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Biomedical subjects

J Young

Publications and source records attributed to J Young.

At least 271 records · Page 15Linked to original sources

What are the information priorities for cancer patients involved in treatment decisions? An experienced surrogate study in Hodgkin's disease.

A total of 165 adult patients with Hodgkin's disease (HD) were questioned following treatment to examine their perceptions of actual and desired involvement and provision of information in the treatment decision-making process. Irrespective of the degree to which patients felt they had been involved in the decision-making process and of the outcome of their particular treatment, patients who felt satisfied with the adequacy of information given were significantly more likely to feel happy with their level of participation in the overall process of decision-making (P < 0.001). As part of a strategy investigating patient priorities, patients were asked to rank a series of possible acute and late treatment-related morbidities. Counter-intuitively, the majority of long-term survivors felt early short-term side-effects were more, or equally, as important as late morbidity with respect to influencing choice of therapy. Unpredictable importance was placed by patients on side-effects such as weight gain and fatigue in relation to other complications such as infertility and risk of relapse. Patients do not necessarily share doctors' priorities in decision-making or place the same emphasis on different types of morbidity. Experienced surrogates may assist us in understanding patients' perspectives and priorities.

Adolescent↗

Vaccination against hydatidosis using a defined recombinant antigen.

Echinococcus granulosus is the causative agent of hydatid disease in humans and animals. Natural transmission of the parasite occurs between dogs as definitive hosts and animal intermediate hosts. There is an urgent need for improved methods to control the parasite's transmission. Here we describe the development of a vaccine based on a cloned recombinant antigen from the parasite egg (oncosphere). Sheep-vaccinated with the antigen, designated EG95, are protected (mean 96-98%) against hydatidosis developing from an experimental challenge infection with E. granulosus eggs. The vaccine will provide a valuable new tool to aid in control of transmission of this important human pathogen. It also has the potential to prevent hydatid disease directly through vaccination of humans.

Amino Acid Sequence↗

Psychiatric interview and psychometric predictors of cardiac transplant survival.

OBJECTIVE: This study prospectively investigated the relation between pretransplant assessment of psychiatric diagnosis, coping skills, and social support and outcome measures of survival and health care utilization. METHOD: Ninety-four heart transplant patients underwent structured interviews and completed a battery of self-report psychometric tests assessing coping style, health status, and psychosocial supports. Follow-up that ranged from 9 to 56 months after transplant produced a group of 63 survivors and 31 nonsurvivors, who were found to be comparable in terms of pretransplant cardiac status and severity of illness. RESULTS: Survival analysis showed that dimensional psychometric measures of coping and social support based on patient self-assessment were the best significant predictors of survival. Considered separately, interview-determined ratings of social support and pretransplant compliance with treatment regimens were also potential predictors. Formal DSM-III-R diagnoses were related specifically to posttransplant hospital utilization (axis I diagnoses) and posttransplant health behavior (axis II diagnoses). CONCLUSIONS: The data demonstrate the value of multifaceted assessment, since psychiatric diagnosis, coping style, and psychosocial support may contribute differently to prediction of such aspects of outcome as mortality and health care utilization.

Adaptation, Psychological↗

Changes in structure, mechanics, and insulin-like growth factor-related gene expression in the lungs of newborn rats exposed to air or 60% oxygen.

Exposure of neonatal rats to > or = 95% O2 for 2 wk, a widely used model of oxidant/antioxidant interactions in neonatal lung injury, results in arrested lung growth without the dysplastic lesions observed in chronic human neonatal lung injury. To determine whether dysplastic lung cell growth would be seen at lesser O2 concentrations, we exposed newborn rats to either 95% O2 for 1 wk followed by 60% O2 for 1 wk, or to 60% O2 for 2 wk. Exposure to 95% O2 for 1 wk profoundly inhibited lung DNA synthesis. Recovery of synthesis did not occur during the 2nd wk in 60% O2, nor were areas of dysplastic growth evident in lung tissue. In contrast, a continuous 2-wk exposure to 60% O2 resulted in a slight increase in lung weight with a significant reduction in lung volume over a range of inflation pressures. Also seen was an overall, but inhomogeneous, reduction in lung cell DNA synthesis. A preliminary analysis of affected cell types suggested that inhibition of DNA synthesis affected endothelial cells more than interstitial cells, whereas DNA synthesis increased in type II pneumocytes. Areas of reduced DNA synthesis were interspersed with patchy areas of parenchymal thickening and active DNA synthesis. These areas of parenchymal thickening, but not other areas, had increased immunoreactive IGF-I and the type I IGF receptor. These data are consistent with a direct effect of O2 on growth factor and growth factor receptor expression in causing dysplastic lung cell growth in chronic neonatal lung injury.

Animals↗

The antigonadotropic activity of progestins (19-nortestosterone and 19-norprogesterone derivatives) is not mediated through the androgen receptor.

To further study the mechanism of the antigonadotropic activity of progestins, the effects of a 19-nortestosterone derivative, norethisterone acetate (NETA), and a 19-norprogesterone derivative, nomegestrol acetate (NOMA), were compared. The aim was to assess whether their action is exerted via the androgen receptor. Ten healthy postmenopausal women were treated for five monthly periods of 24 days separated by 10 days in a randomized cross-over design. Transdermal estradiol, Estraderm TTS (25 micrograms; one patch every 3 days), was given from days 1-24 during the five periods. On the last 12 days, of each estradiol treatment, they all received a placebo, NOMA (5 mg/day), NOMA in association with the nonsteroidal antiandrogen, flutamide (FLU; 250 mg, twice a day), NETA (10 mg/day), or NETA plus FLU. On the other hand, three castrated patients with complete androgen insensitivity (CAI) received NOMA and NETA for two periods of 12 days separated by 3 weeks. In postmenopausal women, the effects of NOMA and NETA on metabolic parameters were studied. Only NETA decreased high density lipoprotein cholesterol. Plasma LH, FSH, and estradiol were measured during each treatment period. A significant decrease in mean plasma LH and FSH levels and their responses to exogenous GnRH was observed with NOMA and NETA treatments compared to placebo (P < 0.001). The pulsatile frequency, but not the amplitude, of LH was significantly decreased during both treatments. Interestingly, the effects of both progestins on gonadotropins were not antagonized by FLU administration. In the patients with CAI, the pulsatile study of gonadotropins was performed before and on day 12 of NOMA and NETA treatments. As in postmenopausal women, both progestins induced similar decreases in LH and FSH. In conclusion, a 19-nortestosterone derivative, NETA, and a 19-norprogesterone derivative, NOMA, have similar antigonadotropic activities. This effect, not antagonized by FLU and observed in patients with CAI, is not mediated via the androgen receptor. The absence of deleterious effects of 19-norprogesterone derivatives on metabolic parameters should favor the therapeutic use of these compounds.

Cholesterol, HDL↗

Different phenotypes in a family with androgen insensitivity caused by the same M780I point mutation in the androgen receptor gene.

Mutations in the coding sequence of the androgen receptor (AR) gene result in a wild range of androgen insensitivity (AI) syndromes. Differences in the clinical expression of the same mutation in unrelated patients have been reported. However, this study reports for the first time strikingly different phenotypes among three patients within the same kindred. Two of the patients had a feminine phenotype, suggesting complete AI, but for some pubic hair. The third subject was male with partial AI, perineoscrotal hypospadias, and cryptorchidism. 5 alpha-reductase activity measured in genital skin fibroblasts and binding capacity of the AR were higher in the male than in the two patients with female phenotype. Northern blot analysis of AR messenger RNA revealed a 10-kb band of normal intensity in the three subjects. Molecular analysis of the coding sequence of the AR revealed a unique M780I mutation in exon 6, changing a methionine 780 to isoleucine in the hormone-binding domain. In conclusion, the same mutation of the AR gene in the same family can result in clinical phenotypes characteristic of complete or partial AI. Therefore, the molecular defect of the AR gene may not alone predict the phenotype in families with AI.

Androgens↗

The treatment of postprandial hypotension in autonomic failure with 3,4-DL-threo-dihydroxyphenylserine.

Postprandial hypotension occurs commonly in patients with autonomic failure and may be due to attenuation of the normal sympathetic nervous system activation in response to meal ingestion. In a randomized, double-blind, placebo-controlled study, we investigated the therapeutic effect of the norepinephrine precursor 3,4-DL-threo-dihydroxyphenylserine (DL-DOPS) on this condition. We measured blood pressure, heart rate, forearm vascular resistance, and plasma DL-DOPS and norepinephrine in 11 patients with autonomic failure. DL-DOPS attenuated the postprandial fall in blood pressure. This was associated with an increase in plasma norepinephrine and forearm vascular resistance. DL-DOPS therapy did not change the postprandial increase in heart rate. There was a trend toward increased supine hypertension associated with DL-DOPS treatment. This study shows that DL-DOPS is a promising treatment for postprandial hypotension and provides support for the hypothesis that postprandial hypotension is, at least in part, due to decreased activation of the sympathetic nervous system.

Adult↗

Hemiplegic shoulder pain (HSP): natural history and investigation of associated features.

The prevalence of hemiplegic shoulder pain (HSP) and associated factors was studied in patients with a stroke followed for 6 months after discharge from hospital. A questionnaire was used to evaluate shoulder symptoms and an examination of the shoulder and arm was carried out three times over 6 months. A total of 108 patients were studied with a mean age of 71 years. Sixty-nine patients (63.8%) developed HSP at some time during the study period. The number with HSP was 39 at discharge from hospital, 59 at 8 weeks post-discharge and 36 at 6 months. Nine carers reported lifting the patient by pulling on the hemiplegic arm, even though six of them had received advice about correct lifting techniques. Reduced shoulder shrug was associated with HSP at all times and reduced pinch grip was also associated with HSP at discharge from hospital. Patients who required help with transfers were more likely to suffer with HSP. There was no difference in the prevalence of HSP in patients treated at the day hospital compared to those who received domiciliary physiotherapy. It is concluded that HSP is common after a stroke and the prevalence increases in the first weeks after discharge from hospital. Stroke patients and their carers need advice about correct handling of the hemiplegic arm, and more work is required to ensure that correct handling occurs after discharge in patients at high risk of this unpleasant complication.

Activities of Daily Living↗

The impact of pre-donated autologous blood and intra-operative isovolaemic haemodilution on the outcome of transfusion in patients undergoing radical retropubic prostatectomy.

OBJECTIVE: To assess the impact of pre-donated autologous blood and intra-operative isovolaemic haemodilution on the outcome of transfusions in patients undergoing radical retropubic prostatectomy. PATIENTS AND METHODS: The charts and transfusion records of 192 consecutive patients undergoing radical retropubic prostatectomy were reviewed retrospectively. RESULTS: Of 192 patients, 14% required homologous transfusions, the rate of which varied significantly depending upon blood availability (autologous, haemodilution or homologous) (P < 0.001): 66% of patients with only autologous blood available were transfused a mean of 1.96 units (range 1-6) of blood, of which 87% received autologous alone. 12% both autologous and homologous and 1% homologous blood only. Of the pre-donated autologous units, 44% were wasted. CONCLUSIONS: Both the pre-donation of autologous blood and intra-operative isovolaemic haemodilution lower the risk of homologous blood transfusion. It is recommended that patients pre-donate 2 units of autologous blood and undergo intra-operative isovolaemic haemodilution before radical prostatectomy.

Blood Transfusion, Autologous↗

Alterations of transforming growth factor-beta 1 receptor type II occur in ulcerative colitis-associated carcinomas, sporadic colorectal neoplasms, and esophageal carcinomas, but not in gastric neoplasms.

BACKGROUND & AIMS: Gastric cancers, sporadic colorectal cancers, and ulcerative colitis (UC)-associated colorectal carcinomas and dysplasias manifest microsatellite instability (MI); however, esophageal carcinomas rarely exhibit MI. Recently, a transforming growth factor-beta 1 type II receptor (TGF-beta 1RII) mutation in a coding microsatellite was described in primary colorectal carcinomas demonstrating MI. No previous studies of TGF-beta 1RII have addressed mechanisms of inactivation other than MI in human tumors; furthermore, MI-negative tumors have not been examined for TGF-beta 1RII mutation. We evaluated 138 primary human neoplasms for mutation in the poly-A microsatellite tract of TGF-beta 1RII. Additionally, a group of esophageal tumors was evaluated for the expression of TGF-beta 1RII messenger RNA (mRNA). METHODS: First, we determined whether MI was present at other chromosomal loci in these lesions. The poly-deoxyadenine (poly-A) microsatellite tract within the TGF-beta 1RII coding region was then PCR-amplified. In a group of MI-negative esophageal tumors, RT-PCR was performed to determine the expression of TGF-beta 1RII mRNA. RESULTS: Among 17 MI+ UC specimens, 3 (18%) demonstrated TGF-beta 1RII poly-A tract mutation (2 cancers and 1 dysplasia), while 2 (4%) of 44 MI-negative UC specimens (1 dysplasia and 1 tumor), and 13 (81%) of 16 MI+ sporadic colorectal cancers, contained TGF-beta 1RII poly-A mutation. No gastric or esophageal tumors contained TGF-beta 1RII mutation. Among 21 MI-negative esophageal carcinomas. 6 cases (28.5%) had TGF-beta 1RII transcripts that were low or undetectable by RT-PCR. CONCLUSIONS: Mutation within the poly-A microsatellite tract of TGF-beta 1RII occurs early in a subset of UC-neoplasms and commonly in sporadic colorectal cancers, but may be rare in MI+ gastric tumors. Diminished expression of TGF-beta 1RII mRNA in esophageal tumors suggests that mechanisms of inactivation in this gene other than MI play a role in esophageal carcinogenesis.

Colitis, Ulcerative↗

Incidence and consequences of falls due to stroke: a systematic inquiry.

OBJECTIVE: To undertake a systematic inquiry into the incidence and consequences of falls in a cohort of elderly patients with stroke after discharge from hospital. DESIGN: Administration of a questionnaire to patients and main carers at discharge from hospital and eight weeks and six months later. SETTING: Bradford Metropolitan District. SUBJECTS: 108 patients recruited to the Bradford community stroke trial. Patients were recruited to the trial if they were 60 years or over and resident at home with some residual disability. MAIN OUTCOME MEASURES: Number of falls, motor club assessment, Barthel index, Frenchay activities index, and Nottingham health profile. Stress in carers was indicated by the general health questionnaire. RESULTS: Of 108 patients, 79 (73%) fell in the six months after discharge from hospital with a total of 270 falls reported. Patients who fell in hospital were significantly more likely to fall at least twice at home after discharge (chi 2 = 8.16; P = 0.004). "Fallers" (two or more falls) were less socially active at six months and more had depressed mood. Carers of these patients were significantly more stressed at six months (53% v 18%; chi 2 = 8.5; P = 0.003). CONCLUSION: Stroke is associated with a risk of falling at home and affects the lives of patients with stroke and their carers. Falling and fear of falling is an important issue which needs to be dealt with by the multidisciplinary team.

Accidental Falls↗

Inhibition of platelet aggregation in whole blood by alcohol.

Our previous studies have demonstrated that addition of moderate volumes of absolute alcohol (34-170 mM final concentration) to whole blood produces concentration-dependent platelet aggregation, due to release of adenosine diphosphate (ADP) from erythrocytes. We have now investigated the effects of exposure of blood to ethanol by a more "physiologic" protocol, in which 7.8% (w/v) alcohol is added to achieve a final concentration of 1 to 85 mM in human and rat blood or platelet rich plasma (PRP). The effects of short incubation with alcohol on platelet aggregation induced by ADP, collagen and arachidonic acid were examined by the impedance method of aggregometry. Aggregation induced by collagen in PRP of either species was significantly inhibited by 85 mM ethanol, with concentrations as low as 4.25 mM inhibiting the response to collagen in rat whole blood. ADP stimulated only primary, reversible aggregation in rat PRP and whole blood, and these responses were unaffected by alcohol. Human platelets responded to ADP with irreversible aggregation, which was significantly attenuated by 85 mM ethanol in whole blood but not PRP. Arachidonic acid evoked irreversible platelet aggregation in all four preparations; this was significantly inhibited by the high dose ethanol in human and rat PRP, but not whole blood. In contrast to our earlier studies with absolute ethanol, there was no evidence of hemolysis (and therefore, ADP release from red blood cells) using the current protocol. The results of these experiments show that alcohol, at physiologically relevant concentrations, has an inhibitory effect on secondary platelet aggregation responses to some agonists in whole blood as well as PRP, possibly by its previously demonstrated effects on arachidonic acid release by phospholipases. The possibility remains to be considered that other blood cells might contribute to the effects of alcohol on platelet aggregation in whole blood.

Adenosine Diphosphate↗

Diffusion of standards of care for cancer pain.

The authors report the results of a symposium on improving the standards of care for patients with cancer pain. The symposium was sponsored by the Advisory Committee on Cancer Control of the National Cancer Institute of Canada and was held Apr. 8 to 10, 1994, in Toronto. Participants included experts on control of cancer pain and on diffusion techniques, patients with cancer and representatives of regulatory agencies. They suggested the following strategies to improve outcomes in patients with cancer pain. Processes for accreditation of health care institutions should require documentation of cancer pain, its treatment and its outcome. Tertiary care facilities that provide cancer treatment should have expert, subspecialty, multidisciplinary programs for pain control and should provide adequate psychosocial support to patients suffering cancer pain. The Canadian Cancer Society should conduct a public-education campaign to encourage patients to report pain to health care providers. The National Cancer Institute of Canada should foster research on cancer pain by restructuring its process for review of pain-research protocols. Examinations for professionals who care for patients with cancer should include a defined number of questions concerning pain and symptom control. Provincial programs to monitor prescribing through the use of triplicate prescription pads should have an educational as well as regulatory purpose.

Administration, Oral↗