Biomedical subjects

R C Stern

Publications and source records attributed to R C Stern.

At least 91 records · Page 5Linked to original sources

PubMed1984

The alpha 2-adrenergic system of the platelet in cystic fibrosis.

The ability of norepinephrine to inhibit prostaglandin E1 (PGE1)-stimulated accumulation of adenosine 3':5' cyclic monophosphate (cyclic AMP) in intact washed platelets was determined in 12 patients with cystic fibrosis, 6 parents of patients with cystic fibrosis, and a total of 21 healthy age-matched controls. Patients with cystic fibrosis and their parents did not differ from their age-matched controls in basal or PGE1-stimulated levels of cyclic AMP, nor in the dose dependent inhibition of cAMP accumulation by norepinephrine. Moreover, binding sites for [3H]-dihydroergocryptine were present in normal numbers and had normal ligand affinity in platelet membranes from patients with cystic fibrosis. In all measures tested, the alpha 2-adrenergic system in the platelet was normal in cystic fibrosis.

Adolescent↗

PubMed1984

Single-dose pharmacokinetics of cefsulodin in patients with cystic fibrosis.

The single-dose pharmacokinetics of cefsulodin were evaluated in 12 patients with cystic fibrosis. Each patient received 3 g of cefsulodin intravenously over 30 min. Multiple plasma and urine samples were obtained during the 6-h study period for the determination of cefsulodin. Pharmacokinetic parameters were determined by model-independent methods. Mean values for t1/2, Vss, and CLp were 1.53 h, 0.242 liters/kg, and 117.3 ml/min per 1.73 m2, respectively. Six-hour urine recovery revealed 73.2% of the administered dose with a corresponding cefsulodin urinary clearance of 75.1 ml/min. These pharmacokinetic data in patients with cystic fibrosis appear consistent with data reported for unaffected individuals.

Adolescent↗

PubMed1984

Calcium-ATPase activity in cystic fibrosis erythrocyte membranes: decreased activity in patients with pancreatic insufficiency.

The activity of Ca-ATPase (Ca2+,Mg2+-ATPase, ATP phosphohydrolase, EC 3.6.1.3) was measured in erythrocyte membrane preparations from 37 cystic fibrosis patients, 27 with pancreatic insufficiency and 10 with pancreatic sufficiency, and from 24 healthy controls. The mean maximal calcium-stimulated specific activities, in the absence and presence of purified calmodulin, of the pancreatic sufficient patients (34.3 +/- 4.2 and 75.9 +/- 6.9 nmol/min/mg) was indistinguishable from that of controls (35.8 +/- 2.6 and 84.3 +/- 4.7 nmol/min/mg), while both activities of patients with pancreatic insufficiency were significantly decreased (28.9 +/- 1.3, p less than 0.02; 65.2 +/- 3.0, p less than 0.001) compared to the control group. Similarly, the mean erythrocyte membrane (Na + K)ATPase activity was decreased only for those patients with a history of steatorrhea and who clinically required pancreatic enzyme therapy and had low immunoreactive trypsin levels (10.6 +/- 0.8 versus control, 13.4 +/- 1.1, and pancreatic sufficient patients, 13.3 +/- 1.4 nmol/min/mg; p less than 0.025). No correlation was found between any of the ATPase activities and the clinical scores of the patients, suggesting the lack of significant contribution of general clinical status to the activities of those cation transporters.

Adolescent↗

PubMed1984

Sexual adaptation among single young adults with cystic fibrosis.

The sexual adaptation of 48 single young adults with cystic fibrosis and a comparably aged single group without chronic disease was assessed using interviews and questionnaires. The patients were also compared to a previously studied group of married patients with cystic fibrosis. Single female patients with cystic fibrosis began dating later, dated less often, felt less attractive, had less sexual desire, and had more sexual problems than did physically healthy female subjects. Single male patients with cystic fibrosis seemed to fare far better than their female counterparts and approximated the healthy male group in all parameters studied. For both the single and married groups with cystic fibrosis, no significant relationship between the severity of disease and sexual health was evident. The single patients were diagnosed at a significantly earlier age and their general health scores were poorer than the married patients. The vulnerability of female patients with cystic fibrosis to psychosexual disruption suggests that attention be focused on the differential effects of other chronic illnesses upon male and female adult sexual adaptation.

Adult↗

PubMed1984

Effects of alpha-tocopherol on platelet membrane function in cystic fibrosis.

Patients with cystic fibrosis and their parents were reported to have abnormal platelet aggregation responses to prostaglandin E1. To determine whether this is a property of the platelets, we studied the adenosine 3':5'-cyclic monophosphate (cAMP) response of washed platelets to prostaglandin E1. The cAMP response to prostaglandin E1 was the same in platelets from obligate heterozygotes for cystic fibrosis and from those of healthy controls. Patients with cystic fibrosis who had deficient vitamin E levels (plasma alpha-tocopherol, less than 500 micrograms/dl) had significantly (p less than 0.01) reduced platelet cAMP response to prostaglandin E1 compared with patients who had sufficient vitamin E, and supplementation with water-miscible vitamin E in these patients resulted in significant increases in plasma alpha-tocopherol levels (p less than 0.01) and in cAMP response to prostaglandin E1 (p less than 0.05). Plasma alpha-tocopherol levels correlated significantly with platelet cAMP response to prostaglandin E1 in patients with cystic fibrosis (r = 0.58, p less than 0.05). However, plasma alpha-tocopherol level was unrelated to the lymphocyte and granulocyte cAMP response to prostaglandin E1 or to the platelet cAMP response to alpha 2-adrenergic stimulation. Our data suggest that patients with cystic fibrosis have no inherited defect in platelet cAMP response to prostaglandin E1. In patients who have sufficient vitamin E, cAMP responses to prostaglandin E1 are normal in all the formed elements of the blood.

Adolescent↗

PubMed1983

Once-daily vs. continuous aminoglycoside dosing: efficacy and toxicity in animal and clinical studies of gentamicin, netilmicin, and tobramycin.

The dosing frequency of aminoglycoside antibiotics may alter efficacy and toxicity independent of total daily dose. Once-daily tobramycin dosing was compared with continuous infusion in three models of efficacy. Acute pneumonia due to Pseudomonas aeruginosa in guinea pigs responded better to once-daily dosing, and chronic pneumonia in rats and endocarditis in rabbits responded equally to both regimens. Dogs given gentamicin, tobramycin, or netilmicin once daily, with maximum serum concentrations of greater than 100 mg/liter, had less nephrotoxicity than dogs given continuous infusions. Tobramycin was given once daily or continuously to 52 patients with cystic fibrosis who in 10 days had no change in creatinine clearance or hearing despite maximum serum tobramycin concentrations of 40 mg/liter. Intermittent dosing of aminoglycosides, causing infrequent large maximum serum concentrations, may be less toxic and equally efficacious as frequent dosing.

Adult↗

PubMed1983

Ceftazidime in cystic fibrosis: pharmacokinetics and therapeutic response.

The pharmacokinetics of ceftazidime were assessed following a single-dose in 20 patients (8 to 30 years) with cystic fibrosis. All patients received 50 mg/kg (0.9 to 3.5 g) bolus over 30 to 60 sec. Multiple timed samples were obtained over 8 h and analysed by a sensitive HPLC technique. Two-compartment pharmacokinetic analysis revealed means (+/- S.D.) T 1/2 alpha, 0.45 (0.20) h; T 1/2 beta, 1.74 (0.63) h; Vd, 270.0 (50.0) ml/kg; Vc, 190.0 (50.0) ml/kg and Cl beta, 133.7 (22.8) ml/min/1.73 m2. Probenecid pretreatment in six patients was without effect on T 1/2 beta and Cl beta. Urinary excretion was (% of dose) 0 to 2 h, 65.4 (11.1); 2 to 4 h, 14.9 (3.4) and 4 to 8 h, 9.8 (5.8). Ceftazidime was used to treat pulmonary exacerbations in 12 adult cystic fibrosis patients with multiply-resistant Pseudomonas species. Each patient received 2 g iv 8-hourly for 14 to 35 days. Ten of 12 patients showed dramatic improvement as determined by increased appetite and weight gain and arterial pCO2. No hepatic, renal or bone-marrow toxicity was noted. Ceftazidime is an effective antipseudomonal agent possessing favourable pharmacokinetic characteristics with potential use in the treatment of pulmonary exacerbations in cystic fibrosis.

Adolescent↗

PubMed1983

Beta adrenergic receptors in lymphocytes and granulocytes from patients with cystic fibrosis.

Intact lymphocytes from patients with cystic fibrosis (CF) produce significantly (P less than 0.001) less adenosine 3':5' cyclic monophosphate (cAMP) than normal lymphocytes in response to isoproterenol (10(-8)-10(-4) M), although the basal cAMP content and the response to prostaglandin E1 are normal. Obligate heterozygotes for CF have significantly (P less than 0.005) reduced cAMP response to isoproterenol as well, suggesting a genetic component in the beta adrenergic deficiency in CF. The number of beta adrenergic receptors, as determined by equilibrium binding of [3H]dihydroalprenolol to lymphocyte particulates, is the same in normal lymphocytes (969 +/- 165 receptors/cell) and lymphocytes from patients with CF (1,333 +/- 263 receptors/cell). Binding properties of the receptor for both antagonist and agonist, as assessed by KD for dihydroalprenolol and Ki for (-)-isoproterenol, are also normal in the CF lymphocytes. Similarly, in granulocytes from patients with CF, the cAMP response to isoproterenol (10(-8)-10(-4) M) is significantly reduced compared with healthy controls (P less than 0.03), as is the response of granulocytes from obligate heterozygotes (P less than 0.05). Again, the basal cAMP levels and the response to prostaglandin E1 are normal. The number of beta adrenergic receptors, as determined by equilibrium binding of [3H]dihydroalprenolol to granulocyte particulates, was the same in normal (1,462 +/- 249 receptors/cell) and CF (1,621 +/- 221 receptors/cell) preparations. Binding properties of the receptor for both agonist and antagonist, as assessed by KD for dihydroalprenolol and Ki for isoproterenol, are normal in CF granulocyte particulates. The lymphocyte and granulocyte beta adrenergic defect in CF cannot be explained by abnormalities of the beta adrenergic receptor or of adenylate cyclase itself. Receptor-cyclase coupling is the most likely site of the heritable beta adrenergic defect in CF.

Adolescent↗

PubMed1983

Exercise and heat stress in cystic fibrosis patients.

Cystic fibrosis (CF) is characterized by high sweat sodium and chloride concentrations. CF patients have long been assumed to be at risk for heat illness, but there has been no quantitative documentation that CF patients actually have a greater loss of sodium and chloride than normals when under environmental stress. We compared thermoregulatory responses of eight CF patients with five normal controls during 90-min exposures to exercise and heat stress. Both groups reached similar peak rectal temperatures and peak heart rates; they had similar sweat volumes and rates. CF patients showed the normal rise in renin and aldosterone and the normal fall in urine sodium excretion; however, CF patients lost significantly more sodium (48.8 +/- 23.4 mEq/liter/m2 versus 20.2 +/- 11.2 mEq/liter/m2) and chloride (46.6 +/- 21.6 mEq/liter/m2 versus 18.5 +/- 11.3 mEq/liter/m2) per unit of surface area than the controls. Serum sodium and chloride concentrations fell in the CF patients but not in the normals. After exercise/heat stress, CF serum chloride was significantly less than normals' (99 +/- 3 mEq/liter versus 104 +/- 1 mEq/liter, P less than 0.01). CF patients have normal temperature, heart rate, hormonal, and renal responses to exercise and heat stress, yet still lose significantly more sodium and chloride than normal. These losses are reflected in part in lower serum concentrations of these ions. There may be important effects of these losses on respiratory tract secretions.

Adolescent↗

PubMed1983

B-lymphocyte function in cystic fibrosis.

The susceptibility of patients with cystic fibrosis to chronic, progressive bacterial pulmonary infections has not been adequately explained. We explored peripheral blood B-cell function in 21 cystic fibrosis patients and in normal controls. All patients were above 10 years of age, and chronically colonized with Pseudomonas aeruginosa. Spontaneous plaque-forming cells, which reflect B-cell differentiation into immunoglobulin-secreting cells in vivo, and plaque-forming cells formed after activation with pokeweed mitogen or staphylococci in vitro, were studied. Cystic fibrosis patients had significantly higher spontaneous plaque-forming cells than normal individuals. This difference was due to the increase of spontaneous plaque-forming cells than normal individuals. This difference was due to the increase of spontaneous plaque-forming cells in patients with less severe pulmonary disease, since patients with advanced pulmonary disease had numbers of circulating immunoglobulin-secreting cells, similar to normal individuals. Both groups of cystic-fibrosis patients have a significant impairment of B-cell differentiation in response to polyclonal activation in vitro. This functional abnormality could not be explained by the presence of increased numbers of adherent suppressor cells, or by the presence of increased suppression by T-lymphocytes. The implications of our data for the increased susceptibility to infection and for the development of antibody-mediated hypersensitivity reactions are discussed.

Adolescent↗

PubMed1983

Inhibition of catecholamine biosynthesis by carbidopa and metyrosine in neuroblastoma.

In three patients with neuroblastoma and high circulating levels of dopamine and dopa, we interfered pharmacologically with catecholamine biosynthesis either at the tyrosine hydroxylase or dopa decarboxylase step in an attempt to 1) improve the efficacy of antitumor therapy and 2) avoid the potential arrythmogenic interaction between elevated circulating catecholamines and an halogenated hydrocarbon anesthetic during surgery. Biochemical evidence indicated that inhibition of catecholamine biosynthesis had occurred but there was no associated significant change in clinical status or response to other therapy.

Carbidopa↗

PubMed1982

Obstructive azoospermia as a diagnostic criterion for the cystic fibrosis syndrome.

In some male patients with findings characteristic of cystic fibrosis, but normal sweat chloride concentrations, the demonstration of obstruction azoospermia has been pivotal in diagnosis. It is proposed that cystic fibrosis be diagnosed if the patient has at least two of three major criteria (marked rise in sweat chloride concentration, chronic obstructive pulmonary disease and pseudomonas infection, and unexplained obstructive azoospermia) or has one major criterion together with one of several minor criteria--including positive family history and childhood onset of exocrine pancreatic insufficiency. Inclusion of unusual variants within the cystic fibrosis syndrome has major theoretical implications for pathogenesis and practical importance for genetic counselling and patient care.

Adolescent↗

PubMed1982

Treatment and prognosis of nasal polyps in cystic fibrosis.

Nasal polyposis complicated the course of fibrosis in 157 (26%) of 605 patients. Onset before age 5 years or after age 20 years was rare. Polyposis was the initial symptom of cystic fibrosis in 13 patients. Common symptoms included obstruction to nasal air flow, mouth breathing, epistaxis, and rhinorrhea. Intranasal and oral corticosteroids and antihistamines were ineffective in preventing recurrences but did occasionally afford symptomatic relief of obstruction. Nineteen (31%) of 62 patients who never had surgery had spontaneous and permanent disappearance of polyps. Simple polypectomy was an adequate procedure for patients with substantial nasal symptoms. There were no visual complications. Other surgical complications were rare. Children and adolescents with nasal polyps should have sweat tests by pilocarpine iontophoresis to rule out cystic fibrosis.

Adolescent↗

PubMed1982

The reproductive endocrine system in cystic fibrosis: 2. Changes in gonadotrophins and sex steroids following LHRH.

Hypothalamic-pituitary-gonadal function was assessed in forty-seven patients with cystic fibrosis (CF) by the 3-hr infusion of 100 microgram of synthetic gonadotrophin-releasing factor. LHRH and the results compared with a group of children being evaluated for short stature and delayed puberty ('controls'). Levels of gonadotrophins and sex steroids were measured prior to and during the infusion. In prepubertal boys, LH and FSH release evoked by LHRH was significantly greater (P less than 0.001) in 'control' subjects than in CF patients. In pubertal boys, LH and FSH release was also greater in 'controls' than in CF, though to a lesser degree (P less than 0.05). In pubertal girls, responses to LHRH were comparable for LH and slightly greater (P less than 0.05) in 'controls' for FSH. In the earliest pubertal groups of both sexes (male-Tanner genitalia stage 2; females-Tanner breast stage 2), LH secretion was similar in patients with CF and 'control' subjects. Significant increments of testosterone and oestradiol in pubertal CF patients do not occur until 6 h after the LHRH infusion begins, in contrast to a rise at 3 h in 'control' subjects. These data suggest that prepubertal boys with CF, who are the most impaired in height, weight and skeletal maturation, also have measurable abnormalities of LHRH-releasable gonadotrophin secretion. Despite continued impaired weight growth, pubertal patients do attain essentially normal gonadotrophin secretory responses to LHRH administration and are similar to subjects with constitutional delayed adolescent development in reproductive endocrine physiology.

Adolescent↗

PubMed1982

Sexual function in cystic fibrosis. Relationship to overall health status and pulmonary disease severity in 30 married patients.

An interview and questionnaire were used to investigate the sexual functioning of married patients with cystic fibrosis. Only 20 percent of patients older than 19 years were married. Nine of the 30 married patients had serious sexual problems. Although these problems were all manifested as decreased desired, they had diverse causes; five of the nine were attributed to the CF. Some patients function quite well sexually, even in the face of severe disease. Physicians can assure adult CF patients contemplating marriage that they have a reasonable chance for normal sexual functioning.

Adult↗

PubMed1982

Treatment and prognosis of rectal prolapse in cystic fibrosis.

Rectal prolapse occurred in 112 (18.5%) of 605 cystic fibrosis patients. In 48 patients prolapse preceded diagnosis of cystic fibrosis, but physicians (pediatricians, pediatric and general surgeons, and proctologists) rarely appreciated its importance as a symptom of this disease. Prolapses frequently cease with institution of pancreatic enzyme replacement therapy following diagnosis of cystic fibrosis. However, even when the disease remains undiagnosed, the symptom is often transient and frequently resolves at 3-5 yr of age. Prolapse occurring initially after cystic fibrosis is diagnosed rarely responds to manipulation of diet or enzyme doses. Many patients develop a method of reduction which involves voluntary abdominal, perineal, and gluteal muscles and does not require manual pressure on the prolapsed segment. Most patients do not need specific treatment for the prolapse. Surgery is rarely necessary. A sweat test should be obtained on any child who has had even a single episode of rectal prolapse.

Adolescent↗

PubMed1982

Multiple microaerophilic streptococcal lung abscesses after orthodontic treatment.

An immunocompetent 12-year-old boy developed multiple microaerophilic streptococcal lung abscesses after application of orthodontic bands ("braces"). The dental work was done in the supine position. The data suggest that the patient aspirated the organisms and, possibly, flecks of dental cement, during orthodontic treatment. "Rubber dams" should be used to help prevent aspiration in children who receive dental work in the supine position. When a rubber dam cannot be used, as with orthodontic treatment, physicians should advise patients who are at risk for developing pulmonary infection (eg, patients with neuromuscular diseases which compromise cough and/or gag, cystic fibrosis, sickle cell anemia, primary immunodeficiency, etc) to have this dental work, including orthodontic treatment, performed in the erect position.

Child↗

PubMed1981

The reproductive endocrine system in cystic fibrosis. I. Basal gonadotropin and sex steroid levels.

Serum gonadotropin and sex steroid levels were measured in 106 patients with cystic fibrosis (CF), 46 males and 60 females, aged 8 to 24 years. The finding of delayed pubertal increments of serum gonadotropin and sex steroid levels in CF patients suggests late maturation of the reproductive endocrine system. Although pubertal changes in reproductive endocrine hormones in patients with CF appear to be temporally delayed, generally appropriate levels of these hormones are finally attained in most patients by the late teenage years. Delayed maturation of the reproductive endocrine system probably is secondary to hypothalamic-pituitary dysfunction, the result of chronic inanition.

Adolescent↗