inter- and intraobserver) with regard to the presence or absence of an early diastolic notch was good. CONCLUSION: Doppler velocimetry of uterine artery blood flow is technically feasible between 10 and 14 weeks of gestation. This study demonstrates that this technique is prone to measurement errors. Quantitatively, the resistance index appears to be the most repeatable and reproducible measurement at this gestational age. Qualitative assessment of the waveform morphology also shows high levels of intra- and interobserver agreement.

Adult↗

PubMed2001

Significance of chromosome 22q11 analysis after detection of an increased first-trimester nuchal translucency.

OBJECTIVE: To determine the value of performing routine fluorescent in situ hybridization (FISH) for microdeletions of chromosome 22q11 when karyotyping fetuses with increased nuchal translucency. DESIGN: This was a prospective observational study carried out over an 18-month period. Fetal karyotyping by chorionic villus sampling was offered to 5429 women attending for a routine booking scan in the first trimester when their nuchal translucency adjusted risk for Down syndrome was > or = 1 in 300. Cytogenetic samples were routinely tested for the 22q11 microdeletion when the nuchal translucency was > or = 3 mm. RESULTS: The prevalence of increased nuchal translucency > or = 2.5 mm was 180 (3.3%) and > or = 3.5 mm was 42 (0.8%). None of 75 fetuses with an increased nuchal translucency and normal karyotype demonstrated a 22q11 microdeletion on FISH analysis. In the same cohort, 3 of 20 (15%) cases of major congenital heart defects in which nuchal translucency was measured, had a nuchal translucency measurement > or = 2.5 mm. CONCLUSIONS: Routine FISH analysis for chromosome 22q11 microdeletions at the time of chorionic villus sampling for increased first-trimester nuchal translucency is of limited value. As a significant proportion of fetuses with increased nuchal translucency will be found to have congenital heart defects later in the pregnancy, FISH analysis for chromosome 22q11 microdeletions can be targeted to fetuses with specific congenital heart defects. Tissue from the chorionic villus sampling should therefore be stored for subsequent analysis, until after detailed echocardiography is performed.

Adolescent↗

PubMed2000

Increased formation and decreased resorption of bone in mice with elevated vitamin D receptor in mature cells of the osteoblastic lineage.

The microarchitecture of bone is regulated by complex interactions between the bone-forming and resorbing cells, and several compounds regulate both actions. For example, vitamin D, which is required for bone mineralization, also stimulates bone resorption. Transgenic mice overexpressing the vitamin D receptor solely in mature cells of the osteoblastic bone-forming lineage were generated to test the potential therapeutic value of shifting the balance of vitamin D activity in favor of bone formation. Cortical bone was 5% wider and 15% stronger in these mice due to a doubling of periosteal mineral apposition rate without altered body weight or calcium homeostatic hormone levels. A 20% increase in trabecular bone volume in transgenic vertebrae was also observed, unexpectedly associated with a 30% reduction in resorption surface rather than greater bone formation. These findings indicate anabolic vitamin D activity in bone and identify a previously unknown pathway from mature osteoblastic cells to inhibit osteoclastic bone resorption, counterbalancing the known stimulatory action through immature osteoblastic cells. A therapeutic approach that both stimulates cortical anabolic and inhibits trabecular resorptive pathways would be ideal for treatment of osteoporosis and other osteopenic disorders.

Animals↗

PubMed1999

The associations of bone mineral density and bone turnover markers with osteoarthritis of the hand and knee in pre- and perimenopausal women.

OBJECTIVE: To determine whether Caucasian women ages 28-48 years with newly defined osteoarthritis (OA) would have greater bone mineral density (BMD) and less bone turnover over time than would women without OA. METHODS: Data were derived from the longitudinal Michigan Bone Health Study. Period prevalence and 3-year incidence of OA were based on radiographs of the dominant hand and both knees, scored with the Kellgren/Lawrence (K/L) scale. OA scores were related to BMD, which was measured by dual-energy x-ray absorptiometry, and to serum osteocalcin levels, which were measured by radioimmunoassay. RESULTS: The period prevalence of OA (K/L grade > or =2 in the knees or the dominant hand) was 15.3% (92 of 601), with 8.7% for the knees and 6.7% for the hand. The 3-year incidence of knee OA was 1.9% (9 of 482) and of hand OA was 3.3% (16 of 482). Women with incident knee OA had greater average BMD (z-scores 0.3-0.8 higher for the 3 BMD sites) than women without knee OA (P < 0.04 at the femoral neck). Women with incident knee OA had less change in their average BMD z-scores over the 3-year study period. Average BMD z-scores for women with prevalent knee OA were greater (0.4-0.7 higher) than for women without knee OA (P < 0.002 at all sites). There was no difference in average BMD z-scores or their change in women with and without hand OA. Average serum osteocalcin levels were lower in incident cases of hand OA (>60%; P = 0.02) or knee OA (20%; P not significant). The average change in absolute serum osteocalcin levels was not as great in women with incident hand OA or knee OA as in women without OA (P < 0.02 and P < 0.05, respectively). CONCLUSION: Women with radiographically defined knee OA have greater BMD than do women without knee OA and are less likely to lose that higher level of BMD. There was less bone turnover among women with hand OA and/or knee OA. These findings suggest that bone-forming cells might show a differential response in OA of the hand and knee, and may suggest a different pathogenesis of hand OA and knee OA.

Adult↗

PubMed1999

Trends in hospitalization and mortality from rotavirus disease in New Zealand infants.

BACKGROUND: Rotavirus illness is associated with significant morbidity and mortality worldwide. We have examined trends in diarrheal disease in New Zealand children to determine the disease burden attributable to rotavirus and to estimate the proportion of hospitalizations preventable by vaccination. METHODS: Hospital admissions data and laboratory records for 1994 to 1996, were obtained for children 0 to 4 years at four sites (serving -60% of the New Zealand population). Rotavirus disease burden was estimated using combined admissions and laboratory data. Severity of disease was estimated in a sample of 150 hospitalizations for rotavirus diarrhea, and the proportion of vaccine-preventable admissions was extrapolated. Mortality attributed to diarrheal causes was determined from national records for 1974 to 1993. RESULTS: Between 1994 and 1996, 4436 children <5 years of age were hospitalized with diarrhea (1047/100000 children per year). Admissions associated with rotavirus were estimated at 1522 to 1535 (315 to 362/100000 annually). Infants between 6 and 17 months were most commonly affected (42% of all cases). More male children than female children were hospitalized (P < 0.001) and mean length of stay was calculated as 1.51 days (SD 2.35). Disease severity scoring revealed that 61.3 and 38.0% of admissions reviewed were severe and very severe, respectively. Deaths from diarrheal causes numbered 138 among children 0 to 4 years old for the 20-year period 1974 to 1993, with 18 deaths occurring between 1984 and 1993 (10 years). CONCLUSION: Current vaccines control severe disease, suggesting that 72% of cases reviewed would be eligible for prevention. A full cost effectiveness analysis is required to demonstrate anticipated benefits of vaccination.

Child, Preschool↗

PubMed1999

Helicobacter pylori treatment and antibiotic susceptibility: results of a five-year audit.

BACKGROUND: Helicobacter pylori eradication treatment has been a rapidly evolving field. Audit of treatment results provides reassurance that trial data can be translated into routine clinical practice. METHODS: Data were collected prospectively over five years. Patients were given four different treatment regimens over the audit period 'standard' triple therapy, two types of clarithromycin-based treatment or ranitidine, amoxycillin and metronidazole. Eradication was proven by a urea breath test at least four weeks after completing treatment. RESULTS: Eradication treatment for H. pylori was given to 665 patients; 89% had follow-up data. H. pylori eradication was significantly associated with treatment type (p<0.0001) and smoking (p=0.04) by univariate analysis, but was not associated with sex, age, alcohol consumption, endoscopic diagnosis, recent treatment with anti-secretory drugs or NSAIDs. By logistic regression analysis, only treatment type was significant (p=0.0001). H. pylori culture and sensitivities were available for 255 patients. Metronidazole resistance was shown for 84 isolates (32%) and clarithromycin resistance for 18 isolates (6.8%). Metronidazole resistance was significantly associated with younger age (p=0.02), ethnicity (p=0.02), female sex (p=0.02), and year of endoscopy (p=0.04), but was not associated with clarithromycin resistance. Clarithromycin resistance was not associated with age, sex, or ethnicity. Metronidazole resistance significantly affected H. pylori eradication for regimens containing metronidazole without clarithromycin. Eradication with metronidazole without clarithromycin was achieved in 90% of sensitive strains but only 55% of resistant strains (p<0.001). Metronidazole resistance was not significantly associated with treatment failure when metronidazole was combined with clarithromycin. Eradication with metronidazole and clarithromycin was achieved in 86% of sensitive strains and 78% of resistant strains (p=0.42). CONCLUSION: Treatment type and antibiotic susceptibility are the most important determinants of treatment success.

Adolescent↗

PubMed1999

Genetic markers, bone mineral density, and serum osteocalcin levels.

We evaluated five genetic markers for products that contribute to skeletal mineralization including the Sp1 polymorphism for type I collagen Ai (COLIA1), the vitamin D receptor (VDR) translation initiation site polymorphism, the promoter of the osteocalcin gene containing a C/T polymorphism, the estrogen receptor (ER) gene containing a TA repeat, and the polymorphic (AGC)n site in the androgen receptor. These markers were evaluated for their potential relationship with bone mineral density (BMD), measured by dual-energy X-ray densitometry, or its 3-year change. Additionally, potential associations of these genotypes and with baseline osteocalcin concentration or its 3-year change (assessed using radioimmunoassay) were evaluated. The study was conducted in 261 pre- and perimenopausal women of the Michigan Bone Health Study, a population-based longitudinal study of musculoskeletal characteristics and diseases. The polymorphic (AGC)n site in the androgen receptor showed a strong association with BMD of the femoral neck (FN) and lumbar spine and remained highly significant after adjusting for body mass index (BMI), oophorectomy/hysterectomy, oral contraceptive (OC) use and hormone replacement use (p < 0.001). The TA repeat at the 5' end of the ER gene was associated with total body calcium (p < 0.05) after adjusting for BMI, oophorectomy and hysterectomy, and OC use. The frequency of oophorectomy and hysterectomy within selected genotypes explained much of the statistically significant association of the ER genotypes with BMD of the FN and spine. There was no association of measures of BMD or bone turnover with the Sp1 polymorphism for COLIA1, the VDR translation initiation site polymorphism, or the C/T promoter polymorphism of the osteocalcin gene. These findings suggest that sex hormone genes may be important contributors to the variation in BMD among pre- and perimenopausal women.

Adult↗

PubMed1999

Vitamin D vs broad spectrum phototherapy in the treatment of seasonal affective disorder.

Seasonal Affective Disorder (SAD) is prevalent when vitamin D stores are typically low. Broad-spectrum light therapy includes wavelengths between 280-320 nm which allow the skin to produce vitamin D. This study was designed to test the hypothesis that vitamin D deficiency might play a role in SAD. A prospective, randomized controlled trial was conducted in a group of 15 subjects with SAD. Eight subjects received 100,000 I.U. of vitamin D and seven subjects received phototherapy. At the onset of treatment and after 1 month of therapy subjects were administered the Hamilton Depression scale, the SIGH-SAD, and the SAD-8 depression scale. All subjects also had serum levels of 25-hydroxyvitamin D (25-OH D) measured before and 1 week after intervention therapy. All subjects receiving vitamin D improved in all outcome measures. The phototherapy group showed no significant change in depression scale measures. Vitamin D status improved in both groups (74% vitamin D group, p < 0.005 and 36% phototherapy group, p < 0.01). Improvement in 25-OH D was significantly associated with improvement in depression scale scores (r2=0.26; p=0.05). Vitamin D may be an important treatment for SAD. Further studies will be necessary to confirm these findings.

Adolescent↗

PubMed1997

Increased serum 1,25-dihydroxyvitamin D after growth hormone administration is not parathyroid hormone-mediated.

To assess the effects of growth hormone (GH) on serum 1,25-dihydroxyvitamin D [1,25(OH)2D], we performed the following prospective crossover study in six healthy, young, adult, white men. During each of two admissions for 2 1/2 days to a general clinical research center, subjects were placed on a daily dietary calcium intake of 400 mg. Serum calcium, phosphorus, 1,25(OH)2D, immunoreactive intact parathyroid hormone (PTH), insulin-like growth factor I (IGF-I), IGF binding protein 3 (IGFBP3), tubular reabsorption of phosphate (TMP/GFR) were measured. Recombinant human GH (rhGH, Humatrope) (25 microg/kg/day subcutaneously for 1 week) was administered prior to and during one of the admissions. Results are expressed as mean +/- SEM. Whereas serum 1,25(OH)2D (58.9 +/- 7.7 versus 51.6 +/- 7.4 pg/ml, P< 0.01), serum phosphorus (4.5 +/- 0.1 versus 3.7 +/- 0.1 mg/dl, P < 0.01), TRP (92.0 +/- 0.5 versus 87.8 +/- 0.7 mg/dl, P < 0.005), TMP/GFR (4.6 +/- 0.1 versus 3.5 +/- 0.2, P < 0.005), and urinary calcium (602 +/- 49 versus 346 +/- 25 mg/day, P < 0.001) increased significantly, serum PTH decreased significantly (19.9 +/- 1.9 versus 26.8 +/- 4.0 pg/ml, P < 0.05) and serum calcium did not change when subjects received rhGH. These findings indicate that in humans, GH affects serum 1,25(oh)2D independently of circulating PTH and that this effect is mediated by IGF-I. We propose, therefore, that one potential mechanism by which GH stimulates increases in bone mass is via modest increases in serum 1,25(OH)2D.

Adult↗

PubMed1997

Serum levels of vitamin D metabolites and the subsequent risk of colon and rectal cancer in Finnish men.

Experimental and human epidemiologic data suggest a protective role for vitamin D in large bowel cancer. To investigate this association, we conducted a nested case-control study within a Finnish clinical trial cohort. Cases (n = 146) were participants diagnosed with primary adenocarcinoma of the large bowel. Controls were matched (2:1) to cases on age, date of baseline blood draw, and study clinic. Prediagnostic serum levels of the vitamin D metabolites, 25-hydroxyvitamin D (25-OH D), and 1,25-dihydroxyvitamin D (1,25-DIOH D) were used as primary exposure measures. The baseline geometric-mean serum level of 25-OH D was 11.6 percent lower in cases than in controls (12.2 cf 13.8 ug/l, P = 0.01) while serum levels of 1,25-DIOH D did not differ by case-control status. No association was seen between serum levels of 1,25-DIOH D and large bowel cancer risk. However, the estimated relative risk (RR) of large bowel cancer decreased with increasing level of serum 25-OH D and the association was more pronounced for rectal cancer (55 cases; RR by quartile = 1.00, 0.93, 0.77, 0.37; trend P = 0.06). Neither exclusion of early cases nor multivariate adjustment for potential confounders materially altered these estimates. There was no evidence of effect modification by level of 1,25-dihydroxyvitamin D or with other known risk-factors for large bowel cancer.

Adenocarcinoma↗

PubMed1997

Evidence of increased cholecalciferol requirement in chicks with tibial dyschondroplasia.

A series of experiments was conducted to test the hypothesis that vitamin D utilization may not be as efficient in chicks with tibial dyschondroplasia (TD). The basal diet contained 1.0% Ca and 0.45% available P with no supplemental cholecalciferol (D3). Chicks from low TD (LTD) and high TD (HTD) selected lines were fed diets supplemented with various levels of vitamin D compounds and examined for rickets and TD. When chicks were fed a D3-deficient diet containing only 1.25 micrograms/kg added D3, HTD chicks had a greater incidence of severe rickets than LTD chicks (P < 0.05). The LTD chicks did not exhibit TD when fed a diet containing adequate (20 micrograms/kg) D3. The LTD chicks fed a diet supplemented with 5 micrograms/kg D3, however, had 22% incidence of TD. When HTD chicks were fed diets supplemented with 5 micrograms/kg D3 [control diet that meets NRC (1994) requirement for D3], 20 micrograms/kg D3, 5 micrograms/kg 1,25-dihydroxycholecalciferol [1,25-(OH)2D3] or the combination of both D3 (20 micrograms/kg) and 1,25-(OH)2D3 (5 micrograms/ kg), TD incidence was highest in HTD chicks fed the control diet. When HTD chicks were fed diets with an increased dietary level of 1,25-(OH)2D3 (10 micrograms/kg) further reduction of TD incidence (P < 0.05) occurred. A potentially toxic level (Soares et al., 1983) of 1,25-(OH)2D3 (15 micrograms/kg) fed to HTD chicks resulted in still greater suppression of incidence of TD even though growth and feed intake in HTD chicks was greater than those of LTD chicks. It is concluded that the development of TD in HTD chicks is associated with subnormal ability to metabolize vitamin D.

Animals↗

PubMed1996

An audit of low dose triple therapy for eradication of Helicobacter pylori.

AIMS: Standard triple therapy remains the recommended first line treatment for Helicobacter pylori in New Zealand. The real eradication rate achieved in busy hospital clinics may be different from data obtained from clinical trials outside of New Zealand. METHODS: One hundred and thirty patients with proven H pylori infection (by at least two tests) were treated with low dose triple therapy (DeNol 1 qid, tetracycline 250 mg qid and metronidazole 200 mg qid for 2 weeks; dosing with meals and at night); 83 were given a standard prescription for triple therapy (dispensed in bottles) and 47 were given a medication pack with times of dosing clearly marked. Eradication was proven by a negative 13C urea breath test at least 4 weeks after finishing treatment. RESULTS: Follow up urea breath test was obtained in 120 patients (92%). The eradication rate for separate bottles was 79% and for the medication pack 76%. Compliance was estimated to be greater than 90% in 92% of patients who attended for followup. H pylori culture and sensitivity results were available for 41 patients. Overall rate of metronidazole resistance was 32%. The eradication rate for metronidazole sensitive strains was 89% and for resistant strains 46%. Mild side effects were reported in 10% and moderate side effects in 10%. No patient stopped treatment because of side effects. There was no effect of age, ethnicity, smoking, alcohol intake, pretreatment with H2-antagonists or endoscopic diagnoses on eradication rates. CONCLUSION: The low dose triple therapy has an acceptable real eradication rate. The most important determinant of success was metronidazole resistance. The eradication rate was not improved by using medication packs.

Adult↗

PubMed1995

Mutational analysis of the double-stranded RNA (dsRNA) binding domain of the dsRNA-activated protein kinase, PKR.

The interferon-induced, double-stranded RNA (dsRNA)-dependent protein kinase, PKR, is an inhibitor of translation and has antiviral, antiproliferative, and antitumor properties. Previously, the dsRNA binding domain had been located within the N-terminal region of PKR and subsequently shown to include two nearly identical domains comprising residues 55-75 and 145-166. We have undertaken both random and site-directed, alanine-scanning mutagenesis in order to investigate the contribution of individual amino acids within these domains to dsRNA binding. Here we identify 2 residues that were absolutely required for dsRNA binding, glycine 57 and lysine 60. Mutation of 2 other residues within the domain (lysine 64 and leucine 75) resulted in less than 10% binding (compared to wild type). We have also identified a number of other residues that influence dsRNA binding to varying degrees. Mutants that were unable to bind dsRNA were not active in vitro and possessed no antiproliferative activity in vivo. However, dsRNA binding mutants were partially transdominant over wild type PKR in mammalian cells, suggesting that binding of dsRNA activator is not the mechanism responsible for the phenotype of PKR mutants.

3T3 Cells↗

PubMed1995

Effect of growth hormone on bone: bone mineral density, trabecular bone volume, and alkaline phosphatase improve or are restored in the dwarf rat treated with growth hormone.

Studies were performed to determine whether serum total alkaline phosphatase (SAP), an index of bone formation; body weight; total body bone mineral density (BMD), measured by dual-energy X-ray absorptiometry; and tibial trabecular bone volume (TBV), measured by histomorphometry, are reduced in 2-week-old female sexually immature Lewis dwarf (dw/dw) rats (DW-CT, n = 9) with isolated growth hormone (GH) deficiency and, if so, whether recombinant human GH (rhGH), 200 micrograms/day subcutaneously for 4 weeks (DW-GH, n = 7), restores them. Studies were also performed to determine if 30% dietary restriction in 2-week-old female Lewis rats (LW-DR, n = 11) alters SAP, body weight, total BMD, or TBV compared with pair-fed controls (LW-CT, n = 7) given an ad libitum diet. Mean SAP (91 +/- 5 versus 109 +/- 5 U/l), body weight (102 +/- 11 versus 140 +/- 10 g), total BMD (88.5 +/- 0.3 versus 101.4 +/- 2.0 mg/cm2), and TBV (19.0 +/- 1.0 versus 27.0 +/- 1.4%) were significantly lower in DW-CT than in LW-CT animals, p < 0.05. In DW-GH, rhGH significantly increased mean SAP (130 +/- 7 U/l), body weight (133 +/- 10 g), total BMD (92.7 +/- 1.3), and TBV (24.0 +/- 1.9) compared with DW-CT animals. Compared with LW-CT rats, mean body weight and TBV were not different, but mean SAP was significantly higher (p < 0.01) and mean total BMD was significantly lower (p < 0.003) in DW-GH rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorptiometry, Photon↗