Daniel Katznelson

Prediction of mortality and timing of referral for lung transplantation in cystic fibrosis patients

Abstract: Lung transplantation (Tx) is an optional treatment for cystic fibrosis (CF) patients with end‐stage lung disease. The decision to place a patient on the Tx waiting list is frequently complex, difficult, and controversial. This study evaluated the current criteria for lung Tx and assessed additional parameters that may identify CF patients at high risk of death. Data were extracted from the medical records of 392 CF patients. Forty of these patients had a forced expiratory volume in 1 s (FEV1) less than 30% predicted, and nine of these 40 patients were transplanted. A comparison was performed between the survival of those transplanted (n = 9) and those not transplanted (n = 31), by means of Kaplan–Meier survival curves. The influence on survival of age, gender, nutritional status, sputum aspergillus, diabetes mellitus, recurrent hemoptysis, oxygen use, and the decline rate of FEV1, were investigated by means of univariate and multivariate analyses. The rate of decline of FEV1 was evaluated employing the linear regression model. CF patients with a FEV1 < 30% and who did not receive a lung transplant had survived longer than CF patients who did receive a lung transplant (median survival 7.33 vs. 3.49 yr, 5‐yr survival 73% vs. 29%). Two factors – rate of decline in FEV1 values and age < 15 yr – were found to influence the mortality rate, while the other parameters examined did not. Our results indicate that the current criterion of FEV1 < 30% predicted, alone is not sufficiently sensitive to predict the mortality rate in CF patients and time of referral for Tx, as many of these patients survive for long periods of time. Additional criteria to FEV1 < 30%, should include rapidly declining FEV1 values and age < 15 yr.

The gene encoding vasoactive intestinal peptide is located on human chromosome 6p21→6qter

SummaryVasoactive intestinal peptide (VIP) is a regulatory neuropeptide involved in a wide variety of functions, among them vasodilation, smooth muscle relaxation, sweat secretion, gastrointestinal peristalsis, and pancreatic function. A deficient VIP-innervation of sweat glands was recently described as a possible pathogenic factor in sweating of cystic fibrosis (CF) patients. To investigate a possible role for a defective VIP-gene in cystic fibrosis, we have used a panel of rodent-human hybrid cells, retaining defined complements of human chromosomes to localize the VIP-gene to the human chromosome region 6p21→6qter. As the CF gene was recently mapped to chromosome 7, we conclude that the VIP-gene is not the primary gene defect in this disease.

Renal Function in Patients with Cystic Fibrosis

Renal handling of sodium, potassium, calcium and phosphorus was investigated in 9 patients with cystic fibrosis (CF). Both under baseline conditions and during saline-induced diuresis, urinary excretion rate of sodium (UNaV), potassium, phosphorus and calcium did not differ significantly from control values although the fractional excretion of sodium was significantly higher in patients with CF during saline diuresis. When distally acting diuretics were administered, this difference between CF patients and controls was magnified and in addition, UNaV in CF patients was also significantly higher than in controls. Following saline loading the increment in glomerular filtration rate (GFR) in patients with CF was significantly lower than that of controls. We conclude that patients with CF when subjected to volume expansion demonstrate a lower tubular reabsorptive capacity of sodium as well as a reduced ability to increase their GFR. The defect in sodium reabsorption is probably located in the proximal tubule.

Disturbed fat absorption following infectious gastroenteritis in children.

Fat absorption was studied in 10 patients recovering from an episode of acute infectious gastroenteritis who failed to gain weight despite adequate caloric intake. Three patients restudied after clinical improvement and three other infants with failure to thrive, unrelated to gastrointestinal problems, served as control subjects. Fat balance studies during the ingestion of a formula containing long-chain fatty acids demonstrated significant degrees of steatorrhea in patients (mean CFA 70.6 +/- 10.7 compared to 90.3 +/- 2.4 in control subjects). The administration of a test meal demonstrated a marked deficiency of duodenal bile acid concentration and of fat incorporation into the micellar phase in patients. Fecal bile acid excretion was significantly increased in patients (mean 33.9 +/- 11.6 microM/kg/day) as compared to control subjects (mean 13.5 +/- 3.1 microM/kg/day). Bacterial overgrowth and abnormalities of the small intestinal mucosa were not constant. Ileal dysfunction and associated bile acid loss are possible causes of disturbed fat assimilation following acute intestinal infection in children.

Growth and puberty arrest due to prolactinoma.

ABSTRACT. A 13‐year‐old male with prolactin secreting pituitary tumor is described. The unusual features were arrested puberty and growth. Previously reported pediatric patients with prolactinoma are reviewed. The importance of serum prolactin measurement and bromocriptine therapy is emphasized.

Increased intracranial pressure in cystic fibrosis.

ABSTRACT. Three cystic fibrosis infants with severe respiratory distress had increased intracranial pressure (with bulging fontanels) which cleared parri passu with improvement in the chest condition. It is proposed that the intracranial hypertension is a result of raised venous pressure, itself secondary to the intrathoracic obstruction to venous return, consequent on the bronchial obstructive disease.

Serum CA 19-9 levels as a diagnostic marker in cystic fibrosis patients with borderline sweat tests

Abstract.Patients with normal or borderline sweat tests present a diagnostic challenge. In spite of the availability of genetic analysis and measurement of nasal potential difference, there is still uncertainty in diagnosing cystic fibrosis in some patients. CA 19–9 is a tumor-associated antigen whose levels were previously found to be elevated in some cystic fibrosis patients. We investigated whether serum CA 19–9 levels can contribute to establishing the diagnosis of cystic fibrosis in patients with a borderline sweat test, and evaluated the influence of different clinical variables on CA 19–9 levels. Serum CA 19–9 levels were measured in 82 cystic fibrosis patients grouped according to their genotype and in 38 healthy individuals. Group A included 50 patients who carried two mutations previously found to be associated with a pathological sweat test and pancreatic insufficiency (ΔF508, W1282X, G542X, N1303K, and S549R). Group B included 13 compound heterozygote cystic fibrosis patients who carried one mutation known to cause mild disease with a borderline or normal sweat test and pancreatic sufficiency (3849+10kb C→T, 5T). Group C included 38 normal controls. Nineteen cystic fibrosis patients carried at least one unidentified mutation. An association between CA 19–9 levels and age, pulmonary function, pancreatic status, sweat chloride, previous pancreatitis, serum lipase, meconium ileus, distal intestinal obstruction, liver disease, and diabetes was investigated. The distribution of CA 19–9 levels was significantly different between the three groups (p<0.01); high CA 19–9 levels were found in 60% (30/50) of group Apatients and in 46.6% (6/13) of group B patients, but in only 5.2% (2/38) of the controls. CA 19–9 levels were inversely related to forced expiratory volume in 1 s, while no association was found with the other clinical parameters examined. Our findings suggest that the serum CA 19–9 in cystic fibrosis patients originates in the respiratory system, and has a useful ancillary role, particularly when diagnostic uncertainty exists. Hence, the diagnosis of cystic fibrosis should be considered in patients with borderline sweat tests and high CA 19–9 levels, but normal levels do not exclude cystic fibrosis.

Familial Clustering of Tonsillectomies and Adenoidectomies

Eighty-one children undergoing tonsillectomies and adenoidectomies (T and A) were compared with a control group of 88 hospital patients. A significantly higher incidence of prior T and A was found to have been performed on the siblings and parents of the T and A group than the controls. Environmental, genetic or attitudinal factors could be responsible for this familial clustering.

Pheochromocytoma and hydralazine-induced myocardial ischaemia in a 14-year-old boy

A 14-year-old patient with pheochromocytoma is described in whom myocardial ischaemia occurred following hydralazine administration. Possible mechanisms and previously reported paediatric cases are discussed. The need for caution in acute hypotension induction in pheochromocytoma is emphasized.

The critical first six months in cystic fibrosis: a syndrome of severe bronchiolitis.

The syndrome of infantile bronchiolitis in cystic fibrosis (CF) carries a high mortality. Fifteen cases of CF encountered over the past 19 years with severe bronchiolitis with onset during the first 6 months of life are described. Treatment included steroids in high doses. All patients recovered. Further progress resembled the usual natural course of CF and showed no evidence of persisting lung damage. The mechanism of this syndrome is not clear and is probably dependent on many factors involved in early lung disease in CF. The frequency of severe bronchiolitis in cystic fibrosis may not be high, but it continues to be seen in clinical practice today. Pediatr. Pulmonol. 1997; 24:134–136.