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Biomedical subjects

J Goldfarb

Publications and source records attributed to J Goldfarb.

At least 55 records · Page 3Linked to original sources

Attitudes of in vitro fertilization and intrauterine insemination couples toward multiple gestation pregnancy and multifetal pregnancy reduction.

OBJECTIVE: To determine attitudes regarding multiple pregnancy and multifetal pregnancy reduction in couples embarking on gonadotropin therapy. DESIGN: Questionnaire given to couples initiating gonadotropin therapy. SETTING: University hospital-based infertility unit. PATIENTS: Twenty-seven couples undergoing IVF and 50 couples undergoing IUI. RESULTS: The groups' responses tended to be quite similar, with all groups reporting declining favorability ratings as the fetal order increased. The IUI group did feel more favorable than the IVF group toward all gestational outcomes and less favorable toward multifetal pregnancy reduction. A history of live births and length of infertility had no significant impact on the results. CONCLUSION: Couples undergoing gonadotropin therapy have an overall favorable attitude toward multiple gestational pregnancies of triplets or twins and an increased willingness to consider multifetal pregnancy reduction for quadruplets and more.

Attitude↗

Comparison study of the immunogenicity and safety of 5- and 10-microgram dosages of a recombinant hepatitis B vaccine in healthy infants.

BACKGROUND: It has been suggested that lower dosages of hepatitis B vaccine may be adequate for vaccinating infants and would be less costly. OBJECTIVES: To compare the immunogenicity and safety of 5 and 10 micrograms of Engerix-B recombinant hepatitis B vaccine given to healthy infants. METHODS: A prospective randomized comparison of 5- and 10-micrograms doses of Engerix-B recombinant hepatitis B vaccine given to infants at 2, 4 and 6 months of age. Seroconversion (antihepatitis B surface antigen (anti-HBs) > or = 1 mIU/ ml) and seroprotection (anti-HBs > or = 10 mIU/ml) rates as well as geometric mean antibody titers were compared at 4, 6 and 8 months. RESULTS: A total of 190 healthy infants were screened and received the first dose of vaccine. Of these infants 153 were eligible to continue in the study. Both dosages proved to be highly immunogenic, producing high seroconversion and seroprotection rates and geometric mean anti-HBs concentrations after 3 doses. Although 10 micrograms induced significantly greater geometric mean concentrations (1641 mIU/ml compared 880 mIU/ml at 8 months of age), the seroprotection rates were identical (98.5%). CONCLUSIONS: Both dosages were well-tolerated and no serious adverse experiences were reported. However, the 5 micrograms of Engerix-B administered at 2, 4 and 6 months of age did not induce as great an anti-Hbs concentration as did 10 micrograms. Long term studies are required to determine whether using the lower dosage would sacrifice long term efficacy.

Dose-Response Relationship, Immunologic↗

Comparison study of the immunogenicity and safety of 5- and 10-microgram dosages of a recombinant hepatitis B vaccine in healthy children.

OBJECTIVE: To compare the immunogenicity and safety of 5 micrograms with 10 micrograms of Engerix-B recombinant hepatitis B vaccine when given to healthy children, 2 to 6 years of age. METHODS: Randomized multicenter study of serongative children 2 to 6 years of age who received Engerix-B hepatitis B vaccine either 5 micrograms/0.25 ml or 10 micrograms/0.5 ml (the current Food and Drug Administration-approved dosage of Engerix-B in children) at 0, 1 and 6 months. Serum was obtained at 1, 3, 6 and 8 months after the first vaccine dose was given for antibody measurement. RESULTS: A total of 223 subjects were screened and received the first dose of vaccine. Of these subjects 193 continued in the study. Both dosages proved to be highly immunogenic, producing high seroconversion and seroprotection rates and geometric mean antibody to hepatitis B surface antigen concentrations after 3 doses. The geometric mean concentrations of seroconverters at Months 6 and 8 were significantly greater for the 10-micrograms group compared with the 5-micrograms group. Both dosages were well-tolerated and no serious adverse events were reported. CONCLUSIONS: There was a significant reduction in geometric mean concentrations on lowering the dosage of Engerix-B from 10 to 5 micrograms in children 2 to 6 years of age. Although a high seroprotection rate was elicited by the 5-micrograms dose, the lower antibody concentrations achieved may make this lower dosage less desirable in the long term. Further studies are required to examine the need for booster doses of vaccine with both dosing schedules.

Child↗

What went wrong: multiple perspectives on an adolescent's decision to refuse blood transfusions.

Persons with religious beliefs that conflict with mainstream medical practice create a tension for clinicians between honoring the different religious perspectives of the individual or carrying out what they believe to be their professional obligation. This is a patient presentation of an adolescent Jehovah's Witness who refuses blood transfusions. The major issue in this patient is the conflict among three values (1) respect for religious beliefs, (2) respect for a competent person's right to refuse treatment, and (3) the ability of an adolescent to make good decisions for himself. Other dilemmas presented by this patient are the lack of a coordinated plan of care, the lack of communication with the patient and family, and the lack of attention to social factors that influence the patient's situation and his resulting care.

Adolescent↗

New antimicrobial agents.

In any discussion of new antimicrobial agents in the 1990s, a warning and a plea are necessary. The spreading emergence of resistance among bacteria raises concerns for the effectiveness of antimicrobial therapy. Penicillin-resistant pneumococci are probably of most significance in pediatrics and are increasing in frequency, in part related to the use of antimicrobial therapy in young children to treat such infections as otitis media. New practice guidelines have suggested the more limited use of antimicrobial agents in treating serious otitis media. When pediatricians do treat, they should select effective agents. Limiting therapy to brief courses with effective and narrow-spectrum agents may be helpful also. Treating long enough to ensure eradication in serious infections is equally important. Methicillin-resistant S aureus are also increasing and are increasingly a concern in community-acquired infections and nosocomial infections. Using topical agents, such as mupirocin, to treat impetigo and other superficial skin infections can limit exposure to systemic agents and may delay the spread of resistance. Vancomycin-resistant enterococcal infections, an infrequent pediatric problem, are most frightening because no alternative therapies are available. Their occurrence is directly related to use of vancomycin in the communities that are affected. Containing the spread of drug-resistant bacteria will likely require a concerted effort by both physicians and the public. The indiscriminate use of antimicrobial agents to treat non-bacterial infections should be contained. The public must be educated to understand that antimicrobial agents are ineffective against viral infections. In the setting of managed care, educating administrators who make practice decisions that cheaper is not always better will be crucial. The issues of day-care infections and spread of potential pathogens must take on increasing attention and methods to decrease infection sought. Curbing inappropriate use of antimicrobial agents will be as important as learning the nuances between new agents.

Anti-Bacterial Agents↗

Ceftibuten vs. penicillin V in group A beta-hemolytic streptococcal pharyngitis. Members of the Ceftibuten Pharyngitis International Study Group.

The efficacy and safety of a 10-day course of ceftibuten oral suspension (9 mg/kg once daily) were compared with those of penicillin V (25 mg/kg/day in 3 divided doses) in children 3 to 18 years old treated for symptomatic pharyngitis and scarlet fever caused by group A beta-hemolytic streptococci (Streptococcus pyogenes). The study was prospective, randomized, multicenter and investigator-blinded; patients were randomized in a 2:1 ratio (ceftibuten:penicillin V). Overall clinical success (cure/improvement) at the primary end point of treatment (5 to 7 days posttherapy) was achieved in 97% (285 of 294) of ceftibuten-treated patients vs. 89% (117 of 132) of penicillin V-treated patients (P < 0.01). Elimination of infecting streptococci 5 to 7 days posttherapy was achieved in 91% (267 of 294) of ceftibuten-treated patients vs 80% (105 of 132) of penicillin V-treated patients (P < 0.01). A significant rise in anti-streptolysin O or anti-DNase B was observed in approximately 30% of patients in both treatment groups. No patient developed rheumatic fever or nephritis. Treatment-related adverse events were similar between the two groups; mild vomiting (2%) was most frequently reported. These data suggest that once daily ceftibuten is as safe as and more effective than three times daily penicillin V for the treatment of group A beta-hemolytic streptococcal pharyngitis.

Adolescent↗

Osmolar changes regulate the paracellular permeability of cultured human cervical epithelium.

Extracellular nucleotides induce a biphasic change in the transepithelial electrical conductance (GT) of human cervical cells grown on filters: a rapid increase (phase I) followed by a sustained decrease (phase II). To probe the involvement of the intercellular space, its magnitude was varied by manipulating cell volume through changes in extracellular osmolarity. Under baseline conditions [GT = 115 mS/cm2 (approximately 9 omega.cm2)] and during phase II, hypertonic challenges resulted in an increase in GT (0.98% .mosmol-1.l-1 and 0.73%.mosmol-1.l-1, respectively). However, a hypertonic challenge during phase I decreased GT (-0.16%.mosmol-1.l-1). Hypotonic challenges decreased GT during baseline, phase I, and phase II conditions by -1%.mosmol-1.l-1. Similar trends were observed with regard to pyranine permeability. Reduction of extracellular calcium increased GT, abrogated the phase II effect of extracellular ATP, and reversed the effect of a hypertonic challenge. The additive nature of the permeability changes in response to osmotic challenges and to ATP during phase II suggests that different sites are involved in each response, i.e., the resistance of the intercellular space changes with osmolarity and that of the tight junction during phase II.

Adenosine Triphosphate↗

Effects of estrogen in vivo on coronary vascular resistance in perfused rabbit hearts.

Estrogen or its vehicle was given daily to three groups of ovariectomized rabbits for various lengths of time, after which coronary flow was measured in their isolated perfused hearts. In one group, intramuscular injections of estrogen (40 micrograms/kg) for 7 or 14 days increased coronary flow by 40-50% (P < 0.05). In rabbits given estrogen intramuscularly for 7 days, the coronary flow returned to the basal level within 7 days after the estrogen injections were discontinued. In a second group of animals, intravenous injections of estrogen (10 micrograms/kg) for 4 days increased the coronary flow by 45% (P < 0.01). In a third group, we administered the estrogen transdermally for 4 days, and we measured the plasma estrogen levels at the end of this period. The coronary flow in this group was increased by 52% (P < 0.001), and the plasma estrogen levels ranged from 39 to 800 pg/ml. In all groups of experiments, the increments in coronary flow evoked by estrogen were virtually abolished by NG-nitro-L-arginine, an inhibitor of nitric oxide synthase. We conclude that estrogen regulates coronary blood flow, in part by upregulating nitric oxide synthase in the coronary vasculature.

Administration, Cutaneous↗

Glycine inhibition of glutamate evoked-release of norepinephrine in the hypothalamus is strychnine-insensitive.

The effects of glycine (GLY), D-serine (D-SER), kynurenic acid (KYN), and 7-Cl kynurenic acid (7-Cl KYN), on the evoked release of endogenous norepinephrine (NE) by L-glutamate (L-GLU) in rat hypothalamic slices was investigated. KYN (500 and 100 microM) and 7-Cl KYN (10 microM) blocked evoked release of NE by L-GLU (1 mM). The inhibitory effects of 100 microM KYN on evoked release of NE by L-GLU were reversed by 10 microM and 100 microM D-SER and, but not 10 or 100 microM GLY. When KYN was not present in the superfusate, superfusion with either 10 or 100 microM GLY alone simultaneously with 1 mM L-GLU blocked the evoked release of NE produced by L-GLU. The addition of strychnine (3 or 100 microM) to the superfusate did not block the inhibitory effects of 10 microM GLY on L-GLU-evoked NE release. These findings suggest that a novel strychnine-resistant GLY receptor is present in the rat hypothalamus.

Animals↗

Comparative study of the immunogenicity and safety of two dosing schedules of Engerix-B hepatitis B vaccine in neonates.

A randomized multicenter study compared the routine hepatitis B vaccine schedule of 0, 1, 6 months with an accelerated schedule of 0, 1, 2 months in newborns. Two hundred ninety-nine infants whose mothers were seronegative for hepatitis B were enrolled in the study and randomized to either the routine or accelerated schedule. All infants had blood drawn for antibody titers to hepatitis B at 2, 3, 6 and 7 months of age. For 222 infants data were evaluable, at least for safety; 193 of these 22 had antibody titers that were evaluable. The infants vaccinated on the accelerated schedule developed seroprotective concentrations of antibody more quickly than the infants vaccinated on the routine schedule; 92.6% vs. 66.1% had seroprotective concentrations (> or = 10 mIU/ml) at 3 months of age (P < 0.001). However, infants in the accelerated schedule had lower geometric mean antibody titers at 7 months, 420.0 vs. 3141.8. We conclude that the accelerated vaccination schedule resulted in the more rapid development of seroprotective concentrations of antibody, but levels of antibodies were not as high as in the routinely vaccinated infants at 7 months. These data suggest that an accelerated vaccine schedule can be used in the newborn period. The effectiveness of the accelerated schedule in preventing perinatal infections compared to the standard schedule and the necessity for booster doses of vaccine remain to be studied.

Drug Administration Schedule↗

Single-dose pharmacokinetics of piperacillin and tazobactam in infants and children.

The pharmacokinetics of piperacillin and tazobactam were assessed after single-dose administration to 47 infants and children. Study subjects ranging in age from 2 months to 12 years were randomized to receive one of two different doses of a piperacillin-tazobactam combination (8:1): a low dose (n = 23) of 50 and 6.25 mg of piperacillin and tazobactam per kg of body weight, respectively, or a high dose (n = 24) of 100 and 12.5 mg, respectively. The pharmacokinetic behavior of tazobactam was very similar to that observed for piperacillin, supporting the use of these two agents in a fixed-dose combination. No differences in the pharmacokinetics of piperacillin or tazobactam were observed between the two doses administered. The elimination parameters half-life and total body clearance decreased and increased, respectively, with increasing age, whereas volume parameters (volume of distribution and steady-state volume of distribution) remained relatively constant for both compounds. The primary metabolite of tazobactam, metabolite M1, was measurable in the plasma of 18 of the 47 study subjects; 17 of these 18 subjects received the high doses. More than 70% of the administered piperacillin and tazobactam doses were excreted unchanged in the urine over a 6-h collection period. These data combined with the known in vitro susceptibilities of a broad range of pediatric bacterial pathogens indicate that a dose of 100 mg of piperacillin and 12.5 of mg tazobactam per kg of body weight administered as a fixed-dose combination every 6 to 8 h would be appropriate to initiate clinical efficacy studies in infants and children for the treatment of systemic infections arising outside of the central nervous system.

Child↗

Comparison of cefuroxime axetil and amoxicillin-clavulanate suspensions in treatment of acute otitis media with effusion in children.

Two hundred sixty-three pediatric patients from the ages of 3 months to 11 years were enrolled in a randomized, investigator-blinded, multicenter study comparing the clinical and bacteriological efficacies and safety of cefuroxime axetil suspension (CAE) with those of amoxicillin-clavulanate suspension (AMX-CL) in the treatment of acute otitis media with effusion. Patients received CAE at 30 mg/kg of body weight per day (n = 165) in two divided doses or AMX-CL at 40 mg/kg/day (n = 98) in three divided doses for 10 days. The primary pathogens among 200 isolates from pretreatment cultures of middle ear fluid were identified as follows: Haemophilus influenzae (39%), over a third of which were beta-lactamase positive; Streptococcus pneumoniae (34%); and Moraxella catarrhalis (16%). Pathogens were eradicated or presumed to be eradicated from 81% (95 of 118) and 76% (50 of 66) of bacteriologically evaluable patients in the CAE and AMX-CL groups, respectively. A satisfactory clinical response (cure or improvement with or without resolution of effusion) occurred in 113 (77%) of 146 clinically evaluable patients in the CAE group and in 66 (74%) of 89 evaluable patients in the AMX-CL group. Clinical failure or recurrence (within 2 weeks following the completion of treatment) occurred in 22 and 26% of CAE- and AMX-CL-treated patients, respectively. Drug-related adverse events occurred in 18% of CAE-treated patients, whereas they occurred in 39% of AMX-CL-treated patients (P < 0.001); diarrhea or loose stools was the most commonly reported adverse event (CAE, 12%; AMX-CL, 31%; P < 0.001). These results indicate that CAE given twice daily is as effective as AMX-CL given three times daily in the treatment of acute otitis media with effusion in pediatric patients, but CAE was associated with significantly fewer drug-related adverse events.

Amoxicillin↗

The decision to breastfeed. The importance of father's approval.

One hundred fifteen postpartum mothers who were within 24 hours of delivery completed a questionnaire to determine factors which may influence a mother's intention to breastfeed and to evaluate specifically the effect of working outside of the home. In our population of mostly middle-class married and insured women, working outside of the home was not significantly related to the decision to breastfeed (67.9% of working mothers, compared to 67.2% of those who did not plan to work postpartum, planned to at least partially breastfeed). The only factors that significantly related to breastfeeding intention pertained to the father's level of education and to his approval of breastfeeding. Strong approval of breastfeeding by the father was associated with a high incidence of breastfeeding (98.1%), compared to only 26.9% breastfeeding when the father was indifferent to feeding choice (P < 0.001).

Attitude↗

Serotonergic modulation of L-glutamic acid-evoked release of endogenous norepinephrine from rat hypothalamus.

Hypothalamic slices (400 mu) from male Sprague-Dawley rats were perfused with a Mg+(+)-free medium containing nomifensine (10 microM) and tyrosine (50 microM). Spontaneous release of endogenous norepinephrine (NE), measured by high-performance liquid chromatography-electrochemical detection, averaged 102 +/- 13 (N = 76) fmol/mg of protein/3 min. L-Glutamic acid (L-GLU) (1 mM) more than doubled the rate of NE release. Preincubation with serotonin (5-HT) (0.1-10 microM) produced no change in spontaneous NE release but caused a concentration-dependent decrease of L-GLU-induced NE release with a maximal reduction of about 60 to 70%. 2-Methylserotonin, a 5-HT3 receptor agonist (0.07-10 microM), mimicked the 5-HT response. A highly selective 5-HT3 receptor antagonist, (3 alpha-tropanyl)1H-indole-3-carboxylic acid ester, 1 nM, inhibited the effect of both agonists. Neither ritanserin (1 microM) nor methylsergide (1 microM) modified either spontaneous or 1 mM L-GLU-evoked release of NE. However, if added to the superfusion medium simultaneously with 5-HT, they potentiated significantly the inhibition produced by 5-HT. Alpha-methylserotonin (1 microM) if added alone to the perfusion medium had no effect on 1 mM L-GLU-evoked release of NE but reversed the inhibition induced by 1 microM 2-methylserotonin. These observations provide direct evidence of a dual modulation by 5-HT of L-GLU-evoked release of endogenous NE from slices of rat hypothalamus: An inhibition mediated by 5-HT3 receptors and an opposing action mediated by receptors of the 5-HT1C/2 type.

Animals↗