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Biomedical subjects

R Nash

Publications and source records attributed to R Nash.

At least 19 recordsLinked to original sources

The results of subintimal angioplasty in a district general hospital.

OBJECTIVES AND DESIGN: we report a prospective study to determine if subintimal angioplasty can be performed in non-teaching centres and to establish its learning curve. MATERIALS AND METHODS: subintimal angioplasty was performed on 50 limbs in 46 patients (34 male) with a median age of 72 years (range 45-93 years). Indication was critical limb ischaemia (27 limbs) or intermittent claudication (23 limbs). Occlusions were located in the superficial femoral artery in 44 limbs, popliteal artery in 4 limbs and the peroneal artery in two limbs. At a median of 7.9 months patients had colour duplex imaging of the vessels that underwent angioplasty to assess vessel patency. RESULTS: primary technical success was achieved in 39 cases (78%). Primary technical success was greater in the second group of 25 consecutive limbs to undergo angioplasty at 92% (23 cases) compared with the first 25 consecutive limbs at 64% (16 cases). At 6 months the overall vessel patency rate on duplex imaging was 57%, improving to 64% in the group having a primarily successful procedure. The equivalent rate of symptomatic improvement was 59 and 66% respectively. Complications occurred in five procedures, most were minor, but a single fatality was directly attributable to the procedure. CONCLUSION: subintimal angioplasty can reasonably be performed outside major teaching institutions. There is a short learning curve associated with the procedure.

Aged↗

Prevention of de novo hepatitis B infection in liver allograft recipients with previous hepatitis B infection or hepatitis B vaccination.

OBJECTIVES: To assess de novo hepatitis B virus (HBV) transmission from liver donors with HBV serum markers (HBM) to their recipients and the need for HBV vaccination before liver transplantation. METHODS: A total of 108 orthotopic liver transplantations for nonviral disease and the risk of developing de novo hepatitis B based on HBMs before transplantation have been studied. Of the 108 patients, 94 met the study criteria and were divided into two groups: 27 who had HBMs before transplantation (from past infection or by previous vaccination) and 67 who had no HBM. Development of de novo hepatitis B was determined by analytical, serological, and histological parameters. RESULTS: No case (0%) of de novo hepatitis B was detected in the pretransplantation HBM group, whereas there were 10 cases (14.5%) in the other group (p < 0.005). CONCLUSIONS: The presence of pretransplantation HBM in liver transplant recipients protects these patients against the development of de novo hepatitis B. This is especially important considering that there is a high prevalence of donors with positive hepatitis B core antibody (especially in some countries), and that these donors transmit HBV infection to recipients without HBM in a significant number of cases. Thus, vaccination against HBV in patients who are candidates for liver transplantation is fundamental to avoid cases of de novo hepatitis B.

Adult↗

Acylated apigenin glycosides from alfalfa (Medicago sativa L.) var. Artal.

Three flavones, including 4'-O-[2'-O-E-feruloyl-O-beta-D-glucuronopyranosyl(1-->2)-O-beta-D-glucuronopyranoside]apigenin, 7-O-beta-D-glucuronopyranosyl-4'-O-[2'-O-E-feruloyl-O-beta-D-glucuronopyranosyl(1-->2)-O-beta-D-glucuronopyranoside]apigenin and 7-O-beta-D-glucuronopyranosyl-4'-O-[2'-O-p-E-coumaroyl-O-beta-D-glucuronopyranosyl(1-->2)-O-beta-D-glucuronopyranoside]apigenin have been identified in alfalfa var. Artal. The known flavone 7-O-[2-O-E-feruloyl-[beta-D-glucuronopyranosyl(1-->3)]-O-beta-D-glucuronopyranosyl(1-->2)-O-beta-D-glucurono-pyranoside] apigenin was also isolated. The structures of these compounds were deduced on the basis of their spectral data.

Acylation↗

Multiple sclerosis flares associated with recombinant granulocyte colony-stimulating factor.

Four of 10 patients who were enrolled on protocols of high-dose immunosuppression with peripheral blood stem cell rescue for MS experienced neurologic worsening while receiving recombinant human granulocyte colony-stimulating factor. There was improvement when methylprednisolone was given to three of the patients, but one patient died of respiratory failure. The mechanism of the neurologic worsening is uncertain.

Adult↗

Enhanced endothelialization and microvessel formation in polyester grafts seeded with CD34(+) bone marrow cells.

The authors have shown accelerated endothelialization on polyethylene terephthalate (PET) grafts preclotted with autologous bone marrow. Bone marrow cells have a subset of early progenitor cells that express the CD34 antigen on their surfaces. A recent in vitro study has shown that CD34(+) cells can differentiate into endothelial cells. The current study was designed to determine whether CD34(+) progenitor cells would enhance vascular graft healing in a canine model. The authors used composite grafts implanted in the dog's descending thoracic aorta (DTA) for 4 weeks. The 8-mm x 12-cm composite grafts had a 4-cm PET graft in the center and 4-cm standard ePTFE grafts at each end. The entire composite was coated with silicone rubber to make it impervious; thus, the PET segment was shielded from perigraft and pannus ingrowth. There were 5 study grafts and 5 control grafts. On the day before surgery, 120 mL bone marrow was aspirated, and CD34(+) cells were enriched using an immunomagnetic bead technique, yielding an average of 11.4 +/- 5. 3 x 10(6). During surgery, these cells were mixed with venous blood and seeded onto the PET segment of composite study grafts; the control grafts were treated with venous blood only. Hematoxylin and eosin, immunocytochemical, and AgNO(3 )staining demonstrated significant increases of surface endothelialization on the seeded grafts (92% +/- 3.4% vs 26.6% +/- 7.6%; P =.0001) with markedly increased microvessels in the neointima, graft wall, and external area compared with controls. In dogs, CD34(+) cell seeding enhances vascular graft endothelialization; this suggests practical therapeutic applications. (Blood. 2000;95:581-585)

Animals↗

Bone marrow transplantation in the treatment of systemic sclerosis.

Systemic sclerosis (SSc) is an uncommon, progressive, sometimes lethal fibrotic disease whose pathogenesis probably includes immunologic elements, especially early in its course. There is no proven therapy for this disease, although some promising results have been obtained with the use of immunosuppressive drugs such as cyclophosphamide. There exists a subgroup of patients who have rapidly progressive disease or who are not responsive to conventional treatment, and who may benefit from intensive immunosuppression with stem cell rescue (stem cell transplantation). The rationale for bone marrow transplantation (BMT), and, more recently, peripheral blood stem cell transplantation (SCT), has been validated by studies on animal models of autoimmunity. Autologous transplantation has shown encouraging anecdotal results, and it is now being evaluated in phase I/II studies in patients with predictably poor outcome. In this light, reliably identifying patients early in the course of SSc is extremely important in order to establish correct eligibility criteria. For patients unable to tolerate transplant regimens, other approaches may be feasible. In this regard, nonmyeloablative approaches, such as immunosuppression without rescue and mixed chimerism, are also discussed.

Bone Marrow Transplantation↗

Striated muscle cells in non-neoplastic lung tissue: a clinicopathologic study.

This study was performed to study the prevalence, origin, and clinical implication of striated muscle cells in congenital non-neoplastic lung abnormalities. Five cases of striated muscle cell proliferation within congenital non-neoplastic pulmonary abnormalities were identified from a series of 31 (16%) resected specimens obtained at King's College Hospital, London, during the period 1992 to 1998. Lung tissue was also obtained from 48 normal human fetuses and serial sections stained for the presence of striated muscle. A histologic and immunohistochemical study of the clinical cases and the fetal material was performed by using phosphotungstic acid hematoxylin staining and immunostaining for myoglobin and desmin. Striated muscle cells were identified either as a diffuse or a focal proliferation within the lung interstitia of five infants. The congenital lung anomalies were intra-abdominal pulmonary sequestration associated with congenital cystic adenomatoid malformation (CCAM), intrathoracic sequestration again with features of CCAM, an intrathoracic sequestration associated with a congenital diaphragmatic hernia, and 2 Stocker type II intrathoracic CCAMs. Striated muscle cells were not identified in any section of lung tissue derived from the fetal series. Striated muscle cells proliferation in non-neoplastic lung tissue is more common than usually reported. Although the exact origin of such cells is speculative, because it is always detected within pulmonary anomalies, a wide morphogenetic error is likely. The clinical implication of its presence has to be further defined. HUM PATHOL 31:1477-1481.

Adult↗

Pain and the administration of analgesia: what nurses say.

Pain of moderate to severe intensity continues to be an important problem for many hospitalized patients. Nurses spend more time with patients than any other health professional group and have a key role to play in the management of patients' pain. This paper reports the findings from a series of focus group interviews which were undertaken to explore nurses' perceptions regarding pain and the administration of narcotic analgesia. Themes identified from participants' comments related to (1) the pivotal role of nurses in pain management; (2) nursing assessment and pain management decisions (3) individual factors influencing nurses' pain management decisions and (4) the influence of others on nurses' pain management decisions.

Analgesics, Opioid↗

Effects on breathing of carotid body denervation in neonatal piglets.

The purpose of these studies was to test the hypothesis that carotid chemoreceptor activity is necessary for postnatal maturation of the ventilatory control system. By using a lateral surgical access, 17 piglets were carotid body denervated (CBD) and 14 were sham denervated at 3-25 days of age. After surgery, there was no irregular breathing in any group. There was no significant hypoventilation when CBD was performed at less than 5 days of age (n = 5) and only a mild (arterial PCO(2) 5 Torr; P < 0.05) to moderate, transient (arterial PCO(2) 8 Torr; P < 0.5) hypoventilation in piglets denervated at 10-15 (n = 6) and 20-25 (n = 6) days of age, respectively. Three weeks after surgery, both breathing of a hypoxic gas mixture and jugular venous NaCN injections elicited a hyperpnea in the CBD piglets that was attenuated compared with that in sham CBD piglets. In the CBD piglets, there was no response to injections of NaCN in the carotid arteries, but there was a response to NaCN injected into the proximal descending aorta, suggesting the residual peripheral chemosensitivity was of aortic origin. Carotid chemoreceptor-intact piglets had carotid and aortic NaCN chemosensitivity by 2 days of age. The carotid response persisted for the 40 days of the study, but the aortic reflex persisted only until approximately 8 days of age. We conclude that 1) the major effect of CBD per se in neonatal piglets is age-dependent hypoventilation and 2) there is a high degree of plasticity in peripheral chemosensitivity in neonates that may contribute to minimizing the changes in breathing after CBD.

Animals↗

Intra-abdominal pulmonary sequestration associated with congenital cystic adenomatoid malformation of the lung: just an unusual combination of rare pathologies?

A case of intra-abdominal pulmonary sequestration associated with histological features of congenital cystic adenomatoid malformation (CCAM) of the lung is reported. The lesion consisted of a Stocker type II CCAM in which numerous striated muscle cells were present. A review of the literature of this rare combination of congenital pulmonary anomalies is presented.

Adult↗

Tacrolimus pharmacokinetics in BMT patients.

The pharmacokinetics of tacrolimus following its administration as monotherapy or in combination with corticosteroids or methotrexate to 31 BMT patients are presented. All patients received i.v. tacrolimus initially and were subsequently switched to p.o. dosing. Patients received methotrexate by i.v. bolus on post-transplantation days 1, 3, 6 and 11. Patients were started on i.v. corticosteroids beginning on post-transplantation day 7. The noncompartmental pharmacokinetics of tacrolimus based on whole blood concentrations were determined following the i.v. and p.o. doses and were not different at steady-state compared to a single dose. The mean terminal elimination half-life of tacrolimus was 18.2 h following i.v. administration; the total body clearance was 71 ml/h/kg, the volume of distribution was 1.67 1/kg. Co-administration of methylprednisolone or methotrexate did not significantly alter tacrolimus pharmacokinetics. The p.o. bioavailability was 31-49%. Trough blood concentrations (Cmin) at 0 h (pre-dose) and 12 h (post-dose) correlated well to AUC(0-12)indicating that, as in solid organ transplantation, Cmin was a good index of drug exposure. Correlation at 0 h (r = 0.92) and at 12 h (r = 0.93) indicate that either time point can be used for therapeutic drug monitoring in patient management.

Administration, Oral↗

Reproducibility in retrospective grading of acute graft-versus-host disease after allogeneic marrow transplantation.

We have undertaken a formal study to evaluate the reproducibility of retrospective assessments for grading the severity of acute GVHD. Using criteria previously established by the Seattle group, three reviewers independently assigned GVHD severity grades for a set of 100 marrow transplant patients. Significant differences were found in the distribution of GVHD grades assigned by one of the reviewers as compared to the other two reviewers. In only 40% of cases did all three reviewers assign the same GVHD grade, and in only 68-71% of cases did all three reviewers assign the same grade within 0-I vs II-IV or 0-II vs III-IV categories. Despite the high rate of disagreement between any two reviewers, at least two reviewers assigned the same overall GVHD grade in 93% of cases. These results suggest that current criteria for assessing the severity of GVHD by a single reviewer are not sufficiently reliable for rigorous clinical studies. As an alternative to the original criteria, we have developed and tested simplified criteria that summarize the clinical course of GVHD as reflected by the progression of disease and the amount of immunosuppressive treatment used to control the disease. Our results suggest that the revised criteria might yield more reproducible retrospective grading than the original criteria. Although the original criteria and the revised criteria might produce different results for individual patients, the overall distributions of grades with the two systems were similar. The proposed revised criteria could be implemented without disrupting the continuity and consistency with previous grading assigned by the original criteria.

Bone Marrow Transplantation↗

The prevalence and perception of pain amongst hospital in-patients.

The aim of this paper is to describe the prevalence and perceptions of pain and pain management amongst hospital in-patients. A cross-sectional descriptive survey of 205 patients was conducted. Presence and severity of pain was assessed using verbal descriptor and visual analogue scales, and perceptions of pain were assessed using multi-item scales. Although the severity of pain reported was consistent across age groups and clinical areas, women in the study sample were significantly more likely to report high levels of pain than men. Differences in how men and women communicate their pain were observed, with women indicating that they were less willing to ask for help with their pain. Results suggest that pain continues to be an important problem for a large number of men and women in hospital, and that the experience of pain impacts negatively upon their well-being. Gender differences in the experience of and response to pain remain important considerations for clinical nurses who have major responsibilities for the management of pain in hospitalized patients.

Adolescent↗

Treating skin tears in nursing home residents: a pilot study comparing four types of dressings.

A pilot study was conducted to compare four types of dressings used to treat skin tears in nursing home residents. Wounds treated with a non-occlusive dressing healed more quickly than those dressed with occlusive dressings. The results suggest that ease of use and product wastage are important considerations when treating skin tears. The pilot study also highlights the need for further research into skin tear management and the need for ongoing education for nurses regarding skin integrity risk assessment and product information.

Aged↗

Cyclosporine or cyclosporine plus methylprednisolone for prophylaxis of graft-versus-host disease: a prospective, randomized trial.

Patients with a lymphohematopoietic malignancy considered to be at high risk for posttransplant relapse were enrolled in a study to compare the use of cyclosporine (CSP) as a single agent with a combination of methylprednisolone (MP) and CSP for graft-versus-host disease (GVHD) prophylaxis after marrow transplantation from an HLA-identical sibling donor. Sixty patients were randomized to receive CSP only and 62 were randomized to receive CSP plus MP. Daily CSP was started on day -1 (5 mg/kg/d intravenously) and administered at gradually reduced doses until day 180. MP was started on day 7 at 0.5 mg/kg/d, increased to 1.0 mg/kg/d on day 15, started on a taper schedule on day 29, and discontinued on day 72. All 104 evaluable patients (surviving > or =28 days) had sustained engraftment. The incidence rates of grades II-IV acute GVHD were 73% and 60% for patients receiving CSP and CSP plus MP, respectively (P = .01). No difference was seen for grades III-IV GVHD. However, chronic GVHD occurred somewhat more frequently in patients receiving CSP plus MP (44%) than in patients receiving only CSP (21%; P = .02). The incidence of de novo chronic GVHD was marginally higher in patients receiving CSP plus MP (P = .08). No significant differences in the risk of infections were observed. There was a suggestion that the risk of relapse was lower in patients receiving CSP plus MP (P = .10) and, although the overall survival in the two groups was not different (P = .44), there was a slight advantage in favor of CSP plus MP-treated patients for relapse-free survival (P = .07). These results suggest that prophylactic MP, when combined with CSP, has only limited efficacy in acute GVHD prevention and may increase the probability of chronic GVHD.

Adolescent↗