Bacterial inhibition of phosphatidylcholine synthesis triggers apoptosis in the brain

Streptococcus pneumoniae is the most common cause of bacterial meningitis of high mortality and morbidity. Neurological sequelae include paralysis, mental retardation, and learning disorders. In humans, neurons of the hippocampus undergo apoptosis as a result of meningitis. Phosphatidylcholine (PtdCho) is an essential component of mammalian cell membranes and PtdCho deficiency, either due to chemicals or altered nutrition, leads to apoptosis, especially in hippocampal neurons. We show that apoptosis of a variety of brain cells after pneumococcal infection arises from inhibition of PtdCho biosynthesis, the first such activity described for a bacterium. Apoptosis inhibitors did not prevent the bacterial-dependent inhibition of PtdCho biosynthesis. Supplementation with exogenous lyso-phosphatidylcholine prevents cell death and treatment of mice with cytidine diphosphocholine attenuates hippocampal damage during meningitis, even after the onset of infection. We conclude that bacterial inhibition of PtdCho biosynthesis activates an apoptotic cascade that is a causative event in pathogenesis and amenable to therapeutic intervention.     

Pneumococcal meningitis: clinical course and resource use in Western Australian children

OBJECTIVES: Paediatric pneumococcal meningitis causes high rates of neurological sequelae and is presenting challenges due to the emergence of antibiotic resistance. Diagnosis can be difficult and management is frequently complicated and resource intensive. This population-based study outlines the diagnosis, clinical course and initial resource use of Western Australian (WA) children diagnosed between 1990 and 2000. METHODS: The charts of all rural and metropolitan children discharged from all WA hospitals with International Classification of Disease 9 and 10 codes of pneumococcal or streptococcal meningitis from the Health Department's Hospital Morbidity Data System were reviewed retrospectively. RESULTS: Ninety-four episodes of pneumococcal meningitis were confirmed (median age 12.4 months). Initial diagnosis was often difficult with a suggestive prodrome in less than one quarter of cases and a median of two reviews until diagnosis (range 1-7). The median duration of hospitalization was 11.6 days, 41.5% were admitted to the Intensive Care Unit (ICU), and 47.9% had seizures. There were eight related deaths and neurological sequelae occurred in 24. Initial hospitalization cost on average $A 19,900. Penicillin resistance was first noted in 1993 and occurred in 4.6% of isolates. Most cases (84.5%) were caused by serotypes contained in the currently available seven-valent conjugate vaccine. CONCLUSIONS: Pneumococcal meningitis is often difficult to diagnose, necessitates long and frequently complicated in-patient stays and has high rates of neurological sequelae. It is possible to prevent most cases with new conjugate vaccines.     

Vestibular schwannoma surgery outcomes: our multidisciplinary experience in 400 cases over 17 years

OBJECTIVES/HYPOTHESIS: The aim of the study was to evaluate the incidence of short- and intermediate-term postoperative complications after vestibular schwannoma surgery. STUDY DESIGN: Retrospective review in a tertiary referral center. METHODS: In 400 patients who underwent surgical removal of vestibular schwannoma from 1984 to 2000,symptoms, preoperative evaluation, surgery, and postoperative complications were analyzed using standardized grading systems. RESULTS: One hundred ninety-four men and 206 women had an operation. Mean age was 53.9 years (age range, 11-78 y). Tumor size according to Koos stage was stage 1 in 39 cases, stage 2 in 122 cases, stage 3 in 87 cases, and stage 4 in 152 cases. Preoperatively, 7.5% of patients had facial nerve dysfunction. Surgical approaches were translabyrinthine in 229 patients, widened retrolabyrinthine in 128 cases, suboccipital in 42 cases, and transotic in 1 case. Mortality was 0.5%. Facial nerve was transected in 15 cases (3.7%) and immediately repaired in 5 cases. A delayed hypoglossal-to-facial nerve anastomosis was performed in 12 cases. At 1 year, House-Brackmann grade in 70.7% of patients was 1 to 2; in 24.3%, 3 to 4; and in 5%, 5 to 6. Poor facial nerve outcome was correlated with tumor size, preoperative irradiation, and nerve dysfunction and was not correlated with the approach used. Most patients had postoperative dizziness, and 30% still had vestibular disturbances after 1 year. Nine patients (2.2%) had a cerebrospinal fluid rhinorrhea, and 24 had a cerebrospinal fluid wound leak (6%). Twenty-two patients (5.5%) had postoperative meningitis. Two patients had a cerebellopontine angle hemorrhage, and three a brainstem infarct. CONCLUSION: Transpetrosal approaches (translabyrinthine, widened retrolabyrinthine) are safe for vestibular schwannoma removal, and rates of postoperative complications and sequelae are decreasing.     

Location and timing of initial osteoid deposition in postmeningitic labyrinthitis ossificans determined by multiple fluorescent labels

OBJECTIVES/HYPOTHESIS: Variable amounts of fibrosis and neo-ossification fill the cochlea following bacterial meningitis. The purpose of the study was to delineate the timing and location of initial ossification following pneumococcal meningitis, as well as subsequent remodeling and resorption, over the 3-month period after infection. STUDY DESIGN: Randomized, double-blind study. METHODS: Fluorochromes are compounds that specifically incorporate into ossifying bone. Sequential addition of different colored fluorochromes during osteoneogenesis define the timing and location of osteoid deposition and mineralization. Mongolian gerbils were infected by intrathecal injection of Streptococcus pneumoniae type 3, and control gerbils received saline. Both groups were injected with calcein on postoperative day 3, followed by xylenol orange, oxytetracycline, and alizarin red on days 7, 14, and 28 respectively. Ten experimental gerbils were killed 24 hours after each label, and an additional group at 84 days after infection. Two groups of 10 control gerbils were killed at 29 and 84 days after treatment. The temporal bones and tibias were harvested, embedded in plastic, and sliced with a diamond saw. Wafers at a thickness of 200 microm were mounted in sequence and examined. RESULTS: Sixteen of 49 experimental animals (33%) were positive for at least one of the fluorescent labels. Fluorescent labeled osteoid was present at all sampling times. Label extended from the endosteal wall into the lumen of the scala tympani between the vestibule and the round window membrane. Discrete sites of fluorescence varied among specimens and were associated with the opening of the cochlear aqueduct, the scala tympani, organ of Corti, and the stria vascularis and spiral ligament in all turns from base to apex. CONCLUSION: The results indicate that osteoid is deposited and begins mineralization by day 3 after infection, at least, and continues, at least, through the first 28 days after infection. There was no apparent resorption of new bone and remodeling by 84 days after infection.     

Clinical results with the Med-El compressed and split arrays in the United States

OBJECTIVE: To determine the indications for which the Med-El compressed and split arrays have been used in the United States, to assess the success achieved in insertion, to determine hearing outcomes, and assess complications associated with using these arrays. STUDY DESIGN: Retrospective review of data gathered during the US clinical trial. METHODS: Data were extracted concerning indications for use, depth of insertion, number of electrodes in use, 3 and 6 month performance outcomes, and complications. The results obtained in postmeningitic patients using the compressed array were compared with results of patients using the split array. RESULTS: Six adults and 22 children have been implanted with the compressed array. The principal indications have been postmeningitis or congenital cochlear malformations. The average improvement seen in the Meaningful Auditory Integration Scale scores was 17.6 for the compressed array group and 13.9 for the split array group. The same number of electrodes was inserted on average for both groups, with comparable numbers of electrodes in use. CONCLUSIONS: The Med-El compressed array is an alternative to a standard or split array in managing patients with postmeningitic deafness or congenital cochlear malformations. Benefits to these patients are most clearly seen in subjective measures.     

Tuberculous meningitis in adults in Turkey: epidemiology,diagnosis, clinic and laboratory [corrected

A retrospective study was performed to assess the epidemiology, diagnosis, clinic, and laboratory of the patients with tuberculous meningitis (TBM) in a multicentral study. The medical records of adult cases with TBM treated at 12 university hospitals throughout Turkey, between 1985 and 1998 were reviewed using a standardized protocol. The diagnosis of TMB was established with the clinical and laboratory findings and/or microbiological confirmation in cerebrospinal fluid (CSF). The non-microbiologically confirmed cases were diagnosed with five diagnostic sub-criteria which CSF findings, radiological findings, extra-neural tuberculosis, epidemiological findings and response to antituberculous therapy. A total of 469 patients were included in this study. Majority of the patients were from Southeast Anatolia (164 patients, 35.0%) and (108 patients, 23.0%) from East Anatolia regions. There was a close contact with a tuberculous patient in 88 of 341 patients (25.8%) and with a tuberculous family member in 53 of 288 patients (18.4%). BCG scar was positive in 161 of 392 patients (41.1%). Tuberculin skin test was done in 233 patients and was found to be negative in 75. Totally 115 patients died (24.5%) of whom 23 died in 24 hour after admittance. The diagnosis was confirmed with clinical findings and CSF culture and/or Ziehl–Nelson staining in 88 patients (18.8%). Besides clinical criteria, there were three or more diagnostic sub-criteria in 252 cases (53.7%), two diagnostic sub-criteria in 99 cases (21.1%), and any diagnostic sub-criteria in 30 patients (6.4%). Since TBM is a very critical disease, early diagnosis and treatment may reduce fatal outcome and morbidity.     

Chronic meningitis: still a diagnostic challenge

Chronic meningitis is characterized by a progressive, subacute onset of lepomeningeal disease and persisting cerebrospinal fluid (CSF) abnormalities such as elevated protein level and pleocytosis for at least one month. The array of aetiologies is very wide comprising non-infectious (carcinomatous, systemic disease, toxic) and infectious (classic and opportunistic pathogens). The evaluation encompasses a careful history, complete physical examination and laboratory tests. The specific diagnosis may remain a challenge in some cases. Algorithms for the differential diagnosis are provided for both immunocompetent and immunocompromised patients. Received: 7 January 2003, Accepted: 30 January 2003     

Serogroup W-135 meningococcal disease during the Hajj, 2000

An outbreak of serogroup W-135 meningococcal disease occurred during the 2000 Hajj in Saudi Arabia. Disease was reported worldwide in Hajj pilgrims and their close contacts; however, most cases were identified in Saudi Arabia. Trends in Saudi meningococcal disease were evaluated and the epidemiology of Saudi cases from this outbreak described. Saudi national meningococcal disease incidence data for 1990 to 2000 were reviewed; cases from January 24 to June 5, 2000, were retrospectively reviewed. The 2000 Hajj outbreak consisted of distinct serogroup A and serogroup W-135 outbreaks. Of 253 identified cases in Saudi Arabia, 161 (64%) had serogroup identification; serogroups W-135 and A caused 93 (37%) and 60 (24%) cases with attack rates of 9 and 6 cases per 100,000 population, respectively. The 2000 Hajj outbreak was the first large serogroup W-135 meningococcal disease outbreak identified worldwide. Enhanced surveillance for serogroup W-135, especially in Africa, is essential to control this emerging epidemic disease.     

The cost of treatment for child pneumonias and meningitis in the Northern Areas of Pakistan

Pneumonia, meningitis, and sepsis place a significant economic burden on health care systems, particularly in developing countries. This study estimates treatment costs for these diseases in health facilities in the Northern Areas of Pakistan. Health facility resources are organized by categories--including salaries, capital costs, utilities, overhead, maintenance and supplies--and quantified using activity-based costing (ABC) techniques. The average cost of treatment for an outpatient case of child pneumonia is dollar 13.44. For hospitalized care, the health system spent an average of dollar 71 per episode for pneumonia, dollar 235 for severe pneumonia, and dollar 2,043 for meningitis. These costs provide important background information for the potential introduction of the conjugate Haemophilus influenzae type b (Hib) and Streptococcus pneumoniae vaccines in Pakistan.     

浅析无菌药品的参数放行

目的:为提高我国无菌药品的质量控制水平提供参考。方法:通过对比传统的无菌检查质量控制方法,参考发达国家的参数放行指南,分析无菌药品参数放行优越性及具体实施方法。结果与结论:对于无菌药品,参数放行能够为最终产品提供更高水平的质量保证,其替代传统的质量控制方法是必然的趋势。