Essential fatty acid deficiency and home total parenteral nutrition patients

The requirements for essential fatty acids in patients on home parenteral nutrition are not well described. We therefore studied the needs of 12 patients receiving parenteral nutrition for at least 4 mo (range: 4 mo-17.3 yr; mean 7.0 +/- 5.2 yr). Prior to the study, each patient had been receiving intravenous lipids either weekly or biweekly and had a triene to tetraene ratio (TTR) on plasma phospholipids performed at least annually. A TTR > or = 0.2 was considered diagnostic for essential fatty acid deficiency (EFAD). The purpose of this study was to determine the required intravenous lipid supplementation in patients on home total parenteral nutrition (HTPN). Patients with an initial TTR of < 0.2 had their intravenous lipid stopped and changes in their serum phospholipid fatty acids were followed every 3-4 wk. Nine of 12 patients had TTRs > 0.2 at some point in the study. Phase I consisted of patients who at initiation of the study had normal TTRs and were taken off lipid supplementation until their TTR became abnormal. Phases II, III, IV, and V consisted of lipid delivered in total nutrient admixtures in biweekly doses of 0.6, 1.2, 1.8, and 2.4 g of fat/kg bodyweight, respectively. Eight patients normalized their TTRs on the biweekly lipid regimens; one patient expired before his ratio normalized; and three patients could not be made deficient in essential fatty acids after 26 or more wk of fat-free parenteral nutrition. Most patients required 1.2 to 2.4 g of lipid/kg bodyweight/biweekly to correct serologic EFAD. The clinical background, as well as the length of small bowel remaining, did not seem to identify those patients who required lipid supplementation nor the final dose of lipid needed to normalize their TTRs.     

Severe Clostridium difficile-associated colitis in young patients with cystic fibrosis

We report four patients with cystic fibrosis and fulminant Clostridium difficile-associated colitis: two died, and one required hemicolectomy. Three of four patients carried the N1303K mutation. Severe and fatal C. difficile colitis can occur in cystic fibrosis patients, possibly with a genotype-specific predilection (i.e., N1303K/other). Because cystic fibrosis patients may have a wide spectrum of gastrointestinal symptoms, disease caused by C. difficile must be considered when these patients have acute abdominal pain, diarrhea, or severe leukocytosis.     

Functional iron deficiency in adults with cystic fibrosis

Functional iron deficiency (transferrin saturation < 16%) was found in 44 (62%) of 71 adult cystic fibrosis (CF) patients. Haemoglobin concentration and mean cell volume were lower in iron-deficient patients, in whom there was a non-significant trend for lower serum ferritin. Ten iron-deficient patients and two patients with transferrin saturation > = 16% (normal iron) were anaemic. There were no significant differences between iron-deficient and normal-iron patients in intake of calories, protein, iron and vitamin C as determined by 4-day records of dietary intake. Dietary iron deficiency is not an important factor in functional iron deficiency in adult CF patients. Impairment of absorption by exogenous pancreatic enzyme supplements is unlikely to be significant as enzyme intake was the same in the two groups. Iron-deficient patients had lower Shwachman-Kulczycki scores and lower percent predicted forced expiratory volume in 1 s (FEV1% predicted) and forced vital capacity (FVC% predicted). There was a non-significant trend for higher values of white cell count and plasma viscosity in the iron-deficient group. Chronic inflammation is likely to be the primary cause of functional iron deficiency in adult CF patients. Fifteen patients completed 3-month courses of oral iron replacement with no deterioration in pulmonary function, but with no effect on haemoglobin concentration.     

Osteoporosis in patients with cystic fibrosis

Decreased bone density and increased risk of fractures are seen in patients with cystic fibrosis. Suboptimal vitamin D levels, nutrition problems, hypogonadism, inactivity, corticosteroid use, and cytokines may contribute to the low bone mass seen in these patients. Treatment recommendations must be individualized and may include nutrition, vitamin D, estrogen or testosterone, and exercise. In high-risk patients calcitonin or growth hormone could be considered.     

Pregnancy in patients with cystic fibrosis

With increasing life span of patients with CF, more women with CF are becoming pregnant and others are seeking information about the risks involved during pregnancy and delivery. A striking limitation of the available information is the lack of large prospective studies of pregnant patients with CF matched for age and disease severity compared with their non-pregnant cohorts. A study investigating the effect of pregnancy on morbidity and mortality is being completed by the Cystic Fibrosis Foundation. We recommend that all women with CF be offered contraceptive measures and counseling on the maternal and fetal risks of pregnancy, including the genetic risks for the child. The issue of who will raise the child in the event of subsequent morbidity or maternal mortality should ideally be prospectively discussed.     

Enhanced oxidative damage in cystic fibrosis patients

Antioxidant depletion and increased free radical production by inflammatory cells have been described in cystic fibrosis (CF) patients. To evaluate oxidative damage intensity, we measured plasma concentrations of malondialdehyde, hydroperoxides and protein carbon groups as markers of oxidative injury to lipids and proteins in a group of 101 CF patients free of acute exacerbation, and in 43-112 controls. Moreover, we estimated antioxidant function by measuring activities of erythrocyte superoxide dismutase, glutathione reductase and vitamin E concentrations. In CF patients, malondialdehyde and hydroperoxide plasma levels were significantly higher than in controls (p < 0.001). Increased lipid peroxidation was documented by these two markers. Parallel rises in protein carbonyls in plasma of CF patients were observed (p < 0.0001). These patients presented biochemical but not clinical vitamin E deficiency. Glutathione reductase and superoxide dismutase activities were significantly higher than in controls. These results show a serious imbalance of CF patients between oxidant-antioxidant status leading to oxidative stress.     

Glucose tolerance in patients with cystic fibrosis

In order to define prevalence and incidence of diabetes mellitus in cystic fibrosis, we followed 191 unselected patients above two years of age (median 13.6) in a five-year prospective study with annual oral glucose tolerance tests. The prevalence of diabetes increased from 11 to 24% during the study period with an annual age-dependent incidence rate of 4-9%. Diabetes was diagnosed at a median age of 21 years (range 3-40). At diagnosis of diabetes, hyperglycaemia, fasting hyperglycaemia (> or = 7.8 mmol/l), and increased haemoglobin Alc levels (> 6.4) were present in 33%, 16% and 16% of the diabetic patients, respectively. Impaired glucose tolerance implied a higher risk than normal glucose tolerance for the development of diabetes (odds ratio 5.6). In 58% of cases with impaired glucose tolerance, however, glucose tolerance was normalised at the next annual test. Normal glucose tolerance was found in only 37% of the patients at all five tests. Within this group of patients, median fasting and two-hour post-load plasma glucose concentrations and haemoglobin Alc levels increased by 6-8% during five years. Thus, the prevalence and incidence of diabetes in patients with cystic fibrosis is very high and increases with age. Since symptoms of hyperglycaemia and increased fasting plasma glucose and haemoglobin Alc levels are inconstant findings in newly diagnosed diabetic cystic fibrosis patients, we recommend annual oral glucose tolerance tests in all cystic fibrosis patients above the age of 10 years.     

Ursodeoxycholic acid improves the hepatic metabolism of essential fatty acids and retinol in children with cystic fibrosis

An ELISA sandwich for the detection of Giardia lamblia antigens in human faeces was standardized. 175 samples were studied: 77 positive, 61 negative to cysts and/or trophozoites by direct faeces test, and 19 positive to other parasite different from G. lamblia. The sensitivity of the technique was 94.8% and the specificity 98.3%. The method detects an antigen concentration of 31 ng. The procedure is simple, sensitive and specific so, it may be useful for diagnosis and in epidemiological studies.     

Vitamin A deficiency and nocturnal vision in teenagers with cystic fibrosis

The aim of this study was to document plasma retinol status and nocturnal vision in ten eutrophic adolescents with cystic fibrosis (CF) receiving daily retinol supplementation. Plasma retinol, alpha and beta carotenes and retinol binding protein were measured in ten clinically stable CF patients (mean age: 14.3 years; Shwachman score: 80-100). Nocturnal vision evaluation was performed with a Beyne optometer. Plasma retinol (mean 0.42 +/- 0.16 mg/l), alpha carotene and beta carotene levels were below the lower limit of normal in all but one patient. Five out of ten patients with normal standard opthalmological examination presented a poor (n = 3 patients) or a pathological (n = 2) dark adaptation test. These two patients showed a dramatic increase in nocturnal vision after 1 year of adapted retinol supplementation. CONCLUSION: Low vitamin A levels occur frequently in clinically stable, eutrophic and retinol supplemented CF adolescents. Since vitamin A deficiency is associated with poor nocturnal vision and since this pattern can be reversed by adapted retinol supplementation, we recommend monitoring plasma vitamin A levels in CF patients and evaluation of dark adaptation in retinol deficient patients.     

Correlates of osteopenia in patients with cystic fibrosis

The responses to heat shock in Tritrichomonas mobilensis, a squirrel monkey parasite and Tritrichomonas augusta, an amphibian trichomonad, were evaluated by means of metabolic labeling with [35S]methionine. Electrophoretically separated trichomonad proteins synthesized at different temperatures were visualized by autoradiography and the label incorporation quantitated by a trichloroacetic acid precipitation procedure. A considerable difference in thermotolerance between the two species was found as the protein synthesis reached a maximum at 41 C in T. mobilensis and 37 C in T. augusta. The latter tolerated temperature increases 13 C above normal cultivation temperatures as compared to only 4 C thermotolerance range above normal in T. mobilensis. Major heat shock proteins (Hsps) were expressed in both T. mobilensis (with apparent Mr 94, 72, and 58 kDa) and T. augusta (Mr 94, 70, and 56 kDa) as revealed by autoradiography. Western blot analysis with polyclonal antibody against DnaK of Escherichia coli showed the presence of antigenic Hsp70 homologs in both trichomonads. Similarly, a polyclonal antibody against Hsp60 with broad interspecies cross-reactivity detected Hsp60 homologs in both T. mobilensis and T. augusta. The anti-DnaK antibody cross-reacted with a T. mobilensis protein localized in Golgi apparatus as demonstrated by immunoelectron microscopy. Immunocytochemistry on trichomonad frozen sections revealed the presence of the Hsp60 homolog in light-microscopic granules corresponding to hydrogenosomes.     

Pharmacokinetics of famotidine in patients with cystic fibrosis

Famotidine pharmacokinetics were studied in 13 patients with severe cystic fibrosis (CF) ranging from 10 to 47 years of age and 25 to 72 kg in weight. Patients were randomized to first receive famotidine either 20 mg intravenously or 40 mg orally. Twelve patients were crossed over to the alternate treatment. Repeated blood samples were obtained over 12 hours after intravenous and oral administration and urine was collected over 24 hours for quantitation of famotidine by means of high-performance liquid chromatography (HPLC). A compartment model-dependent approach was used to characterize the disposition of famotidine. From the intravenous data, the mean +/- standard deviation elimination half-life (t1/2) was 2.11 +/- 0.75 hours, the total clearance (Cl) was 0.79 +/- 0.41 L/kg/hr, the renal clearance was 0.57 +/- 0.26 L/kg/hr, the fraction eliminated unchanged in the urine was 83% +/- 16%, and the apparent volume of distribution (Vdss) was 1.33 +/- 0.53 L/kg. The bioavailability determined from comparison of intravenous and oral area under the curve data was 71% +/- 27%. Results of this study support an initial famotidine dose of 20 mg intravenously or 40 mg orally every 12 hours in patients with CF who are older than 9 years of age.     

Anaesthesia for liver transplantation in cystic fibrosis patients

INTRODUCTION: Cystic fibrosis (CF) is a disease caused by an inherited genetic defect. While pulmonary and pancreatic abnormalities predominate the clinical spectrum, other organ involvement is common, including liver. The severity of liver disease does not appear to be related to the severity of exocrine pancreatic or lung function. We discuss anaesthesia in four CF patients undergoing liver transplantation. METHODS: We studied haemodynamic and oxygenation modifications during anaesthesia in four patients affected by CF with end-stage liver disease and mild to moderate pulmonary abnormalities. The patients received pancreatic enzyme prior to transplantation and two had insulin-dependent diabetes mellitus. All patients were treated with broad-spectrum antibiotic therapy. After a waiting time ranging one week to three months, all patients were successfully transplanted. General anaesthesia was induced with fentanyl, thiopental and pancuronium, and maintained with isoflurane supplemented by fentanyl in O2:air. Haemodynamic and oxygenation evaluations were made during the main phases of the transplant. After the intubation and at the end of the procedure all patients received a broncho-alveolar toilet through fiberoptic bronchoscopy. RESULTS: During anaesthesia for liver transplantation, PaO2 increased proportionally to the decreasing of Qs/Qt. In postoperative follow-up, Fev1 and FVC improved from preoperative time in all patients. In conclusion, even if cystic fibrosis is a multisystem disease, liver transplantation can be offered to CF patients with endstage liver disease and mild to moderate pulmonary function abnormalities. The four patients are still alive, enjoying good health. The improved respiratory function and quality of life of these children is remarkable.     

Psychosocial functioning of young adults with cystic fibrosis and their families

BACKGROUND: The psychosocial functioning of adolescents and young adults with cystic fibrosis still living in the parental home was investigated. With its proven genetic aetiology cystic fibrosis is an ideal model with which to assess the impact of a chronic and life threatening disorder on family and individual psychological and social functioning. METHODS: Twenty nine patients with cystic fibrosis and their families were compared with those of 27 patients with anorexia nervosa and 31 well controls. Assessments were made using self reporting, interview, and observational methods. RESULTS: Most patients with cystic fibrosis were in robust psychological health and only differed from their healthy peers in that they were much less likely to be in employment. Mothers of patients with cystic fibrosis or anorexia nervosa were more likely than the mothers of the well group to be emotionally distressed, although this was not so for fathers. Young people in both illness groups were more likely to have parents with high levels of expressed emotion. Most families of patients with cystic fibrosis had good problem solving abilities. CONCLUSIONS: In spite of the burden of illness in cystic fibrosis psychological functioning in many respects matches that of well young people.     

Infections in patients with cystic fibrosis following lung transplantation

BACKGROUND: There is controversy over whether colonization with drug-resistant organisms is a contraindication to lung transplantation. METHODS: We undertook a retrospective review of the results of lung transplantation for patients with cystic fibrosis (CF) at Duke University Medical Center. RESULTS: As of May 1996, 21 patients with CF underwent bilateral lung transplantation. The first patient died within 24 h of transplantation from sepsis due to Stenotrophomonas maltophilia. Of the remaining 20 patients, 17 (85%) are alive and in stable condition. The three deaths were related primarily to bronchiolitis obliterans at 4 and 18 months in two patients and to cytomegalovirus pneumonitis at 5 months in the other patient. The 17 surviving patients have been followed up for a mean of 13 months (range, 0.5 to 34 months). Most of them were colonized and infected with multidrug-resistant organisms before transplantation. Following transplantation, 11 patients had complications from infections. One patient had bacteremia due to a panresistant Burkholderia cepacia and was treated successfully. Two patients had bacteremia and wound infection due to Burkholderia gladioli, previously thought to be pathogenic only in plants. Both patients were treated successfully. Of the six patients with Aspergillus fumigatus isolated from cultures before transplantation, only one had invasive disease following transplantation and responded to treatment. CONCLUSION: The organisms present before transplantation were not the primary cause of mortality in our patient population. Our findings suggest that lung transplantation should be considered in CF patients infected with multidrug-resistant organisms.     

Chemotactic factors in bronchial secretions of cystic fibrosis patients

To understand chronic neutrophil attraction into cystic fibrosis airways, both global chemotactic activity and individual chemotactic factors were studied in bronchial secretions. Bronchial secretions of 8 cystic fibrosis patients, collected on the first day of admission for antibiotic treatment, showed a high chemotactic index (19.4 +/- 5.7, n = 8). Fractionation by gel filtration of bronchial secretions resulted in three chemotactic fractions. The first factor corresponded to interleukin-8, and the second activated neutrophils via the FMLP receptor. The third factor, which was of lower molecular weight, did not activate FMLP or leukotriene B4 receptors, and its nature is still under investigation. Treating patients with antibiotics reduced global chemotactic activity, mainly by reducing the activity due to stimulation of the FMLP receptor.     

Neutrophil collagenase in sputum from patients with cystic fibrosis

The potential role of neutrophil elastase in causing lung damage and exacerbating the inflammatory response in cystic fibrosis (CF) has received considerable attention. Although another potent neutrophil-derived enzyme, collagenase, is implicated in tissue destruction in several interstitial lung disorders, there has been no reference to this enzyme in CF. The objective of this study was to determine whether neutrophil collagenase is present in active form in CF sputum and, if so, whether it is related to disease severity. High levels of active collagenase were detected in sputum from patients with CF, and the majority of the enzyme present was of neutrophil origin. In a group of 16 patients with CF, negative relations between sputum collagenase activity and Shwachman score (r = -0.55, p < 0.05) and FEV1 (r = -0.59, p < 0.02) were noted, indicating an association between high collagenase activity and severity of disease. A positive correlation was observed between sputum collagenase and elastase activity (r = 0.62, p < 0.05). These results suggest that both neutrophil elastase and collagenase may play a significant role in lung destruction in CF.