Biomedical subjects

A Davis

Publications and source records attributed to A Davis.

At least 19 recordsLinked to original sources

PubMed1992

Genetic manipulation of the mouse via gene targeting in embryonic stem cells.

Gene targeting applied to totipotent embryonic stem (ES) cells is a very powerful means of creating highly specific mutations of genes in the mouse. The successful application of this technology is however constrained by both the types of mutations that can be generated at a target locus and the ability to reconstruct a germline chimera from the manipulated cells. We have developed two cell lines that can be routinely transmitted through the germline of chimeras after cloning and prolonged selection in tissue culture. We have also established a variety of methods for generating non-selected mutations at the X-linked hprt locus in ES cells. Our observations at this locus have enabled us to generate successfully a subtle mutation at the non-selectable Hox-2.6 locus.

Animals↗

PubMed1992

Prepubertal initiation of sexual experiences and older first partner predict promiscuous sexual behavior of delinquent adolescent males--unrecognized child abuse?

Sexual experiences of 1580 delinquent adolescent males ages 9-19 years admitted to a juvenile detention center from January 1985 to July 1990 were determined through a structured health history interview. A total of 89.6% admitted to prior sexual activity; 26.8% claimed sexual experience by age 11 years. Only 3.2% reported sexual abuse or incest. Of 334 sexually active adolescents who revealed both age of their first partner and their age of first intercourse, 42% had their first experience with a female 2 or more years older. Males who had their first sexual experience before age 11 years or with a female 2 or more years older, reported significantly larger numbers of sexual partners in their lifetime and during the year preceding their incarceration. Girls with similar first sexual experiences in terms of age of initiation and age difference from partner are considered to be abused. Practitioners who work with children and adolescents need to recognize the possibility of sexual activity among pre-adolescent males and to be aware of its implications.

Adolescent↗

PubMed1992

Modifying the mouse: design and desire.

Genetic modification of endogenous genes in mice has become possible by applying gene targeting techniques to embryonic stem (ES) cells and using specific clones of cells to generate mice. Despite the experimental opportunities offered by the creation of organisms with specific genetic changes, there are considerable technical obstacles which can confound the routine implementation of this technology. This review addresses some recent advances in the ability to construct mice with a variety of genetic modifications. These include an increased understanding of the basic cell biology and in vitro growth characteristics of ES cells, which has facilitated germ line transmission of manipulated clones on a routine basis. The techniques that are used to isolate "targeted" clones of ES cells have been summarized, and the current status of strategies which have been successfully used to make very specific modifications of the genome are discussed.

Alleles↗

PubMed1992

A national model of faculty development in addiction medicine.

Increasing the number of faculty with expertise in addiction medicine is one of the challenges facing the medical community in the 1990s. To meet this challenge, the Society of Teachers of Family Medicine created a faculty development course to increase the expertise of family practice faculty involved in teaching residents. The authors describe the development, implementation, and consequences of the five-day intensive course that was taught to 165 participants at ten sites in 1990. The participants' self-reporting before and three months after the course showed significant increases in the numbers of participants who taught addiction medicine in eight of 11 clinical situations. The authors conclude that the course represents a model of faculty development in addiction medicine that is applicable to other specialties and health professions.

Evaluation Studies as Topic↗

PubMed1992

Coexpression of the simian immunodeficiency virus Env and Rev proteins by a recombinant human adenovirus host range mutant.

Recombinant human adenoviruses (Ads) that replicate in the intestinal tract offer a novel, yet practical, means of immunoprophylaxis against a wide variety of viral and bacterial pathogens. For some infectious agents such as human immunodeficiency virus (HIV), the potential for residual infectious material in vaccine preparations must be eliminated. Therefore, recombinant human Ads that express noninfectious HIV or other microbial proteins are attractive vaccine candidates. To test such an approach for HIV, we chose an experimental model of AIDS based on simian immunodeficiency virus (SIV) infection of macaques. Our data demonstrate that the SIV Env gene products are expressed in cultured cells after infection with a recombinant Ad containing both SIV env and rev genes. An E3 deletion vector derived from a mutant of human Ad serotype 5 that efficiently replicates in both human and monkey cells was used to bypass the usual host range restriction of Ad infection. In addition, we show that the SIV rev gene is properly spliced from a single SIV subgenomic DNA fragment and that the Rev protein is expressed in recombinant Ad-SIV-infected human as well as monkey cells. The expression of SIV gene products in suitable live Ad vectors provides an excellent system for studying the regulation of SIV gene expression in cultured cells and evaluating the immunogenicity and protective efficacy of SIV proteins in macaques.

Adenoviridae↗

PubMed1992

Faecal unconjugated bile acids in patients with colorectal cancer or polyps.

The unconjugated faecal bile acid profiles of 14 patients with colorectal cancer, nine patients with polyps and 10 controls were compared using gas liquid chromatography, controlling for such confounding variables as cholecystectomy, gall stones and hepatic function. Patients with adenomatous polyps had a higher concentration of faecal bile acids (5.23 mumol/g, 2.16-13.67 (median, range) v 1.96, 0.91-6.97; p = 0.016) lithocholic acid (2.41, 0.88-3.22 v 1.07, 0.38-2.03; p = 0.013) and total secondary bile acids (5.23, 2.16-13.4 v 1.96, 0.73-6.63; p = 0.02) compared with control subjects. Patients with colorectal cancer had an increased (p = 0.029) proportion of secondary faecal bile acids (mol%) compared with controls (100, 96.5-100 v 95.19, 81.73-100) and the ratios of the primary bile acids, cholic and chenodeoxycholic acid, to their respective derivatives (secondary bile acids) were significantly lower in cancer patients compared with control and patients with polyps (p = 0.034 to 0.004). This study lends further support to the theory that bile acids may play a role in the development of polyps and colorectal cancer.

Adenocarcinoma↗

PubMed1992

Improving resources for foster care.

The number of foster children and their psychological and medical morbidity are growing. To gain insight into how to recruit and retain foster homes, characteristics of 64 foster families were determined by interview. Foster parents had low-to-moderate incomes, were approaching middle age, had underutilized home space, and wanted more children. Most enjoyed foster care and planned to continue. Twenty-three percent of the 64 had half of all foster children in the study in their homes at interview and had cared for seven times as many children in the past, including 66% of all the teens and 83% of all the handicapped children who had been in the 64 homes. These "high providers" functioned like group homes for mentally handicapped individuals. Adapting the group-home concept to foster homes could improve care, especially for children with special needs.

Adult↗

PubMed1992

Fresh osteochondral allografts for post-traumatic defects in the knee. A survivorship analysis.

Fresh osteochondral allografts were used to repair post-traumatic osteoarticular defects in 92 knees. At the time of grafting, varus or valgus deformities were corrected by upper tibial or supracondylar femoral osteotomies. A survivorship analysis was performed in which failure was defined as the need for a revision operation or the persistence of the pre-operative symptoms. There was a 75% success rate at five years, 64% at ten years and 63% at 14 years. The failure rate was higher for bipolar grafts than for unipolar and the results in patients over the age of 60 years were poor. The outcome did not depend on the sex of the patient and the results of allografts in the medial and lateral compartments of the knee were similar. Careful patient selection, correction of joint malalignment by osteotomy, and rigid fixation of the graft are all mandatory requirements for success. We recommend this method for the treatment of post-traumatic osteochondral defects in the knees of relatively young and active patients.

Adolescent↗

PubMed1992

Clinical pure-tone versus three-interval forced-choice thresholds: effects of hearing level and age.

Hearing threshold levels were measured at 2 kHz using both a standard clinical procedure and a three-interval forced-choice procedure. The 240 subjects (aged 50-75 years) embraced both normal hearing and symmetrical sensorineural hearing impairment. The sample was carefully constructed to dissociate hearing threshold level from age, by oversampling the young impaired and the older normally hearing. The forced-choice threshold was found to be generally acuter than the clinical threshold. This was related to increasing severity of hearing loss at 1.7 dB per 10 dB HL and to age at 1.6 dB HL per 10 years. Hearing threshold accounted for 12% of the variance in the discrepancy between the two types of threshold, while age accounted for only 4% due to the narrow range used. After control for these thresholds and age, there were also significant associations with a self-estimate of hearing ability and with the neuroticism score from a personality questionnaire. When interpreting epidemiological findings, particularly in longitudinal studies, the separation between sensory and cognitive factors in threshold measures needs to be considered. The obtained discrepancies as a function of hearing level and age were applied to a statistical model for population prevalences for hearing impairment. The results suggested that the choice of method could have material effects on overall prevalence estimates and on the magnitude of the apparent age effect.

Age Factors↗

PubMed1992

Hearing impairments in middle age: the acceptability, benefit and cost of detection (ABCD).

The major epidemiological investigations of hearing impairment, disability and handicap show that the elderly are the group most disabled by their hearing impairment. There is considerable debate concerning the most efficient way of reducing this inevitable burden of age-related hearing impairments in the next generation. Early fitting of 'targeted' individuals with hearing aids may help but there are a large number of methodological problems associated with conducting and evaluating such a programme of research (especially retrospectively). The logical prerequisite to early fitting as a means of reducing later disability is to ascertain the acceptability of and benefit given by intervention at this early stage. This study therefore set out to investigate the age/sex register provided by the primary physician (GP) as an appropriate base to identify candidates for early aid fitting among a sample of middle-aged patients (50-65 years) living in Roath, Cardiff. Of the 662 who replied to an initial contact letter (1050 were on the age/sex register), 21 already possessed hearing aids. After screening and examination 66 people were offered some form of management which was accepted by 43 during the course of the study. Aid use thereby increased from about 3% to over 9% in this middle-aged group. A 2 year follow-up indicated continued use of the aids, and benefit on a speech reception task was measured. The cost of detecting those who might benefit was calculated using a two-question 'paper and pencil' screen as the first step. A national programme for Wales would cost at least 188,000 pounds per annum at 1990 prices over an initial 5 year span if a criterion which aimed to find at least 45 dB HTL impairments over mid-frequencies was implemented. For a criterion of 35 dB the cost would be 378,000 pounds pa.

Auditory Threshold↗

PubMed1992

The epidemiology of childhood hearing impairment: factor relevant to planning of services.

In the Nottingham District Health Authority we found that one in 943 babies born between 1983-1986 have a sensorineural or mixed hearing impairment (at 50 dB HL or greater in the better ear averaged over the frequencies 0.5, 1, 2, 4 kHz) that is either congenital or progressive in nature. If this figure is broken down between non-neonatal intensive care unit babies and neonatal intensive care unit (NICU) graduates, we find that one in 174 NICU graduates have a hearing impairment compared with one in 1278 non-NICU babies. Excluding from the non-NICU baby population those with a known family history of hearing impairment, and those with a known relevant syndrome at birth, there is a 10.2 to 1 odds ratio for babies in NICU to have such hearing impairments compared to this restricted 'normal' baby population. In addition NICU babies with a hearing impairment were considerably more likely to have another disability (odds ratio 8.7 to 1). Acquired sensorineural or mixed impairments comprised about 9% of the children with impairments by 3 years of age. Twenty per cent of the patients seen at the Children's Hearing Assessment Centre (CHAC) with better-ear impairment of 95 dB HL or greater had acquired hearing impairments. The mean age of referral for congenital hearing impairments was found to be a function of severity and NICU status. For children with better-ear hearing impairments of 80 dB HL or greater, the mean and median ages of referral were both 8 months (s.d. 4 months).

Audiometry, Pure-Tone↗

PubMed1992

Induction of cholangiocarcinoma in the Golden Syrian hamster using methylazoxymethyl acetate.

The Golden Syrian hamster, which has a bile acid profile similar to that of humans, is often used as an experimental model for cholangiocarcinoma. Unfortunately, most chemical carcinogens result in other tumour types also being induced which can be disadvantageous. In the present study, we describe the development of cholangiocarcinoma associated with precursor lesions of bile duct proliferation and dysplasia which occurred following a single i.v. dose of methylazoxymethyl acetate (10, 20 or 40 mg/kg body weight). Moreover, no other tumours were induced. This model may, therefore, prove useful in investigating the steps involved in the carcinogenesis of cholangiocarcinoma.

Adenoma, Bile Duct↗

PubMed1992

Selective population chemotherapy among schoolchildren in Beheira governorate: the UNICEF/Arab Republic of Egypt/WHO Schistosomiasis Control Project.

Selective population chemotherapy using a single dose of praziquantel (40 mg per kg body weight), which was offered to 29,365 schoolchildren in Abu El Matameer and 40,241 in Abo Homos districts, Beheira governorate in the Nile delta, reduced the prevalence of schistosomiasis from 75.4% to 40.9% (reduction of 45.8%) and from 80.5% to 30.8% (reduction of 61.7%), respectively. Of those with only S. mansoni infection, 10.6% before treatment and 1.7% one year later had more than 800 eggs per gram of faeces. The prevalence of S. haematobium in Abu El Matameer was reduced from 35.4% to 7.4% after a single treatment. Infections with both S. mansoni and S. haematobium were reduced by more than 90% after one year. These reductions in prevalence and intensity of schistosomiasis in the face of continuing transmission and water contact augur well for the future role of chemotherapy in control programmes.

Adult↗

PubMed1992

Dentin phosphoprotein gene locus is not associated with dentinogenesis imperfecta types II and III.

Dentinogenesis imperfecta (DGI) is an autosomal dominant inherited dental disease which affects dentin production and mineralization. Genetic linkage studies have been performed on several multigeneration informative kindreds. These studies determined linkage between DGI type II and III and group-specific component (vitamin D-binding protein). This gene locus has been localized to the long arm of human chromosome 4 in the region 4q11-q21. Although this disease has been mapped to chromosome 4, the defective gene product is yet to be determined. Biochemical studies have suggested abnormal levels of dentin phosphoprotein (DPP) associated with DGI type II. This highly acidic protein is the major noncollagenous component of dentin, being solely expressed by the ectomesenchymal derived odontoblast cells of the tooth. The purpose of the present study was to establish whether DPP is associated with DGI types II and III, by using molecular biology techniques. The strategy was to use a synthetic degenerative DPP oligonucleotide probe to map this sequence to the long arm of human chromosome 4, 4q13-q21, by using somatic cell hybrids. Our results indicated that DPP is not localized to any region of human chromosome 4, thus suggesting that the DPP gene is not directly associated with DGI type II or DGI type III. Our data do not exclude the possibility that other proteins associated with DPP posttranslational modifications might be responsible for this genetic disease.

Adult↗

PubMed1991

Advocacy. Necessary to achieve cancer control goals.

As resources become increasingly scarce, oncology professionals and consumers of oncology services are increasingly engaging in advocacy efforts to achieve goals in cancer control. Effective advocacy includes both legislative and direct educational efforts.

Aged↗

PubMed1991

Superiority of granisetron to dexamethasone plus prochlorperazine in the prevention of chemotherapy-induced emesis.

Trials of selective 5-hydroxytryptamine3 receptor antagonists have shown excellent antiemetic activity for chemotherapy containing cisplatin when compared with high-dose metoclopramide. There is little information about the efficacy of these new agents for chemotherapy other than for high-dose cisplatin. We performed a double-blind, randomized trial comparing a single dose of the 5-hydroxytryptamine3 receptor antagonist granisetron (BRL 43694A) as a single intravenous dose with dexamethasone plus prochlorperazine in 152 patients receiving their first course of moderately emetogenic chemotherapy (mainly doxorubicin- and cyclophosphamide-containing combinations). During the first 24 hours, there was a statistically significant advantage for the granisetron group in terms of the prevention of both nausea and emesis. There was no difference in the frequency of reported adverse events. We conclude that granisetron is more effective than dexamethasone plus prochlorperazine in patients who are receiving moderately emetogenic cytotoxic agents.

Antiemetics↗

PubMed1991

Effect of rimantadine on the immune response to influenza A infections.

The effects of rimantadine on lymphocyte responses to mitogens CON-A and PHA, natural killer cell activity, and the development of serum and local antibodies were studied during an epidemic outbreak of influenza A (H3N2). Twenty-three families consisting of 38 adults and 46 children had a member who developed a flu-like illness and were randomly assigned to receive placebo or rimantadine either as treatment or post exposure prophylaxis. Nasal washings for virus isolation and IgG and IgA determination were collected on days 1, 5, and 10 of illness. Blood samples for immunologic studies were obtained on days 1 and 5 of clinical illness and on day 21. No differences in lymphocyte responses to CON-A and PHA or in natural-killer cell activity were noted between placebo and rimantadine groups. The development of neutralizing antibodies to influenza H3N2 was also not affected by rimantadine. However, the presence of IgA in nasal secretions was significantly diminished in the rimantadine group compared to the placebo group (0/9 vs. 6/9, P less than 0.005). The findings indicate that rimantadine had no adverse affect on the systemic immune system. However, local immune response was diminished in individuals taking rimantadine possibly due to the presence of less immunogen resulting from reduction of virus in secretions of individuals taking antivirals.

Antibody Formation↗

PubMed1991

Functional outcome in patients treated with surgery and irradiation for soft tissue tumours.

One hundred five consecutive patients underwent surgical resection and adjuvant irradiation in treatment of soft tissue sarcoma or aggressive fibromatosis. All patients were entered in a prospective study evaluating functional outcome and 88 patients were examined at 12 months following surgery. Outcome was characterized using the Enneking system as well as documenting employment/recreational status and limb edema. Sixty-eight of 88 patients had functional scores of 21 or better (out of a possible total of 35). Forty-four patients were serially evaluated at 12 and 24 months and there was no difference in their outcome at the 2 time points. Univariate analysis demonstrated that large tumour size, postoperative complications, and neural sacrifice were associated with poor functional outcome.

Adolescent↗