Effect of sinus surgery on pulmonary function in patients with cystic fibrosis

The rare case of neurilemmoma of the larynx was presented. The difficulties in histopathologic diagnosis of such tumors were emphasized. The tumor was removed by surgery from external approach.     

Intravenous aminophylline in patients with cystic fibrosis. Pharmacokinetics and effect on pulmonary function

Intravenous aminophylline was administered to ten patients with cystic fibrosis (CF) to determine if the medication would improve pulmonary function and to study theophylline pharmacokinetics. Intravenous normal saline was given on another day as a control. Thoracic gas volume and airway resistance, measured in a volume displacement body plethysmograph, and maximal expiratory flow-volume curves were performed before and after each infusion. No significant improvement was noted in pulmonary function after normal saline infusion. Following aminophylline infusion. Following aminophylline infusion, significant improvement in thoracic gas volume, residual volume, specific airway conductance, and maximal expiratory flow at 60% of total lung capacity was noted. The pharmacokinetic analysis revealed a mean half-life of 4.7 hours, a total clearance of 91 mL/hr/kg, and a volume of distribution of 574 mL/kg. Intravenous aminophylline can acutely decrease airway obstruction in children with CF.     

Relationship between abnormalities on high-resolution CT and pulmonary function in systemic sclerosis

STUDY OBJECTIVES: To determine the predictive value of abnormalities on high-resolution CT (HRCT) on pulmonary disease in systemic sclerosis. PATIENTS: Fifty-two patients suffering from systemic sclerosis. DESIGN: Pulmonary disease was defined by pulmonary function test abnormalities, ie, total lung capacity (TLC) <80% of predicted value and/or diffusion of carbon monoxide (DLCO) <75% of predicted value, without any pulmonary event other than systemic sclerosis in the medical history. Patients were divided in two groups, group A with pulmonary disease (29 patients) and group B without pulmonary disease (23 patients). HRCT abnormalities were scored on whole lungs. A decision matrix was constructed to determine sensitivity, specificity, positive and negative predictive values, and false-positive and false-negative rates. A receiver operating characteristic curve was constructed to determine the best compromise between sensitivity and specificity. RESULTS: HRCT total scores were higher in group A (9.0+/-4.3) than in group B (5.0+/-2.8) (p < 0.001) and they correlated with TLC (r =-0.39, p < 0.005) and DLCO (r = -0.50, p < 0.0002). An HRCT score of 7 corresponded to the best compromise between sensitivity (0.60) and specificity (0.83), with a positive predictive value of 0.82. Taking into account a value of 10 for the HRCT score increased specificity to 1 but decreased sensitivity to 0.41. CONCLUSION: A minimum score of 7 would be required to consider HRCT abnormalities in systemic sclerosis as predictive of pulmonary disease. An HRCT score of 10 makes it possible to establish the diagnosis of lung involvement severe enough to impair pulmonary function.     

Diagnostic abilities of high-resolution CT, dynamic CT, and 201T1 SPECT in evaluating of pulmonary masses

The purpose of this study was to evaluate the diagnostic abilities of high-resolution CT (HRCT), dynamic CT (DCT), and T1-201 SPECT (T1) in determinating benignancy and malignancy (b-m) in pulmonary mass lesions. The diagnoses (35 adenocarcinomas, 10 squamous cell carcinomas, 6 other primary lung carcinomas, 8 tuberculomas, 13 other benignancies) were made in 20 patients (pts) by surgery, in 46 pts by biopsy or cytology, and in 6 pts by clinical course. In 72 pts (51 malignancies, 21 benignancies) who underwent DCT, increased attenuation of lesions at 90 seconds after the injection of contrast medium was a discriminative indicator, and the b-m threshold was defined as 22HU and 15HU for lesions of < or = 3cm and 3cm < in maximum diameter. In 56 pts (43 malignancies, 13 benignancies) examined by T1, lesion-to-contralateral normal lung ratios at 15 min (ER) and 3 hr (DR) were calculated, and the retention index (RI) was defined as (DR-ER)/ER 100. The b-m threshold of RI proved to be-6 for lesions of all sizes. In 40 pts (29 malignancies, 11 benignancies) who underwent both DCT and T1, HRCT was read on the basis of morphology by 7 observers (3 experienced, 2 senior, and 2 junior radiologists). Sensitivity and specificity were 88.2% and 71.4%, respectively, for DCT in 72 pts and 83.7% and 84.6% for T1 in 56 pts. A-receiver-operating characteristics (ROC) analysis revealed that only 2 experienced radiologists were superior to DCT and T1 in diagnostic accuracy. Sensitivity and negative predictive value were 100% and 100%, respectively, for the combination of DCT and T1, and 96.6% and 85.7% for the combination of the 2 experienced radiologists. In conclusion, the combination of DCT and T1 has excellent clinical efficacy in assessment b-m in pulmonary mass lesions.     

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.     

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.     

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.     

Comparisons of pulmonary and sinonasal lesions in patients with cystic fibrosis. Evaluation using computerized tomography

INTRODUCTION: Cystic fibrosis is a recessive genetic systemic exocrinopathy caused by a variety of mutations in the cystic fibrosis transmembrane conductance regulator gene (CFTR). The disease is characterized by alterations of the secretions, which become thickened and viscous. Both the paranasal sinuses and the lung parenchyma are involved in all cases. The aim of this study was to assess a correlation between the rhinosinusal and lung parenchyma changes in cystic fibrosis patients. MATERIAL AND METHODS: Eighteen patients (11 men and 7 women, age range: 8 to 22 years) were examined with chest HRCT and sinonasal low dose CT. Lung symptoms were found in all patients; 13 of them, also affected with rhinosinusal symptoms, had been examined with ENT and nasal endoscopy. The other 5 patients, without rhinosinusal symptoms and previously examined with ENT, were evaluated as control group. Chest CT was performed with the high-resolution technique, 2 mm slice thickness and 10 mm table feed. Rhinosinusal CT was performed with the low dose technique, acquiring contiguous 2-4 mm thickness coronal sections. The CT patterns were analyzed by two radiologists and scored as slight, medium and diffuse involvement of both districts. RESULTS: No statistically significant correlation between lung and sinonasal damage was found in our study. Parenchymal lung involvement appeared more severe than sinonasal involvement in 14/18 patients. The retention of secretions in the paranasal sinuses, even if limited, was demonstrated in all symptomatic and asymptomatic patients. CONCLUSIONS: The absence of correlation between pulmonary and sinonasal damage and more generally, the different severity of cystic fibrosis can be caused by different allele mutations of the cystic fibrosis transmembrane conductance regulator gene, the most frequent of which is Delta F-508.     

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.     

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.     

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.     

Composition of nasal secretion in patients with cystic fibrosis

Quantitative examination of nasal secretion in patients with cystic fibrosis revealed a significantly greater than normal concentration of calcium, a finding in keeping with the hypothesized importance of this ion in the pathophysiology of the disease.     

Exercise limitations and training for patients with cystic fibrosis

Exercise has much to offer to cystic fibrosis patients. Overcoming the limits of decreased pulmonary function by increasing fitness has a considerable potential to improve patients' quality of life; decreased breathlessness allows greater mobility and participation with peers in social and sporting activities, improves confidence and self-esteem and creates a greater pleasure in life for the individual patient. There are also immediate therapeutic gains and potentially long-term gains with improved survival. Above all, cystic fibrosis patients enjoy and prefer exercise as a therapeutic option to most other forms of therapy.     

Efficiency of two pancreatic extracts in patients with cystic fibrosis

Mechanical cell damage was studied in vitro with three types of prostheses: Starr-Edwards, Kay-Shiley and Bj?rk-Shiley valves. Mechanical cell damage was found to be closely related to the flow characteristics in the prosthesis. Considering valves of similar orifice diameter, Bj?rk-Shiley valves produced the lowest rate of haemolysis. This is due to the improved haemodynamic characteristics of the valve which resulted from the laminar type of flow. With Starr-Edwards valves, smaller sizes produced unacceptably high rates of haemolysis. Increasing the mean forward flow across the valve resulted in a disproportionate rise in the energy loss and the rate of haemolysis when compared with Bj?rk-Shiley valves of similar annulus diameters.     

Pharmacokinetics of once-daily amikacin dosing in patients with cystic fibrosis

PURPOSE: To report the injection of tissue plasminogen activator into a retinal vein to treat central retinal vein occlusion. METHODS: An 81-year-old woman with visual loss of the right eye secondary to central retinal vein occlusion developed central retinal vein occlusion and visual loss in her left eye. Treatment of her left eye with topical ocular hypotensive medications, pentoxifylline, and laser chorioretinal anastomosis was without benefit. Thereafter, she underwent vitreoretinal surgery, including tissue plasminogen activator injection into a branch retinal vein of her left eye. RESULTS: The patient reported subjective improvement in the vision of her left eye. Ophthalmoscopic and fluorescein angiographic improvement were also noted. CONCLUSION: The feasibility of cannulating a retinal vein for treatment has been demonstrated.