Prevention of hearing loss from meningitis.
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Biomedical subjects
Publications and source records attributed to S L Kaplan.
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Five-day-old infant rats were injected intraperitoneally (i.p.) with anti-CD11b monoclonal antibody (1 B6) at a dose of 2 mg/kg or phosphate-buffered saline (PBS) either 1 h before or 3 or 24 h after inoculation with 10(5) cfu Haemophilus influenzae type b (Hib). When administered 1 h before infection, 23% of the 1B6- versus 17% of the PBS-treated rats and 87% of the 1B6- versus 83% of the PBS-treated animals died at 24 and 48 h, respectively. There was a similar mortality for 1B6 or PBS treatment at 3 h after infection. Thirteen of 15 (87%) 1B6 animals versus 16/17 (94%) PBS animals had positive CSF cultures at 48 h. No differences in mortality were observed in separate experiments where animals received 1B6 or PBS 3 or 24 h after infection with Hib and were treated with a single ampicillin dose (100 mg/kg) 24 h after infection. The median CSF white blood cell count/mm3 was 5627 and 4860 for the animals with meningitis receiving 1B6 and PBS, respectively, although the 1B6-treated animals had a lower percentage of polymorphonuclear cells in the CSF (P = 0.05). Histologic examination of the meninges, choroid plexus and cochlea showed a slight decrease in the numbers of inflammatory cells in animals treated with 1B6. 1B6 did not change the incidence of meningitis and only slightly decreased the degree of inflammation within the central nervous system, although animals treated with 1B6 have an altered CSF leucocyte response with the presence of more mononuclear cells as opposed to polymorphonuclear cells in their CSF. 1B6 may play a role in inhibiting neutrophil emigration to sites of inflammation within the central nervous system but is not beneficial in decreasing mortality in an infant rat model of H. influenzae type b sepsis and meningitis.
We report nine consecutive children and adolescents [five females and four males; aged 2 yr 8 months (m) to 18 yr 1 m] studied over the last 5 yr with idiopathic central diabetes insipidus. In addition to vasopressin deficiency, anterior pituitary hormone deficiencies were detected, either on evaluation at presentation or during follow-up studies over the following 3 yr. Four patients had an increased concentration of plasma PRL. One patient had multiple pituitary hormone deficiencies at diagnosis, and two others developed the same by 21 m of follow-up. Brain magnestic resonance imaging scans, performed at presentation, were originally interpreted as normal in four of nine patients, except for absence of the bright posterior pituitary signal; after retrospective review, two of nine were considered normal. All of the brain magnetic resonance imaging (MRI) scans showed positive findings by 14 m of follow-up. The first abnormal finding in all patients was isolated pituitary stalk thickening. Evaluation of cerebrospinal fluid (CSF) for hCG was positive in three of eight evaluated patients; the three positive CSF values were found at presentation and 3 and 9 m after presentation. All eight patients assessed were negative for CSF alpha-fetoprotein and cytology, and no patient had serum tumor markers. Transsphenoidal biopsy of the lesion in seven of nine patients showed a germinoma in six patients and inflammatory cells in one. The six patients with documented germinoma comprise 31% of the intracranial germinomas diagnosed in this age group at the University of California-San Francisco during the last 5 yr. The patient with mononuclear inflammatory cells on biopsy along with one other patient have had spontaneous resolution of their stalk thickening. So-called "idiopathic" central diabetes insipidus warrants close follow-up to determine the etiology, especially if anterior pituitary hormone deficiencies are detected. Normal brain MRI scans or scans that show isolated pituitary stalk thickening merit follow-up with serial contrast enhanced brain MRI for the early detection of an evolving occult hypothalamic-stalk lesion. CSF evaluation is recommended at presentation because elevated CSF hCG may precede MRI abnormalities.
As part of a larger study of prescribing practices in inpatient child and adolescent settings, 1,117 stat (emergency) and pm (as needed) doses administered to 150 child and adolescent inpatients at a state hospital, a private hospital, and a county-university hospital in the New York metropolitan area during 1991 were examined. Stat dosing was most common (p < .001) at the state hospital, where 76 percent of the medicated sample received at least one stat dose of medication; prn dosing was most common (p < .001) at the county-university hospital, where 80 percent of the medicated sample received at least one prn dose. Antihistamines were the most frequently used stat and prn medications at the state hospital. Antipsychotics were the most frequently used stat and prn medications at the private hospital. At the county-university hospital, the most frequently used stat medications were the minor tranquilizers, and the most frequently used prn medications were the antipsychotics. At all three hospitals, a high proportion of patients receiving stat or prn antipsychotics were receiving standing antipsychotics. At all three hospitals agitation was the predominant indication for stat or prn medication of any type.
Suppurative disease of the liver and/or spleen is a rare and serious complication of human brucellosis. In the English-language literature, only nine cases have been reported, all involving adults with chronic infection. We report the case of a young child in whom abscesses of the liver and spleen developed during acute brucellosis. Brucella melitensis was cultured from an aspirate of the liver and from the bone marrow. After percutaneous drainage of the liver abscess, the patient responded to a 56-day course of antimicrobial therapy. To our knowledge, this is the first reported case of hepatosplenic abscess due to a Brucella species in a child.
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Genetically engineered mice, which lack normal expression of intercellular adhesion molecule 1 (ICAM-1), were used to study the role of ICAM-1 in the host defense against disseminated candidiasis. The responses of ICAM-1-deficient mice and normal wild type mice were compared following an intravenous challenge with Candida albicans. ICAM-1-deficient mice lost more weight (P < .001) and had a significantly higher mortality (P < .001). Quantitative cultures revealed a greater tissue fungal burden in ICAM-1-deficient mice compared with normal mice, in both the kidney (P < .001) and the brain (P = .007). Extensive inflammation, composed primarily of histiocytes admixed with lymphocytes and occasional neutrophils, was present in the renal tissue of ICAM-1-deficient mice; this contrasted with a more localized and predominantly neutrophilic infiltrate in normal mice. This work suggests that the loss of ICAM-1 significantly impairs host defense against C. albicans, by impairing either neutrophil migration or phagocyte activation or both.
OBJECTIVE: To study a proposed relationship between anxiety disorders and neurological soft signs by determining whether children of agoraphobic parents would have an increased prevalence of soft signs compared to children of parents without agoraphobia. METHOD: Family study methodology was used to compare 25 children of agoraphobic adults and 25 age- and sex-matched children of nonagoraphobic adults on a structured soft signs examination and on structured psychiatric interviews. Also, soft signs of 12 agoraphobic adults were compared with soft signs of 16 control adults. RESULTS: Children of agoraphobic adults had significantly more right- and left-side motor slowness on finger tapping and hand patting (p values < .05) than did children of controls. Seventy-six percent of the children of agoraphobic adults had at least one slow motor sign, compared with 28% of the control children (p < .001). There were no significant differences in soft signs between agoraphobic and control adults. CONCLUSIONS: The study provides additional support for a relationship between soft signs and anxiety disorder.
PURPOSE: Recent studies in the rat suggest that early exposure to exogenous testosterone accelerates the loss of androgen receptors and compromises eventual penile length. To determine whether this is true in men we measured adult penile length of patients treated in childhood for sexual precocity. MATERIALS AND METHODS: We examined 21 men with sexual precocity due to true precocious puberty (12) or congenital adrenal hyperplasia (9) who had been followed at our institution since childhood. Penile lengths were compared with data from normal men. RESULTS: Mean stretched penile length plus or minus standard deviation was 12.7 +/- 2.6 cm. in all patients, 12.1 +/- 2.6 cm. in those with true precocious puberty and 13.6 +/- 1.6 cm. in those with congenital adrenal hyperplasia. These lengths were not significantly different from those of normal men (12.4 +/- 2.7 cm.). CONCLUSIONS: In contrast to findings in rats, exposure to endogenous testosterone during gestation and/or childhood does not reduce adult penile length in men. Thus, the use of testosterone to treat childhood genitourinary anomalies would likely not compromise mature penile size.
Two oxazolidinones and ceftriaxone, imipenem, rifampin, and vancomycin were tested against 162 penicillin-intermediate and 68 penicillin-resistant strains of pneumococci. U-100592 is two- to fourfold more active than U-100766 against penicillin-resistant pneumococci. The MICs of U-100592 at which 90% of the isolates were inhibited were 0.25 and 0.5 microgram/ml for penicillin-intermediate and -resistant strains, respectively, and 0.5 microgram/ml for ceftriaxone-susceptible, -intermediate, and -resistant strains. U-100592 MICs for 7 of 230 strains (2 from blood, 3 from middle-ear fluid, and 2 from the upper respiratory tract) were 1 microgram/ml.
In June 1993, the National Committee for Clinical Laboratory Standards (NCCLS) recommended stringent new interpretive guidelines for antibiotics indicated for Streptococcus pneumoniae meningitis. To assess the predictive values of the recommended breakpoints, retrospective data were collected from patients who had S. pneumoniae infections and were treated with cefotaxime monotherapy. Susceptibilities based on the NCCLS interpretative categories were compared with clinical and bacteriologic outcomes. In 76 evaluable patients, the most common infections were bacteremia-septicemia (n = 49), meningitis (n = 37), and lower respiratory tract infection (n = 14). Under the NCCLS breakpoints proposed in 1993, 55 isolates would have been classed as susceptible to cefotaxime (MIC, < or = 0.25 microgram/ml), 18 would have been classed as intermediate (MIC, 0.5 to 1.0 microgram/ml), and 2 would have been classed as resistant (MIC, > or = 2 micrograms/ml). Of 75 cefotaxime-treated patients for whom cefotaxime MICs were recorded, 73 were clinically cured or improved (37 of 37 with meningitis and 36 of 38 with other infections). One case of bacteremia and one case of bone-and-joint infection were scored as therapeutic failures because initial monotherapy had to be modified because of an adverse drug reaction. Excluding these patients, there were 18 patients infected with S. pneumoniae that would have been classed as not fully susceptible (i.e., MICs > or = 0.5 microgram/ml); all of these patients were cured or improved. The results of this analysis demonstrate that successful treatment with cefotaxime did not correlate well with the guidelines for the susceptibility of pneumococcal isolates to either penicillin or cefotaxime established by the 1993 NCCLS breakpoint recommendations. Because of this study and other similar findings, the NCCLS adopted more clinically relevant guidelines in 1994.
PURPOSE: To describe the clinical presentation and successful management of an orbital infection caused by Mycobacterium abscessus, a formerly unrecognized cause of orbital disease after penetrating trauma. METHODS: An orbital infection due to M. abscessus is described, and previously reported ocular and extraophthalmic infections caused by M. abscessus are reviewed. RESULTS: A 5-year-old boy had acute, painless visual loss shortly after being struck in his left lower eyelid with a fishing rod. Radiologic evaluation established a mass in the orbital apex. Initial biopsy and cultures of the apex mass were negative; however, additional orbital exploration and cultures demonstrated M. abscessus to be the causative organism. The orbital infection was treated successfully with long-term oral clarithromycin. Review of the literature on ocular/adnexal and soft tissue infections caused by atypical mycobacteria shows characteristic clinical and histopathologic features. CONCLUSIONS: To the authors' knowledge, only seven patients with atypical mycobacterial infections of the ocular adnexa have been reported. The patient reported in the current study illustrates the difficulty in establishing the preoperative diagnosis of atypical mycobacterial infections of the orbit. A chronic draining wound or a localized orbital abscess, after penetrating trauma, should alert the physician to the possibility of an M. abscessus infection. Clarithromycin, an oral macrolide antibiotic, appears to be the most effective medical therapy for these patients.
Routine dexamethasone therapy for bacterial meningitis in pediatric patients is controversial. Two experts debated this topic at the 1993 meeting of the Infectious Diseases Society of America. Both experts agreed that for management of Haemophilus influenzae meningitis, dexamethasone significantly reduced sensorineural hearing loss and probably reduced other long-term sequelae. Because relatively few patients with pneumococcal and meningococcal meningitis have been studied, no conclusions could be reached regarding the effectiveness of dexamethasone. Dr. Urs Schaad emphasized the impressive anti-inflammatory effects of dexamethasone in experimental pneumococcal meningitis and the lack of any adverse events when given to children for 2 or 4 days. He recommended routine use of dexamethasone in treating pediatric patients with bacterial meningitis. Dr. Sheldon Kaplan expressed concern regarding the effectiveness of steroids in treating pneumococcal meningitis, especially when penicillin-resistant and cephalosporin-resistant isolates are present, and he addressed the question of the long-term effects of administration of dexamethasone in children with viral meningitis. He advised against the routine use of dexamethasone for non-H. influenzae meningitis.
Whipple's disease is a rare, chronic, multisystem illness that is pathologically characterized by the accumulation of macrophages in the involved tissue that have a positive periodic acid-Schiff reaction. It is typically seen in middle-aged white men, and only four cases involving persons younger than 15 years of age have been reported. CNS Whipple's disease without intestinal manifestations is rare; only six cases have been reported in the literature, all involving adults. We report the case of a young boy with clinical, laboratory, radiographic, and pathological signs and symptoms consistent with CNS Whipple's disease who responded to therapy with trimethoprimsulfamethoxazole.
Mice genetically deficient in the gene encoding for intercellular adhesion molecule-1 (ICAM-1) production were compared with wild-type mice after injection with Haemophilus influenzae type b (Hib) or Streptococcus pneumoniae. The incidence of Hib bacteremia was greater in the ICAM-1-deficient mice than wild-type mice (P = .007), but mortality was greater for wild-type mice at 24 h (P = .03). In contrast, the incidence of S. pneumoniae bacteremia was equivalent but mortality was greater in ICAM-1-deficient mice at 24 h (P = .0003). More ICAM-1-deficient mice had cerebrospinal fluid cultures (CSF) positive for Hib (P = .04), whereas all animals at sacrifice had CSF cultures positive for S. pneumoniae. CSF white blood cell counts and histology of the meninges and cochlea were no different between groups for either organism. ICAM-1 deficiency may be protective early in Hib infection but has a detrimental effect in S. pneumoniae infection.
The contribution of intercellular adhesion molecule 1 (ICAM-1) during systemic and local bacterial infections was studied in transgenic ICAM-1-deficient and control mice that were injected intraperitoneally (ip) or intradermally (id) with Escherichia coli, Pseudomonas aeruginosa, or Staphylococcus aureus. Mortality rates, blood cultures, white blood cell (WBC) counts and absolute neutrophil counts (ANCs) were obtained daily until cultures were sterile. Six and 24 h after injections, autopsies were done on randomly selected ip-inoculated mice and biopsies were done on randomly selected id-inoculated mice. Survival rates were similar. In ICAM-1-deficient mice, ip P. aeruginosa resulted in higher incidences of bacteremia at 24 h (P = .003) and 48 h (P = .002); id S. aureus resulted in larger skin lesions (P = .026). Leukocytosis persisted in ICAM-1-deficient mice 6 h after ip injection of E. coli; however, WBC counts and ANCs in peritoneal fluid did not differ. Although the inflammatory responses were similar histologically in ICAM-1-deficient and normal mice, differences in site- and stimulus-specific susceptibilities were noted.
Surveillance by 33 laboratories in 19 states during a 4 1/2 month period between December 1993 and April 1994 found that 263 of 1627 (16.2%) isolates of Streptococcus pneumoniae were resistant to penicillin. One hundred and seventy (10.4%) isolates were determined to be intermediately resistant to penicillin (MICs 0.1-1.0 mg/L and 93 (5.7%) were found to be highly resistant to penicillin (MICs > 2.0 mg/L). MIC90s for intermediately penicillin resistant strains were: amoxycillin/clavulanate 2.0 mg/L, cefaclor 64 mg/L, cefixime 32 mg/L, cefprozil 8 mg/L and loracarbef 128 mg/L. MIC90s for highly penicillin resistant strains were: amoxycillin/clavulanate 4.0 mg/L, cefaclor > or = 128 mg/L cefixime 64 mg/L, cefprozil 32 mg/L and loracarbef > or = 128 mg/L.
Pulmonary abscess is an infrequent but significant problem in children. We retrospectively reviewed the charts of 45 children with documented lung abscesses admitted and treated at Texas Children's Hospital, Houston, over the 11-year period from January, 1982, to December, 1993, and report their presenting symptoms, bacteriology, clinical management and outcome.