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Biomedical subjects

J Chamberlain

Publications and source records attributed to J Chamberlain.

At least 91 records · Page 5Linked to original sources
PubMed1993

Potency of 5-hydroxytryptamine1a agonists to inhibit adenylyl cyclase activity is a function of affinity for the "low-affinity" state of [3H]8-hydroxy-N,N-dipropylaminotetralin ([3H]8-OH-DPAT) binding.

In this study, the radiolabeled 5-hydroxytryptamine1A agonist, [3H]8-hydroxy-N,N-dipropylamino tetralin ([3H]8-OH-DPAT), was shown to have both a high (Kd, 0.7 +/- 0.2 nM) and a low (Kd, 17 +/- 4 nM) affinity binding component in rat hippocampal homogenate preparations in the absence of guanine nucleotides. The high-affinity binding component was markedly reduced by the elimination of Mg++ from the incubation medium and the addition of both the nonhydrolyzable guanine nucleotide guanylylimidodiphosphate (Gpp(NH)p) (100 microM) and 1.0 mM EDTA to the incubation medium. Under these latter conditions, a single binding affinity component was observed with a Kd of 11 +/- 1 nM, a value in good agreement with the value for the low-affinity component measured in the absence of Gpp(NH)p. Further, the Bmax value for the single low-affinity binding component measured in the presence of Gpp(NH)p was essentially equivalent to the total of the two Bmax values found in the absence of Gpp(NH)p. A binding assay was developed using 15 nM [3H]8-OH-DPAT to determine the affinities of serotonergic drugs for the low-affinity component of [3H]8-OH-DPAT binding and these values were compared with their affinities for the high-affinity binding component as well as their potencies in a hippocampal adenylyl cyclase assay. For agonists, the Ki value for the high-affinity binding component was always less than the low-affinity Ki value, whereas the antagonist spiperone had similar values for both the high-affinity and low-affinity binding components.(ABSTRACT TRUNCATED AT 250 WORDS)

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1992

Randomised controlled trial of effects of coordinating care for terminally ill cancer patients.

OBJECTIVES: To measure effects on terminally ill cancer patients and their families of coordinating the services available within the NHS and from local authorities and the voluntary sector. DESIGN: Randomised controlled trial. SETTING: Inner London health district. PATIENTS: Cancer patients were routinely notified from 1987 to 1990. 554 patients expected to survive less than one year entered the trial and were randomly allocated to a coordination or a control group. INTERVENTION: All patients received routinely available services. Coordination group patients received the assistance of two nurse coordinators, whose role was to ensure that patients received appropriate and well coordinated services, tailored to their individual needs and circumstances. MAIN OUTCOME MEASURES: Patients and carers were interviewed at home on entry to the trial and at intervals until death. Interviews after bereavement were also conducted. Outcome measures included the presence and severity of physical symptoms, psychiatric morbidity, use of and satisfaction with services, and carers' problems. Results from the baseline interview, the interview closest to death, and the interview after bereavement were analysed. RESULTS: Few differences between groups were significant. Coordination group patients were less likely to suffer from vomiting, were more likely to report effective treatment for it, and less likely to be concerned about having an itchy skin. Their carers were more likely to report that in the last week of life the patient had had a cough and had had effective treatment for constipation, and they were less likely to rate the patient's difficulty swallowing as severe or to report effective treatment for anxiety. Coordination group patients were more likely to have seen a chiropodist and their carers were more likely to contact a specialist nurse in a night time emergency. These carers were less likely to feel angry about the death of the patient. CONCLUSIONS: This coordinating service made little difference to patient or family outcomes, perhaps because the service did not have a budget with which it could obtain services or because the professional skills of the nurse-coordinators may have conflicted with the requirements of the coordinating role.

Anxiety↗
PubMed1992

Identification of new markers in Xp21 between DXS28 (C7) and DMD.

Characterization of Xp21 distal to Duchenne muscular dystrophy (DMD) in the region containing the genes for adrenal hypoplasia congenita (AHC) and glycerol kinase deficiency (GKD) has been limited due to a paucity of probes. Two probes were localized between DXS28 (C7) and AHC, the yeast artificial chromosome insert YHX39 (DXS727) and the polymorphic phage clone QST59 (DXS319). A genomic clone, FT1 (DXS726), 3' to DMD, was also characterized. Portions of the three probes were sequenced and primer pairs were generated to amplify a sequence-tagged site within each probe. Amplification of DNA from patients confirmed the deletion results obtained by Southern blot analysis, and these three sequence-tagged sites were successfully combined for triplex PCR. In addition to facilitating molecular genetic diagnosis in Xp21, these probes can be used to identify additional YACs and other probes to further increase the genomic information and diagnostic capabilities in this region.

Base Sequence↗
PubMed1992

Fibromuscular dysplasia of visceral arteries.

The case histories of two patients with combined renal and extra-renal fibromuscular dysplasia are presented. Readers are reminded of this rare but important condition as a cause of obscure abdominal symptoms and abdominal bleeding in the absence of atherosclerotic aortic aneurysm. The aetiology, histology, and management of the condition are discussed.

Adult↗
PubMed1992

Localization of dystrophin gene transcripts during mouse embryogenesis.

The spatial and temporal expression of the dystrophin gene has been examined during mouse embryogenesis, using in situ hybridization on tissue sections with a probe from the 5' end of the dystrophin coding sequence. In striated muscle, dystrophin transcripts are detectable from about 9 d in the heart and slightly later in skeletal muscle. However, there is an important difference between the two types of muscle: the heart is already functional as a contractile organ before the appearance of dystrophin transcripts, whereas this is not the case in skeletal muscle, where dystrophin and myosin heavy chain transcripts are first detectable at the same time. In the heart, dystrophin transcripts accumulate initially in the outflow tract and, at later stages, in both the atria and ventricles. In skeletal muscle, the gene is expressed in all myocytes irrespective of fiber type. In smooth muscle dystrophin transcripts are first detectable from 11 d post coitum in blood vessels, and subsequently in lung bronchi and in the digestive tract. The other major tissue where the dystrophin gene is expressed is the brain, where transcripts are clearly detectable in the cerebellum from 13 d. High-level expression of the gene is also seen in particular regions of the forebrain involved in the regulation of circadian rhythms, the endocrine system, and olfactory function, not previously identified in this context. The findings are discussed in the context of the pathology of Duchenne muscular dystrophy.

Animals↗
PubMed1991

242 breakpoints in the 200-kb deletion-prone P20 region of the DMD gene are widely spread.

Using whole cosmids as probes, we have mapped 242 DMD/BMD deletion breakpoints located in the major deletion hot spot of the DMD gene. Of these, 113 breakpoints were mapped more precisely to individual restriction enzyme fragments in the distal 80 kb of the 170-kb intron 44. An additional 12 breakpoints are distributed over the entire region, with no significant local variation in frequency. Furthermore, deletion sizes vary and are not influenced by the positions of the breakpoints. This argues against a predominant role of one or a few specific sequences in causing frequent rearrangements. It suggests that structural characteristics or a more widespread recombinogenic sequence makes this region so susceptible to deletion. Our study revealed several RFLPs, one of which is a 300-bp insertion/deletion polymorphism. Abnormally migrating junction fragments are found in 81% of the precisely mapped deletions and are highly valuable in the diagnosis of carrier females.

Chromosome Deletion↗
PubMed1991

The specificity of technetium-labelled-leucocyte imaging of aortic grafts in the early postoperative period.

Radio-labelled-leucocyte imaging is becoming accepted as the investigation of choice when infection of prosthetic arterial bypass grafts is suspected. However, alternative sources of inflammation, such as haematoma and, perhaps, the healing and incorporation of newly inserted bypass grafts, are potential causes of false positive results. This study examines the use of technetium-labelled-leucocyte imaging during the postoperative in-hospital period following aortic bypass surgery. Two labelled-leucocyte scans were carried out serially in 20 patients randomly allocated to receive either of two types of Dacron aortic graft in regular use. The earlier scans were undertaken at 2-5 days after surgery and only two of these scans were positive. None of the later scans, undertaken at 7-10 days after surgery, was positive. None of the patients had a graft injection as evidenced by clinical features, leucocyte counts, and C-reactive protein measurements. These results suggest that recent surgery does not in itself significantly reduce the specificity of technetium-labelled-leucocyte imaging.

Aged↗
PubMed1991

Verification of the cause of death in the trial of early detection of breast cancer. UK Trial of Early Detection of Breast Cancer Group. Trial Co-ordinating Centre.

The limitations of case review as a means of identifying errors in death certificates among breast cancer patients in a non-randomised trial of screening are illustrated by the findings of this large study. Records of 928 out of 990 deaths were available for review but were very variable in quality. Definite errors were found in 1%, errors were suspected in a further 5% and uncertainty about the cause of death, despite review, was recorded for 27%. The overall bias in reporting breast cancer deaths was less than 1%. It was concluded that the certified underlying cause of death without review provides an adequate endpoint for evaluating breast cancer screening programmes in the UK.

Age Factors↗
PubMed1990

Four and a half year follow up of women with dyskaryotic cervical smears.

OBJECTIVE: To determine the proportion of women with mild or moderate dyskaryosis in cervical smears who (a) progress to cervical intraepithelial neoplasia grade III or worse or (b) regress. DESIGN: Four and a half year cytological follow up study of women with mild or moderate dyskaryosis in cervical smears. SETTING: 666 Women (mean age 28 (SD 8) years; range 14-74) found to have borderline, mild, or moderate dyskaryosis on routine screening. RESULTS: 45 Women (6.8%) had a cone biopsy recommended on the basis of an abnormal follow up smear (severe dyskaryosis suggestive of cervical intraepithelial neoplasia grade III or invasive cancer), and in one patient cervical intraepithelial neoplasia grade III was reported in a biopsy specimen after dilatation and curettage. Life table analysis gave a 14% probability of a patient being recommended for a biopsy after four and a half years of follow up (95% confidence interval 12% to 15%). There was a significant excess incidence of invasive cancer of the cervix in the series compared with the general population (five cases observed compared with less than 0.1 expected). 157 Patients (24%) showed reversion to a normal cell pattern sustained in several smears over more than 18 months but a single negative smear was an unreliable indicator of apparent regression. Having two successive smears showing mild dyskaryosis or a smear at any time showing moderate dyskaryosis was a significant predictor of a subsequent severely dyskaryotic smear. CONCLUSIONS: Women found to have mild or moderate dyskaryosis in cervical smears should be kept under regular surveillance. The optimum management of these patients--by cytology or colposcopy--needs to be determined by randomised controlled trials.

Adolescent↗
PubMed1990

New isotopic technique for detecting prosthetic arterial graft infection: 99mTc-hexametazime-labelled leucocyte imaging.

Early and accurate detection of prosthetic arterial graft infection is important because this serious complication of vascular surgery carries high morbidity and mortality rates. This report describes the use of a new method of isotopic imaging to detect graft infection using 99mTc-hexametazime-labelled leucocytes. Seventeen patients with potentially infected arterial grafts were imaged in addition to routine investigations but were managed according to our normal surgical practice. 99mTc-imaging was positive in eight patients with proven graft infection and falsely positive in one patient with a groin haematoma (89 per cent specificity). There were no false negatives (100 per cent sensitivity) after an average follow-up of 6 months (range 3-9 months). This technique has proved a reliable and rapid method of confirming graft infection.

Aged↗
PubMed1990

Percutaneous transluminal angioplasty of the innominate, subclavian, and axillary arteries.

Percutaneous balloon angioplasty offers an alternative to surgery for the alleviation of symptoms in upper limb arterial disease. This report documents 28 per-femoral dilatation procedures in 27 patients for 33 subclavian, two innominate, and two axillary lesions. Thirty-four stenoses and three occlusions were treated, with multiple dilatations in five patients. Indications for treatment were: arm ischaemia (15 patients); neurological (steal syndrome) symptoms (8); and combined ischaemia plus steal (5). Angioplasty was technically successful in 27 procedures with symptomatic relief in 25 cases up to a mean follow-up of 24 months (median 20 months, range 2-90 months). One patient had successful repeat angioplasty for recurrent ischaemic symptoms after 30 months. Angioplasty improved pulse deficits in all but two patients and reduced arm blood pressure differential to less than 30 mmHg in all but three patients. There were three complications: a femoral artery occlusion and a groin haematoma required surgical intervention and another patient suffered an extension of a contralateral stroke. Percutaneous balloon angioplasty has proved safe and effective. We recommend angioplasty as the first line treatment for ischaemic or neurological symptoms in upper limb vascular disease.

Angioplasty, Balloon↗
PubMed1989

Randomised, controlled trial of faecal occult blood screening for colorectal cancer. Results for first 107,349 subjects.

To assess the effectiveness of screening by faecal occult blood tests, 107,349 people without symptoms of colorectal disease identified from general practitioner records have been randomly allocated to test and control groups. 53,464 test subjects were invited to carry out the screening test; 27,651 (53%) of the 52,258 who received the tests did so. Further investigation of the 618 (2.3%) with positive tests showed 63 cancers (52% stage A) and 367 adenomas (266 subjects). Rescreening of subjects with negative results every 2 years (9510 first rescreen, 3639 second) has shown a significant fall in the rate of positive results (1.7% of 7344; 0.3% of 2906). Cancers have also been diagnosed in 20 subjects presenting in the interval between a negative test and rescreening, and in 83 non-responders. The incidence of cancer in the control group (123 subjects; 10.6% stage A) was 0.72 per 1000 person-years. Cancers detected by screening were at a less advanced pathological stage, but it is too early to show any effect of screening on mortality from colorectal cancer.

Adenocarcinoma↗