β-Lactam antibiotics in the treatment of neuroborreliosis in children: Preliminary results

Summary In vitro -lactam antibiotics like ceftriaxone and penicillin G sodium have been shown to be active againstBorrelia burgdorferi. Results of quantitative determinations of both antibiotic substances in the CSF for children are limited. Seventy-five children (median age 96 months, range 10 to 176 months) with probable or definite neuroborreliosis were treated with ceftriaxone (1×50–90 mg/kg/day) or penicillin G sodium (4×80,000–120,000 IU/kg/day) intravenously. On day 10 of therapy levels of penicillin G sodium (1, 1.5, 2, 3, 4, 5, or 6 h after i.v. administration), and ceftriaxone (1, 2, 4, 6, 12 or 24 h after i.v. administration) in serum and CSF were measured with a micro agar diffusion bioassay. Results demonstrate that after 5 h penicillin G sodium in CSF was above the minimal inhibitory concentration (MIC) but after 6 h penicillin G sodium levels were below the determination limit in 60% of the cases. All ceftriaxone results in CSF — even after 24 h — were above MIC. Penicillin G sodium serum values ranged from 46.6 to 0.1 mg/l (1 to 6 h post dose) and ceftriaxone serum values from 261 to 5 mg/l (1 to 24 h post dose). The role of penicillin G sodium and ceftriaxone and administration intervals of both antibiotics in the therapy of neuroborreliosis in children are discussed.

---

-Lactam Antibiotika zur Behandlung der Neuroborreliose im Kindesalter: Vorläufige Ergebnisse

Zusammenfassung Ceftriaxon und Natrium-Penicillin G sind gegenBorrelia burgdorferi in vitro wirksam. Zur Pharmakokinetik beider Substanzen im Liquor cerebrospinalis von Kindern ist hingegen wenig bekannt. 75 Kinder im Alter von 10 bis 176 Monaten (Median 96) mit einer definitiven oder möglichen Neuroborreliose wurden intravenös mit Ceftriaxon (1×50–90 mg/kg/Tag) oder Penicillin G (4×80000–120000 I.E./kg/Tag) behandelt. Am 10. Therapietag wurden die Liquor-Spiegel von Penicillin G (1, 1.5, 2, 3, 4, 5, oder 6 Stunden nach Gabe) bzw. Ceftriaxon (1, 2, 4, 6, 12, oder 24 Stunden nach Gabe) in Serum und Liquor aus gepaarten Proben mittels einer Mikroagar Diffusions-Methode gemessen. Die Ergebnisse zeigen, daß Penicillin G 5 Stunden nach Gabe noch über der minimalen Hemmkonzentration lag, daß aber 6 Stunden nach Gabe die Konzentration des Antibiotikums in 60% der Liquorproben bereits unterhalb der Meßgrenze lag. Die Ceftriaxon Liquorspiegel lagen durchwegs über der MHK — auch noch 24 Stunden nach der letzten Gabe. Die Serumkonzentrationen von Penicillin G lagen zwischen 46,6 und 0.1 mg/l, die Serumkonzentrationen von Ceftriaxon zwischen 261 und 5 mg/l. Die vorgestellten Ergebnisse werden im Hinblick auf den Stellenwert der beiden Antibiotika in der Therapie der Neuroborreliose im Kindesalter diskutiert.

     

Intraocular silicone lenses in silicone oil: an experimental study

Background: To evaluate a potential effect of silicone oil on flexible silicone intraocular lenses, four lenses (STAAR AA-4203) were stored in silicone oil under sterile conditions for periods between 1 month and 3 years. Method: The edge and surface of the lenses were examined by scanning electron micrography and the findings compared with a lens of the same model which had been stored in Ringer's solution for 2 years. Results: After 1 year of silicone oil exposure, droplets of different sizes adherent to the surface of the lens were found. These changes proceeded to a wave-like appearance of the surface after 2 and 3 years of storage, so that a continuous layer of silicone oil polymers is probably covering the intraocular lens. Conclusion: Optical interference has to be considered a possibility if it turns out that the droplets cannot be removed during silicone oil evacuation. Consequently silicone intraocular lenses without hydrophilic preparation of the surface should not be implanted in eyes undergoing combined anterior and posterior segment surgery with silicone oil tamponade or in eyes with high risk for vitreoretinal complications.The authors state that they have no proprietary interest in the marketing of the products mentioned herein or competing products     

Flexible fiberoptic sigmoidoscopy—The monroe clinic experience

Analysis of 5000 consecutive flexible fiberoptic sigmoidoscopies form the basis of this report. It is concluded that this method of examination of the distal large bowel is not only safe and comfortable for the patient but is a more appropriate examination than the rigid proctosigmoidoscopy because of the significant increase in pathologic material found. This examination has proven practical and acceptable in a multispecialty clinic setting and has completely replaced rigid proctosigmoidoscopy. Flexible sigmoidoscopy is now the standard "routine" examination of the rectum and distal colon. The rationale for this conclusion is presented in this timely report.     

Sensory nerve pathology in amyotrophic lateral sclerosis

Summary A detailed morphometric study was performed on sural nerve biopsies to determine the consistency of sensory nerve pathology in amyotrophic lateral slcerosis (ALS) and to seek a correlation between the severity of peripheral nerve pathology and disease duration. Nerve biopsies from patients with ALS consistently showed evidence of early axonal atrophy, increased remylination and a shift in the diameter distributions curve towards smaller fiber diameters. Importantly, the severity of sensory nerve pathlogy in ALS patients correlated with disease duration. The peripheral nerve sodium pump concentration of patients was not reduced. It is concluded that an ingravescent dorsal root ganglion neuronopathy is seen in the incipient stages of ALS, preferentially affecting the largest neurons and resulting in turn in progressive axonal atrophy, secondary demyelination-remyelination and finally in nerve fiber degeneration. Etiologically, a parallel involvement of motor and sensory neurons suggests a more widespread metabolic disturbance in ALS than simply sick motor neurons.Supported by a grant from the New Zealand Neurological Foundation     

Changes in cognitive functioning following treatment of late-life depression

OBJECTIVE: Knowledge of the relationship between various clinical characteristics and cognitive functioning is advancing, but little is known about the cognitive response to treatment for geriatric depression. The purpose of this study was to examine the cognitive response to treatment for patients with late-life depression. METHOD: Subjects included 45 nondemented, elderly depressed patients who achieved remission after 12 weeks of antidepressant treatment and 20 elderly comparison subjects. All subjects were administered a battery of clinical measures, including cognitive screening instruments, before and after treatment. RESULTS: As a group, the elderly depressed patients showed a small improvement in overall cognitive functioning after treatment. Among depressed patients with concomitant cognitive impairment at baseline, performance on the Mattis Dementia Rating Scale domains of conceptualization and initiation/perseveration improved significantly relative to those of depressed patients with normal cognition. Despite the improvement following treatment, the overall level of cognitive functioning in the elderly depressed patients with cognitive impairment at baseline remained mildly impaired, especially in the memory and initiation/perseveration domains. CONCLUSIONS: Elderly depressed patients with cognitive impairment may experience improvement in specific domains following antidepressant treatment but may not necessarily reach normal levels of performance, particularly in memory and executive functions. This subgroup of late-life depression patients is likely at high risk of developing progressive dementia.     

Indium-111-capromab pendetide radioimmunoscintigraphy and prognosis for durable biochemical response to salvage radiation therapy in men after failed prostatectomy.

PURPOSE: We evaluated the prognostic significance of indium-111 (111In)-capromab pendetide imaging for patients with prostate cancer who underwent salvage radiotherapy (RT) for recurrent disease after prostatectomy. PATIENTS AND METHODS: Records were reviewed for all men who underwent 111In-capromab pendetide imaging at a single institution from February 1997 through December 1999. We identified 30 eligible men who were radiographically negative for metastatic disease, who had increasing serum prostate-specific antigen (PSA) after primary radical prostatectomy, and who received salvage RT. Clinical interpretations of indium monoclonal antibody (In-mab) scan results were compared with postsalvage RT PSA response. RESULTS: Using an American Society of Therapeutic Radiation and Oncology definition of PSA failure, in men with a positive scan in at least one location (n = 14), the cumulative 2-year PSA control after salvage RT was 0.38 +/- 0.13 (+/- SE) compared with 0.31 +/- 0.13 for men with a normal antibody scan in and outside the prostate fossa (n = 15; proportional hazard ratio [PHR] = 1.32; 95% confidence interval [CI], 0.52 to 3.36). For men with a positive antibody scan limited to the prostate fossa (n = 9), PSA control at 2 years was 0.13 +/- 0.12 (PHR 1.77; 95% CI, 0.65 to 4.85). The 2-year probability of PSA control after salvage RT for men with positive scan results outside the prostate bed irrespective of In-mab findings in the prostate fossa (n = 5) was 0.60 +/- 0.22 (PHR 0.81; 95% CI, 0.17 to 3.78). CONCLUSION: In contrast to previous reports, for patients with postprostatectomy biochemical relapse who received salvage RT, presalvage RT In-mab scan findings outside the prostate fossa were not predictive of biochemical control after RT.     

Characterization of human lymphocyte antigen class I antigen-processing machinery defects in renal cell carcinoma lesions with special emphasis on transporter-associated with antigen-processing down-regulation.

The HLA class I antigen-processing machinery (APM) plays a crucial role in the generation of peptides from endogenously synthesized proteins and in their presentation to cytotoxic T lymphocytes. The potential role of defects of APM components in immune escape mechanisms used by malignant cells has prompted us to analyze their expression in renal cell carcinoma (RCC) lesions with special emphasis on TAP because of its critical role in the loading of HLA class I antigens with peptides. Immunohistochemical staining of 51 formalin-fixed RCC lesions and autologous normal renal epithelium detected transporter associated with antigen processing (TAP)1 and tapasin deficiencies in 63 and 80% of the tumor lesions. Impaired low molecular weight protein (LMP)2 and LMP7 expression was found in 73 and 33% of the RCC lesions analyzed, respectively. In contrast to the high frequency of APM component down-regulation, HLA class I heavy chain and beta(2)-microglobulin defects were detected in only 12 and 10% of the lesions, respectively. Concomitant TAP1 and LMP2 deficiencies were found in approximately 57% of RCC lesions, whereas a coordinated down-regulation of all APM components occurred only in 5% of the tumor specimens analyzed. The presence of APM defects was independent of tumor stage and grade but varied significantly among the RCC subtypes. TAP abnormalities do not appear to be attributable to structural alterations because no mutations in TAP1 were detected in TAP1-deficient RCC lesions. These data suggest that TAP defects in RCC lesions are caused by regulatory abnormalities. Therefore, T-cell-based immunotherapy may benefit from the administration of cytokines that up-regulate TAP expression.