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Biomedical subjects

J Wallwork

Publications and source records attributed to J Wallwork.

At least 217 records · Page 12Linked to original sources
PubMed1990

The histological changes in transbronchial biopsy after treatment of acute lung rejection in heart-lung transplants.

Transbronchial lung biopsies taken during episodes of acute lung rejection in heart-lung transplant patients were examined histologically. When the diagnosis was confirmed by microscopy, the patients were treated with augmented immunosuppression by high-dose corticosteroids. A second biopsy was obtained an average of 23.5 days after commencement of treatment. These biopsies were examined to determine the histological changes caused by treatment. In most cases, there were both quantitative and morphological differences between the infiltrates in acute rejection and in the remaining perivascular infiltrates after treatment. In acute rejection, 26 of 28 biopsies contained perivascular lymphocytic infiltrates, lymphocytes being large and blast-like. Although 20 of 28 follow-up biopsies still contained perivascular infiltrates, they were smaller and the lymphocytes smaller in size. Half the biopsies in rejection contained neutrophils, but less than half contained eosinophils in the perivascular infiltrates. After treatment, all these cells were less numerous. Another feature of treated rejection was the presence of haemosiderin around vessels suggesting earlier acute vascular injury. However, haemosiderin persists long after the cellular infiltrate has disappeared and cannot be considered a reliable feature of recently treated acute lung rejection. The bronchiolar infiltrates showed a similar pattern of responses to the perivascular infiltrates.

Adult↗
PubMed1990

Validation of impedance cardiography measurements of cardiac output during limited exercise in heart transplant recipients.

Twenty-one patients were studied at rest and during exercise after heart transplantation to compare cardiac output measured by thermodilution and impedance cardiography. Exercise was performed on a bicycle ergometer over a limited range of work load (25 and 50 watt) whilst metabolic gas exchange was recorded. One patient was studied at rest whilst his circulation was maintained by a Jarvik-7 artificial heart. The values of cardiac output measured by impedance cardiography corresponded closely with the flow rate from the artificial heart. There was also close agreement between the impedance and thermodilution measurements of cardiac output at rest and during exercise. Both measurements followed the changes in heart rate and oxygen consumption. Both thermodilution and impedance cardiography methods elicited good reproducibility of cardiac output measurements at rest and during exercise. These observations suggest that the noninvasive and continuous record of cardiac output obtained by impedance cardiography can be used for the postoperative monitoring of heart transplant recipients.

Adult↗
PubMed1990

Intensive care management of children following heart and heart-lung transplantation.

We report the intensive care management of 23 children (age 3-15 years) following orthotopic heart (HT) and combined heart and lung transplantation (HLT) performed at our 2 institutes between February 1985 and August 1989. Cyclosporin A, azathioprine and steroids were given as routine immunosuppression, whilst anti-thymocyte globulin (ATG) was used for the first 3 post-operative days. Mean ventilation time was 24.6 h (range 4-74 h). Cardiovascular support comprised isoprenaline infusions in all patients (mean period 65.7 h) whilst dopamine and other inotropic agents were used less frequently. Sequential atrioventricular pacing was required more often in the HT patients (n = 9) than in the HLT patients (n = 4). Fluid input was restricted to maintain a plasma osmolality of 290-300 mosm/kg. There were 2 perioperative deaths both due to acute right heart failure. Other post-operative complications included: bleeding (n = 3); acute graft rejection (n = 4); infection (n = 3); systemic hypertension (n = 6); neurological abnormalities (n = 2); renal dysfunction (n = 6) and hyperglycaemia (n = 6).

Adolescent↗
PubMed1990

Management following heart and lung transplantation: five years experience.

Since April 1984, 70 patients have received heart-lung transplants at our institution. Actuarial survival is 76% at 1 year and 68% at 2 years. All but 4 surviving patients have an unrestricted life style. Rejection was confirmed by lung transbronchial biopsy (TBB) on 277 occasions in 66 patients. Forty-two percent of episodes occurred within 1 month of surgery. Eight patients have developed evidence of chronic rejection with progressive irreversible fall in FEV1, of whom 4 have died or undergone single lung retransplantation. Seven patients had primary cytomegalovirus (CMV) of whom 4 patients died. Eight patients developed pneumocystis pneumonia of whom 1 died. Seven episodes of herpes simplex pneumonitis occurred of which one episode was fatal. Heart-lung transplantation is a valuable treatment for terminal cardiopulmonary disease and offers increasing hope of long-term survival.

Biopsy↗
PubMed1990

Cystic fibrosis: a new challenge for cardiothoracic surgery.

Cystic fibrosis (CF) is the most common fatal inherited disease in caucasian populations. Between 80-120 CF patients die each year in England and Wales, the majority from pulmonary disease. Since October 1985, 17 patients with CF have undergone heart-lung transplantation (HLT) at our institution. Only 3 early deaths have occurred in the first 2 postoperative months. Another patient died 9 months after transplantation. Thirteen patients are now alive 1-46 months (mean 14 month) post transplantation. Actuarial survival at 6 months is 80% for CF patients compared to 73% for non-CF patients. Both groups of patients have similar profiles of rejection and infection. In the Caucasian population, CF patients form the largest potential recipient group for HLT and our experience suggests that those CF patients who undergo HLT have a favourable outcome.

Actuarial Analysis↗
PubMed1990

Primary pulmonary hypertension: diagnosis, medical and surgical treatment.

Primary pulmonary hypertension continues to present both diagnostic and therapeutic challenges to the physician, reflecting the lack of understanding about the basic mechanism of the disease. The natural history of the condition has been described only recently, and this has allowed a reasonably accurate prognosis for the individual patient to be determined. New treatments have been found effective, including heart-lung transplantation, which can now offer improved survival. Long-term intravenous infusion of prostacyclin has a place in the treatment of severely affected patients awaiting heart-lung transplantation. However, the major impact of prostacyclin has been, perhaps, to concentrate research upon the role of the endothelial cell in the development of this disorder, in particular the potential role of an impairment of release of the recently described endothelium-derived relaxing factor in certain forms of pulmonary hypertension. We have attempted in this review to focus on the problems of diagnosis and treatment together with current developments in the understanding of primary pulmonary hypertension.

Heart-Lung Transplantation↗
PubMed1990

Altered pharmacokinetics of cyclosporin in heart-lung transplant recipients with cystic fibrosis.

The cyclosporin dose versus blood concentration relationship for 11 heart-lung transplant recipients with cystic fibrosis was studied retrospectively. Eleven patients, closely matched for age and gender, who received heart-lung transplantation for other diseases were selected as controls. Cystic fibrosis patients received 16.7 (SD 7.2) mg/kg/day of oral cyclosporin compared with 8.2 (SD 1.9) mg/kg/day given to the control patients (p less than 0.01). Nine of the cystic fibrosis patients received higher mean daily doses of cyclosporin. Mean blood cyclosporin concentrations were, however, not significantly different (p = 0.58), and there were no apparent differences in clinical outcome in terms of rejection, infection, and nephrotoxicity in the two groups. The apparent oral clearance of cyclosporin was significantly higher (p less than 0.01) in cystic fibrosis patients. Cyclosporin dosage individualization with the aid of cyclosporin blood concentration measurements is critically important in this subpopulation of heart-lung transplant recipients.

Administration, Oral↗
PubMed1990

Herpes simplex virus infection in heart-lung transplant recipients.

We report our experience of herpes simplex virus infection in a series of 51 recipients of heart lung transplantation (HLT). Nine patients, all of whom were seropositive for the virus preoperatively, developed HSV infection. Seven episodes of culture-proved mucocutaneous HSV infection without evidence of pulmonary involvement occurred in four patients. Six episodes of HSV pneumonia were seen in a further five patients, one of whom died. Diagnosis of HSV pneumonia was by histological appearances on transbronchial biopsy, together with culture of lung tissue or bronchoalveolar lavage. Concomitant cytomegalovirus infection occurred in four patients. All patients who developed HSV pneumonia did so within the first two postoperative months; in four patients following augmented immunosuppression. We now suggest that HLT recipients who are HSV antibody-positive should receive prophylactic acyclovir for the first two months after surgery and at times of augmented immunosuppression.

Acyclovir↗
PubMed1990

Altered sensitivity to amiloride in cystic fibrosis. Observations using cultured sweat glands.

1. Using cultured epithelia from sweat glands, derived from both cystic fibrosis and normal subjects, the relationship between amiloride concentration and the inhibition of electrogenic sodium transport was measured, under short circuit conditions. 2. The Kd for amiloride in cultures from normal subjects was 0.64 microM (n = 6) while in cultures derived from CF patients the value was 1.07 microM (n = 4). The values were significantly different (P less than 0.02, ANOVA). 3. In cultures from normal sweat glands, bathed in solutions free of permeable anions (chloride/bicarbonate), the Kd for amiloride rose to a value greater than found in CF tissues (2.3 microM). In CF epithelia subject to the same conditions the abnormally high value increased further, so that in solutions without permeable anions normal and CF cultures behaved similarly. 4. In cultures derived from normal and CF tissues lowering the sodium concentration to 10 mM also lowered the Kd for amiloride, however the shift was greater for CF cultures. 5. Several possible explanations for the results are discussed. The most probable is that the relatively more positive apical membrane potential in CF epithelia opposes the interaction of amiloride with the sodium channel, implying that complex formation is potential sensitive.

Adolescent↗
PubMed1990

Impairment of pulmonary endothelium-dependent relaxation in patients with Eisenmenger's syndrome.

A comparison has been made between the endothelium-dependent relaxation of pulmonary arteries (PA) obtained at heart-lung transplantation from 4 patients with Eisenmenger's syndrome and secondary pulmonary hypertension, and PA obtained at lobectomy from 4 patients with lung carcinoma, the controls. All vascular rings were studied immediately after lung excision. PA rings from control patients dose-dependently relaxed to cumulative doses of acetylcholine (ACh, 10(-10) to 10(-5) M), achieving a maximal relaxation of 80 +/- 5% (mean +/- s.e. mean) from precontraction with phenylephrine. By contrast, PA rings from Eisenmenger's syndrome patients achieved a maximal relaxation of only 34 +/- 12% (P less than 0.05, unpaired t test), with even paradoxical contraction at high doses of ACh (10(-6) to 10(-5) M). Sodium nitroprusside (10(-4) M) relaxed all PA rings, with and without endothelium (carefully removed before study), obtained from both control and Eisenmenger's syndrome patients. These results provide the first evidence that endothelium-dependent relaxation of PA mediated by endothelium-derived relaxing factors is impaired in Eisenmenger's syndrome patients with secondary pulmonary hypertension.

Acetylcholine↗
PubMed1990

Immunohistochemical demonstration of human cardiac innervation before and after transplantation.

Knowledge about the distribution and origins of peptide-containing nerves in the innervated and transplanted heart is lacking. Immunohistochemical and histochemical techniques were used to visualize human cardiac innervation before and after transplantation. In the recipient heart cardiac nerve fibers and fascicles displayed immunoreactivity for general neural (protein gene product 9.5 and synaptophysin) and Schwann cell markers (S-100). A major proportion of cardiac nerves displayed neuropeptide tyrosine and tyrosine hydroxylase immunofluorescence staining. Subpopulations of nerves contained somatostatin, vasoactive intestinal polypeptide, calcitonin gene-related peptide, substance P- or neurokinin-like immunoreactivity, and acetylcholinesterase activity. Tissues from cardiac allografts (5 weeks to 63 months after transplantation) contained nerves and ganglion cells that were acetylcholinesterase positive and immunoreactive for the general neural markers. These nerves were less numerous than in recipient hearts and rarely displayed neuropeptide immunostaining. Atrial natriuretic peptide immunoreactivity was localized to myocardial cells in transplanted hearts as well as explanted recipient and postmortem hearts. While most human cardiac allografts remain functionally extrinsically denervated, they appear to contain viable intrinsic nerves, and myocardial cells retain the capacity to produce atrial natriuretic peptide.

Adolescent↗