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Biomedical subjects

R Gold

Publications and source records attributed to R Gold.

At least 235 records · Page 13Linked to original sources

Adverse effects of immunization. Is prevention possible?

Vaccination rates must be kept high to prevent epidemics of infectious disease. At the same time, parents must be informed of the rare possibility of serious adverse effects, including seizure and allergic reaction. Every physician who administers vaccine therefore needs to become familiar with the reactions that may occur with each immunologic agent used. The best safeguard against litigation, when and if a serious reaction follows vaccination, is the indication that these considerations were discussed and that an informed choice was made.

Adult↗

Prevalence of hepatitis B surface antigen and antibody (hepatitis B virus markers) in personnel at a children's hospital.

After two cases of acute hepatitis B infection occurred in phlebotomists at The Hospital for Sick Children in 1985, a seroprevalence survey of hepatitis B virus markers was undertaken. Directors in high-risk areas were advised by phone and memorandum to screen employees. Participation was entirely voluntary, and employees who did not respond were contacted six weeks after initial notification. Information obtained from each participant through a self-administered questionnaire included age, duration of employment in current pediatric occupation, history of blood transfusions, immune globulin prophylaxis, needlestick injury, and country of birth (North America/United Kingdom or other). Sera identified by code were tested by radioimmunoassay. Interactions were analyzed by using a multiple logistic regression model. A total of 10% of the personnel in high-risk areas, in which there was frequent exposure to blood or blood products, had hepatitis B markers in their blood, compared with 2% who did not have this exposure. Birthplace and occupation have independently significant effects on the likelihood of having hepatitis B markers. There appears to be an increased risk to employees in pediatric units, depending on the patient (and parent) population being served, although the risk may be lower than in adult hospitals.

Adult↗

Acetaminophen prophylaxis of adverse reactions following vaccination of infants with diphtheria-pertussis-tetanus toxoids-polio vaccine.

The effect of acetaminophen on reducing the frequency and severity of adverse reactions following diphtheria-pertussis-tetanus toxoids-polio vaccine was studied in a randomized clinical trial involving 519 vaccinations in 383 infants 2 to 6 months of age and 70 infants 18 months of age. Significantly fewer local and systemic reactions were reported in acetaminophen-treated infants at 2 to 6 months of age. Acetaminophen also reduced the incidence of fever greater than 38.0 degrees C from 44% to 27%. Only 0.9% of acetaminophen-treated infants had overall behavioral changes rated as severe by parents compared to 13% of the placebo group. Infants vaccinated at 18 months of age had higher rates of systemic and local reactions than younger infants. Acetaminophen did not result in significant reductions in reaction rates after the booster at 18 months. We conclude that acetaminophen administered at the time of primary vaccination with diphtheria-pertussis-tetanus toxoids-polio can significantly reduce the frequency and severity of common adverse reactions.

Acetaminophen↗

Chronic recurrent multifocal osteomyelitis: a noninfectious inflammatory process.

We report seven patients with chronic recurrent multifocal osteomyelitis, an uncommon childhood disease of unknown etiology. These patients presented with insidious onset of bone pain at one or more sites associated with erythema, swelling and tenderness. Scintigraphy and radiography were consistent with osteomyelitis at multiple sites. Bone biopsies confirmed osteomyelitis but no organisms were consistently isolated. During a 1- to 3-year follow-up, most patients developed new symptomatic lesions. The disease was unaffected by antimicrobial therapy. Two of our patients had psoriasis and all were rheumatoid factor-, antinuclear factor- and HLA-B27-negative. We speculate that chronic recurrent osteomyelitis is a noninfectious inflammatory condition, a seronegative spondyloarthropathy. Chronic recurrent osteomyelitis is a clinical entity that should be recognized so that invasive diagnostic procedures and antimicrobial therapy are appropriately used. The patient may be reassured that this is not a malignant condition although there may be exacerbations over many years.

Adolescent↗

Arthritis associated with Haemophilus influenzae meningitis: septic or reactive?

We reviewed 165 pediatric cases of Haemophilus influenzae type b meningitis and found 11 (6.7%) with associated arthritis. Synovial fluid culture and Gram stain suggested that only three of these 11 cases were caused by a septic process. In all three children with septic arthritis, joint symptoms were present on admission or within 24 hours. In contrast, of the eight who had reactive arthritis, arthritis did not appear in six until after 1 week of antibiotic therapy. Patients with septic arthritis were older than patients with reactive arthritis (mean 31 months vs 17 months), had a longer duration of symptoms before the start of antibiotic therapy (mean 6.0 days vs 2.5 days), and were more likely to have a positive blood culture (67% vs 18%). It is probable that the majority of episodes of synovitis occurring after H. influenzae meningitis occur as a result of a reactive rather than a septic process. Treatment of reactive arthritis should be with anti-inflammatory agents rather than with multiple joint aspirations and prolonged antibiotic therapy.

Arthritis↗

Inhaled antibiotics in cystic fibrosis: is there a therapeutic effect?

Antibiotics are administered to patients with cystic fibrosis to eliminate or suppress sputum bacteria. Aerosol administration is attractive because it delivers antibiotic directly to the site of infection. Effective aerosol administration is compromised by the inefficiency of nebulizers to generate small-particle aerosols, adverse airway reaction to the drug, potential emergence of resistant bacteria, and cost. Studies evaluating aerosol treatment have not always controlled for confounding factors and have used a variety of outcome indicators. Results of controlled studies are contradictory with regard to the beneficial effect of aerosol therapy on pulmonary function, sputum bacterial density, and frequency of hospitalization. Therefore, until additional well-controlled trials are completed, routine aerosol administration of antibiotics in cystic fibrosis is not warranted because of cost, potential side effects, and the propensity to select resistant organisms.

Aerosols↗

Sequelae of acute bacterial meningitis in children treated for seven days.

The sequelae of acute bacterial meningitis in children who were treated with ampicillin or chloramphenicol for seven days during the period January 1979 to June 1983 were assessed prospectively. The 235 patients (117 boys and 118 girls) ranged in age from four days to 18 years (mean 26.4 months). Haemophilus influenzae type b was isolated in 70% of patients, Streptococcus pneumoniae in 20%, and Neisseria meningitidis in 10%. The mortality rate was 6.4%. No relapses occurred. Of the 220 survivors, 171 had neurologic psychometric, audiologic, and ophthalmologic assessments performed for a minimum of 1 year following their illness. One hundred thirty-six (80%) children had no detectable sequelae; 20% had mild to severe handicaps. The frequency of sequelae was greatest among children with S pneumoniae meningitis (57%) and least among children with N meningitidis (0%). The sequelae observed included: sensorineural hearing loss (12.9%), developmental delay (5.3%), speech defect (4.7%), motor defect (3.0%), hydrocephalus (1.7%), and seizure disorder (1%). The frequency of observed sequelae among these patients is similar to that previously reported in children treated for ten to 14 days. Our findings indicate that seven days of intravenous antibiotic therapy is adequate for the treatment of bacterial meningitis in children.

Adolescent↗

A new histologic approach to the differentiation of enchondroma and chondrosarcoma of the bones. A clinicopathologic analysis of 51 cases.

Fifty-one cases of central, hyalin cartilage tumors of the long and flat bones were analyzed. Although Grade 2 and 3 chondrosarcomas could be diagnosed on the basis of cytologic features alone, low-grade chondrosarcoma could not be adequately differentiated from pure, benign enchondroma(s) by cytology alone. The tumors can be distinguished by a new histologic approach based on tissue patterns. The crucial enchondroma patterns consist of multiple nodules of hyalin cartilage separated by normal marrow in conjunction with partial to complete encompassing plates of lamellar bone that conform to the irregular shapes of the cartilage nodules. The chondrosarcomatous patterns consist of a single confluent mass of cartilage, which commonly permeates the marrow, "trapping" host lamellar bone on all sides, and which forms bands of fibrosis between the confluent peripheral cartilage lobules. Other less common patterns included cartilagenous infiltration of the Haversian systems or marrow fat and/or the development of a soft tissue mass. A central secondary chondrosarcoma is defined as one that shows the combination of both the enchondromatous and chondrosarcomatous patterns. All 18 of the pure enchondromas diagnosed by the methods proposed in this article behaved with strict benignity (i.e., without evidence of recurrence or metastasis with an average follow-up period of 7.2 years). The 33 primary and secondary chondrosarcomas diagnosed using the described patterns behaved with the predicted frequency of recurrence, metastasis, and patient demise.

Adolescent↗

Analysis of the mouse gamma-crystallin gene family: assignment of multiple cDNAs to discrete genomic sequences and characterization of a representative gene.

Blot hybridization analysis of mouse DNA with gamma-crystallin-specific cDNAs has detected the presence of a multigene family comprised of at least four related genes. The detailed structure of one of these genes, mouse gamma 4-crystallin (M gamma 4.1), and its corresponding cDNA has been determined. The gene spans approximately 2.6 kilobases (kb) and contains two introns. The gene predicts a polypeptide of 174 amino acids that shares extensive sequence homology with gamma-crystallin polypeptides of other species. The two similar structural domains of the protein correspond exactly to the second and third exons of the gene, supporting an exon-duplication model of gene evolution. The similarity in structure of this gene to that recently reported for a gamma-crystallin gene of the rat (1) suggests that a common structure may exist for all gamma-crystallin genes of the two species. Moreover, a highly conserved region, 50 nucleotides in length, immediately precedes the TATA box of both the mouse and rat genes, suggesting that this sequence may be important in gene regulation.

Amino Acid Sequence↗

Sizes, laminar and topographic origins of cortical projections to the major divisions of the red nucleus in the monkey.

The retrograde transport of horseradish peroxidase was used to study the topographic and laminar origins of the cortical projections to the parvocellular and the magnocellular divisions of the red nucleus in Macaca mulatta and Macaca fascicularis. Approximately 90% of the corticorubral projection is directed to the parvocellular division of the nucleus. Corticoparvocellular (CRp) neurons are pyramidally shaped, are smaller in size than corticospinal neurons, and are more numerous. They are found principally in sublamina Va of cytoarchitectonic areas 4 and 6, and in moderate quantities in sublamina Vb of posterior area 8 and area 5. In areas 4 and 6, the cells are grouped in clusters of three to 15 neurons each and are arranged in cellular bands of varying rostrocaudal thickness which course mediolaterally. With respect to functionally defined zones, CRp neurons are found throughout the supplementary motor area and the precentral motor cortex. In addition, they are found in parts of areas 5, 6, and 24 that project to these cortical motor areas, and that are thought to have "premotor" or movement-programming functions. The corticomagnocellular (CRm) projection arises principally from cells in sublamina Vb of the precentral arm and leg areas (area 4), and from adjacent parts of posterior area 6, CRm cells are pyramidally shaped, and their size distribution is bimodal, with peaks that correspond, respectively, to the modal diameters of CRp and of corticospinal neurons. These results and those of previous studies suggest that CRm neurons are involved principally in the control of hand and foot movements, with little effect on more proximal musculature. The massive CRp projection, however, is clearly part of a large cerebrocerebellar communication system, with motor and/or movement programming functions that have yet to be clearly defined.

Animals↗

Cloxacillin absorption and disposition in cystic fibrosis.

Because of reports of lowered antibiotic serum concentrations in patients with cystic fibrosis (CF), a bioavailability and pharmacokinetic study of cloxacillin was conducted in 12 control and 16 patients with CF after intravenously and orally administered doses of cloxacillin 25 mg/kg. The patients had mild to moderate CF and were in stable condition. Significantly lower serum concentrations in CF were a result of a 78% increase in total body clearance (P less than 0.005) and a 38% increase in the apparent volume of distribution (P less than 0.025). The bioavailability in CF (0.50) was not significantly different than in controls (0.38), but more variability was seen in the group with CF. After the intravenously given dose the fraction of cloxacillin excreted in the urine unchanged was similar in controls (0.644) and patients with CF (0.547). Compared with that in the control subjects, the mean renal clearance in patients with CF was 30% greater (P less than 0.10) and the nonrenal clearance was 144% greater (P less than 0.07). Enhanced nonrenal clearance explains most of the demonstrated difference between serum concentrations in controls and patients with CF after identical weight-adjusted doses. The data suggest enhanced cloxacillin biotransformation in CF.

Administration, Oral↗

Pseudomonas cepacia infection in cystic fibrosis: an emerging problem.

The prevalence of Pseudomonas cepacia infection increased from 10% in 1971 to 18% by 1981 in a population of approximately 500 patients with cystic fibrosis. Carriage of P. aeruginosa has remained unchanged at 70% to 80% over the same period. Patients infected with P. cepacia have greater impairment of pulmonary function than those with P. aeruginosa. A syndrome characterized by high fever, severe progressive respiratory failure, leukocytosis, and elevated erythrocyte sedimentation rate has occurred in eight patients over the past 3 years, with a 62% fatality rate. Because P. cepacia strains are uniformly resistant to ticarcillin, piperacillin, and aminoglycosides, and because ceftazidime is ineffective despite in vitro activity, treatment of these infections is very difficult. Prevention of acquisition and effective treatment of P. cepacia in patients with cystic fibrosis are now major clinical problems in our clinic.

Adolescent↗

Drug-induced modulation of locomotor hyperactivity induced by picrotoxin in nucleus accumbens.

Locomotor hyperactivity was induced in rats by bilateral injection of picrotoxin (PIC) into the nucleus accumbens (NAC) followed by intraperitoneal (IP) or intra-accumbens (IA) injection of agents affecting dopamine (DA), acetylcholine, serotonin, or GABA receptors. IP injection of haloperidol and diazepam attenuated PIC-induced hypermotility in a dose-dependent manner. Low (sedative) doses of the DA agonists apomorphine (APO) and lisuride, or pretreatment with reserpine abolished PIC-induced hypermotility. Independent of a preceding IA injection of PIC, higher IP doses of APO produced the well-known locomotor effect. LSD, and the atypical neuroleptic, sulpiride, potentiated PIC-induced hypermotility strongly whereas clozapine was ineffective. IA injection of carbachol or haloperidol, in doses which antagonized hypermotility induced by APO IP, did not influence PIC-induced hypermotility. The atypical neuroleptics, clozapine and sulpiride, and the benzodiazepine, diazepam, inhibited PIC-induced hypermotility. The results suggest that there is a complex involvement of GABA, DA and serotonin functions in the effectuation of PIC-induced hypermotility and that PIC-induced hypermotility may be affected by DA-sensitive structures situated outside the NAC.

Animals↗

Ceftazidime disposition in acute and stable cystic fibrosis.

Ceftazidime disposition after an intravenous dose of 50 mg/kg infused over 20 min was followed in 10 subjects with cystic fibrosis (CF) hospitalized with acute pulmonary exacerbations and in 10 healthy subjects. Serum ceftazidime elimination t 1/2 decreased from 105.3 +/- 12.4 min (mean +/- SD) in controls to 90.0 +/- 11.1 min in subjects with CF. Calculated distribution volumes were both larger in subjects with CF. When normalized for body surface area, total body clearance (Cl) was 41.9% greater in the CF group (142.4 +/- 16.9 and 100.5 +/- 10.3 ml/min/1.73 m2). Normalization for body weight revealed 64.8% greater Cl in subjects with CF. Fraction of dose recovered in urine was of the same order for each group, while renal clearance (ClR) was 40.9% greater in the subjects with CF (130.1 +/- 11.4 and 92.7 +/- 11.6 ml/min/1.73 m2). Five subjects with CF were restudied while infection-free 119 to 219 days after the original study day. With the exception of a 10% increase in the volume of distribution at steady state while infection-free, kinetic parameters were much the same. No changes in Cl or ClR were evident from one study day to the next. Acute pulmonary infection does not appear to alter ceftazidime clearance in CF. The mechanism underlying increased ceftazidime Cl and ClR in CF is not apparent from the present data.

Adolescent↗