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Biomedical subjects

R Jenkins

Publications and source records attributed to R Jenkins.

At least 127 records · Page 7Linked to original sources
PubMed1994

Ageing in learning difficulties: the development of health care outcome indicators.

A system of outcome indicators for the health and social care of ageing people with learning disabilities is required to ensure that clinicians, planners, purchasers and policy makers can monitor and evaluate the impact of health and social care. As longevity is increasing in people with learning disabilities, special problems are found in the physical health, psychological health and social wellbeing of the elderly. This paper reviews theoretical aspects of outcome indicators, and uses the various classes of outcome measures available to draw up a system of indicators for clinicians, researchers and planners. This paper represents the personal view of the authors, prepared for a conference in August 1992.

Adult↗
PubMed1994

Investigation into the duration of action of sustained-release ibuprofen in osteoarthritis and rheumatoid arthritis.

The duration of action of sustained-release ibuprofen ('Brufen Retard') was investigated in a 14-day double-blind study involving 14 osteoarthritis and 10 rheumatoid arthritis patients. The recommended once-daily dosage of this preparation (1600 mg taken in the evening) provided effective control of arthritic symptoms for both patient groups, with significant overall improvements in pain and stiffness compared to baseline. Substitution of placebo for a single dose of the active treatment resulted in a trend towards worsening of pain and stiffness in the rheumatoid group; however, the only statistically significant change involved impaired quality of sleep (p = 0.03) during the night after placebo administration, over 24-hours after the previous dose of active medication. In this particular study, symptom control was also clearly achieved for the osteoarthritis patients, as this group showed no deterioration within the same period. The 24-hour clinical action underlying these findings is consistent with ibuprofen plasma profiles obtained with the sustained-release preparation in earlier pharmacokinetic studies. It is likely that the greater sensitivity of rheumatoid patients to withdrawal of a single day's active treatment in this study reflects a more severe inflammatory disease process than that of the osteoarthritis patients.

Aged↗
PubMed1993

Treatment of hepatocellular carcinoma using doxorubicin/ethiodized oil/gelatin powder chemoembolization.

BACKGROUND: Hepatocellular carcinoma (HCC) is a common malignancy worldwide with limited effective therapeutic options available or appropriate for cirrhotic patients. METHODS: Chemoembolization, using sequential intra-arterial doxorubicin/ethiodized oil and gelatin sponge particle/ethanol embolization, was used to treat patients with unresectable HCC localized to the liver. Fifty-two patients were treated in this manner from 1988 to 1992. The objective response was determined by sequential computed tomography (CT) scans. RESULTS: Of the 47 patients evaluable for response, 20 (43%) achieved a partial response, and 12 (26%) achieved a minor response. Sixteen patients underwent repeated chemoembolization for locally recurrent disease as many as three times after the initial procedure. All 52 patients were evaluable for survival and toxicity, with a median follow-up of 14 months. Twelve-month survival was 60%, and median survival was 16 months. This compares favorably with values reported in the literature of approximately 20% and 6-14 weeks, respectively. There was a 17% 30-day mortality, with a slightly higher risk for patients with portal vein obstruction. Other toxicities generally were mild and transient, including fever, pain, encephalopathy, and malaise. CONCLUSIONS: Chemoembolization may enhance survival for patients with unresectable, localized HCC. It appears to be an effective alternative to standard treatment, even in cirrhotic patients.

Adult↗
PubMed1993

Cytomegalovirus immune globulin prophylaxis in liver transplantation. A randomized, double-blind, placebo-controlled trial.

OBJECTIVE: To study the effect of cytomegalovirus immune globulin (CMVIG) on prevention of cytomegalovirus (CMV) disease and its complications in patients receiving liver transplants. DESIGN: Randomized, multicenter, placebo-controlled, double-blind trial. SETTING: Four university-affiliated transplant centers in Boston (Boston Center for Liver Transplantation). PATIENTS: One hundred forty-one liver transplant recipients completed the study. INTERVENTION: CMVIG or placebo (1% albumin) given in a dose of 150 mg/kg body weight within 72 hours of the transplant, then at weeks 2, 4, 6, and 8, and at 100 mg/kg at weeks 12 and 16. MEASUREMENTS: Patients were observed for 1 year after transplantation for the development of CMV infection, disease, pneumonia, as well as for opportunistic fungal infections, graft survival, and mortality. Weekly cultures were taken of urine, buffy coat, and throat wash for CMV for 2 months, then monthly, and at any clinical illness. RESULTS: Using a Cox proportional hazards model, CMVIG was shown to reduce severe CMV-associated disease (multi-organ CMV disease, CMV pneumonia, or invasive fungal disease associated with CMV infection) from 26% to 12% (relative risk, 0.39; 95% CI, 0.17 to 0.89). When we controlled for the use of monoclonal antibodies to T cells (OKT3), CMVIG use was still protective (relative risk, 0.39; CI, 0.17 to 0.90). Rates of CMV disease were reduced from 31% to 19% (relative risk, 0.56; CI, 0.3 to 1.1) in CMVIG recipients although no effect on rates of CMV infection, graft survival, or patient survival at 1 year were shown. When we controlled for the urgency of transplantation and OKT3 use, a reduction in CMV disease (relative risk, 0.22; CI, 0.06 to 0.81) was shown for globulin recipients for all serologic groups except for the highest risk group (the CMV-seropositive donor, CMV-seronegative group). CONCLUSION: CMVIG reduced the rate of severe CMV-associated disease in patients undergoing orthotopic liver transplantation. No effect of CMVIG on CMV donor-positive, recipient-negative liver transplant recipients was shown, suggesting a need for additional prophylactic strategies.

Acyclovir↗
PubMed1993

Application of chromosome microdissection probes for elucidation of BCR-ABL fusion and variant Philadelphia chromosome translocations in chronic myelogenous leukemia.

Fluorescence in situ hybridization (FISH) has become an increasingly important method for assessing chromosome rearrangement. The reciprocal translocation constituting the Philadelphia (Ph) chromosome [t(9;22)(q34;q11)] characterizes more than 90% of patients with chronic myelogenous leukemia (CML). However, in the remaining cases the Ph chromosome (genetically characterized by the fusion of the BCR-ABL genes) is thought to arise through complex translocations that are often not readily apparent using routine chromosome-banding analysis. For this reason we have developed unique band-specific probes for two-color FISH that detect unequivocally the Ph chromosome, and its derivatives. Results of the application of these probes are illustrated by analysis of 11 cases of CML (9 of which contain "variant" translocations). The probes were generated by chromosome microdissection and in vitro amplification of the bands involved in the Ph translocation, leading to an extremely fast and sensitive approach to identify this alteration in leukemic cell populations.

Base Sequence↗
PubMed1993

Expression of c-Jun as a response to dorsal root and peripheral nerve section in damaged and adjacent intact primary sensory neurons in the rat.

It was previously shown that the immediate early gene, c-jun, was highly expressed over long periods, in both peripheral sensory and motor neurons following axon damage or block of axoplasmic transport. Here we have examined the question of whether the expression of c-Jun protein is related to axon injury per se or to the process of axon growth. We have examined dorsal root ganglion (DRG) cells subjected to different manipulations which are associated with varying degrees of regrowth, as follows: (i) after peripheral nerve section, where it appears that all damaged neurons make some regenerative effort. 1-24 days after sciatic nerve section and ligation most cells in L4/L5 DRG were c-Jun-positive; (ii) after section of the central processes of the DRG cells, which then showed a slow and limited regrowth of their axons towards, but not into, the spinal cord. This resulted in a variable, but significant, expression of c-Jun in a small number of DRG cells; (iii) in intact sensory neurons that were offered the opportunity to sprout into adjacent denervated peripheral tissue. The sciatic nerve was ligated and the response of cells in the L3 ganglia (many of which project to the saphenous nerve) was measured. A small but significant number of cells were c-Jun-positive; (iv) in intact sensory neurons that were offered the opportunity to sprout centrally into partialy denervated neuropil of the spinal cord. We examined neurons in the L3 DRG after rhizotomy of the adjacent L4/L5 dorsal roots. Previous work suggests that sensory neurons show at best a very limited growth under these conditions.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Differential expression of immediate early genes in rubrospinal neurons following axotomy in rat.

Many immediate early genes are rapidly and transiently expressed in the central nervous system following a variety of stimuli. Damage to the axons of peripheral and certain central neurons has been shown to result in a long-term increase in expression of c-Jun in the parent cell bodies. In the peripheral nervous system this increased expression of c-Jun protein and mRNA develops over 24 h following sciatic nerve section and is maintained if the damaged nerve is ligated, but returns to basal levels if the peripheral nerve is allowed to regenerate. Here, we report on the response of rubrospinal neurons to spinal cord hemisection at levels C3 and T10. c-Jun expression was first seen at 12 h post-lesion in a limited number of rubral neurons. The number of positively stained neurons increased up to 10 days post-lesion and then declined over the following weeks. By 7 weeks post-lesion there was still evidence of c-Jun immunoreactivity in both large and other clearly atrophic rubrospinal neurons. c-Fos immunoreactivity was seen only at 12-48 h in a small number of rubrospinal neurons. Evidence from retrograde tracing experiments following fluorogold application to the hemisected cord suggested that all c-Jun-positive neurons projected into the spinal cord. No c-Jun response was seen following a lesion at T10.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Neoadjuvant therapy for unresectable pancreatic adenocarcinoma.

The purposes of this study were to determine whether continuous infusion of fluorouracil combined with external-beam radiation therapy improved the resectability and survival of patients with pancreatic carcinoma. Sixteen patients with unresectable disease confined to the pancreas and celiac nodes were treated, and their outcome was compared with that of 24 patients with potentially resectable disease who were treated concurrently. The neoadjuvant therapy was completed with acceptably few toxic effects but with only a minor decrease in tumor size. Two patients underwent resection and remained free of disease 20 and 22.5 months later. However, the median survival of the entire neoadjuvant group was 8 months. All 24 patients with potentially resectable carcinoma underwent surgical exploration. Fifteen of the 24 patients underwent resection and survived a median of 12.5 months. Neoadjuvant chemoradiation may have improved outcome and resectability for two (12.5%) of 16 patients with unresectable pancreatic carcinoma, but more effective therapy options must be developed to improve outcome.

Adenocarcinoma↗
PubMed1993

Conditions for glutamate dehydrogenase activity in heart mitochondria.

Although heart mitochondria contain glutamate dehydrogenase, it has not been thought to play a role in their metabolism. We investigated this matter to define the conditions under which it is active. We found modest activity in the presence of glutamate and malate and a continuous source of ADP when pyruvate is added. This increases several fold as the osmolarity is increased from 296 to 370 mosM. At the higher osmolarity ammonia formation is brief, associated with a lower intramitochondrial alpha-ketoglutarate from citrate does not make up for the drop in glutamate conversion to alpha-ketoglutarate. Mitochondrial content of nucleotides and CoA compounds are not altered by pyruvate addition. The rate of glutamate deamination by GDH in sonicated heart mitochondria agrees with the rate of ammonia formation in intact mitochondria in the presence of pyruvate (20 nmol/min/mg of mitochondrial protein). We conclude pyruvate lowers mitochondrial oxalacetate which decreases alpha-ketoglutarate formation by transamination. The lower mitochondria alpha-ketoglutarate level permits glutamate deamination until alpha-ketoglutarate reaches a level that inhibits the forward reaction. Further proof of the key role of alpha-ketoglutarate is seen with aminooxyacetate which blocks transamination. In its presence ammonia formation occurs at the same rate (18 nm/min/mg of mitochondrial protein), is not dependent upon pyruvate, and does not stop after a couple of minutes. Leucine, which decreases alpha-ketoglutarate inhibition of GDH, also results in ammonia formation, further supporting the concept of regulation by alpha-ketoglutarate. The higher osmolarity increases GDH activity by increasing alpha-ketoglutarate transport from mitochondria.

Adenosine Diphosphate↗
PubMed1993

Localisation of glutamate receptor binding sites and mRNAs to the dorsal horn of the rat spinal cord.

The autoradiographic distribution of binding sites for [3H]AMPA, [3H]kainate, [3H]MK-801 and [3H]L-glutamate and the in situ hybridization of GluR-A, GluR-B, GluR-C and GluR-D in rat spinal cord sections were determined. All of the radioligands had similar localisations with the dorsal horn being the most intensely labelled region. In the in situ hybridization experiments only the GluR-B mRNA was detected at high levels in the spinal cord with predominant expression in the substantia gelatinosa. These results support electrophysiological evidence for the presence of glutamate activated neurones in the spinal cord and suggest that these excitatory pathways are confined mainly to the dorsal horn.

Animals↗
PubMed1993

Immune response of human volunteers and animals to vaccination with egg-grown influenza A (H1N1) virus is influenced by three amino acid substitutions in the haemagglutinin molecule.

Inactivated subunit vaccines were prepared from high-growth reassortants derived from two separate egg isolates from a single clinical specimen of influenza A (H1N1) virus. One of these reassortants, NIB-14, was antigenically indistinguishable from isolates made in tissue culture, while the other, NIB-17, was antigenically different and typical of egg isolates. The viruses differed by three amino acid residues in the haemagglutinin (HA) molecule and the anti-HA serological response induced was studied in animal models and human volunteers. In the volunteer groups both vaccines induced very high levels of circulating haemagglutination inhibition antibodies but with different serological specificities. Both NIB-14 and NIB-17 vaccines induced high levels of cross-reactive antibodies capable of reacting with both strains, but only NIB-14 vaccine induced significant levels of strain-specific antibodies capable of reacting exclusively with the homologous strain. Antisera containing only cross-reactive antibodies proved as capable of virus neutralization as antisera containing high levels of strain-specific antibodies. We extended the argument that epidemic strains are antigenically more closely related to tissue culture isolates and established that viruses which differ by only single amino acids at critical points in the HA structure can induce a significantly different immune response when used as inactivated vaccines.

Adolescent↗
PubMed1993

c-jun expression in substantia nigra neurons following striatal 6-hydroxydopamine lesions in the rat.

The proto-oncogene c-jun is thought to play a role in the control of growth and differentiation of many cell types. It has been demonstrated previously that damage to axons of peripheral motor or sensory neurons resulted within 24 h in substantially increased levels of the c-jun gene in the parent cell bodies. These increased levels of c-jun protein and messenger RNA are maintained if the damaged nerve is ligated, but return to basal levels if the peripheral nerve is allowed to regenerate. We have examined the expression of immediate early genes in central neurons of the rat and now show that a 6-hydroxydopamine-induced axotomy of the dopaminergic nigrostriatal pathway results in a substantial increase in the levels of c-jun (but not c-fos) messenger RNA and protein within neurons of the substantia nigra pars compacta. However, the central neuronal response differs from the peripheral nerve response in that it becomes maximal at four to eight days post-lesion and is transient, declining to control levels in nigral neurons by 14 days post-lesion. These expression patterns may be related to the differential capacity of central and peripheral neurons to regenerate. The precise role of c-jun in these processes, or in the regenerative response, is unclear but it remains possible that c-jun activation following axon damage leads to an increased expression of genes which are essential for the regenerative response. The nature of the mechanism by which c-jun levels are attenuated in central neurons is also unclear, but inhibitory factors, generated by the central environment, may play a role.

Animals↗
PubMed1993

Ependymal cells of the choroid plexus express tumour necrosis factor-alpha.

Tumour necrosis factor-alpha (TNF alpha) is a major proinflammatory cytokine which appears in the cerebrospinal fluid very early after endotoxin challenge, and is likely to be produced locally. Following in vivo and in vitro challenge with endotoxin, we have demonstrated immunocytochemically and by in situ hybridization that pig and guinea-pig choroid plexus ependymal cells can produce TNF alpha. Immuno-electron microscopy shows that this protein is localized within ependymal cells to the cytoplasm and microvilli. We suggest that this TNF alpha may be important in the initiation of the inflammatory response in bacterial meningitis.

Animals↗
PubMed1993

Enhancing appropriateness of acute bed use: role of the patient hotel.

OBJECTIVE: This study aimed to assess the appropriateness of bed use by determining patients' suitability for patient hotel accommodation and day treatment and by examining timeliness of discharge, and to assess patient and staff views about patient hotels. DESIGN: Patients were assessed by a doctor and nurse in terms of an agreed case definition for patient hotel use. Patient suitability was validated and patient acceptability measured by semi-structured interviews with a random sample of patients judged suitable for hotel accommodation. All senior medical and nursing staff completed a further questionnaire. SETTING: The study took place at University Hospital of Wales, Cardiff (856 beds), and all specialties, except intensive care wards, participated. SUBJECTS: Patients occupying a total of 3972 bed days, accumulated over seven randomly chosen census days, were studied. RESULTS: Data were available for 88% of eligible inpatients. Ten per cent (405 of 3972) of patients were judged suitable for a patient hotel. Specialties indicating major use were obstetrics and gynaecology, general surgery, and general and geriatric medicine. Sixty three per cent (254 of 405) of these subjects required low level investigation or treatment. Preoperative and postoperative and antenatal patients were often suitable also. Three per cent (119 of 3972, 95% confidence interval 2.5, 3.6%) of inpatients were judged suitable for day treatment/investigation. Seventy nine per cent (291 of 369) of patients suitable for discharge were discharged on the same or the next day. The patient hotel idea was acceptable to 58 of 68 (85%) randomly selected patients and to 84 of 93 (90%) staff. CONCLUSIONS: With allowance for non-response, our study indicates that a general hospital of this size generates the need (inpatients, relatives, and ward attenders) for a mean of 72 patient hotel beds. There is also residual scope for increasing day treatment/investigation and for releasing beds by speeding discharge. The patient hotel idea is highly acceptable to both patients and staff and should be widely considered as a means of making patient care more efficient.

Adolescent↗