Isolated lung transplantation for end-stage lung disease: a viable therapy.

Since January 1990, we have performed 29 isolated lung transplantations in 28 patients with end-stage lung disease (12 single, 16 bilateral). Recipient diagnoses were: cystic fibrosis (11), chronic obstructive pulmonary disease (6), pulmonary fibrosis (6), eosinophilic granulomatosis (1), postinfectious lung disease (1), adult respiratory distress syndrome (1), and primary pulmonary hypertension (2). There have been four deaths, two in patients with pulmonary fibrosis and two in patients with primary pulmonary hypertension. Four patients have undergone transplantation while on ventilatory support for respiratory failure (2 with cystic fibrosis, 1 having redo lung transplantation with cystic fibrosis, and 1 with adult respiratory distress syndrome); all of these have survived. Six patients required cardiopulmonary bypass, which was associated with increased transfusion requirement. All patients 2 months after discharge have returned to an active life-style, except for 2 patients who currently await retransplantation. Preoperative pulmonary rehabilitation has resulted in significant improvement in exercise performance in all patients. Immunosuppression consists of cyclosporine, azathioprine, and antilymphoblast globulin (University of Minnesota), withholding systemic steroids in the early postoperative period. We have employed bronchial omentopexy in all but four transplants; there has been one partial bronchial dehiscence, two instances of bronchomalacia requiring internal stenting, and one airway stenosis. Cytomegalovirus disease has been seen frequently (15 cases), but has responded well to treatment with ganciclovir. Other complication shave included one drug-related prolonged postoperative ventilation, thrombosis of a left lung after bilateral lung transplantation requiring retransplantation, five episodes of unilateral phrenic nerve palsy after bilateral lung transplantation (4 resolved), and the requirement of massive transfusion (greater than 10 units) in 5 patients.(ABSTRACT TRUNCATED AT 250 WORDS)     

Parenting stress among caregivers of children with congenital cataracts.

OBJECTIVE: To examine parenting stress among caregivers of young children with congenital cataracts and to assess whether diagnostic and/or treatment differences are associated with differences in perceived parenting stress. METHODS: Parents of 41 preschool-age children with congenital cataracts (13 with bilateral cataracts [BCCs] and 28 with unilateral cataracts [UCCs], of whom 14 were aphakic and 14 were pseudophakic) completed the Parenting Stress Index (PSI) and/or a disease-specific parental stress measure, ie, the Ocular Treatment Index (OTI). RESULTS: The 28-item OTI had excellent internal consistency (alpha = 0.94) and supported three of four a priori validity hypotheses. Parents of children with congenital cataracts reported normal parenting stress levels on the PSI. Parents of children with UCCs tended to report higher levels of stress, but not significantly so, than did parents of children with BCCs. Among parents of children with UCCs, those whose children were aphakic reported higher levels of stress on the OTI and all of the PSI subscales than did parents of pseudophakic children. These differences were statistically significant for two subscales (Adaptability [P =.03] and Mood [P =.01]). CONCLUSIONS: Although parents of children with congenital cataracts generally did not report increased parenting stress levels, clinicians should be aware that parenting stress can adversely impact patients' families. We did observe higher stress levels in parents with children who had UCCs and did not receive an intraocular lens-particularly stress related to their child's reaction to sensory stimulation and mood-compared with parents of pseudophakic children. Thus, clinicians may want to consider parenting stress levels when choosing a treatment for children with UCCs, especially because such stress has been associated with poor treatment compliance for children with other chronic conditions.     

Identification and characterization of insulin receptors in basolateral membranes of dog intestinal mucosa

Little is known about hormonal regulation of substrate transport and metabolism in the mucosal lining of the small intestine. Because insulin regulates these functions in other tissues by binding to its receptor, we have investigated the presence of insulin receptors in canine small intestinal mucosa with basolateral membranes (BLM) and brush border membranes (BBM) prepared by sorbitol density centrifugation. A14-[125I]iodoinsulin was used to study binding and structural characteristics of specific insulin receptors in BLM. Analysis of receptors in BLM identified binding sites with high affinity (Kd 88 pM) and low capacity (0.4 pmol/mg protein) as well as with low affinity (Kd 36 nM) and high capacity (4.7 pmol/mg protein). Binding was time, temperature, and pH dependent, and 125I-labeled insulin dissociation was enhanced in the presence of unlabeled insulin. Cross-reactivity of these receptors to proinsulin, IGF-II, and IGF-I was 4, 1.8, and less than 1%, respectively. Covalent cross-linking of labeled insulin to BLM insulin receptors with disuccinimidyl suberate revealed a single 135,000-Mr band that was completely inhibited by unlabeled insulin. There was a 16-fold greater specific binding of insulin to BLM (39.0 +/- 2.4%) than to BBM (2.5 +/- 0.6%). These results demonstrate the presence of a highly specific receptor for insulin on the vascular, but not the luminal, surface of the small intestinal mucosa in dogs, and suggest that insulin may play an important role in the regulation of gastrointestinal physiology.     

The effects of phorbol esters with different biological activities on protein kinase C

The sapintoxins are a series of naturally occurring fluorescent phorbol esters with a range of selective biological activities (e.g. pro-inflammatory but non-tumour promoting). Their ability to activate protein kinase C (PKC) in vitro has been studied. Both tumour promoting and non-promoting phorbol derivatives activate the enzyme in vitro at low concentrations. 12-deoxyphorbol-13-phenylacetate-20 acetate (DOPPA) acts as a partial agonist in the activation of protein kinase C. Structurally distinct phorbol esters may therefore preferentially activate different forms of protein kinase C. α-sapinine, a biologically inactive compound, binds to protein kinase C without stimulating the enzyme and prevents subsequent activation by phorbol esters such as 12-O-tetradecanoyl phorbol-13-acetate (TPA).