Oral aminoglycoside and ofloxacin therapy in the prevention of gram-negative sepsis after irradiation

To investigate whether oral gentamicin or ofloxacin therapy protects against gram-negative sepsis after irradiation, B6D2F1 mice were exposed to 7.5 Gy of radiation from 60Co, infected with 10(7) Pseudomonas aeruginosa or Klebsiella pneumoniae orally 3 days after irradiation, and treated with oral (15 mg/kg/day) or intramuscular (im; 7.5 mg/kg/day) gentamicin or oral (40 mg/kg/day) ofloxacin. For P. aeruginosa, gentamicin therapy was started orally 10 and 24 h and im 24 h after inoculation. For K. pneumoniae, gentamicin was started orally 24, 48, and 72 h and im 24 h after inoculation; ofloxacin was started 24 h after inoculation. Mice that received oral gentamicin early (10 h for P. aeruginosa, 24 h for K. pneumoniae), im gentamicin, or oral ofloxacin showed significantly (P less than .05) reduced colonization, translocation, and mortality compared with mice that received oral gentamicin late. These data support the use of selective antimicrobial therapy to reduce colonization, translocation, and mortality from gram-negative bacteria in irradiated animals.     

Clinical diagnosis of disorders of puberty

The authors emphasize the orderly sequence of events (consonance) characteristic of normal puberty. Loss of consonance of normal puberty indicates an underlying endocrine disorder.     

The 24-hour growth hormone secretion in a boy with giantism

The endocrinological and radiological findings in a 7.5-year-old boy with giantism are reported and compared with an age and sex matched normal tall boy. A 24-h GH profile demonstrated a persistently elevated GH concentration (mean GH concentration: giant 19.3 mU/l; tall boy 5.4 mU/l) with loss of the dominant GH periodicity of 3 h seen in the boy with tall stature and substitution with one of 8 h. These data support the view that giantism and acromegaly are similar diseases occurring prior to and following epiphyseal fusion, respectively.     

Regulation of peripheral-type benzodiazepine receptors in cultured astrocytes by monoamine and amino acid neurotransmitters

Exposure of primary cultured astrocytes for 3 days to 1 μM of either dopamine, serotonin or norepinephrine resulted in upregulation (25–34% increase in B_max) of the peripheral-type benzodiazepine receptors (PBRs) labeled with [³H]Ro5-4864. A similar treatment with γ-aminobutyric acid [GABA] caused a 2-fold increase in the affinity (K_d) of [³H]Ro5-4864. The monoamines tested and GABA had no effect on the binding parameters of [³H]PK 11195, another selective PBR ligand. The present study indicates that Ro5-4864 binding sites are susceptible to regulation by specific neurotransmitters and provides further evidence for the distinction between Ro5-4864 and PK 11195 binding sites of the PBRs in cultured astrocytes.     

Administration of Half-Dose Theophylline Together with Ketotifen to Asthmatic Children—A Double-Blind, Placebo-Controlled Study

Administration of theophylline to asthmatic children is frequently associated with an adverse influence on their behavior. The efficacy and behavioral effects of the administration of high-dose theophylline (T) and ketotifen (K) in various combinations were evaluated prospectively in a double-blind, placebo controlled study in 55 children with moderately severe perennial asthma. During a baseline period of 2 weeks, theophylline (serum level of 10-20 μg/ml) was administered to all the children. After this period the patients were randomly allocated into four comparable groups. The children were treated during a 12-week period with: T + K-Placebo (T group); T + K (T + K group); half-dose T + K (T/ 2 + K group); or placebo of both T and K (P group). During the 12-week treatment period, as compared to the baseline period, only the three groups of children who received active therapy (T + P, T + K, T/2 + K) showed a similar reduction in the number of days with asthmatic symptomatology, improvement of the total asthmatic symptoms score, and increased PEFR. The behavioral activity of the children (assessed by the Conner's rating scale) improved significantly only in the groups receiving placebo or T/2 + K. The results of this study suggest that a combination therapy of half the recommended therapeutic dose of theophylline with ketotifen can be clinically as effective as therapy with a full dose of theophylline, but with significantly less adverse behavioral effects.     

RESULTS OF EXTERNAL BEAM RADIOTHERAPY IN 448 PATIENTS WITH CLINICALLY LOCALIZED ADENOCARCINOMA OF THE PROSTATE

The results of external beam radiotherapy for clinically localized adenocarcinorna of the prostate in 448 patients treated in the period 1980–90 were reviewed. The average follow up was 4.9 years. The patients were aged 44–87 years (median 69 years) and all had histopathological evidence of adenocarcinoma by needle biopsy or transurethral resection of prostate. The histopathological grading was: 127 G₁; 154 G₂; 127 G₃; 12 G₄; 28 G_x. Clinical staging according to TNM (American Urological Association) was: 29 T₀ (A2); 4 T₁ (B1); 173 T₂ (B2); 176 T₃ (C1); 63 T₄ (C2); 3 T_x. Routine surgical pelvic lymph node staging was not performed but patients had radiological (computerized tomography scan or lymphogram) nodal staging: 350 N₀; 22 N₁; 12 N₂; 64 N_x. High energy linear accelerator external beam radiotherapy was given by multiple fields to total doses of 50–70 Gy (median 60 Gy). The majority of patients (307, 69%) was treated by a uniform policy under the care of one radiation oncologist (HM). The rates of local and distant failure at 5 years were 10% (s.e. = 2%) and 42% (s.e. = 3%), respectively. The late complication rate at 5 years was 25% (s.e. = 2%), comprising mild 16%, moderate 7% and severe 1.3%. The 5 year overall survival rate was 64% (s.e. = 2%) and the cancer-specific survival rate was 74% (s.e. = 3%). Both histological grade and clinical stage were strongly predictive of overall survival and distant failure. Only histological grade was predictive of local failure. Treatment with external beam radiotherapy for this common cancer resulted in survival and disease control rates that compare favourably with other published radiotherapy series and has been accompanied by acceptably low morbidity.     

Immediate root canal disinfection with ultraviolet light: an ex vivo feasibility study.

OBJECTIVE: The study was designed to test application of ultraviolet light to root canal walls, as a mean of complementary immediate disinfection after the use of sodium hypochlorite. STUDY DESIGN: Root canals were infected ex vivo with Enterococcus faecalis for 48 hours. Non-attached bacteria were washed away, and the remaining attached bacteria were subjected to disinfection, with 5% sodium hypochlorite alone or followed by exposure to ultraviolet light (254 nm, 300 mJ/cm(2)). Root canals were then tested for remaining viable bacteria. Canals were obturated and tested again after 14 days. RESULTS: Sodium hypochlorite alone achieved negative cultures in only 47% of the cases, but 96% was achieved with sodium hypochlorite followed by ultraviolet light (P < .001). This status was also maintained after 14 days. CONCLUSIONS: Illumination of root canals with ultraviolet light may be an effective supplementary means to achieve immediate disinfection of infected root canals.     

Trehalose dimycolate enhances resistance to infection in neutropenic animals.

Bacterial infections are lethal complications of neutropenia, and antibiotics alone are inadequate therapy for these infections. Irradiated mice become severely neutropenic and remain susceptible to infection for 2 to 3 weeks, depending on the dose and quality of radiation. Some bacterial cell wall derivatives stimulate nonspecific host defense mechanisms against a variety of microbes which might cause postirradiation infection. In this study we determined if the cell wall glycolipid trehalose dimycolate (TDM), derived from Mycobacterium phlei, or a synthetic preparation of TDM was able to (i) enhance survival in mice when given before or after lethal doses of 60Co radiation and (ii) increase nonspecific resistance to postirradiation infection. Treatment with TDM oil-in-water emulsions and with synthetic TDM significantly enhanced survival before and after lethal doses of 60Co irradiation. This result correlated with the ability of TDM to reduce the translocation of intestinal bacteria and to stimulate hematopoiesis. With respect to nonspecific resistance to infection, TDM injected 1 h after sublethal irradiation increased resistance to a lethal Klebsiella pneumoniae challenge (10 50% lethal doses of K. pneumoniae in 30 days [LD50/30]) 4 or 14 days later. Increasing the dose of K. pneumoniae to 5,000 LD50/30 on day 4 overwhelmed the ability of TDM-treated mice to overcome infection. However, TDM treatment 1 h postirradiation combined with ceftriaxone antibiotic therapy (days 5 through 14) enhanced survival, even when the higher dose of bacteria (5,000 LD50/30) was used. These results indicate that in irradiated mice, TDM can be used to enhance survival and, as a potent stimulant of nonspecific resistance to infection in neutropenic mice, can act synergistically with antibiotic therapy to reduce sepsis and mortality.