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Biomedical subjects

B Whitehead

Publications and source records attributed to B Whitehead.

At least 37 records · Page 2Linked to original sources

Cardiac transplantation in childhood cancer survivors in Great Britain.

The aim of this study was to identify patients treated in Great Britain for childhood cancer and subsequently referred for cardiopulmonary transplantation in order to assess diagnosis, cancer treatment, management and outcome. Computerised record linkage between the National Registry of Childhood Tumours and the national transplant database held and maintained by the United Kingdom Transplant Support Service Authority (UKTSSA) was used to identify patients. Verification and clinical details were then obtained from the oncology and transplant centres. 16 patients were identified from the 31992 cases of childhood malignancy diagnosed in Britain since 1970. These comprised 13 heart transplants, 2 heart/lung transplants and 1 patient who died while on the heart transplantation waiting list. All 14 potential heart transplant patients had cardiomyopathy presumed secondary to anthracycline therapy. The original diagnoses were acute myeloblastic leukaemia (3), Wilms' tumour (4), rhabdomyosarcoma (2) and one each of five different solid tumours. Median age at diagnosis was 44 months (range 4-165 months). Median anthracycline dose was 413 mg/m2 (range 240-680 mg/m2). 13 of the 14 potential cardiac transplantation patients were more than 2 years from end of their cancer treatment before requiring transplantation and the transplantation was performed 2-126 months after onset of cardiac failure at a median age of 163 months. Five year actuarial survival from transplantation was 74%. There was no recurrence of the original malignancy in any of these patients. Both heart/lung patients died, 3 and 11 months after the transplant. These heart transplantation data suggest that, in Britain, survival compares favourably with that of patients whose heart transplant was required for other causes of cardiomyopathy. This indicates that patients successfully treated for childhood cancer should not be excluded from transplant programmes.

Adolescent↗

Voice onset time in speech produced during simultaneous communication.

This study investigated speaking rate and voice onset time (VOT) in speech produced during simultaneous communication (SC) by speakers with normal hearing. Stimulus words initiated with voiced and voiceless plosives were embedded in a sentence that was spoken and produced with SC. VOT measures were calculated from acoustic recordings and results indicated significant differences between speech-only and SC conditions, with speech produced during SC demonstrating both slower speaking rate and increased VOT of voiceless consonants. VOTs produced during both SC and speech-only conditions followed English voicing rules and varied appropriately with place of articulation. The somewhat enlarged voicing contrast during SC was consistent with previous findings regarding the influence of rate changes on the temporal fine structure of speech (Miller, 1987) and was similar to the voicing contrast results reported for clear speech by Picheny, Durlach, and Braida (1986).

Communication↗

Ventricular expression and circulating levels of insulin-like growth factor I in heart transplant recipients.

1. Insulin-like growth factor I is a major mediator of growth-promoting activities. We studied the ventricular insulin-like growth factor I gene expression at mRNA and peptide levels in 24 heart transplant recipients (14 children and 10 adults), using 'slot blot' hybridization with insulin-like growth factor I cDNA probe and a specific radioimmunoassay. 2. Ventricular insulin-like growth factor I mRNA was detected in all the cardiac transplant children but was below the limit of detection in the cardiac transplant adults. Ventricular insulin-like growth factor I levels were significantly higher in the transplant children [174 +/- 15 (SEM; range 39-950) pg/mg soluble protein] than in transplant adults [39 +/- 2 (range 14-85) pg/mg soluble protein, P < 0.01, n = 14]. Circulating levels of insulin-like growth factor I in the cardiac transplant children [164 +/- 10 (range 105-192) ng/ml] and adults [176 +/- 15 (range 126-244) ng/ml] were within normal ranges for children and adults. 3. These results suggest that the human heart is a site for insulin-like growth factor I production and provide support for an autocrine role for insulin-like growth factor I in the ventricle, despite cardiac denervation.

Adolescent↗

Evaluation of a training course on sexual counselling in a drug work setting.

It has been repeatedly reported that while risks associated with the injecting behaviour of drug users has been reduced, no parallel changes have been made in sexual risk behaviour. Counselling advice to clients attending drug unit services has not focused sufficiently on the sexual behaviour of this client group. The present study evaluates the impact of a 4-day tailored training course on the counselling practices of two teams of drug workers at a London hospital. The course was designed following the experience and evaluation of a more general training course on sexual issues, and included information, group discussions, experiential learning and skills training. Results indicate that though there were no significant behavioural changes, some attitudinal changes have taken place; training appears to have increased the staff's awareness of the importance of sexual counselling and reduced the perceived difficulty of discussing certain specific sexual issues. The implications of single-agency training courses are discussed and recommendations are made for future training courses on the basis of the findings of this study.

Acquired Immunodeficiency Syndrome↗

Paediatric incidence of acute rejection and obliterative bronchiolitis: a comparison with adults.

Obliterative bronchiolitis (OB) continues to be a major cause of morbidity and mortality following heart-lung transplantation. We compared the incidence of death from obliterative bronchiolitis in 19 children and 72 adults following heart-lung transplantation at our institutes. The incidence of death from OB at 2 years was 38% for children compared with 17% for adults, this difference was significant (Cox-Mantel Z value = 2.243, P < 0.05). The frequency of acute lung rejection and persistent lung rejection, previously described as risk factors for OB in adults, were significantly more common in children, P = 0.004 and P = 0.001, respectively. Average forced expiratory volume in 1 s was lower in children than in adults for each 3-month period after transplantation (P < 0.001). In conclusion, identified risk factors for the development of OB were more common, and the risk of death from OB was greater in children than in adults following heart-lung transplantation.

Adolescent↗

Ventricular expression and circulating levels of immunoreactive dynorphin in heart transplant recipients.

1. Dynorphin, an endogenous opioid peptide, acts on specific kappa-opioid receptors in the rat heart for the local regulation of atrial natriuretic peptide release. No known study has examined the expression of dynorphin in the human heart. 2. In the present study a specific radioimmunoassay technique was used to determine ventricular expression of dynorphin at the peptide level in endomyocardial biopsy specimens and in plasma obtained from 13 heart transplant recipients. Ventricular biopsy specimens collected from 10 patients without cardiac complications during necropsy (less than 24 h from time of death) and plasma samples from 10 normal healthy subjects were used as controls. 3. The immunoreactive level of ventricular dynorphin was higher in heart transplant recipients (mean +/- SEM 141 +/- 32 pg/mg of soluble protein, range 7-573 pg/mg of soluble protein, P < 0.001) than in control subjects (16 +/- 3 pg/mg of soluble protein, 2-34 pg/mg of soluble protein). The plasma concentration of immunoreactive dynorphin was also higher (P < 0.001) in heart transplant recipients (mean +/- SEM 14 +/- 1 pg/ml, range 5-39 pg/ml) than in normal healthy subjects (7 +/- 0.4 pg/ml, 5-10 pg/ml). No relationship was observed between ventricular and plasma levels of dynorphin. 4. These results show that immunoreactive levels of dynorphin in plasma and ventricle are increased after heart transplantation, suggesting a possible pathophysiological role for dynorphin in the heart.

Adolescent↗

Ventricular expression of brain natriuretic peptide gene following orthotopic cardiac transplantation in children--a three year follow up.

OBJECTIVE: The aim was to examine ventricular brain natriuretic peptide (B-type natriuretic peptide, BNP) gene expression and to determine its relationship with ventricular BNP and circulating BNP levels in paediatric cardiac transplant recipients, over a three year period after transplantation. METHODS: Total RNA extracted from endomyocardial right ventricular biopsy tissues (n = 26) of 13 cardiac transplant recipients (age range 5-17 years) and 10 normal hearts obtained at necropsy (age range 19-76 years) as controls was analysed by northern and slot blot hybridisations. Specific radioimmunoassay techniques were used to determine levels of BNP and atrial natriuretic peptide (A-type natriuretic peptide, ANP) in plasma (n = 26) and ventricular biopsy (n = 26) samples. RESULTS: Ventricular BNP messenger ribonucleic acid (mRNA) levels from slot blot hybridisations in the transplanted heart [122(3) arbitrary units, range 97-143] were significantly higher (p < 0.01) than in the normal heart [63(5) arbitrary units, range 37-98]. Northern blot hybridisations confirmed this result and gave a major BNP mRNA transcript of approximately 900 nucleotides. There was no significant relationship between ventricular BNP mRNA levels and ventricular BNP (r = 0.15, p = 0.5, n = 26) or plasma BNP levels (r = 0.16, p = 0.4, n = 26). There was also no significant relationship between ventricular BNP mRNA levels and any of the haemodynamic variables, or immunosuppressive drugs. A ventricular ANP RNA transcript of approximately 900 nucleotides was detected in the transplanted heart but was below the limit of detection in the normal heart. For the long term study, increased levels of BNP and ANP in both plasma and ventricular samples were observed in the first year after transplantation, with a significant reduction (p < 0.01) in levels three years later. CONCLUSIONS: Ventricular BNP gene expression is increased at the mRNA level after heart transplantation in children. Expression of both ventricular BNP mRNA and ANP mRNA in the transplanted heart may be an important response in the modulation of cardiac function after transplantation.

Adolescent↗

Technique and use of transbronchial biopsy in children and adolescents.

Since July 1988, a total of 92 transbronchial biopsies (TBB) have been performed in 18 patients (aged 3-16 years). Twelve patients (67%) were heart-lung transplant (HLT) recipients undergoing surveillance for pulmonary graft rejection and infection. The remainder included immunocompromised patients at risk of opportunistic infections (n = 4), patients with fibrosing alveolitis (n = 1) and a collagen vascular disorder with suspected lung involvement (n = 1). TBB was performed through either a fiberoptic (n = 50) or a rigid (n = 41) bronchoscope, all under general anesthesia. On one occasion a cardiac bioptome was used through an endotracheal stent. The sensitivity of TBB for diagnosing acute and chronic rejection in HLT patients was 88% and 60%, respectively (specificity, 91% and 100%). Definitive diagnoses were made in 4 (67%) of the non-HLT group. Bronchoalveolar lavage (BAL) was performed during each procedure for microbiological and cytological examination. Thirty-four pathogenic organisms including Pseudomonas aeruginosa (16/34), Staphylococcus aureus (8/34), and Candida albicans (5/34) were isolated from BAL culture. Complications included pneumothorax (8%), transient pyrexia (7%), and dyspnea (2%).

Acquired Immunodeficiency Syndrome↗

Heart-lung transplantation for cystic fibrosis. 1: Assessment.

Forty five patients with cystic fibrosis (age 5-15 years) were assessed for heart-lung transplantation between September 1987 and March 1990. The two main conditions for acceptance were (i) life expectancy less than 2 years and (ii) a severely impaired quality of life. Patients were accepted onto an active waiting list (n = 26), a provisional waiting list (n = 15), or not accepted (n = 4). Selection was made on clinical grounds with objective measurements used as an aid in assessment. As expected, the mean values for objective measures were significantly different between patients on the active waiting list compared with the provisional waiting list/not accepted group for resting heart rate (118/minute v 101/minute), percentage of ideal weight (83.2% v 93.1%), forced expiratory volume at one second as percent of predicted normal (27.3% v 47.6%), Shwachman-Kulczycki score (33.6 v 52.5), Chrispin-Norman x ray score (25.8 v 22.1), 12 minute walk (540 m v 854 m), and minimal oxygen saturation (81.5% v 92%). Psychological evaluation demonstrated a 55% incidence of individual and a 50% incidence of family morbidity. Of the 26 patients accepted onto the active waiting list, 11 have been transplanted (mean waiting time 3.3 months), 10 have died within a mean of 3.7 months of acceptance, and five remain on the active list (mean 5.6 months).

Adolescent↗

Heart-lung transplantation for cystic fibrosis. 2: Outcome.

From March 1988 to March 1990, 11 children with cystic fibrosis (age 5-15 years) underwent combined heart-lung transplantation at our institutes. Maintenance immunosuppression consisted of cyclosporin and azathioprine with corticosteroids and antithymocyte globulin used perioperatively and during rejection episodes. Six patients (55%) survive from 1.5-23 months all of whom have improved life quality. Actuarial survival to 1 year was 55%. At six months after transplant, mean forced expiratory volume at one second was 73.5% of predicted normal, compared with 25% before transplant. There was one perioperative death, three later deaths associated with obliterative bronchiolitis at two, eight, and nine months, and one from mediastinitis at four months. Of the 15 children accepted for transplantation but not receiving grafts, 10 have died (eight within four months of being placed onto the transplant list). Early postoperative problems included acute reversible rejection (n = 10), meconium ileus equivalent (n = 3), and pancreatitis (n = 1). There was a high incidence of later pulmonary rejection with a mean of 5.7 episodes per patient in the first six months. Pulmonary infection occurred relatively infrequently, with Pseudomonas aeruginosa being the most common pathogen. Persistent diabetes mellitus requiring insulin occurred in four and systemic hypertension developed in one.

Adolescent↗

Heart and lung transplantation for terminal cystic fibrosis. A 4 1/2-year experience.

From among 112 patients with cystic fibrosis who were assessed for heart-lung transplantation, 83 were accepted. Twenty-six died while awaiting heart-lung transplantation and 32 had the operation. The management and the outcome of these 32 patients is reported. Survival, infection, and rejection rates among these patients were compared with those of 61 patients without cystic fibrosis who underwent heart-lung transplantation between 1984 and 1990. The cumulative survival rate was 72.29% +/- 94.91% at 1 year and 55.59% +/- 7.50% at 3 years. The mortality rate was slightly higher in the group with cystic fibrosis during the first year after the operation but it was lower at 3 years. The difference, however, could have been due to chance alone (p = 0.308). The same was true for the prevalence of rejection (up to 6 months: chi 2 = 1.8141, p = 0.17), and infection (up to 6 months: chi 2 = 2.20, p = 0.14), between the two groups. It is concluded that cystic fibrosis does not constitute an additional risk in terms of survival and morbidity after heart-lung transplantation.

Adolescent↗

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↗

Congenital self-healing Langerhans cell histiocytosis with persistent cellular immunological abnormalities.

We describe an infant who presented at birth with numerous haemorrhagic and encrusted skin lesions, hepatomegaly, lymphadenopathy, raised hepatic transaminases, leucopenia and thrombocytopenia. The diagnosis of Langerhans cell histiocytosis was confirmed by immunohistochemistry, which demonstrated the presence of CD1, S-100 and DR positive cells in the skin infiltrate. The skin lesions resolved spontaneously after 6 weeks but recurred at 3 months and again were self involuting with resolution by 9 months. Persistent circulating T-cell abnormalities, including T-cell lymphopenia and the presence and persistence of peripheral blood CD1 + cells were noted throughout the first year of life.

Cell Count↗

Transbronchial biopsies in children after heart-lung transplantation.

Sixty transbronchial biopsies have been performed in eight children after heart-lung transplantation. The selection of fiber-optic bronchoscope or a small (4 mm; 30 cm) rigid bronchoscope was made according to the size of endotracheal tube required at surgery. If the endotracheal tube was size 7.5 or greater, a fiber-optic bronchoscope was used, whereas if the endotracheal tube size was below 7, a rigid bronchoscope was used. For the diagnosis of lung rejection, the histology of biopsies revealed a sensitivity of 91% and specificity of 69% (similar to the result in adults). The histology also distinguished lung infection from rejection. Complications included three pneumothoraces and two clinically significant episodes of hemorrhage, one of which led to a cardiorespiratory arrest, which may have been caused by hypoxia. As a result, arterial oxygen saturation is now monitored during the procedure using a pulse oximeter.

Adolescent↗

Early experience of heart-lung transplantation.

We report our experience of heart-lung transplantation for the treatment of children with terminal respiratory disease. Between May 1987 and October 1988 we performed heart-lung transplantation in five children under the age of 16 (age range 11-15). All the patients were severely disabled by dyspnoea and hypoxia. Two had primary pulmonary hypertension, two cystic fibrosis, and one had Eisenmenger's syndrome. All five children are alive and well five to 17 months after operation and have returned to activities normal for their age. Three of the five patients had episodes of infection after operation. These were staphylococcal pneumonia, herpes simplex pneumonitis and, in one of the patients with cystic fibrosis, persistent purulent sputum. The mean number of episodes of rejection per child was 2.7 per half year. Heart-lung transplantation is a practical treatment for children in these disease groups with terminal respiratory failure.

Adolescent↗