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Biomedical subjects

J Wilkins

Publications and source records attributed to J Wilkins.

At least 127 records · Page 7Linked to original sources

Additional evidence against measles vaccine administration to infants less than 12 months of age: altered immune response following active/passive immunization.

Quantitative serologic responses following the inoculation of infants less than one year of age with live, further-attenuated measles virus vaccine were compared to those of infants and children inoculated after one year of age. Active/passive immunization resulted in reduced antibody formation in some infants especially those less than 9 months of age. Thirty-seven infants identified as "vaccine failures" following their initial inoculation at less than one year of age were revaccinated after one year of age. Fifty-one percent had no detectable HI antibody by eight months postrevaccination, contrasted to 6.8% of the vaccinees with no detectable HI antibody following one inoculation after one year of age; 49% responded optimally to revaccination. In face of an observed altered response in many infants less than one year of age, it would appear prudent to withhold vaccine in this age group until the consequences of such an approach are better defined.

Age Factors↗

Epidemiologic survey of juvenile-onset diabetes in Montreal.

Active search of hospital records was used to survey insulin-dependent juvenile-onset diabetics younger than 17 years resident in General Montreal at the time of onset of symptoms during a seven-year period (1971-1977). A mean annual incidence of 8.8/100,000 was found with variation from year to year (5.8 to 10.3). Eighty percent were five years of age or more at time of diagnosis, and the increase with advancing age was similar to that seen in other studies including the somewhat earlier increase in incidence among females. Seasonal peaks were noted in some but not all years and were more marked in years of high incidence and among males. More cases occurred in areas of high socioeconomic level as measured by average family income. The estimated incidence among siblings of diabetics is 15 times the incidence in the general population. Ten percent of diabetics have a first degree relative who is insulin dependent.

Adolescent↗

Evidence for reinstatement of infants 12 to 14 months of age into routine measles immunization programs.

The hemagglutination inhibition (HI) serologic responses of 851 measles-susceptible infants and children to the live, further-attenuated measles virus vaccine were evaluated over a ten-year period. The response by age at 23-day intervals was determined. Infants inoculated at 12 through 14 months of age demonstrated seroconversion rates by HI assay comparable to those in infants and children inoculated at 15 months of age or older. This finding does not support the recent recommendation that routine active immunization with measles vaccine should be postponed until 15 months of age. We emphasize the possible consequence of electively leaving infants 12 throught 14 months of age vulnerable to measles because of the current endemicity of this disease in the United States. We also present evidence for the reinstatement of infants 12 through 14 months of age into routine measles immunization programs and for the need to further evaluate the causes for vaccine failure in vaccines after the loss of maternal antibody.

Antibody Formation↗

Differential inactivation of cephapirin vs. cephalothin by penicillin-resistant strains of Staphylococcus aureus: a preliminary study.

The bactericidal effectiveness of cephapirin and cephalothin against small (approximately 10(5)) and large (approximately 10(8)) inocula of penicillin-resistant Staphylococcus aureus was evaluated. With the smaller inoculum, no differences in bactericidal activity between the two drugs (tested at 2 and 40 microgram/ml) were seen after incubation for 2, 4, 6, or 24 hr. Neither cephalosporin effectively killed a larger inoculum in a concentration of 250 times the minimal bactericidal concentration for selected strains. Total inactivation of cephapirin (40 microgram/ml) by eight of 13 strains was demonstrated with the larger inoculum. These preliminary studies indicate that inactivation of cephapirin is pH-dependent. No strain inactivated cephapirin in less than or equal to 4 hr. Inactivation was independent of temperature at 37 C and 42 C. Although cephalothin was resistant to inactivation under the same conditions, the inoculum required to inactivate cephapirin was not killed by 100 microgram of cephalothin/ml. Although strains of S. aureus that slowly inactivate cephapirin appear to be prevalent, no strain that rapidly inactivates this cephalosporin was identified.

Cephalosporins↗

Failure of cefamandole in treatment of meningitis due to Haemophilus influenzae type b.

The in vitro activity of cefamandole was determined against 58 isolates of Haemophilus influenzae type b; 47 were beta-lactamase-negative (ampicillin-susceptible), and 11 produced beta-lactamase (ampicillin-resistant). Ampicillin-susceptible strains were susceptible to cefamandole with a median minimal bactericidal concentration (MBC) of 0.4 microgram/ml. Ampicillin-resistant strains had a median MBC of 0.8 microgram/ml. Prior studies have documented these concentrations of cefamandole in cerebrospinal fluid in the presence of inflamed meninges. Three children with meningitis due to H. influenzae type b were treated with cefamandole (200 mg/kg per day), including one child with disease due to an ampicillin-resistant strain. All patients showed clinical improvement during therapy. However, sterility of the cerebrospinal fluid was never achieved in two patients during 72--96 hr of therapy with cefamandole. The third patient relapsed with a recurrence of positive cultures during the seventh day of cefamandole therapy. Therefore, cefamandole does not appear to be a useful agent for treatment of meningitis due to H. influenzae type b irrespective of in vitro susceptibility or evidence of penetration into the cerebrospinal fluid.

Ampicillin↗

Plasma neurophysin and vasopressin in the rat: response to adrenalectomy and steroid replacement.

Impaired excretion of a water load is known to occur in adrenal insufficiency and to be corrected by administration of glucocorticoid. Such impairment has been related to either a loss of a permissive effect of glucocorticoids on the diluting segments of the nephron or to an alteration of release, turnover, or action of antidiuretic hormone. Specific and sensitive RIAs for arginine vasopressin and neurophysin were utilized to measure plasma and pituitary levels of neurohypophyseal peptides at baseline and after an intragastrically administered water load. Conscious, unanesthetized, and nonstressed sham-operated, adrenalectomized, and adrenalectomized prednisone-treated rats were studied. The results demonstrate a significant elevation in vasopressin and neurophysin in plasma in adrenalectomized rats maintained in a normal state of hydration. After water loading, the adrenalectomized rats diluted their plasma osmolality but had a decreased urinary volume, increased urinary osmolality, and elevated vasopressin and neurophysin in their plasma. In the pituitary, vasopressin and neurophysin were depleted in adrenalectomized rats, indicating increased secretion of these peptides. It is concluded that elevated vasopressin in plasma may be an important factor in the incomplete water diuresis in adrenal insufficiency.

Adrenalectomy↗

The role of antibiotics, immunizations, and adenoviruses in pertussis.

Sixty-five patients with pertussis were identified by a clinical criterion, and Bordetella pertussis was isolated from 75% of these patients or their symptomatic household contacts. Negative nasopharyngeal cultures were usually associated with either a history of antibiotic therapy with erythromycin or tetracycline (two of three patients), two or more diphtheria and tetanus toxoids with pertussis (DTP) vaccines (six of eight patients), or both (two of three patients). Erythromycin therapy resulted in the elimination of B. pertussis from the nasopharynx in 2 to 7 days (mean, 3.6 days) compared with 7 to 17 or more days (mean, greater than 12 days) in patients treated with no antibiotics, but had no effect on the duration or severity of illness as judged by length of hospitalization. Adenoviruses were recovered from five of 44 patients cultured. Four of these isolates were from throat swabs obtained early in the illness and the remaining isolate was from one of 33 repeated viral cultures obtained two to three weeks later; B. pertussis was also isolated from these five patients. Paired serum samples were obtained from only two of these patients. Neither demonstrated a fourfold rise in adenoviral complement-fixing antibodies. Therefore, in these patients, adenoviral isolation may have been secondary to reactivation of a latent viral infection by infection with B. pertussis.

Adenoviridae↗

Antibody of polyribophate of Haemophilus influenzae type b in infants and children: effect of immunization with polyribophosphate.

Antibody to polyribophosphate, the capsular polysaccharide of Haemophilus influenzae type b, was measured in healthy ambulatory children by a radioactive antigen-binding assay. Titers fell from birth through nine months of age, then increased until six years, when they plateaued. Antibody activity was not correlated with the child's sex, ethnic status, or area of residence. Doses of 0.2-50 microgram of polyribophosphate given as single or booster doses had similar effects on antibody activity. Of 368 doses given to infants two to six months of age, 7% produced a significant antibody response; of 95 doses given to infants seven to 12 months old, 17% produced a response. The geometric mean titers of antibody resulting from immunization with polyribophosphate given at various times in relation to diphtheria-pertussistetanus vaccine did not differ significantly from one another or from titers observed in infants given only the latter vaccine. These data indicate that purified polyribophosphate will not provoke humoral immunity in young infants against H. influenzae type b and that it should no longer be considered as a candidate vaccine for this purpose.

Age Factors↗

Comparative trial of carbenicillin and ampicillin therapy for purulent meningitis.

A randomized therapeutic trial of carbenicillin (CB) or ampicillin (AMP) in purulent meningitis was performed in 86 pediatric and adult patients (41 Haemophilus influenzae, 22 Streptococcus pneumoniae, 13 Neisseria meningitidis, and 10 of unknown etiology). All isolates, incuding H. influenzae, were susceptible to CB and AMP. Median cerebrospinal fluid (CSF) antibiotic concentrations were 0.85 and 1.60 mug/ml for CB and AMP, respectively, during administration of daily doses of 400 mg/kg and 0.65 and 0.45 mug/ml, respectively, on daily doses of 200 mg/kg. Higher CSF concentrations, up to a median concentration of 4.5 mug/ml, were observed in patients with CSF protein concentrations >/=75 mg/100 ml. Clinical responses were equivalent on either antibiotic regimen. Among AMP patients (45), 8 had significant residua and 3 died; among CB patients (41), 5 had residua and none died. However, 38% of H. influenzae patients treated with CB had positive CSF cultures on day 1 follow-up lumbar punctures, compared with only 5.8% of AMP patients with H. influenzae. The significance of a delay of CSF sterilization among CB-treated patients is unknown, since there was no correlation between persistence of hemophilus organisms and the frequency of adverse outcome. AMP and CB are equivalent for the treatment of bacterial meningitis due to susceptible organisms.

Adolescent↗

Penetration of cefamandole into spinal fluid.

Twelve patients, aged 6 months to 62 years, with proven bacterial meningitis, were given a single intravenous dose of cefamandole (33 mg/kg) 75 to 140 min before a routine lumbar puncture. Infecting organisms included Haemophilus influenzae (eight cases), Streptococcus pneumoniae (two cases), and Neisseria meningitidis and beta-hemolytic streptococcus (one each). Cerebrospinal fluid (CSF) was analyzed by microbiological assay for cefamandole. The median concentration was 0.60 mug/ml, ranging from undetectable to 7.4 mug/ml. CSF cefamandole concentrations correlated with CSF protein: in six patients with CSF protein less than 100 mug/dl, the range of drug concentration was 0 to 0.62 mug/ml; and in six patients with CSF protein above 100 mg/dl, the range was 0.57 to 7.4 mug/ml. No significant correlation was noted between severity of illness, type of organism involved, or patient age and concentration of drug achieved.

Adolescent↗

Evidence for preferential effects of parathyroid hormone, calcitonin and adenosine on bone and periosteum.

In order to explore the distribution of hormone-responsive cells in skeletal tissues, we have examined the effects of synthetic bovine parathyroid hormone N-terminal peptide (bPTH 1-34) and salmon calcitonin (sCT) on cyclic AMP levels in periosteum-free rat calvaria, segments of periosteum, and in isolated cells dispersed from each tissue by collagenase digestion. Synthetic bovine PTH increased cyclic AMP levels to a greater degree in calvaria and in isolated bone cells than in the periosteal segments and cells, whereas sCT was more effective in the periosteal than in the bone systems. Primary cultures prepared from bone and periosteal cell populations exhibited progressive increases in their responsiveness to bPTH (1-34) and progressive decreases in responsiveness to sCT. After six days in the culture, bone cells failed to respond to sCT, and sCT did not modify their response simultaneously added bPTH (1-34). Six-day periosteal cell cultures exhibited residual sCT responsivity and an additive response upon simultaneous exposure to high concentrations of bPTH (1-34) and sCT suggesting separate sites of hormone action. Adenosine, a known stimulator of bone cell adenylyl cyclase, caused a greater increase in periosteal cell than in bone cell cyclic AMP. bPTH (1-34)-responsive cells which enrich periosteum-free bone may be osteoblasts, in view of their histological prominence in this tissue and in the bone cell isolates. Periosteal cells which responded to sCT and to adenosine preferentially are unidentified. Although periosteal segments contained numerous fibroblast-like cells, skin fibroblasts cultured from the same fetuses were sCT-insensitive. Growth in primary culture appears to alter the number of hormone-responsive cells or responsiveness of existing cells to each hormone, or both.

Adenosine↗

Mixed bacterial meningitis: a complication of ventriculo- and lumboperitoneal shunts.

Infectious complications of ventriculo- and lumboperitoneal shunts in two patients are presented. Cerebrospinal fluid infection due to aerobic and anaerobic enteric flora was characteristic of each case. Both infections occurred several months after shunt surgery and were associated with colonic perforation by the distal limb of the peritoneal catheter. These cases emphasize this unusual hazard of peritoneal shunts and demonstrate methods for diagnosis and effective therapy.

Adult↗

Bactericidal studies of penicillin-gentamicin combinations against group B streptococci.

The bactericidal activity of penicillin-aminoglycoside combinations was studied in 16 strains of Group B streptococci. Minimal inhibitory concentrations (MIC) against kanamycin or gentamicin were greater than 50 microgram/ml, whereas ampicillin or penicillin inhibitory concentrations were uniformly less than 0.1 microgram/ml. Although all strains had bactericidal concentrations (MBC) less than 0.1 microgram penicillin/ml, penicillin at a concentration equal to each strains respective MBC reduced inoculum colony forming units (CFU) 2 logs in only 6 of 16 strains in bactericidal kinetic studies. However, the addition of gentamicin in concentrations of 5.0 or 10.0 microgram/ml to penicillin markedly enhanced bactericidal activity in all strains tested. The addition of lower concentrations of gentamicin (1.0 microgram/ml) had minimal advantage over penicillin alone. No distinct advantage was noted for combinations including either ampicillin or kanamycin. The theoretical advantage of penicillin-aminoglycoside combinations in experimental conditions, suggests that the use of antibiotic combinations in clinical infections due to Group B streptococci, may result in a more rapid eradication of these organisms.

Ampicillin↗