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Biomedical subjects

J Warner

Publications and source records attributed to J Warner.

At least 37 records · Page 2Linked to original sources
PubMed2001

The correlation between colposcopically directed cervical biopsy and loop electrosurgical excision procedure pathology and the effect of time on that agreement.

OBJECTIVE: The goal of this study was to evaluate whether colposcopically directed cervical biopsy accurately predicts histopathology found on loop electrosurgical excision procedure specimen and to assess whether this correlation was affected by a delay in treatment of greater than 12 weeks. METHODS: A retrospective review was performed of all cervical biopsy and loop electrosurgical excision procedure pairs performed at University of Arizona Medical Center between March 1992 and March 2000. Agreement was assessed by kappa statistics and Spearman rho coefficients. A subgroup analysis was performed to assess the effect of a delay greater than 12 weeks between cervical biopsy and loop excision on the histopathologic correlation. RESULTS: An 84% agreement was found between cervical biopsy histopathology and loop electrosurgical excision procedure histopathology when compared to within 1 degree (kappa = 0.78, P < 0.0001; Spearman rho = 0.40, P < 0.0001). This agreement remained strong (87%) even when loop electrosurgical excision procedure was delayed greater than 12 weeks (kappa = 0.81, P = 0.01). CONCLUSION: Colposcopically directed cervical biopsy correlated strongly with loop specimen histopathology. A delay in loop electrosurgical excision procedure greater than 12 weeks does not negatively affect this correlation. This delay of 12 weeks may be used safely in the future to test chemotherapeutic dysplasia treatments.

Adolescent↗
PubMed2001

Burkholderia pseudomallei virulence: definition, stability and association with clonality.

Clinical presentations of melioidosis, caused by Burkholderia pseudomallei are protean, but the mechanisms underlying development of the different forms of disease remain poorly understood. In murine melioidosis, the level of virulence of B. pseudomallei is important in disease pathogenesis and progression. In this study, we used B. pseudomallei-susceptible BALB/c mice to determine the virulence of a library of clinical and environmental B. pseudomallei isolates from Australia and Papua New Guinea. Among 42 non-arabinose-assimilating (ara(-)) isolates, LD(50) ranged from 10 to > 10(6) CFU. There were numerous correlations between virulence and disease presentation in patients; however, this was not a consistent observation. Virulence did not correlate with isolate origin (i.e. clinical vs environmental), since numerous ara(-) environmental isolates were highly virulent. The least virulent isolate was a soil isolate from Papua New Guinea, which was arabinose assimilating (ara(+)). Stability of B. pseudomallei virulence was investigated by in vivo passage of isolates through mice and repetitive in vitro subculture. Virulence increased following in vivo exposure in only one of eight isolates tested. In vitro subculture on ferric citrate-containing medium caused attenuation of virulence, and this correlated with changes in colony morphology. Pulsed-field gel electrophoresis and randomly amplified polymorphic DNA typing demonstrated that selected epidemiologically related isolates that had variable clinical outcomes and different in vivo virulence were clonal strains. No molecular changes were observed in isolates after in vivo or in vitro exposure despite changes in virulence. These results indicate that virulence of selected B. pseudomallei isolates is variable, being dependent on factors such as iron bioavailability. They also support the importance of other variables such as inoculum size and host risk factors in determining the clinical severity of melioidosis.

Animals↗
PubMed2001

Can parents accurately perceive hyperactivity in their child?

In all, 1872 children were recruited as part of a larger study concerning food additives and behaviours in preschool children. This figure represented 70% of the whole population of 3 1/4 -year-old children resident on the Isle of Wight, UK. Parents completed an assessment concerning their perceptions of their child's behaviour. The results of this assessment were compared with scores on two validated parental questionnaires, the Weiss Werry Peters (WWP) hyperactivity scale and the Emotionality, Activity and Sociability Temperament Questionnaire (EAS), which were used to assess hyperactivity. The accuracy of parents in perceiving hyperactivity in their children was found to be around 50% if the child was hyperactive, and 89% if the child was not hyperactive. The implications of these findings for services are discussed. Frequencies of potential risk groups for future Attention Deficit Hyperactivity Disorder (ADHD) and Conduct Disorder were also suggested.

Child Behavior↗
PubMed2001

Aortic dissection after angioplasty and stenting of an aortic coarctation: detection by intravascular ultrasonography but not transesophageal echocardiography.

In this case report, an iatrogenic dissection of the descending aorta occurred during balloon angioplasty and stenting of a recurrent coarctation. The dissection was not seen by transesophageal echocardiography, but intravascular ultrasonography, performed routinely during such procedures at this institution, identified the dissection and guided further therapeutic stent placement.

Adult↗
PubMed2001

The relationship between age and fever magnitude.

BACKGROUND: Infections are an important cause of morbidity and mortality in older people; however, they are often difficult to diagnose because the signs and symptoms of infection in older people are frequently atypical. Fever, one of the most important signs of infection, is a case in point. Preliminary evidence suggests that the febrile response in older persons is blunted, leading to the clinical maxim, "the older, the colder." The objective of this study was to assess the effect of age on the febrile response to moderate-to-severe pneumonia in hospitalized patients adjusted for the effect of anatomic site at which the temperature was measured. METHODS: This is a retrospective cohort study of 320 hospitalized patients with moderate-to-severe pneumonia. The study was designed to assess the effect of age on the febrile response to moderate-to-severe pneumonia in hospitalized patients, adjusting for the effect of the anatomic location of the temperature measurement. The highest temperature of each day and the anatomic sites at which temperatures were taken (axillary, oral, rectal, or other) on days 1 and 2 of infection and at hospital discharge. Baseline demographic information, including age, were obtained for each patient. RESULTS: There were 320 patients (median age, 64 years; range, 18-97 years). Using a linear regression model, significant inverse correlations were found between age and the temperature for patients on the first and second days of hospitalization (P < 0.001). For each decade increase in age, the average temperature on the first 3 days of infection was lower by 0.15 degrees C. Temperature at discharge, a surrogate for baseline temperature, also decreased at an equal rate with age. CONCLUSION: In this study, the febrile response to infections was reduced with increasing age and baseline temperatures were generally lower in older patients.

Adult↗
PubMed2001

Divining dementia.

Explore the source record for details and available documents.

Age Distribution↗
PubMed2001

Evaluating the use of benzodiazepines following recent bereavement.

BACKGROUND: There is no evidence to support current advice not to use benzodiazepines after bereavement. AIMS: To determine the role of benzodiazepines in the management of bereavement. METHOD: We conducted a randomised, double-blind, placebo-controlled evaluation of the use of diazepam after recent bereavement. Participants were randomised to either 2 mg diazepam or identically packaged placebo up to three times daily. The primary outcome measure was the Bereavement Phenomenology Questionnaire. RESULTS: Thirty subjects were randomised. No evidence was found of an effect of benzodiazepines on the course of the first 6 months of bereavement (estimated mean difference of combined follow-up assessments=0.3 in favour of placebo; 95% Cl - 6.2 to +6.7). CONCLUSION: We found no evidence of a positive or negative effect of benzodiazepines on the course of bereavement.

Aged↗
PubMed2001

Molecular effects of novel mutations in Hesx1/HESX1 associated with human pituitary disorders.

The homeobox gene Hesx1/HESX1 has been implicated in the establishment of anterior pattern in the central nervous system (CNS) in a number of vertebrate species. Its role in pituitary development has been documented through loss-of-function studies in the mouse. A homozygous missense point mutation resulting in a single amino acid substitution, Arg160Cys (R160C), is associated with a heritable form of the human condition of septo-optic dysplasia (SOD). We have examined the phenotype of affected members in this pedigree in more detail and demonstrate for the first time a genetic basis for midline defects associated with an undescended or ectopic posterior pituitary. A similar structural pituitary abnormality was observed in a second patient heterozygous for another mutation in HESX1, Ser170Leu (S170L). Association of S170L with a pituitary phenotype may be a direct consequence of the HESX1 mutation since S170L is also associated with a dominant familial form of pituitary disease. However, a third mutation in HESX1, Asn125Ser (N125S), occurs at a high frequency in the Afro-Caribbean population and may therefore reflect a population-specific polymorphism. To investigate the molecular basis for these clinical phenotypes, we have examined the impact of these mutations on the regulatory functions of HESX1. We show that Hesx1 is a promoter-specific transcriptional repressor with a minimal 36 amino acid repression domain which can mediate promoter-specific repression by suppressing the activity of homeodomain-containing activator proteins. Mutations in HESX1 associated with pituitary disease appear to modulate the DNA-binding affinity of HESX1 rather than its transcriptional activity. Wild-type HESX1 binds a dimeric homeodomain site with high affinity (K(d) 31 nM) whilst HESX1(S170L) binds with a 5-fold lower activity (K(d) 150 nM) and HESX1(R160C) does not bind at all. Although HESX1(R160C) has only been shown to be associated with the SOD phenotype in children homozygous for the mutation, HESX1(R160C) can inhibit DNA binding by wild-type HESX1 both in vitro and in vivo in cell culture. This dominant negative activity of HESX1(R160C) is mediated by the Hesx1 repression domain, supporting the idea that the repression domain is implicated in interactions between homeodomain proteins. Our data suggest a possible molecular paradigm for the dominant inheritance observed in some pituitary disorders.

Animals↗
PubMed2001

An open-label acceptability study of Norditropin SimpleXx--a new liquid growth hormone formulation.

A new liquid formulation of hGH (Norditropin SimpleXx) has been developed to avoid the need for reconstitution before administration. In addition, the liquid GH formulation has been combined with an advanced pen delivery system, either with or without a needle auto-insertion mechanism. This study was designed to assess the acceptability of the new system compared with the patient's previous system. A total of 103 children with GH deficiency received a daily injection of Norditropin liquid GH for 12 weeks with a choice of a pen/auto-insertion system. Acceptability was determined by nurse-supervised questionnaires administered to the patients and parents. Following treatment, 94% of patients preferred the Norditropin liquid GH system. This preference was irrespective of the previous system in use, patient age or length of GH therapy. More patients found it the less painful system (50% vs 13%), 92% of patients found it more convenient, and the formulation was well tolerated. In conclusion, Norditropin liquid GH was very well accepted and preferred by the majority of patients. It avoided reconstitution which had been a major cause of dissatisfaction with the patients' previous systems, and resulted in greater convenience and reduced levels of pain associated with injection.

Adolescent↗
PubMed2001

Can legislation prevent debauchery? Mother gin and public health in 18th-century England.

The "gin epidemic" of 1720 to 1751 in England was the first time that government intervened in a systematic fashion to regulate and control sales of alcohol. The epidemic therefore provides an opportunity to gauge the effects of multiple legislative interventions over time. Toward that end, we employed time series analysis in conjunction with qualitative methodologies to test the interplay of multiple independent variables, including real wages and taxes, on the consumption of distilled spirits from 1700 through 1771. The results showed that each of the 3 major gin acts was successful in the short term only, consistent with the state's limited resources for enforcement at the local level, and that in each instance consumption actually increased shortly thereafter. This was true even of the Gin Act of 1751, which, contrary to the assumptions of contemporaries and many historians, succeeded by accident rather than by design. The results also suggest that the epidemic followed the inverse U-shaped trajectory of more recent drug scares and that consumption declined only after the more deleterious effects of distilled spirits had been experienced by large numbers of people.

Alcohol Drinking↗
PubMed2001

Multiple lysosomal trafficking phenotypes in metastatic mouse mammary tumor cell lines.

Although altered synthesis and trafficking of lysosomal proteins and their receptors are associated with a wide range of human and rodent malignancies, the basis for their involvement remains obscure. Here we describe findings on a set of mouse mammary tumor cell lines that we are using as a model to study the role of these proteins in oncogenesis and tumor progression. Three distinct proteinase-secreting phenotypes were identified among the metastatic cell lines of the set. Two phenotypes displayed a high level of secretion of cathepsin L and the third was characterized by elevated secretion of matrix metalloproteinase 9 (MMP-9). The two cathepsin L-secreting phenotypes were distinct in that they displayed differences in cathepsin trafficking, expression of mannose 6-phosphate/insulin-like growth factor receptor and expression of proliferin, a mannose-phosphorylated angiogenic factor. Although cells representing all three phenotypes are capable of dissemination to distant organs when implanted into mouse mammary glands, only cells with the MMP-9 phenotype were found to be capable of direct intravasation. These findings indicate that multiple proteinase-secreting phenotypes can arise from the same tumor and suggest that cathepsin L and other lysosomal proteins may play a role in dissemination of tumor cells via the lymphatic system.

Animals↗
PubMed2001

Moxifloxacin versus amoxicillin clavulanate in the treatment of acute maxillary sinusitis: a primary care experience.

In this prospective, multicentre, randomised, non-blinded phase III clinical trial, 475 adult patients with acute sinusitis received a 10-day oral regimen of either moxifloxacin (400 mg once daily) or amoxicillin clavulanate (875 mg twice daily). The primary measure of efficacy was clinical resolution. Secondary outcome measures included clinical relapse at follow-up and evaluation of patient reported outcomes. Of 471 adults comprising the intent-to-treat population (234 moxifloxacin, 237 amoxicillin/clavulanate), moxifloxacin treatment was statistically equivalent to amoxicillin/clavulanate at the test-of-cure visit (85% vs 82%; 95% CI -6%, 13%). Analysis of the efficacy evaluable population, confirmed statistical equivalence (86% vs 84%; 95% CI -7%, 13%). Of note, by day 3 of treatment, significantly more moxifloxacin-treated patients (n = 47; 24%), than amoxicillin/clavulanate-treated patients (n = 28; 14%), reported feeling better (p < 0.02). Frequency of drug-related adverse events were similar between groups: nausea (11% moxifloxacin, 5% amoxicillin/clavulanate) and diarrhoea (3% moxifloxacin, 10% amoxicillin clavulanate). In conclusion, once-daily moxifloxacin is as effective and safe as twice-daily amoxicillin/clavulanate in the treatment of acute sinusitis. Moxifloxacin is associated with more rapid symptomatic relief.

Acute Disease↗
PubMed2001

Randomized comparative study of 3 versus 8-month neoadjuvant hormonal therapy before radical prostatectomy: biochemical and pathological effects.

PURPOSE: A prospective phase 3 trial was initiated to determine whether 8 compared with 3-month neoadjuvant hormonal therapy reduces prostate specific antigen (PSA) recurrence rates after radical prostatectomy. Our interim analysis includes secondary end points of differences in biochemistry, pathology and adverse events between the 2 groups. MATERIALS AND METHODS: Men with clinically confined prostate cancer were randomized to receive 7.5 mg. leuprolide intramuscularly monthly and 250 mg. flutamide orally 3 times daily for 3 or 8 months before radical prostatectomy. Our study was powered to detect a 35% decrease in PSA recurrence, assuming a 30% recurrence rate in the 3-month arm after 3 years. RESULTS: A total of 547 men were randomized between August 1995 and April 1998. Men in the 8 and 3-month groups were equally stratified for T stage (29% T1c, 70% T2), Gleason grade (68% less than 4, 32% 4 or greater) and pretreatment PSA (63% less than 10, 27% 10 to 20 and 10% greater than 20 microg./l.). Mean pretreatment PSA was slightly higher in the 8-month compared with the 3-month group (11.64 versus 9.95 microg./l., respectively, p = 0.0539). A total of 44 men withdrew from study before surgery and, therefore, were nonevaluable. Preoperative PSA nadir was less than 0.1 microg./l. in 43.3% versus 75.1% (p <0.0001), and 0.3 microg./l. or greater in 21% versus 9.2% after 3 versus 8 months, respectively (p <0.0006). Mean serum PSA decreased 98% to 0.12 microg./l. after 3 months, with a further 57% to 0.052 microg./l. from 3 to 8 months. Transrectal ultrasound determined that prostatic volume decreased 37% from a mean of 40.6 to 25.4 cc after 3-month neoadjuvant hormonal therapy (p = 0.0001) and a further 13% to 22.2 cc after 8 months (p = 0.03). Mean hemoglobin decreased 15% (148.2 to 125.4 gm./dl.) after 3-month neoadjuvant hormonal therapy but stabilized thereafter. Radical prostatectomy was completed in 500 men, while surgery was aborted intraoperatively in 3. Positive margin rates were significantly lower in the 8 than 3-month group (12% versus 23%, respectively, p = 0.0106). There were no fatal adverse events and no differences between the 2 groups in the severity or causality (p = 0.287, 0.0564) of adverse events, or incidence of increased liver enzymes or diarrhea (p = 0.691, 0.288, respectively). However, men in the 8-month group noticed a higher number of newly reported adverse events (4.5 versus 2.9, p <0.0001) and higher incidence of hot flushes than the 3-month group (87% versus 72%, respectively, p <0.0001). CONCLUSIONS: Ongoing biochemical and pathological regression of prostate tumors occurs between 3 and 8 months of neoadjuvant hormonal therapy, suggesting that the optimal duration of neoadjuvant hormonal therapy is longer than 3 months. Longer followup is needed to determine whether longer therapy alters PSA recurrence rates.

Androgen Antagonists↗