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Biomedical subjects

J Hunter

Publications and source records attributed to J Hunter.

At least 91 records · Page 5Linked to original sources
PubMed1996

Crosstalk between the thyroid hormone and peroxisome proliferator-activated receptors in regulating peroxisome proliferator-responsive genes.

Peroxisome proliferators and thyroid hormones have overlapping metabolic effects and regulate a similar subset of genes involved in maintaining lipid homeostasis. Transcriptional activation by peroxisome proliferators is mediated by peroxisome proliferator-activated receptors (PPARs) that bind to specific peroxisome proliferator-response elements (PPREs) through heterodimerization with retinoid X receptors (RXRs). We examined the effect of thyroid hormone receptor alpha (TR alpha) on DNA binding in vitro and transcriptional activation in vivo by rat PPAR. Gel mobility shift assays using in vitro translated receptors demonstrated that TR alpha was capable of binding on its own and cooperatively with RXR alpha to the rat acyl-CoA oxidase PPRE and of inhibiting the binding of rat PPAR/RXR alpha heterodimers to this element. This inhibition was the result of competition between TR alpha and PPAR for limiting amounts of the heterodimerization partner RXR alpha and for binding to the PPRE. Interestingly, cotransfection of a TR alpha expression plasmid into mammalian cells resulted in potentiation of the peroxisome proliferator- and PPAR/RXR alpha-dependent transcriptional induction of a reporter gene containing the acyl-CoA oxidase PPRE. TR alpha therefore appears to cooperate with RXR and PPAR to positively modulate peroxisome proliferator-dependent transactivation in vivo. Our findings suggest that there is crosstalk between the thyroid hormone and peroxisome proliferator signaling pathways in the regulation of peroxisome proliferator-responsive genes.

Acyl-CoA Oxidase↗
PubMed1996

Frontonasal malformation and cloacal exstrophy: a previously unreported association.

We report on a child with frontonasal malformation (FNM) and cloacal exstrophy, a combination of findings that have not been reported previously. In FNM and cloacal exstrophy, associated malformations are rare. FNM and cloacal exstrophy both represent abnormalities of the development of the midline field; this combination of anomalies in this patient suggests an impairment of caudal and cranial midline development during blastogenesis.

Abnormalities, Multiple↗
PubMed1996

Teaching basic video skills as an aid in laparoscopic suturing.

BACKGROUND: There is a perception among surgeons that performing laparoscopic suturing is unduly difficult. The purpose of this study is to document a program which aides in learning laparoscopic suturing. METHODS: Fourteen volunteer medical students without prior experience were taught laparoscopic suturing. Videoscopic pelvitrainers were utilized for a 2-h training session. Extracorporeal and intracorporeal knot tying was demonstrated utilizing a three-throw square knot. After a 2-h practice session each student's time to complete an extracorporeal and intracorporeal suture was recorded. RESULTS: The average times required for completion were: extracorporeal suture and knot 1 min 54 s; intracorporeal suture and knot 3 min 12 s. CONCLUSIONS: Novice students were able to perform at extra and intracorporeal suturing with 2 h of practice, utilizing a systematic program of teaching basic video skills.

Humans↗
PubMed1996

Systematic literature review: outcome measures for child and adolescent mental health services.

BACKGROUND: Outcome measurement is an important component of health care service evaluation. The aim of this paper is to review child and adolescent mental health outcome measures and identify outcome measurement tools for use in routine clinical practice. METHOD: A systematic literature review was undertaken, using Medline and Psych Info and supplemented by correspondence with relevant institutions and authorities in the field. The review identifies potential specific outcome measurement tools. These tools are evaluated using the scientific criteria of validity and reliability, responsiveness to change, and appropriateness of each tool's format for use in routine clinical practice. RESULTS: Three broad categories of outcome are identified: population outcomes, specific outcome and performance indicators. Nineteen specific outcome measurement tools are short-listed and compared in detail. No single tool is suitable for use as a comprehensive outcome measurement tool in routine clinical practice. CONCLUSION: A combination of some of the tools short-listed will cover all the necessary outcome items. However, the increase in assessment time will reduce clinical usefulness. Further research is needed to modify or created appropriate outcome measurement tools for use in routine clinical practice.

Adolescent↗
PubMed1996

An experimental study of the effects of craniofacial growth on the long-term positional stability of microfixation.

Recent clinical reports have documented a potential problem associated with the use of microfixation in the growing craniofacial skeleton, i.e., the finding of microplates and microscrews within the endocranial cavity during repeat surgery. This animal experiment using Yorkshire pigs was designed to determine if this type of passive internal displacement could be demonstrated in an animal model, the frequency of internal displacement, and the potential consequence of such events from a neurohistological standpoint. Ten female Yorkshire piglets underwent left unilateral fronto-orbital advancement at age 3 weeks, fixation being achieved with microplates and screws. The position of the hardware was determined by direct inspection, after they were killed at 6 months of age (skeletal maturity). Ten microplates (28%) showed complete intracranial translocation, whereas nine (27%) remained on the ectocranial surface. The majority, 16 (44%), were between the outer and inner cortices of the calvaria. Gross examination of the brain tissue underlying the translocated hardware showed indentation "pits" forming as a result of such translocation. Histological examination of the cerebrum and meninges of these pits revealed loss of the most superficial connecting cell layer, with focal neuronal distortion. The leptomeninges were intact and there was no cerebritis, gliosis, or hypoxic change. These findings confirm that in this pig model microfixation hardware will undergo passive intracranial ranial translocation and that there are demonstrable histological alterations in the underlying brain and meninges. The long-term effects of these observed anatomical changes are unknown.

Animals↗
PubMed1996

Community attitudes on the family of issues surrounding the death of terminal patients.

In two studies, respondents made recommendations for the medical treatment of a terminally ill elderly woman. The woman was or was not experiencing intractable pain, and had requested either heroic medical efforts or euthanasia. Respondents' recommendations were influenced by both the specific wishes of the patient and the pain the person was experiencing. However, participants were not completely swayed by the patient's wishes: only about half of the sample recommended euthanasia even when the patient was in intractable pain and had requested death; also, many subjects would not resuscitate the patient whose heart or lungs failed, even though she had requested heroic measures. Respondent attitudes toward euthanasia predicted recommendations in the expected directions. We suggest that there is less dissent on the issues that arise for medical treatments at the end of life than has been widely assumed.

Advance Directives↗
PubMed1996

Disappearing subdural hematomas in children.

Subdural hematomas in infants and young children are uncommon, usually occurring from nonaccidental trauma in infants or from trauma associated with motor vehicles. We report 4 children with apparent unilateral convexity subdural hematomas, 3 of which occurred from household falls and 1 occurring from a fall out of a window. These injuries were characterized by clinical symptoms consistent with the apparent forces involved, which were relatively minor in the first three instances. The clots resolved spontaneously within the first 1-2 days after injury. Such collections are likely located at least partly within the subarachnoid space, but may mimic more clinically significant subdural hematomas. Their recognition may influence decisions regarding both surgical evacuation and the likelihood of nonaccidental injury. Clinical and radiographic features distinguishing these 'disappearing subdurals' from more typical subdural hematomas are discussed.

Accidental Falls↗
PubMed1996

What happens to patients awaiting arthritis surgery?

The length of orthopaedic waiting lists attracts much interest, but the needs of patients awaiting surgery gain little attention. We studied 97 patients awaiting lower-limb surgery (49 osteoarthritis, 41 rheumatoid arthritis, seven other diagnoses). Ninety had pain; 44 significant night pain. Psychological and social problems were common (44 and 45 cases respectively). Only 11 were employed full-time. Sixty-eight required help with daily activities, usually from relatives and neighbours. Forty-three patients walked less than 120 metres in 12 minutes. After review we recommended further aids in 32, medication changes in 27, and additional professional support in six cases. Clinical changes whilst on the waiting list caused alterations in the priority for surgery in 32 cases; the planned procedure was no longer appropriate in 12 of these. We suggest that patients awaiting surgery require clinical review to maintain quality of life; and that waiting lists require administrative review so that patients in need of surgery receive it as soon as possible.

Activities of Daily Living↗
PubMed1995

Targeted delivery of a substrate for P-glycoprotein to renal cysts in vitro.

Bodipy-verapamil has been tested as a fluorescent substrate for P-glycoprotein-mediated transepithelial secretion in MDCK-C5A epithelia. Net transepithelial secretion (Jnet) of [3H]vinblastine from basal-to-apical surfaces of monolayer epithelia is inhibited by taxotere, verapamil and Bodipy-verapamil primarily by a reduction in basal to apical vinblastine (Jb-a) transport. Bodipy-verapamil is itself subject to transepithelial net secretion by MDCK-C5A epithelia; at 5 microM a Jnet of -310 +/- 32 nmol cm-2 h-1 (n = 3) was observed. When MDCK-C5A cells are grown to form enclosed cysts in hydrated collagen gel. Bodipy-verapamil is accumulated within the cyst lumen showing that epithelial P-glycoprotein function may be used to target substrates to renal cysts.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1995

HLA-B27 screening by flow cytometry.

A flow cytometric assay for lymphocyte HLA-B27 expression using a two-color direct immunofluorescent assay was compared to traditional microlymphocytotoxicity testing on 209 clinical samples. For the flow cytometric assay, whole blood was mixed with a monoclonal anti-B27 conjugated to fluorescein-isothiocyanate (FITC) and anti-CD3 conjugated to phycoerythrin (PE). The samples were analyzed with flow cytometry by gating on CD3 positive events and anti-B27 staining intensity was evaluated as median channel fluorescence of the histogram peak. The median channel fluorescence was least with B27 negative and B7 negative samples (84 +/- 17), intermediate with samples that were B27 negative but B7 positive (118 +/- 13), and greatest with samples that were B27 positive (155 +/- 13). In addition to cross-reactivity with the B7 antigen (n = 38), the monoclonal anti-B27 cross-reacted with HLA-B37 positive samples (n = 3) and HLA-B39 positive samples (n = 3). Using a median channel fluorescence cutoff of 136, 39 of the 40 B27 positive samples gave positive results in the flow cytometric assay for a sensitivity of 97.6%. The specificity was 95.9% with 7 false positives of 169 B27 negative samples. The flow cytometric HLA-B27 assay is a convenient, useful screening test. For greatest specificity, samples positive by flow cytometry should be confirmed by conventional microlymphocytotoxicity or by use of other monoclonal antibodies directed against B27.

Flow Cytometry↗
PubMed1995

Unrelated bone marrow donor transplants for children with leukemia or myelodysplasia.

Allogeneic bone marrow transplantation is the treatment of choice for many childhood leukemias. The donor of choice-an HLA matched sibling-is only available about 30% of the time. Unrelated donors are an alternative choice. In this report, we describe the results of unrelated donor bone marrow transplants (BMT) in 50 children with leukemia (25 acute lymphoblastic leukemia [ALL], 3 acute myeloid leukemia [AML], 3 juvenile chronic myelogenous leukemia [JCML], 10 chronic myeloid leukemia [CML]) or myelodysplastic syndrome (MDS; 9). The median age of the 31 male and 19 female patients was 9 years (range 2 to 18). Only 13 patients were serologically matched at HLA-A, B, DR, and DQ with their donors; 6 of these were reactive in mixed lymphocyte culture. The other 37 patients were mismatched for one (36 patients) or more (1 patient) HLA antigens. Pretransplant conditioning included cytosine arabinoside, cyclophosphamide, fractionated total body irradiation (TBI) (with lung, liver, and more recently, kidney shielding), and methylprednisolone. High-risk patients also received busulfan. Graft-versus-host disease (GVHD) prophylaxis consisted of T-cell depletion with IgM monoclonal antibody T10B9 plus complement and posttransplant cyclosporine-A. Forty-nine patients (98%) engrafted. Median times to greater than 500 polymorphonuclear leukocytes (PMN)/microL and greater than 25,000 platelets/microL were 18 and 20 days, respectively. Acute GVHD > or = grade II occurred in 16 patients (33%); 13 (81%) of these died. Chronic GVHD developed in 30 of 40 patients at risk, but was extensive in only 5. Event-free survival (EFS) for all patients was 44% +/- 7% (median follow-up was 49 months), and overall survival was 50 +/- 7%. Patients with low-risk disease (ALL or AML in first or second remission and CML in chronic phase) had a better EFS than children with high-risk disease (60% v 34%, P = .07). There was no significant difference in EFS between patients who were serologically matched with their donors (46%) and those who were partially mismatched (43%) (P = .97). These data compare favorably with published reports for children transplanted with HLA-matched sibling donors and should encourage earlier consideration of unrelated donor BMT in children with leukemia or myelodysplasia.

Actuarial Analysis↗
PubMed1995

Chronic cough and hoarseness in patients with severe gastroesophageal reflux disease. Diagnosis and response to therapy.

Gastroesophageal reflux may be responsible for atypical symptoms such as chronic cough and hoarseness. Our aim was to evaluate and treat patients with severe gastroesophageal reflux and chronic cough or hoarseness with intensive antireflux therapy. Twenty-seven patients with typical heartburn symptoms in addition to significant cough or hoarseness were treated with aggressive antireflux therapy. We recorded the response of each symptom to the antireflux therapy. Two patients were lost to follow-up. Twenty of the 25 (80%) patients showed some improvement in cough or hoarseness, nine (36%) had no atypical symptoms at follow-up. The response of heartburn to therapy was strongly predictive of successful therapy for the atypical symptoms. Cough and hoarseness improved in only two of the five patients with residual heartburn symptoms compared to 18 of 20 patients with no heartburn (P < 0.04). Only patients with no heartburn symptoms at follow-up had complete resolution of atypical symptoms. There were no important differences on ambulatory pH monitoring between partial and complete responders. Improvement in atypical reflux symptoms, such as chronic cough and hoarseness, is common with aggressive antireflux therapy. There are no findings on ambulatory esophageal pH monitoring that uniquely identify patients who are likely to respond to antireflux therapy.

Case-Control Studies↗
PubMed1995

Problems with registration of cutaneous malignant melanoma in England.

The aim of the study was to assess the completeness and accuracy of cancer registration for cutaneous malignant melanoma. The study was conducted in seven health districts in England and one health board in Scotland from 1987 to 1989 with a total resident population of 3.6 million. Records from pigmented lesion clinics and pathology laboratories collected during the Cancer Research Campaign's health education programme to promote the early detection of melanoma were matched with cancer registrations from a total of five regional cancer registries. In England 74% out of a total of 642 cases of invasive malignant melanomas (ICD 172) and 44% out of a total of 155 in situ melanomas (ICD 232) had been registered compared with 96% and 100% respectively in Scotland. A significantly higher proportion of late-stage cases was found among registered than among non-registered cases in England (P < 0.001). In all registries the majority of superficial spreading in situ melanomas were miscoded as invasive cases. The annual incidence of invasive malignant melanoma in the English study areas was found to be seven per 100,000 in men and 11 per 100,000 in women, similar to that reported in Scotland. The registries are best at recording thick or late-stage melanomas. As the skin cancer target for Health of the Nation depends on monitoring trends in the incidence of malignant melanoma, future improved ascertainment of cases and changes in the type of cases being registered must be taken into account.

England↗
PubMed1995

Cancer Research Campaign health education programme to promote the early detection of cutaneous malignant melanoma. I. Work-load and referral patterns.

From 1987 to 1989 a campaign to promote the early detection of cutaneous malignant melanoma was conducted in the areas of seven health authorities in England and Scotland (total population 3.6 million). Data were collected on 17,155 patients attending pigmented lesion clinics (PLCs) in each study area during the campaign. After a dramatic rise in PLC referral rates in the first month of the campaign the average monthly referral rate among the target population in the study period settled to an average of 13 per 10(5), a twofold increase compared with the pre-campaign period. Over 85% of patients at all PLCs were seen within 4 weeks of referral from their general practitioners. The melanoma to non-melanoma detection ratio was (1:33). The organization of future early detection initiatives needs careful review and planning, in order to improve their effectiveness in all sections of the population, and to enable health services to cope with the increased work-load.

Adult↗
PubMed1995

Cancer Research Campaign health education programme to promote the early detection of cutaneous malignant melanoma. II. Characteristics and incidence of melanoma.

The effect on the detection and characteristics of melanoma, resulting from the Cancer Research Campaign's health education programme to promote the early detection of melanoma in the general population, was studied from 1987 to 1989. The seven study areas in England and Scotland yield a target population of 3.6 million. Data were collected from local clinic-based registers, pathology laboratories, and the cancer registries. The average annual incidence rates of melanoma were seven and 12 per 10(5) in males and females, respectively, age-standardized to England and Wales, 1988. These rates are similar to the national figures for Scotland, where there is a national melanoma register, but higher than those reported by the English and Welsh cancer registries. The incidence was significantly higher in females than males (P < 0.001), and increased with age. Fifty-three per cent and 65% of cases in males and females, respectively, were thin (Breslow thickness < or = 1.5 mm), similar to the national figures from Scotland. No significant decrease in the incidence of late-stage tumours was found in either sex as a result of the campaign. Because of difficulties with ascertainment of cases in England, the main evaluation will focus on future trends in mortality rates for melanoma.

Adult↗
PubMed1995

Does routine screening for breast cancer raise anxiety? Results from a three wave prospective study in England.

OBJECTIVE: To investigate whether mammography raises anxiety in routinely screened women who receive a negative result. DESIGN: Prospective design in which women completed questionnaires at three key points in the breast screening process: at baseline (before being sent their invitation for breast screening), at the screening clinic immediately before or after screening, and at follow up, about nine months after baseline. Information was obtained from non-attenders as well as from attenders. SETTING: Bromley District Health Authority, served by the South East London Breast Screening Service. PARTICIPANTS: Two overlapping samples were used. Sample A comprised 1500 women aged 50-64 who were due to be called for first round screening at a mobile screening unit. Altogether 1021 (68%) returned a usable questionnaire and 795 of these (78%) also provided adequate information at nine month follow up: there were 695 attenders (including 24 women who received false positive results) and 100 non-attenders. Sample B consisted of 868 women who attended the screening unit in a three month period, 732 (84%) of whom provided adequate data. A total of 306 attenders (including 10 who received false positive results) occurred in both samples and provided adequate information on all occasions. The main analyses were based on these 306 women plus the 100 non-attenders. The analysis of retrospective anxiety took advantage of the larger sample size of 695 attenders. MAIN RESULTS: On average, the women were not unduly anxious at any of the three points in the screening process. Among attenders, there was no difference between anxiety levels immediately before and immediately after screening. Anxiety was lowest at the clinic and highest at baseline but the changes were very small in absolute terms. Anxiety did not predict attendance: there were no differences in anxiety levels between attenders and non-attenders at baseline. As expected, women who received false positive results recalled feeling extremely anxious after they had received the referral letter but their retrospective anxiety was also higher than in the negative screenees at earlier stages in the breast screening process. They also reported having experienced more pain and discomfort during the x ray. CONCLUSIONS: Anxiety does not seem to be an important problem in routinely screened women who receive a negative result. This finding is very reassuring in relation to a major criticism of breast screening programmes. Thus, apart from maintaining current procedures such as keeping waiting times to a minimum, there seems to be no need to introduce special anxiety reducing interventions into the national programme. On the other hand, the findings for women who received false positive results suggest that there are aspects of the experience of being recalled for assessment after an abnormal mammogram that warrant further attention. The relationship between contemporaneous and retrospective anxiety should also be studied.

Anxiety↗