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Biomedical subjects

J Goldfarb

Publications and source records attributed to J Goldfarb.

At least 19 recordsLinked to original sources
PubMed1995

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↗
PubMed1995

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↗
PubMed1995

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↗
PubMed1994

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↗
PubMed1992

Release of endogenous norepinephrine from rat hypothalamus by stimulation of N-methyl-D-aspartic acid receptors.

Release of endogenous dopamine and norepinephrine (NE) from rat hypothalamic slices superfused with Mg(++)-free medium in the presence of nomifensine and tyrosine was measured by high-performance liquid chromatography coupled to an electrochemical detector. Superfusion with L-glutamic acid or N-methyl-D-aspartic acid elicited a concentration-dependent release of NE but not of dopamine. The release of NE was transient, returning toward basal values despite the continued presence of the amino acid. Superfusion with 20 mM K+ caused a release of NE that declined at a slower rate. Mg++, DL-2-amino-5-phosphonopentanoic acid and MK-801 (D-5-methyl-10,11,dihydro-5H-dibenzo[a,d] cyclohepten-5-10-imine maleate), but not 6-cyano-7-nitroquinoxaline-2,3-dione, inhibited the L-glutamic acid-evoked release of NE. The release of NE by L-glutamic acid was virtually abolished by tetrodotoxin and by elimination of Ca++ from and inclusion of 2 mM ethylene glycol bis(beta-aminoethyl ether)-N,N'-tetraacetic acid in the superfusion medium. Repeated L-glutamic acid applications displayed a decreased response, whereas repeated exposure to 20 mM K+ did not. Exposure to L-glutamic acid in the absence of Ca++ (plus 2 mM ethylene glycol bis(beta-aminoethyl ether)-N,N'-tetraacetic acid) or in the presence of DL-2-amino-5-phosphonopentanoic acid did not reduce the effects seen on subsequent exposure to L-glutamic acid. Exposure to L-glutamic acid in the absence of Mg++ reduced the effect of a subsequent exposure to L-glutamic acid. These observations provide evidence for an indirect modulation of rat hypothalamic endogenous NE by the N-methyl-D-aspartate receptor.

Animals↗
PubMed1991

Non-isotopic polymerase chain reaction methods for the detection of HIV-1 in Ugandan mothers and infants.

Two non-isotopic polymerase chain reaction (PCR) methods were evaluated by testing blood from 41 HIV-1-seropositive and 16 HIV-1-seronegative Ugandan mothers and 56 of their children (aged 0.5-15.0 months). Amplification of HIV-1 sequences was performed in duplicate using a biotinylated primer pair to the gag region (SK 462-431) and nested primer pairs (JA 17-20) to the pol region of HIV-1. gag sequences were hybridized using a microtiter plate coated with the SK 102 probe followed by colorimetric detection using an avidin-horseradish peroxidase conjugate and tetramethylbenzidine/peroxide substrate. pol sequences were detected on agarose gel stained with ethidium bromide. Results of HIV-1 PCR analysis showed that 40 out of 41 (98%) seropositive mothers and 10 out of 29 (34%) seropositive children had detectable HIV-1 gag and pol sequences. None of the 16 seronegative mothers nor 27 seronegative or Western blot-indeterminate children had detectable HIV-1 sequences. Our results suggest that non-isotopic PCR methods are sensitive, specific, and potentially useful in the early diagnosis of HIV-1 infection in developed and developing countries.

Adolescent↗
PubMed1991

Serotonergic modulation of the release of endogenous norepinephrine from rat hypothalamic slices.

Ca+(+)-dependent release of endogenous norepinephrine (NE) and dopamine from superfused rat hypothalamic slices was stimulated by 40 mM K+. 20 mM K+ released only NE. Two consecutive exposures to 20 mM K+ (S1 and S2, respectively) produced NE release of similar magnitude (S2/S1 = 1.03 +/- 0.08). Serotonin (5-HT), 3 to 10 microM, in the presence of methylsergide or ritanserin (antagonists at 5-HT1-like and 5-HT2 receptors), caused a concentration-dependent decrease of K(+)-evoked NE release. 5-HT alone did not alter K(+)-evoked NE release. 2-Methyl-serotonin, 2-methyl-5-hydroxytryptamine, 3 to 10 microM (a selective 5-HT3 agonist), mimicked the 5-HT response in the presence and in the absence of ritanserin. A highly selective 5-HT3 antagonist, (3 alpha-tropanyl)1H-indole-3-carboxylic acid ester (ICS 205-930), 1 nM, inhibited the effect of both agonists. The isomers of another highly selective 5-HT3 antagonist, zacopride, inhibited the effect of 2-methyl-serotonin, 2-methyl-5-hydroxytryptamine, at a concentration range, 0.03 to 20 nM, characteristic of their interaction with 5-HT3 receptors. alpha-Methyl-serotonin, alpha-methyl-5-hydroxytryptamine, a selective 5-HT1-like/5-HT2 agonist, failed to affect the K(+)-evoked NE release, but antagonized the effect of 2-methyl-serotonin, 2-methyl-5-hydroxytryptamine. These observations provide direct evidence that, in rat hypothalamus, 5-HT modulates release of endogenous NE through activation of 5-HT3 and, possibly, 5-HT1C receptors.

Animals↗
PubMed1990

Receptor-mediated mutual-effect amplification elicited by phenylephrine and serotonin in isolated rabbit aorta.

Phenylephrine (PE) and 5-hydroxytryptamine (5-HT) were utilized to study the effects of simultaneous coactivation of the alpha-1 and 5-HT2 receptors, respectively, on the contractile response of isolated rabbit aortic rings. A mutual-effect amplification of the PE-induced contractile response was observed with concentration-response curves (CRC) elicited by mixtures of PE and 5-HT, using a novel drug concentration paradigm. The theoretical CRC constructed using the Poch and Holzman method of equiactive agonist substitution demonstrated that the observed mutual-effect amplification was more than the result of simple additivity. Thus, the Leff model of mutual-effect amplification was utilized to predict the location of observed CRCs to mixtures of PE and 5-HT. Efficacy (tau) and slope factor estimates were determined using the Black and Leff operational model of pharmacological agonism and these values were used to predict the location of CRCs elicited by mixtures of PE and 5-HT. We demonstrated that the Leff model was insufficient to explain the observed degree of mutual-effect amplification.

Animals↗
PubMed1990

Functional interactions in smooth muscle: kinetic characterization of the relaxation and desensitization responses to a beta adrenergic agonist in the rabbit aorta.

Vascular smooth muscle tone is continuously modulated in vivo by the functional interaction of a variety of vasoconstrictor and vasodilator stimuli. Endogenous substances such as epinephrine simultaneously activate alpha adrenergic receptors that elicit muscle contraction and beta adrenergic receptors that relax the muscle. This study characterizes the beta adrenergic response in the isolated rabbit aorta precontracted with 1 microM phenylephrine. The beta adrenergic agonist isoproterenol (0.03-10 microM) produces a biphasic response that is composed of a rapid relaxation followed by a slower regaining of tension, which is identified as desensitization. An exploratory kinetic model that describes both the relaxation and the desensitization as first-order processes provides a good fit to the experimental data. The parameters used to describe the isoproterenol response are: 1) the observed rate constant for relaxation and its magnitude (krel and R, respectively), 2) the observed rate constant for desensitization and its magnitude (kdes and D, respectively) and 3) the observed delay in the onset of the desensitization response (td). Both the krel and the fractional relaxation were dependent on concentration of isoproterenol in a saturable manner (EC50 = 0.017 and 0.067 microM, respectively). No concentration dependence was observed for kdes, fractional desensitization and td (the average values +/- S.E.M. of these parameters are (4.7 +/- 0.2). 10(-3) sec-1, 0.83 +/- 0.02 and 191 +/- 6 sec, respectively). This work demonstrates that a kinetic approach is necessary to characterize the desensitization response and is also very useful in characterizing the kinetic and steady-state parameters of the relaxation response.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Intracellular and surface acetylcholine receptors during the normal development of a frog skeletal muscle.

125I-alpha-bungarotoxin (125I-alpha BT) was used to measure the pool sizes of surface and intracellular acetylcholine receptors (AChRs) in the myotomal muscle of Xenopus laevis over a developmental period (stages 23-48; 1.03-7.5 d) which ranged from initial to mature stages of neuromuscular synaptogenesis. The surface pool increased progressively throughout development. The intracellular pool increased more slowly and also underwent a transient decrease. Linear regression indicated that AChRs begin to appear intracellularly and in the surface membrane at embryonic ages of 13.2 and 18.5 hr, respectively. The findings also suggest that newly synthesized AChRs contribute much more to the intracellular pool than do AChRs internalized from the surface membrane and that the rates of supply and/or intracellular resident times of these 2 sources of intracellular AChRs change during the course of normal development. Carbamylcholine, even at concentrations 10-fold greater than needed to block completely 125I-alpha BT binding to surface AChRs, blocked specific intracellular binding by only 80%. Considered in the light of previous studies on cell cultures, these results suggest that 20% of the intracellular sites are on alpha-subunits not yet assembled into pentameric AChRs. Light microscope radioautography revealed an essentially uniform distribution of intracellular AChRs along the length of the muscle cells. It is concluded that during the normal development of Xenopus myotomal muscle the accumulation and maintenance of AChRs in the postsynaptic membrane occurs in the absence of any preferential concentration of intracellular AChRs in the subsynaptic region.

Animals↗
PubMed1989

Chronic estrogen effects on 5-hydroxytryptamine-mediated responses in hippocampal pyramidal cells of female rats.

Intracellular recording techniques were used to assess the effect of chronic estrogen treatment of ovariectomized (OVX) rats on CA1 pyramidal cell properties and serotonin (5-HT)-mediated responses in the dorsal hippocampus. The magnitude of the 5-HT1A-mediated hyperpolarization and concomitant change in membrane resistance elicited by 15 microM 5-HT was greater in pyramidal cells from OVX rats treated with estrogen (OVX + ES) than in pyramidal cells from OVX rats. Estrogen treatment did not alter the cellular membrane properties or the reduction in AHP amplitude elicited by 15 microM 5-HT. The modulation of 5-HT neurotransmission by estrogen may contribute to variations in mood which are associated with the menstrual cycle.

Animals↗
PubMed1989

Parvovirus infection in children.

Human parvovirus, discovered fortuitously in 1975, is probably most often associated with an asymptomatic or mild nonspecific illness. This small DNA virus, like other members of the Parvoviridae, has a predeliction for rapidly growing cells, especially the erythroid precursor cells of bone marrow. The virus has now clearly been associated with specific clinical syndromes. Epidemiologic and experimental evidence clearly document human parvovirus as the etiologic agent of the acute aplastic crisis associated with various forms of chronic hemolytic anemia. It is also the etiologic agent of erythema infectiosum, the most frequent presentation of acute parvovirus infection in the normal child. The rash of erythema infectiosum is faint and evanescent and may not always be present or recognized, especially in black children. Frequently this infection may occur as a nonspecific viral syndrome in children or adults, accounting for the high incidence of seropositivity among adults despite an infrequent history of erythema infectiosum. The attack rate is highest among 7- to 10-year old contacts. Severe infection in the fetus has been associated with second trimester abortion. Persistent infection in an immunocompromised child has been associated with chronic aplasia of all marrow elements, suggesting the importance of a normal host immune system to contain this infection. The arthritis and arthralgia seen in older patients, especially women, occur after the viremia has ended, suggesting a possible immunologic pathogenesis for this complication. Volunteer studies have delineated the time course of the various manifestations of parvovirus infection. The ability to infect volunteers intranasally and the finding of virus in respiratory secretions suggests that this may be the route of spread to susceptible contacts.

Child↗
PubMed1989

Release of endogenous dopamine by stimulation of 5-hydroxytryptamine3 receptors in rat striatum.

5-Hydroxytryptamine (5-HT) caused a persistent, concentration-dependent increase of spontaneous release of endogenous dopamine (DA) from superfused rat striatal slices. 2-Methyl-5-HT, a selective 5-HT3 agonist, mimicked the 5-HT response with a potency only slightly less than that of 5-HT. A highly selective 5-HT3 antagonist, ICS 205-930 [(3-alpha-tropanyl)1H-indole-3-carboxylic acid ester], inhibited the effect of both agonists with a pKB value characteristic of 5-HT3 receptors. 5-HT-evoked DA release was resistant to antagonism by methiothepin and methysergide, antagonists at 5-HT 1-like and 5-HT2 receptors. Neither (2,5-dimethoxy-4-iodophenyl)-2-aminopropane, the selective 5-HT2 receptor agonist, nor 5-carboxamidotryptamine, the selective 5-HT 1-like receptor agonist, altered DA release. The release of DA by 5-HT3 stimulation was Ca++-dependent and partially sensitive to tetrodotoxin. 5-HT and 2-methyl-5-HT also increased K+-evoked DA release. These observations constitute direct, unambiguous evidence that in rat striatum 5-HT3 receptors modulate release of DA.

Animals↗