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Biomedical subjects

J D Nelson

Publications and source records attributed to J D Nelson.

At least 181 records · Page 10Linked to original sources

A pharmacologic evaluation of penicillin in children with purulent meningitis.

We undertook a prospective study of the pharmacokinetics of penicillin G (administered intravenously every four hours for a total of b50,000 U per kilogram per day) in the cerebrospinal fluid of children with purulent meningitis. Both the absolute mean cerebrospinal-fluid penicillin concentration (0.8, 0.7 and 0.3 microgram per milliliter) and the percentage of the simultaneous serum penicillin concentration measurable in the cerebrospinal fluid (18.4, 9.9, 4.9 per cent) declined on the first, fifth and 10th days of therapy, respectively. A mean peak cerebrospinal-fluid penicillin concentration of 0.96 micrograms per milliliter was measured at least transiently on all three study days. This pharmacokinetic pattern correlated with the return of cerebrospinal-fluid protein concentration toward normal (P less than 0.01). Penicillin G in the dosage studied is adequate therapy for most streptococcal and meningococcal meningitis in children; an increased dosage may be necessary when the minimal inhibitory concentration of penicillin to the etiologic agent is unusually high.

Age Factors↗

Distribution of lipopolysaccharide and the detection of a new subfraction in the cell envelope of a marine pseudomonad.

The three outer layers of the cell envelope of marine pseudomonad B-16, the loosely bound outer layer, the outer membrane, and the periplasmic space layer, are the only ones containing appreciable amounts of both lipid and carbohydrate. These layers and a fraction released into the medium during growth of the cells were examined for the presence of common antigens by double immunodiffusion using anti-whole serum. Each of the layers, the medium fraction, and lipopolysaccharide (LPS) isolated from the organism were shown to contain two or more diffusible components showing reactions of identity. Thus LPS is found in each of the three outer layers of the cell envelope of this gram-negative bacterium. The periplasmic space layer was found to contain a fraction accounting for 20% of the dry weight of the layer, which was sedimentable at 30,000 x g and contained lipid, protein, and carbohydrate. Double-immunodiffusion tests indicated that the fraction contained at least one of the two antigens present in isolated LPS. A particulate material was released by the cells during growth which gave a positive test for 2-keto-3-deoxyoctulosonic acid and cross-reacted serologically with LPS.

Antigens, Bacterial↗

Glycosyltransferase and UDP-galactose pyrophosphatase activities in the endometrium during oestrous cycle of the rat.

UDP-galactose: glycoprotein galactosyltransferase, CMP-sialic acid: glycoprotein sialyltransferase and UDP-galactose pyrophosphatase activities were measured in the endometrium of rat uteri during the oestrous cycle. The galactosyltransferase activity started to increase at dioestrus and reached a maximum on the afternoon of pro-estrus. The UDP-galactose pyrophosphatase activity changed in a direction opposite to that of galactosyltransferase. The sialyltransferase activity was low during metoestrus and dioestrus, but began to rise on the morning of pro-oestrus, reaching a peak on the morning of oestrus. Previously, we have shown that oestradiol administration stimulated galactosyl- and sialyltransferase and inhibited pyrophosphatase activities several-fold in the endometrium of ovariectomized rats. Progesterone prevented the oestradiol effect on the enzymes. The changes in glycosyltransferase and pyrophosphatase activities during the oestrous cycle possibly bear a direct relationship to the ovarian hormones in the rat during the normal oestrous cycle. This relationship will then be conducive to increased synthesis of glycopolymers during ovulation. Furthermore, the lag of 18 h for a maximal rise of sialyltransferase following that of galactosyltransferase is consistent with the normal sequence of glycosylation that occurs in glycoprotein secretion.

Animals↗

Otitis media in children less than 12 weeks of age.

Cases of otitis media in infants under 12 weeks of age were reviewed to delineate the frequency, clinical features, and etiologic agents involved. Tympanocentesis was performed in 42 infants, 0 to 5 weeks of age, and in 17, from 6 to 11 weeks of age. The most common symptoms were irritability/lethargy (69%), fever (52%), cough (36%), vomiting (21%), diarrhea (20%), tachypnea (20%), and anorexia (18%). Associated illnesses were present in 33 (54%) of the patients, the most common being pneumonia (9), bronchiolitis (7), meningitis (6), conjunctivitis (4), and omphalitis (4). No peripartum infections or severe perinatal problems were found. Common respiratory pathogens were the predominant etiologic organisms, but coliform organisms were identified in 18% of the infants under 6 weeks of age. Cultures were sterile or grew organisms of questionable pathogenicity ("nonpathogens") in 39% of specimens. Since the signs and symptoms of otitis media in children less than 12 weeks of age are nonspecific and frequently associated with other major illnesses, the physician caring for these infants needs to be more aware of this disease and the therapeutic problems it presents.

Anti-Bacterial Agents↗

Gonorrhea in preschool- and school-aged children. Report of the prepubertal gonorrhea cooperative study group.

Single-dose antibiotic therapy was evaluated in 108 episodes of culture-confirmed, uncomplicated gonorrhea in 100 prepubertal children. There were 15 boys and 85 girls between 14 months and 14 years of age. Penicillin G procaine, 100,000 units/kg intramuscularly, was compared with amoxicillin trihydrate, 50 mg/kg orally. Probenecid, 25 mg/kg, was given simultaneously. Both drugs provided prompt bacteriological and clinical response. Multiple episodes of gonorrhea, presumably caused by reexposure, occurred in six girls. Oral and anal cultures were negative in all of 47 Costa Rican cases but were commonly positive in US children. Anal cultures yielded gonococci in 52% of girls and 25% of boys, and oral cultures were positive in 18% and 13%, respectively. In three instances, rectal cultures confirmed the diagnosis when vaginal cultures were negative. Gonorrhea should be considered in every child with vaginal or urethral discharge. Single-dose penicillin-probenecid or amoxicillin-probenecid treatment is curative.

Administration, Oral↗

Residual effects of septic arthritis in infancy and childhood.

Septic arthritis affects weight-bearing joints in three fourths of cases. When the disease occurs in infancy, joint dysfunction may not be apparent until many months later. We located 49 children who had had 50 episodes of septic arthritis from 1 1/2 to 12 years earlier (mean, 4.3 years). Thirteen patients (27%) had sequelae, and in eight (16%), there was impairment of ambulation. Residual damage was more common with hip and ankle involvement than with knee joint disease. Sequelae were equally common after Haemophilus influenzae and Staphylococcus aureus infection. Evaluation at the time of hosiptal discharge correctly identified only four of the 13 children with sequelae, and four others who were normal at follow-up had been thought to have permanent damage at discharge. Children with sequelae tended to have been sick longer before diagnosis, and drainage of pus was delayed.

Age Factors↗

Effect of estradiol and progesterone on UDPgalactose pyrophosphatase activity in the endometrium of ovariectomized rats.

Rat endometrium was found to contain a UDPgalactose pyrophosphatase for the hydrolysis of UDPgalactose into galactose 1-phosphate and UMP. The adminstration of 17beta-estradiol to ovariectomized rats resulted in a significant decrease in the activity of the enzyme in endometrium while have little effect on that in myometrium. The response was linear with the dose of estradiol and as little as 0.07 mug per 100 g body weight produced maximum inhibition of the enzyme. Progesterone on its own had little effect on the enzyme activity but in combination with estradiol, it effectively prevented the inhibitory effect of estradiol. This inhibitory effect of estradiol on the activity of UDPgalactose pyrophosphatase may function in the regulation of glycoprotein biosynthesis in endometrium.

Animals↗

Trimethoprim-sulfamethoxazole therapy for shigellosis.

Twenty-eight infants and children hospitalized for severe shigellosis were treated orally either with ampicillin trihydrate (100 mg/kg/day administered in divided doses every six hours) or with trimethoprim-sulfamethoxazole (trimethoprim, 10 mg; sulfamethoxazole, 50 mg/kg/day in divided doses every 12 hours) for five days. Four patients with ampicillin-resistant shigellae continued to have diarrhea and positive stool cultures during therapy. Patients with susceptible shigellae treated with ampicillin and all patients treated with trimethoprim-sulfamethoxazole responsed promptly and comparably within an average of 1.6 and 1.7 days, respectively, until stool cultures were negative, and 3.1 and 2.9 days, respectively, until diarrhea stopped. Patients with ampicillin-resistant shigellae responded to treatment with trimethoprim-sulfamethoxazole. It is concluded that trimethoprim-sulfamethoxazole is the best currently available drug for treatment of shigellosis in areas where multiple antibiotic resistance of shigellae is common.

Age Factors↗

Otitis media of infancy and early childhood. A double-blind study of four treatment regimens.

A double-blind, randomized trial of four antimicrobial regimens was conducted in 383 infants and children with acute otitis media. The drugs used were penicillin V, amoxicillin trihydrate, erythromycin estolate, and erythromycin estolate with trisulfapyrimidines. Aspiration of middle ear fluid for culture was done before treatment and repeated during treatment if fluid persisted. Etiologic bacteria were most commonly pneumococci (31%) or Haemophilus sp (22%), and an additional 5% of patients had both organisms. Amoxicillin was the most effective in promoting initial response in pneumococcal infection. For Haemophilus infections, the cure rates with amoxicillin and the erythromycin-trisulfapyrimidines mixture were significantly better than with the other two regimens, and serous otitis did not occur during the follow-up period; however, new episodes of otitis were comparable in the four groups. Amoxicillin and the erythromycin estolate-trisulfapyrimidines combination appear to be somewhat more effective than penicillin V or erythromycin estolate.

Acute Disease↗

Comparison of trimethoprim-sulfamethoxazole and ampicillin theraphy for shigellosis in ambulatory.

One-hundred seventy-four infants and children with acute diarrhea were treated as ambulatory patients with either ampicillin (100 mg/kg/day orally in four divided doses) or trimethoprim sulfamethoxazole (10 mg TMP and 50 mg SMX/KG/day orally in two divided doses). There were 65 patients with shigellosis. Responses of those treated with TMP/SMX and of those with susceptible Shigella treated with ampicillin were comparable. Patients with resistant organisms failed to respond to ampicillin. All Shigella, including ampicillin-resistant strains, were suseptible in vitro to TMP/SMX, and patients with ampicillin-resistant strains responded favorably to treatment with TMP/SMX. TMP/SMX appears to be the best, currently available drug for the treatment of shigellosis.

Ambulatory Care↗

A prolonged nursery epidemic associated with a newly recognized type of group A streptococcus.

During a six-month period 69 infants in a newborn nursery were colonized with group A streptococci. Fifty-one had omphalitis, two infected circumcision wounds, and one each had meningitis, primary peritonitis, and conjunctivitis. Thirteen infants were asymptomatically colonized. Control of the epidemic was difficult. Benzathine penicillin prophylaxis to all infants suppressed active infection but did not eradicate asymptomatic colonization of the umbilical cord. Triple dye treatment of the umbilical cord plus benzathine penicillin prophylaxis eradicated the infection from the nursery. The epidemic streptococcus was a newly recognized ""skin strain,'' provisional type strain 5656-S, not previously known to cause epidemic disease or serious systemic infections.

Disease Outbreaks↗

Commentary: An appraisal of tobramycin usage in pediatrics.

Tobramycin is a newly marketed aminoglycoside which closely resembles gentamicin in antimicrobial activity, pharmacology, clinical efficacy, and toxicity. It is somewhat more active in vitro against Pseudomonas aeruginosa than is gentamicin and may have a lower ototoxic potential. Tobramycin should be considered a limited-purpose drug for pediatric patients until greater clinical experience has been gained. At the present time the major indication for its use is for treatment of infections caused by coliforms or pseudomonas resistant to kanamycin and gentamicin. Demonstration of in vitro susceptibility is mandatory because resistance to tobramycin and the other aminoglycosides may be mediated by the same episome (R-factor). The recommended dosage is 2 mg/kg every 12 hours (4 mg/kg/day) intramuscularly or as a two-hour intravenous infusion to neonates, with the possible exception of full-term infants over seven days of age who may require administration every eight hours. Beyond the neonatal period, the dosage should be 1.0 to 1.5 mg/kg every eight hours (3 to 4.5 mg/kg/day). Larger dosages may be required for treatment of meningitis, but presently there is no information on which to base a recommendation. Neither is there experience with intrathecal use in infants. It is desirable to monitor tobramycin serum concentration to be certain that peak values are within the therapeutic range of 3 to 8 mug/ml. Dosage must be reduced in patients with impaired renal function and monitoring of serum concentrations is imperative. All patients should be evaluated for evidence of renal and eighth nerve toxicity.

Adult↗

Reevaluation of kanamycin dosage in infants and children.

It was recently reported that the dosage of kanamycin formerly recommended for neonates of 7.5 mg/kg every 12 h did not produce therapeutic serum concentrations of 15 to 25 mug/ml, but a larger dosage of 10 mg/kg every 12 h was required. Reevaluation of the pharmacokinetics of kanamycin in infants and children was therefore undertaken. Sixteen time-concentration curves after a dose of 5 mg/kg were obtained from patients 2 months to 12 years of age; the mean peak serum kanamycin concentration was 10.9 (range, 3.6 to 17.9) mug/ml at 0.5 h. Ten time-concentration curves were obtained after a dose of 10 mg/kg; the mean peak serum concentration was 17.6 (range, 8.4 to 30) mug/ml. Eight patients were studied on successive days, and there was doubling of the 1-h peak serum concentration when the dose of kanamycin was increased from 5 to 10 mg/kg. Standard serum bactericidal tests were done against Escherichia coli and Enterobacter cloacae strains, each with a minimal bactericidal concentration of 5 mug of kanamycin per ml. All 3 sera containing 21 mug or more of kanamycin per ml demonstrated a bactericidal titer, whereas only 2 of 23 sera containing less than 21 mug of kanamycin per ml did so. The currently recommended dosage of kanamycin for infants and children fails to produce serum concentrations in the therapeutic range, and preliminary data suggest that the dosage should be increased to 10 mg/kg per dose every 8 h.

Child↗

Incidence of Salmonella spp., Clostridium botulinum, and Vibrio parahaemolyticus in an estuary.

A study of the incidence of Salmonella spp., Vibrio parahaemolyticus-like organisms, and clostridium botulinum in samples collected at five stations located in the Upper Chesapeake Bay, a major estuary on the Atlantic Coast of the United States, was conducted in December 1973 through December 1974. C. botulinum types B and E were detected in 12.3% of the total sediment samples examined. V. parahaemolyticus was recovered from 10.4% of a total of 86 water, sediment, and suspended sediment samples. Of 131 samples examined for the presence of Salmonella spp., approximately 3% were found to be positive for serologically confirmed Salmonella isolates. Shellfish examined during the investigation were also found to be free of enteric pathogens. The low frequency of occurrence of V. parahaemolyticus was attributed to the low salinities encountered at the sites included in the study. A low incidence of Salmonella spp. in the Upper Chesapeake Bay samples was found, whereas the distribution of C. botulinum appeared to be both random and autochthonous. A strong relationship between presence of potential pathogens and other generally accepted microbiological indicators of pollution was not observed.

Animals↗