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Biomedical subjects

J Hinton

Publications and source records attributed to J Hinton.

At least 19 recordsLinked to original sources
PubMed1999

The progress of awareness and acceptance of dying assessed in cancer patients and their caring relatives.

Awareness and acceptance of dying were assessed weekly by semistructured interviews in a randomized sample of 76 hospice cancer patients and caring relatives. During the final eight weeks of the study, patients' awareness showed only slight increase (about 42% fully certain) while relatives' certainty clearly progressed (from 53% to 81% certain). Depression was linked with greater awareness in relatives but not patients. Patients were more anxious if death seemed probable rather than certain or no more than possible. Acceptance usually increased, with 51% of patients and 69% of relatives becoming nearly/fully accepting. Many individuals diverged from the average progress of awareness and acceptance; 18% of patients and 24% of relatives showed fluctuating or falling acceptance. Patients' and relatives' levels of awareness were positively correlated (r = 0.46), as was acceptance (r = 0.47). Relatives accepted more if patients were over 70 years, weak, unable to concentrate or had a quality of life index (QLI) below five, but patients were more accepting if female and if the QLI was above five. Pain did not increase acceptance. Acceptance was described in terms of death's inevitability, faith and spiritual values, life's diminishing rewards, completing life, final benefits, humour, sharing, etc. Individuals often used more than one concept. Generalizing exact figures from this sample needs caution, but some patterns of progress, possible influential factors and ways of acceptance may apply widely.

Adaptation, Psychological↗
PubMed1998

Novel nonpeptide CCK-B antagonists: design and development of quinazolinone derivatives as potent, selective, and orally active CCK-B antagonists.

We have designed a novel series of CCK-B receptor antagonists by combining key pharmacophores, an arylurea moiety of 1 and a quinazolinone ring of 3, from two known series. Our earlier studies showed that compounds with methylene linkers in our "target" produced moderate binding affinity and selectivity for CCK-B receptors, whereas its higher and lower homologues resulted in loss of affinity. Introduction of -NH- as a linker dramatically enhanced binding affinity and selectivity for CCK-B receptors, thus providing several compounds with single-digit nanomolar binding affinity and excellent selectivity. Analogous to the earlier studies of the series of quinazolinone derivatives 3, we also found 3-isopropoxyphenyl as a preferred substitution on the N-3 quinazolinone. Electron-withdrawing substitutions on the urea terminal phenyl ring enhanced the CCK-B potency. Representative compounds of this series were tested in the functional assay and showed pure antagonist profiles. Compounds 51 and 61 were orally active in the elevated rat X-maze test. These compounds were also evaluated for their pharmacokinetic profile. The absolute oral bioavailability of compound 61 was 22% in rats.

Administration, Oral↗
PubMed1998

Comparison of accuracy of scintimammography and X-ray mammography in the diagnosis of primary breast cancer in patients selected for surgical biopsy.

Mammography, whilst remaining the first line imaging investigation of suspected primary breast cancer, can be difficult to interpret in patients with fibrous or dense breasts. Radionuclide imaging of the breast (scintimammography) has been suggested as an additional test. The aim of this study was to perform prospectively a comparison of the two techniques in a population with suspected breast cancer. Seventy such patients, mean age 54 years (range 57 years, 28-85) with 74 suspicious breast lesions were studied. They were imaged 5-10 min after intravenous injection of 740 MBq of Tc-99m sestamibi. Prone lateral and anterior supine views with and without markers were performed. All patients had histological confirmation of the nature of the breast lesions by limited incisional biopsy or definitive wide local excision, or cytological confirmation on fine needle aspiration. All patients had X-ray mammography. There were 53 malignant breast tumours and 21 benign lesions. Scintimammography correctly diagnosed 47 breast cancers, and yielded true-negative results in 12 benign breast lesions. There were six cases of false-negative results and nine false-positive results. Four scans were reported as equivocal. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were 89%, 52%, 84% and 67%, respectively. X-ray mammography diagnosed correctly 37 malignant tumours, and in 12 benign lesions the results were true negatives. Ten studies were reported as equivocal. The sensitivity, specificity, PPV and NPV were 70%, 57%, 80% and 43%, respectively. The accuracy of Tc-99m sestamibi scintimammography was better than X-ray mammography though this was not significant (McNemar's test). Fewer equivocal results were obtained with scintimammography. Scintimammography may therefore have a role in the diagnosis of primary breast cancer when X-ray mammography is equivocal or unhelpful.

Adult↗
PubMed1998

Use of 99Tcm-MIBI in the assessment of patients with suspected recurrent breast cancer.

A prospective trial was performed to assess the accuracy of 99Tcm-methoxyisobutyl isonitrile (99Tcm-MIBI) scintimammography and X-ray mammography in 18 patients (mean age 58 years, range 46-79 years) with suspected recurrent breast cancer in the breast and/or loco-regional tissues. All patients had been diagnosed to have breast cancer 1-23 years before scintimammography. Two patients had undergone mastectomy, so that a total of 34 breasts were studied with X-ray mammography and with prone-lateral and anterior scintimammography. Any abnormalities on X-ray mammograms and scintimammograms were noted, as was any additional local or nodal uptake of 99Tcm-MIBI. The nature of any lesion seen with either modality, or in which there was a clinical suspicion of recurrence, was confirmed by cytological or histological examination of tissue samples. There were nine breasts with recurrent cancer in eight patients. X-ray mammography identified six of these cancers. 99Tcm-MIBI scintimammography identified eight of nine recurrent breast cancers (the one cancer not seen was positive on X-ray mammography). In the 26 breasts without cancer, two were reported as having changes consistent with cancer and one was reported equivocal. There were three false-positive and one equivocal scintimammograms. The accuracy of 99Tcm-MIBI scintimammography within the breast (85%) was similar to X-ray mammography (82%). Axillary lymph node recurrence occurred in five patients, four of whom were positive with 99Tcm-MIBI. An additional patient had focal uptake of 99Tcm-MIBI at the site of recurrent cancer on the anterior chest wall. In conclusion, 99Tcm-MIBI scintimammography may provide useful complementary information in patients with suspected recurrence of cancer in the breast or loco-regional tissues.

Aged↗
PubMed1998

Hepatic histology in hepatitis C virus carriers coinfected with hepatitis G virus.

BACKGROUND: A novel flavivirus has been described recently and designated hepatitis G virus (HGV). The virus is transmitted by the parenteral route but it is uncertain whether it is associated with chronic liver disease because liver biopsy is difficult to justify in this group. AIMS: To examine histological features of liver biopsy in patients infected with hepatitis C virus (HCV) according to the presence or absence of HCV and HGV RNA. METHODS: One hundred and thirty one consecutive HCV carriers undergoing staging liver biopsy were studied retrospectively. In each, HCV RNA and HGV RNA were detected by reverse transcription polymerase chain reaction on serum samples collected at the time of biopsy. The presence of each RNA was correlated with histological features blind to the RNA results; individual histological features of inflammation or fibrosis were scored separately. RESULTS: Nineteen patients were positive for both HGV and HCV RNA in serum, 91 were positive for HCV RNA alone, two were positive for HGV RNA alone, and 19 were negative for both RNA species. Neither age nor sex differed between the groups; a greater proportion of intravenous drug users were HGV RNA positive, but this was not statistically significant. There was no effect of HGV coinfection on the stage of fibrosis or any other histological parameter except steatosis; patients with HCV and HGV RNA had a higher mean score for fat than those patients with HCV RNA alone (p < 0.05). CONCLUSIONS: HGV coinfection has no important effects on histological features in chronic HCV carriers. It is unlikely that HGV infection causes chronic liver disease.

Adult↗
PubMed1996

How reliable are relatives' retrospective reports of terminal illness? Patients and relatives' accounts compared.

To assess the accuracy of relatives' recollections of patients' terminal illness 71 out of 77 caring relatives were re-interviewed about 4 months after they and the patients had given regular interviews throughout care. Current and retrospective ratings of problems and feelings have been compared for agreement, using the kappa index. Several volunteered symptoms showed poor agreement, notably pain, anorexia and depression (kappa = 0.03-0.21), but vomiting, dyspnoea and immobility ratings agreed moderately well (kappa = 0.43-0.68). Current ratings from patients' and relatives' were always in better agreement with each other than with the relatives retrospective ratings. Bias sometimes altered apparent prevalence; pain was described as more severe in retrospect, but weakness, malaise, depression and relatives' stress were under-rated later. Ratings of "discomfort only" became less common for all symptoms retrospectively. The regular current assessments of patients' and relatives' emotional state also agreed only slightly with relatives' follow-up accounts of depression but somewhat better for anxiety. Patients stated knowledge of diagnosis, awareness and acceptance of dying matched the relatives' retrospective assessments moderately well (kappa = 0.70, 0.50 and 0.41). This study and other available evidence indicate that relatives' retrospective reports of terminal illness, measured against current ratings, are moderately reliable for some items but can vary or be potentially misleading over other aspects, including pain. This could affect evaluations of care.

Affect↗
PubMed1996

Services given and help perceived during home care for terminal cancer.

Separate accounts of care were recorded weekly from staff, patients and relatives in a randomised sample of patients with terminal cancer referred to a home care service with readily available beds. Various services were involved but nurses made most contacts, 3.0 visits and 2.4 phone calls weekly, rising sharply in the last week. General practitioners averaged 0.4 visits/week but their considerable variation evoked either praise or criticism. Maintaining contact, giving explanations and support were reported to help as often as physical treatments and practical nursing, although staff's and recipients' accounts differed slightly. Help succeeded for many problems, but weakness was common, often grew worse and led to more admissions than pain. Difficulties in relieving fatigue and strain in relatives also curtailed home care. Subsequent home care team reorganisation to strengthen linkage between particular nurses and patients and the improvement of day care services were associated with successive but modest rises from the original 27% to 34% of patients dying at home. Implications of the results for services and skills required for home care are discussed, noting the problems that deserve further attention.

Adult↗
PubMed1996

Novel stimuli for obtaining nasalance measures from young children.

The use of novel stimuli for obtaining nasalance measures in young children was the focus of this study. The subjects were 20 children without a history of communication disorders and 20 children at risk for velopharyngeal insufficiency (VPI). Each subject recited three passages; the standard Zoo Passage, and two novel stimuli that were named the Turtle Passage and the Mouse Passage. Like the Zoo Passage, the Turtle Passage contained no normally nasal consonants. The Mouse Passage was about 11% nasal consonants, which is similar to the Rainbow Passage. Statistical analysis showed no significant difference between the mean nasalance for the Zoo Passage and the Turtle Passage for either the subjects without risk of VPI (15.4% vs 15.7%) or for those at risk (30.4% vs 28.8%). Nasalance measures for the Mouse Passage were significantly higher than for either the Zoo Passage or the Turtle Passage. Listeners rated the stimuli on a 5-point equal-appearing intervals scale. The correlation coefficient between listener judgments of hypernasality and nasalance was significant for the Zoo Passage (r = 0.70) and for the Turtle Passage (r = 0.51) but not significant for the Mouse Passage (r = 0.32). Using cut-off scores of 22% for nasalance and 2.25 for hypernasality, the sensitivity for the Zoo Passage was 0.72, and for the Turtle Passage, 0.83.

Child↗
PubMed1995

Effect of CI-988 on cholecystokinin tetrapeptide-induced panic symptoms in healthy volunteers.

A randomized, placebo-controlled, double-blind, three-way crossover design was used to evaluate the effectiveness of single oral 100 mg doses of CI-988, a cholecystokinin B (CCKB) antagonist, in attenuating panic symptoms induced by intravenous injection of cholecystokinin-tetrapeptide (CCK-4). Thirty healthy men received the following treatments on three separate occasions: placebo capsules/placebo, placebo capsules/CCK-4, or CI-988 capsules/CCK-4. There was no marked difference in the number, time to onset, or duration of panic symptoms between CI-988/CCK-4 and placebo/CCK-4. There was, however, a 14% difference in sum intensity scores between these treatments that was statistically significant (p = 0.039). The symptoms most affected by CI-988 were cold chills/hot flushes, chest pain/discomfort, and anxiety/fear/apprehension. Panic attack frequency also decreased following CI-988 treatment (8/30 vs. 16/30; p = 0.035). This decrease, amid otherwise modest effects, could be explained by a preferential effect of CI-988 on the subjective experience of anxiety/fear/apprehension. Possible reasons for the relatively modest effects of CI-988 on CCK-4-induced panic symptoms are discussed.

Adult↗
PubMed1995

Limited proteolysis of native proteins: the interaction between avidin and proteinase K.

Avidin is a tetramer of 16-kDa subunits that have a high affinity for biotin. Proteolysis of native apoavidin by proteinase K results in a limited attack at the loop between beta-strands 3 and 4, involving amino acids 38-43. Specifically, sites of proteolysis are at Thr 40-Ser 41 and Asn 42-Glu 43. The limited proteolysis results in an avidin product that remains otherwise intact and which has enhanced binding for 4'-hydroxyazobenzene-2-benzoic acid (HABA), a chromogenic reporter that can occupy the biotin-binding site. Saturation of the biotin-binding site with the natural ligand protects avidin from proteolysis, but saturation with HABA enhances the rate of proteolysis of the same site. Analysis of the three-dimensional structures of apoavidin and holoavidin reveals that the 3-4 loop is accessible to solvent and scores highly in an algorithm developed to identify sites of proteolytic attack. The structure of holoavidin is almost identical to the apoprotein. In particular, the 3-4 loop has the same structure in the apo and holo forms, yet there are marked differences in proteolytic susceptibility of this region. Evidence suggests that the 3-4 loop is rather mobile and flexible in the apoprotein, and that it becomes constrained upon ligand binding. In one crystal structure of the apoprotein, this loop appears constrained by contacts with symmetry-related molecules. Structural analyses suggest that the "lid" to the biotin-binding site, formed by the 3-4 loop, is displaced and made more accessible by HABA binding, thereby enhancing its proteolytic susceptibility.

Amino Acid Sequence↗
PubMed1995

Factors affecting non-response to cervical cytology screening in Norfolk, England.

A geographic information system was used to integrate information on the uptake of cervical cytology screening for general medical practices in Norfolk with other data on the characteristics of the practices and the population they served. Regression analysis was employed to explore the extent to which variations in non-response were associated with explanatory factors. Non-response to the earlier system of opportunistic screening was found to be associated with the size of practice, the presence of a female doctor, the District Health Authority in which the practice was located, the age structure of the practice population, its degree of socio-economic deprivation and levels of rural remoteness. Compared with the earlier system, the new population-based call and recall system was found to be reaching a larger proportion of the population at risk. The former relationships were weaker under the new system, but non-response was still significantly associated with both social and organisational factors.

Adult↗
PubMed1994

Can home care maintain an acceptable quality of life for patients with terminal cancer and their relatives?

This prospective study was designed to assess whether patients with terminal cancer, and their relatives, find that competent home care sufficiently maintains comfort and helps adjustment. A random sample from a home care service with readily available beds comprised 77 adults and their relatives who were able and willing to be interviewed separately each week. They were asked the nature and degree of current problems and regular assessments were made of some qualities of life including mood, attitude to the condition, perceived help and preferred place of care. These patients had 90% of their care at home; 29% died at home but 30% were finally admitted for one to three days and 41% for longer. In the final eight weeks, tolerable physical symptoms were volunteered by a mean of 63% each week and psychological symptoms by 17%. Some distress was felt by 11% of patients; this was usually from pain, depression, dyspnoea, anxiety or weakness, and generally did not persist. Relatives suffered grief, strain or their own ill health. Patients' and relatives' reports generally matched except for the strain on carers. Regular assessments found that 64% of patients thought death certain or probable, and 27% thought it possible. Various proportions coped by optimism, fighting their disease, partial suppression or denial, but 50% reached positive acceptance. Relatives were more aware and accepting. About three-quarters of patients and half the relatives were composed, often enjoying life. Serious depression affected 5% of patients and anxiety 4%, but relatives' manifest depression in the later stages increased to 17% and anxiety to 14%. Many consciously disguised their feelings. Treatment was usually praised but realistic preference for home care fell steadily from 100% to 54% of patients and 45% of relatives. At follow-up most relatives approved of where patients had received care and died.

Adaptation, Psychological↗
PubMed1994

Which patients with terminal cancer are admitted from home care?

The factors related to admission of patients with terminal cancer who had been referred to a reputable home care service were examined in 415 patients referred in a two-year period and in a prospective study of a randomized one in three sample of the 232 adults still alive one week after referral, who were able to converse and be at home with caring relatives. The reasons given by staff for intermediate admissions were mostly to improve symptom control or provide respite; for final admissions the reasons were symptom control, patients' deteriorated state and relatives needing relief. Independent weekly assessments usually concurred in showing increasing problems or distress preceding final admission, particularly patients' weakness, pain, depression and anxiety, and relatives' fatigue, anxiety or depression. Examination of selected demographic and illness factors indicated that few patients living alone or with unfit relatives stayed at home; breast cancer led to more deaths as an inpatient, whereas stomach cancer favoured deaths at home. The proportion of patients admitted steadily increased as care lengthened. Assessments of psychological factors showed that initial attitudes of denial, conscious fighting of disease, and optimism were linked with increased late admissions; earlier awareness of dying in patients and stoicism in relatives favoured home deaths. A growing preference for inpatient care usually preceded or accompanied admission. Recognition of both immediate and underlying causes of admission can indicate where further treatment or assistance is needed and also improve understanding so that patients and relatives may be suitably supported or helped to adjust.

Adaptation, Psychological↗
PubMed1992

Screening and genetic counselling for relatives of patients with breast cancer in a family cancer clinic.

Family history is the major risk factor in the aetiology of breast cancer. Breast screening is currently available to women from the age of 50 to 64 through the National Breast Screening Programme. There is, however, an equivalent risk of developing breast cancer below 50 for first degree relatives of women diagnosed with breast cancer premenopausally. We have estimated the risk of breast cancer for relatives of women affected at different ages and used these to establish a family cancer clinic offering breast screening based on individual risk. In three years we have seen 851 patients. Compliance for annual radiology was in excess of 83% over this period and of five cancers detected one had a lump at presentation, two developed interval breast lumps, and two were asymptomatic.

Adult↗
PubMed1992

A statewide public and professional education program on fragile X syndrome.

Fragile X syndrome is reported to be the most common inherited cause of mental retardation known, but the majority of affected individuals are as yet undiagnosed. The project described in this paper was developed to increase the public and professional awareness of fragile X syndrome in the state of New Jersey. As a result there were increased efforts at diagnostic screening, provision of client and family support services, and prevention. This educational program proved to be a cost-effective method for increasing community awareness of a genetic disease on a statewide level.

Adolescent↗