Warren J. Warwick

Diabetes mellitus associated with cystic fibrosis

The prevalence of overt diabetes mellitus and carbohydrate intolerance was studied in 448 patients with cystic fibrosis (CF). Insulin-dependent diabetes (IDDM) developed in 7.6% of patients (13 male and 21 female). Survival was significantly lower (P less than 0.01) in the IDDM-CF group, with fewer than 25% surviving to age 30 years, whereas nearly 60% of the nondiabetic CF population reached this age. A significant deterioration in CF clinical status, based on NIH score, became apparent 2 years before onset of overt IDDM (P less than 0.05 at 2 years prior, P less than 0.01 at IDDM diagnosis). Total glycosylated hemoglobin (HbA1) was significantly (P less than 0.001) higher for the total CF population (7.3% +/- 1.2%) than for the general non-CF population (6.5% +/- 0.7%), and in the IDDM-CF group (P less than 0.05) compared with normoglycemic CF control patients. Female patients had a higher mean HbA1 after 12 years of age than their male counterparts did (P less than 0.02). HBA1 did not predict the development of IDDM, but there was a weak inverse relationship between HbA1 and both NIH clinical score (r = -0.41, P less than 0.02) and standard pulmonary function tests (forced vital capacity, r = -0.25, P less than 0.01) in the general CF population. Therefore, impaired carbohydrate tolerance in CF is associated with progressive clinical deterioration.

The unborn patient.

Gregg and Hutchinson (p 1059) tell of 15 infants who would probably have died as fetuses save for intrauterine exchange transfusion and who, at an average age of 2 years, have normal physical and mental development. Their report confirms the hopes that have led mothers and physicians to accept risks, discomforts, and complications in order that the techniques of intrauterine exchange transfusion might be developed and refined. The report will also be a stimulus for the many who have watched such studies with reservations to undertake treatment of the unborn child with isoimmune hemolytic disease. Most important, however, the report will compel us to enlarge our concepts of the patient-doctor contract, the contract that exists whenever there is a sick patient and a doctor who will provide care. The qualities of choice, knowledge, and direct interaction that are crucial to the doctor-patient relationship are not basic to the patient-doctor contract.

The impact of family functioning on health changes in children with cystic fibrosis

Family stress, family and personal resources, and parental coping were operationalized from self-report questionnaires completed by mothers and fathers in 72 two-parent families who had a child with cystic fibrosis (CF). Three-month and 15-month changes in clinically recorded measures of the CF childs height and weight data and pulmonary functioning were correlated with the family functioning variables. Each of the four criterion indices of CF child health changes were regressed separately on the significant family functioning variables. Twenty-two percent of the variance in 15-month height and weight changes were explained by family stress, family resources, and parental coping. Family functioning variables also explained 17% of the variance in 3-month pulmonary functioning changes and 15% of the variance in 3-month height and weight changes. These findings suggest that the way in which the family functions has indirect effects on critical indices of a CF childs health. These data lend support to an increased focus by physicians and other medical professionals on the health of the total family system as a way to enhance outcomes for children with CF.

Axonal dystrophy in the gracile nucleus in congenital biliary atresia and cystic fibrosis (mucoviscidosis): beneficial effect of vitamin E therapy.

In 63 patients with malabsorption syndromes, 16 with congenital biliary atresia (BA) and 47 with cystic fibrosis (CF), axonal dystrophy in the gracile nucleus (ADG) was studied. Of the 16 patients with BA, ADG of considerable severity was observed in all 10 over one year of age. Of the 47 patients with CF, it was observed in 32, 61, and 80% of the cases in the first, second, and third decades, respectively. Evidence is presented that there has been a substantial decrease in the incidence of ADG in CF patients in recent years and that the decreased incidence is attributable to vitamin E (Aquasol E) therapy. The beneficial effect of vitamin E supplementation in CF patients is proffered as strong evidence that ADG in BA and CF is related to vitamin E deficiency. The present study indicates that BA and CF patients require vitamin E supplementation to maintain a normal integrity of axons related to the gracile and perhaps other sensory nuclei. Critical neurological evaluation for possible dysfunction of the sensory nuclei in these patients with malabsorption syndromes is advised.

An international/multicentre report on patients with cystic fibrosis (CF) over the age of 40 years.

BACKGROUND The lifespan of patients with cystic fibrosis (CF) is increasing significantly. The objective of this international pilot study was to study the characteristics of these long-term survivors. METHODS Four centres with large CF clinics from London (UK), Minneapolis (USA), Toronto (Canada) and Verona (Italy) identified 366 patients who had survived 40 years and longer. RESULTS At all centres males survived longer than females. There were more pancreatic sufficient patients in Verona (60%) and Toronto (40%) than in London (16%) and Minneapolis (21%). The percentage of DeltaF508 homozygous patients varied between 47% in London and 45% in Minneapolis to only 26% in Toronto and 9% in Verona. Average FEV(1) and BMI values of the surviving population appeared to stabilise after 40 years of age. FEV(1) was on average 12% higher in patients who were pancreatic sufficient (p > 0.0001). There was no difference in survival between the centres. The overall median survival after the age of 40 was 13 years. The estimated annual death rate was approximately 3.4% from the age of 40-60 years. CONCLUSIONS Significant numbers of patients are now surviving to 40 years or more, and it is hoped that an in-depth study of these patients may identify the factors contributing to longer survival.

Neutrophil granulocyte function in patients with pulmonary infection

Neutrophil granulocyte function was evaluated in patients with pulmonary disease to determine if a change in function occurred during active pulmonary infections. Twenty-five patients with cystic fibrosis of the pancreas were studied. Ten patients were asymptomatic and 15 patients had symptoms and signs of active pulmonary infection. Leukotaxis, random migration, and nitroblue tetrazolium dye reduction by neutrophils were compared in the asymptomatic and symptomatic patients. The leukotactic activity of circulating neutrophils was markedly increased in all of the patients with active pulmonary infection and spontaneous nitroblue tetrazolium dye reduction by neutrophils was increased in 13 of 15 patients. Bacterial infection confined to the respiratory tract is capable of stimulating circulating neutrophils making them more responsive to chemotactic factors as well as increasing nitroblue tetrazolium reduction.

Cancer risk among patients with cystic fibrosis

Increased risks of cancer have been described with several constitutional disorders, including Down syndrome, neurofibromatosis, and many others. Speculation on whether cystic fibrosis should be added to this list is based in part on several case reports of cancer among persons with CF 112 and a report of an increased number of deaths from leukemia among family members of patients with CFJ 3 The recent finding of the proximity of the CF gene to the met oncogene has added to interest in such a clinical association. As aggressive pulmonary therapies have increased the life expectancy of patients with CF, an inherited predisposition to malignancy, previously obscured by the short life span of these patients, may become evident.

Feasibility and compliance studies of a home measurement monitoring program for cystic fibrosis

A home measurement monitoring system has been developed for assessing progress and planning changes in care for patients with cystic fibrosis. Daily diary recording of specified measurements, quantitative symptom data, and free text are to be used for early detection of deteriorating trends before serious complications develop. Daily measurements made at home are lung capacity, body weight, breathing rate, and pulse. The program has been in place for the past two years, and has maintained a 75-80% consistent diary response rate among the 111 patients initially committed to the program. Measurements are easy to perform, equipment design is simple and rugged, and data handling routines designed for the program using the INSIGHT clinical data base system perform satisfactorily. Checking for data entry errors and validity checks of home measurements are a regular part of the data handling activity. Patient acceptance and long-term compliance in this program agrees very favorably with reports of other diary programs in chronic disease. Diary compliance was significantly greater among younger patients and those who lived long distances from the hospital. This study has demonstrated that home monitoring is a feasible program for patients with cystic fibrosis. It presents the possibility of detecting adverse health trends earlier than is now practical, so that patients can be treated before serious complications develop, thereby preventing the large fluctuations in health status that often accompany CF.

Open thoracotomy and pleural abrasion in the treatment of spontaneous pneumothorax in cystic fibrosis.

The various treatments of spontaneous pneumothorax in cystic fibrosis are examined over a 15-yr period. Open thoracotomy with pleural abrasion is compared to observation, tube thoracostomy, and tube thoracostomy with instillation of quinacrine. Open thoracotomy with pleural abrasion has been performed 31 times in 20 patients. Discussion centers around selection of patients, preoperative preparation, operative technique, and postoperative care and follow-up, including analysis of pulmonary function studies. In our experience, open thoracotomy with pleural abrasion is a safe and effective method that should be utilized in the management of pneumothorax in patients with cystic fibrosis.

Doubling time α-aminoisobutyrate transport and calcium exchange in cultured fibroblasts from cystic fibrosis and control subjects

Abstract Population doubling time, kinetics of transport of α-aminoisobutyrate (AIB) and calcium (Ca) exchange were studied in skin fibroblast monolayers obtained from 5 subjects with cystic fibrosis (CF) and 5 age- and sex-matched controls. Population doubling time as estimated from cell count, protein and DNA was no different in the two groups. KM, Vmax, maximal uptake and time of half maximal uptake of AIB were no different in the two groups. Intracellular Ca pool size based on exchange of 45Ca with unlabelled Ca was significantly greater in monolayers from CF subjects.