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Biomedical subjects

R C Stern

Publications and source records attributed to R C Stern.

At least 55 records · Page 3Linked to original sources

The spectrum of appendiceal disease in cystic fibrosis.

A retrospective review of 1,220 cystic fibrosis (CF) patients between 1965 and 1989 identified 60 patients who underwent appendectomy. Ten had appendectomy prior to referral and 16 had an incidental appendectomy (primarily meconium ileus). Among the remaining 34 patients, acute appendicitis was present in 19 (1.8% incidence). "Classic appendicitis"--acute abdominal pain shifting to the right lower quadrant (RLQ), focal RLQ tenderness, and elevated white blood cell (WBC) count--was present in 15. Four additional inflamed appendixes were removed in patients following incorrect preoperative diagnosis. Thirteen of these 19 were perforated. Complications included wound infection (2), pelvic abscess (1), ileal obstruction requiring ileostomy (1), and pelvic hematoma (1). There were no deaths. One patient with acute RLQ pain and tenderness had a normal appendix. Seven patients (mean, 20 years) had chronic, intermittent, focal RLQ pain and tenderness not originating periumbilically with a normal WBC count and temperature. At exploration, these appendixes were enlarged and tensely distended with inspissated mucus. Microscopic examination showed no inflammation. Appendectomy resulted in resolution of symptoms without complications. Four additional patients with intermittent RLQ pain and tenderness and a history of recurrent intussusception presented with ileocolic intussusception. Persistent postreduction symptoms in three and failure of reduction in the fourth necessitated celiotomy at which time tensely distended appendixes were removed. Appendectomy led to resolution of symptoms. Three additional enlarged noninflammed appendixes were incidentally removed in asymptomatic patients undergoing unrelated intraabdominal procedures. Appendiceal disease in CF patients represents a spectrum ranging from simple mucous distention to acute appendicitis with perforation. CF patients with pain secondary to a noninflamed distended appendix represent a distinct syndrome cured by appendectomy.(ABSTRACT TRUNCATED AT 250 WORDS)

Abdominal Pain↗

Bronchial artery embolization to control hemoptysis in cystic fibrosis.

Severe hemoptysis in cystic fibrosis can be life-threatening because of acute blood loss or because it interferes with sustaining physical therapy of the chest. Hemoptysis was controlled in 19 of 20 cystic fibrosis patients by means of embolization with a combination of 250-590-microns particles of polyvinyl alcohol foam and absorbable gelatin pledgets. Repeat embolization was needed in eight patients to achieve or maintain effective hemostasis. One or more aberrant bronchial arteries were found in seven patients (35%), and a spinal artery branching from a vessel that also supplied bronchial circulation was present in 11 patients (55%). The data suggest that although embolization has a wider applicability than previously reported, care should be taken during angiography to evaluate the bronchial circulation because aberrant bronchial vessels and spinal arteries arising from bronchial circulation are common.

Adolescent↗

Elimination kinetics of sevoflurane and halothane from blood, brain, and adipose tissue in the rat.

Using the rat as an animal model, the elimination kinetics of sevoflurane and halothane from brain, blood, and adipose tissue were compared. Elimination of sevoflurane and halothane from blood and brain was biexponential. The rapid, alpha-elimination rates of sevoflurane from blood and brain were faster than the corresponding rates for halothane. However, the slower beta-elimination rates from brain and blood, as well as the elimination rates from adipose tissue, were similar for both volatile anesthetics. Thus, the potential for residual postoperative impairment from subanesthetic tissue concentrations of halothane and sevoflurane may be similar even though sevoflurane is initially eliminated more rapidly from blood and brain.

Adipose Tissue↗

Weight and menstrual function in patients with eating disorders and cystic fibrosis.

Many patients with eating disorders have menstrual dysfunction. In patients with anorexia nervosa, amenorrhea has been linked to weight loss. However, many patients with bulimia nervosa, even those of average or greater than average weight, also experience menstrual abnormalities, including amenorrhea. It was hypothesized that low weight per se is not responsible for menstrual dysfunction in patients with eating disorders. First, 16 patients with bulimia nervosa of average weight and 29 patients with cystic fibrosis of below average weight of similar menstrual age were compared. Of the patients with bulimia nervosa, 11 (73%) had had secondary amenorrhea at some time compared with 8 (28%) of the patients with cystic fibrosis (P less than .01). At the time of study, 6 (40%) of the patients with bulimia nervosa and 21 (78%) of the patients with cystic fibrosis were having regular cycles (P less than .01). Next 18 patients with anorexia nervosa were compared with 18 patients with cystic fibrosis matched for weight and menstrual age. Although 18 (100%) of the patients with anorexia nervosa had had secondary amenorrhea, only 6 (33%) of the patients with cystic fibrosis had amenorrhea. Although only 1 (6%) of the anorexia nervosa group was currently having regular cycles, 14 (78%) of the patients with cystic fibrosis were (P less than .0001). Closer approximation to ideal body weight was associated with regular menses only in the cystic fibrosis group. Exercise did not appear related to regularity of menstruation in any group. Body weight is not the major factor responsible for menstrual abnormalities in patients with eating disorders.

Adolescent↗

Pneumothorax in cystic fibrosis: a 26-year experience.

We reviewed the records of all patients with cystic fibrosis and radiologically demonstrated pneumothorax at Rainbow Babies and Childrens Hospital between 1959 and 1987. There occurred 144 pneumothoraces, 71 right and 73 left, in 99 patients, 48 female and 51 male. The median survival from the date of the first pneumothorax was 29.9 months. Primary therapy included the following: observation; tube thoracostomy; tube thoracostomy with instillation of quinacrine hydrochloride, tetracycline, silver nitrate, or talc; or partial pleurectomy. Complications were minimal in each group. The surgical group did significantly better than all other groups except the group given talc. We conclude that pneumothorax is a late and ominous complication of cystic fibrosis. The primary treatment of pneumothorax should be partial pleurectomy. Talc instillation should be reserved for patients in respiratory failure who are too ill to undergo operation and for the occasional patient in whom surgical intervention fails.

Adolescent↗

The pathology of fungal infection and colonization in patients with cystic fibrosis.

We used methenamine silver stains to retrospectively evaluate the prevalence of fungi and their associated inflammatory reactions in 63 patients with cystic fibrosis (CF) autopsied between 1982 and 1987. Fungi were detected in 13 patients (21%) who fell into three groups: respiratory tract colonization (five patients); localized infection (five patients); and disseminated infection (three patients). Hyphae consistent with Aspergillus sp were present in five patients; yeast-like cells and/or pseudohyphae consistent with Candida sp occurred in eight patients; and Histoplasma capsulatum produced fibrocaseous lymph node and splenic granulomas in one patient. Acute inflammation typified most fungal lesions, while bronchocentric granulomatosis affected one patient. Compared with patients with no fungi, those with fungi were more frequently treated with indwelling central venous catheters (P less than .05). Autopsy reports on 156 CF patients from 1964 to 1982 disclosed only one with disseminated mycosis (P less than .05). We conclude that stainable fungi can be found in CF patients at autopsy more frequently than previously realized. Fungi usually represent respiratory tract colonization or minimal localized infection, but the prevalence of fatal disseminated infection (4.8%) has also increased. Fungal infection in CF appears to be most closely associated with aggressive therapeutic intervention.

Adolescent↗

The primary care physician and the patient with cystic fibrosis.

Although CF has increasingly become a "subspecialty disease," the decisions and practice style of the patient's pediatrician or family physician are extremely important. The primary physician's handling of everything from the timing of infant immunizations to teenage advice about sex and drug abuse have far-reaching medical and psychosocial implications and must be carefully considered.

Adolescent↗

Isoflurane uptake and elimination are delayed by absorption of anesthetic by the Scimed membrane oxygenator.

Although isoflurane is frequently used during hypothermic cardiopulmonary bypass (CPB), its pharmacokinetics in these circumstances have not been described for systems employing membrane oxygenators. The current study details isoflurane uptake and elimination in an ex vivo model of hypothermic CPB, which uses a Scimed membrane oxygenator. Isoflurane uptake and elimination by blood are markedly delayed by the membrane oxygenator in this system. This is because the oxygenator membrane absorbs large amounts of anesthetic; the Scimed oxygenator membrane has a capacity for anesthetic equivalent to approximately 17 L of blood. As isoflurane absorption by the oxygenator may also delay anesthetic uptake and elimination in patients during CPB, further studies in human subjects are needed to define the clinical significance of anesthetic absorption by the membrane oxygenator.

Cardiopulmonary Bypass↗

Lack of unique ciprofloxacin pharmacokinetic characteristics in patients with cystic fibrosis.

The single-dose pharmacokinetics of oral ciprofloxacin 750 mg were evaluated in six subjects with cystic fibrosis (CF subjects) and six age, sex and approximate weight-matched control subjects (controls). In addition, the effect of concurrently administered oral pancreatic enzyme replacement on the pharmacokinetics of ciprofloxacin was studied in 12 CF subjects. Ciprofloxacin t1/2, VSSF, CLF, and CLR in the matched CF subjects averaged 4.5 hours, 2.8 L/kg, 2.73 mL/min/kg and 5.7 mL/min/kg, respectively. Forty-two percent of the ciprofloxacin dose was excreted in the urine (0-48 hours) as the parent compound. No statistically significant differences in these ciprofloxacin pharmacokinetic parameter estimates were observed between CF and control subjects. In three CF subjects and two controls, the urinary excretion of ciprofloxacin and four of its metabolities were similar. In contrast, CF subjects demonstrated a prolonged tmax (2.3 versus 1.3 hours P less than .05) though ciprofloxacin Cmax was similar (4.7 versus 3.8 mg/L, NS). The concurrent administration of oral pancreatic enzyme replacement had no effect on the pharmacokinetics of ciprofloxacin. Apparent ciprofloxacin pharmacokinetic parameters in sputum were similar to those observed in serum. Sputum ciprofloxacin concentrations lagged behind serum concentrations but, on average, exceeded serum concentrations for 20 hours of the 24-hour sampling period. These sputum ciprofloxacin concentrations exceeded the reported MIC90 for Pseudomonas aeruginosa for approximately 15 hours. These data suggest an oral ciprofloxacin dose of 750 mg administered q8h to promote accumulation and maintenance of sputum drug concentrations well above pathogen MICs for the majority of a dosing interval in patients with CF.

Adolescent↗

Serum IgG antibody to outer membrane antigens of Pseudomonas cepacia and Pseudomonas aeruginosa in cystic fibrosis.

IgG antibody to the outer membrane of Pseudomonas cepacia was quantified in sera from controls without cystic fibrosis (CF) and from Pseudomonas aeruginosa- and P. cepacia-infected and noninfected patients with CF. The mean antibody titer in the P. cepacia-infected group was significantly higher than that in the other three groups; the mean titer in the P. aeruginosa-infected group was significantly higher than that in the noninfected and control groups. Preabsorption of CF sera with P. cepacia outer membrane produced a significantly lower mean antibody concentration than did matched samples preabsorbed with an equal amount of lipopolysaccharide. By western blot, significantly more P. cepacia-infected patients produced IgG to the 27- than the 36-kilodalton (kDa) porin protein of P. cepacia; 12 of 16 P. aeruginosa-infected patients produced IgG to the 27-kDa porin. Sera from all patients in both groups contained IgG to the porin protein of P. aeruginosa by western blot. We conclude that the 27-kDa porin of P. cepacia is antigenic in most P. cepacia-infected patients with CF and that some P. cepacia outer membrane components may be antigenically related to those of P. aeruginosa.

Adolescent↗

The effect of exocrine pancreatic function on chloramphenicol pharmacokinetics in patients with cystic fibrosis.

The effect of exocrine pancreatic function on the pharmacokinetics of the choramphenicol oral capsule (CAP-base), chloramphenicol palmitate oral liquid (CAP-P), and chloramphenicol succinate intravenous (CAP-S) formulations was evaluated in 10 patients, aged 16-30 yr, with cystic fibrosis. Pancreatic insufficiency was assessed in each patient by measuring the absorption of p-amino-benzoic acid after oral administration of N-benzoyl-L-tyrosyl-p-aminobenzoic acid which requires chymotrypsin to cleave p-aminobenzoic from the parent molecule. In a controlled cross-over design, the overall biodisposition of each formulation was assessed in each patient with or without concurrent administration of oral pancreatic enzymes. The relative amounts of active chloramphenicol available in systemic circulation was CAP-base greater than CAP-S greater than CAP-P. Pancreatic enzyme replacement had little effect on the biodisposition parameters for the CAP-base and CAP-S formulation, but significantly increased the peak concentration and bioavailability of the CAP-P formulation. Although pancreatic enzyme replacement improved the absorption characteristics of the CAP-P formulation, absorption remained prolonged and unreliable. Serum concentration-time profiles for either CAP-base or CAP-S consistently exceeded the MIC of important nonpseudomonal pathogens. This finding was not observed after CAP-P administration independent of pancreatic enzyme replacement. The results of this study support the continued clinical use of either CAP-base or CAP-S, but the cautious use of CAP-P formulations in CF patients with concurrent pancreatic insufficiency.

Administration, Oral↗

Pseudomonas cepacia-associated pneumonia in cystic fibrosis. Relation of clinical features to histopathologic patterns of pneumonia.

We studied lungs at autopsy from 40 patients with cystic fibrosis (CF) to determine the structural and clinicopathologic features of pneumonia associated with Pseudomonas cepacia respiratory tract colonization. Three clinical groups were identified: group A included 11 patients exhibiting a fulminant course following P cepacia colonization; group B included 20 patients who declined slowly following colonization; and group C included nine patients without P cepacia colonization. Acute pneumonia occurred in all groups but was most extensive and necrotizing in group A. Chronic lobular pneumonia involved all groups equally, whereas interstitial pneumonia predominated in group B. Diffuse alveolar damage occurred infrequently in all groups. Combinations of structural patterns were frequently seen. We conclude that, although there is great overlap in the structural appearance of pneumonia among patients with CF with different bacterial colonization histories, the evidence suggests that P cepacia is a cause of necrotizing pneumonia in some patients. Factors that predispose to this fulminant lung infection are poorly understood.

Acute Disease↗

Ciprofloxacin monotherapy for acute pulmonary exacerbations of cystic fibrosis.

Ciprofloxacin has potent in vitro activity against Pseudomonas aeruginosa and Pseudomonas cepacia strains isolated from cystic fibrosis patients. Our previous single-dose pharmacokinetic and pharmacodynamic studies identified important differences between cystic fibrosis patients and age- and sex-matched controls. Based on these data, 30 acutely ill cystic fibrosis patients (aged 18 to 44 years) received 750 mg of ciprofloxacin orally every eight hours for 21 days. Multiple timed serum, urine, and sputum samples for pharmacokinetic analysis were obtained on Days 3, 12, 14, and 21 of the study. Estimates of steady-state pharmacokinetic parameters averaged (+/- SD): t1/2 beta, 3.8 (1) hours; Vd/F, 4.4 (2) liters/kg; Cl/F, 772.9 (301) ml/minute/1.73 m2; Fe, 46 percent; peak, 5.4 (2) mg/liter; and trough, 1.8 (0.8) mg/liter. Serum ciprofloxacin concentrations and pharmacokinetic estimates remained unchanged throughout the study. Sputum ciprofloxacin concentrations exceeded those observed in serum. Sputum cultures revealed 43 P. aeruginosa (MIC90 = 2 micrograms/ml) and 15 P. cepacia (MIC90 = 16 micrograms/ml) strains. Sputum ciprofloxacin concentrations exceeded the MIC90 for P. aeruginosa approximately fivefold, yet only eight isolates were fully suppressed. Posttreatment sputum cultures revealed 35 P. aeruginosa (MIC90 = 16 micrograms/ml) and 15 P. cepacia (MIC90 = 16 micrograms/ml). All patients showed clinical improvement based upon the results of pulmonary function tests and an acute clinical efficacy score (median pre 49/post 60). No patients experienced drug-related toxicity. Ciprofloxacin monotherapy is effective for the acute treatment of cystic fibrosis patients. The development of pathogen resistance during oral therapy may limit its utility in ambulatory patients.

Adolescent↗

Recreational use of psychoactive drugs by patients with cystic fibrosis.

We assessed unprescribed psychoactive drug use in 173 adults with cystic fibrosis. Twenty (11%) regularly smoked tobacco. Cigarette smoking ranged from 1 to 30 years (2 to 60 pack-years). Alcohol was used by 60%, and marijuana by 20% of the patients. Pulmonary symptoms were often increased the day after alcohol ingestion. Alcohol occasionally caused nausea, vomiting, and headache if the patient was taking some cephalosporin derivatives (such as cefsulodine) or chloramphenicol. Marijuana often aggravated chronic pulmonary symptoms, although some patients reported transient relief during use. Comparison with a retrospectively selected control group did not show faster short-term pulmonary deterioration in the tobacco smokers. Physicians who deal with cystic fibrosis and other chronic illnesses should be cognizant of interactions of unprescribed and prescribed drugs. Recreational use of unprescribed psychoactive drugs should be considered if unexpected symptoms occur in older patients.

Adolescent↗

Randomized double-blind evaluation of ceftazidime dose ranging in hospitalized patients with cystic fibrosis.

Eighty-five patients with cystic fibrosis who were experiencing an acute infectious exacerbation of their disease were randomized in double-blind fashion to receive either 50 or 75 mg of ceftazidime per kg (body weight) per dose administered intravenously every 8 h for 14 days. Three patients were dropped from the study within 4 days of enrollment for reasons unrelated to drug administration. The total daily dose of ceftazidime administered was restricted by protocol design and was independent of the body weight of the patient. Thus, for datum analysis, patients were separated into three ceftazidime dosage groups (denoted as range of milligrams per kilogram per dose): group 1, 22 to 44.5; group 2, 46.3 to 56.6; and group 3, 66.7 to 80.6. Ceftazidime monotherapy had no effect on sputum colony counts for any Pseudomonas cepacia isolate. In contrast, a substantial reduction in Pseudomonas aeruginosa sputum colony counts was observed, and from 19 to 31% of isolates were suppressed greater than or equal to 10(5) CFU/ml after 14 days of therapy. Bacterial resistance in vitro was not observed, although a trend for increasing ceftazidime MICs was observed for group 1 patients (P less than 0.05). Overall, clinical response appeared independent of drug dose, and no relationship could be identified between the reduction in P. aeruginosa sputum colony counts and clinical outcome. Adverse effects of ceftazidime were mild and transient, necessitating drug discontinuation in one patient. These data suggest that the clinical response to ceftazidime in patients with cystic fibrosis may be maximal with 50 mg/kg per dose (150 mg/kg per day) up to a total daily dose of 6 g.

Adolescent↗