Seizures complicating infantile and childhood bacterial meningitis

In this study, 116 patients, at least 1 month of age but younger than 5 years, were identified with culture-proven bacterial meningitis. A comparison was made between the clinical data of the patients with and without seizures during hospitalization. Seizures during acute bacterial meningitis accounted for 47% (55/116) of the episodes. Time interval between the onset of bacterial meningitis and that of seizures was 1 to 20 days (mean, 4 days). Twelve of these 55 patients had one or more afebrile seizures after completing the treatment. At follow-up of at least 1 year after completing treatment, 26 patients had good outcomes, whereas the other 29 patients had poor outcomes. A strong correlation between the findings of abnormalities through neuroimaging and the occurrence of seizures during hospitalization was observed. The long-term outcomes of patients with infantile and childhood bacterial meningitis, who had seizures during the acute phase of bacterial meningitis, were worse than the outcomes of those who did not have such seizures. No child developed late seizures unless there were acute seizures. Factors associated with seizures during acute bacterial meningitis include disturbed consciousness on admission, abnormal neuroimaging findings, and low glucose and high concentration of total proteins in cerebrospinal fluid.     

Paralytic ileus in MELAS with phenotypic features of MNGIE

This report describes a child having the syndrome of overlapping phenotypic features of mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) and mitochondrial neurogastrointestinal encephalopathy syndrome (MNGIE). Mitochondrial DNA analysis revealed a point mutation at position A3243G, whereas activity of thymidine phosphorylase and its corresponding gene analysis were normal. The most striking feature of this case was paralysis of one segment of the terminal ileum observed on laparotomy. The electron microscopic findings of the resected ileum and colon by limited right hemicolectomy disclosed accumulation of numerous enlarged mitochondria with ill-defined cristae which were similar to mitochondria reported in three previous MELAS cases and one MNGIE case with intestinal dysmotility. We emphasize that the MELAS and MNGIE phenotypes overlapped in this case and that the mechanism of acute ileus in MELAS was associated with functional paralysis of the intestine.     

Quality of life and its correlates in HIV/AIDS male outpatients receiving highly active antiretroviral therapy in Taiwan

Long-term care of human HIV and AIDS cases has raised quality of life (QoL) issues. The aim of this study was to identify QoL in HIV/AIDS male outpatients receiving highly active antiretroviral therapy (HAART) and its correlates in Taiwan. In total, 41 HIV/AIDS male outpatients receiving HAART yet presenting few symptoms of infection, were recruited for the study. Their QoL levels were measured with the Taiwan version of the Short Form of the World Health Organization Quality of Life questionnaire (WHOQOL-BREF). The relationships between QoL and demographic characteristics, social support, negative stressors, depression, characteristics of HIV infection, attitude toward HIV infection, and adverse effects of HAART, were examined. The results of the analysis reveal that multiple factors affect QoL for HIV/AIDS male outpatients receiving HAART, including severity of depression, deterioration of work function, inconvenience resulting from medication schedules and medical appointments, lack of social support, negative stressors, and adverse effects of HAART. The results provide screening factors so that clinicians can intervene to improve the QoL for their HIV patients.     

Neuromuscular disorders in severe acute respiratory syndrome

OBJECTIVE: To delineate and clarify neuromuscular disorders in patients with probable severe acute respiratory syndrome (SARS). DESIGN: Case series with follow-up ranging from 3 weeks to 2 months. SETTING: National Taiwan University Hospital, Taipei. PATIENTS: We investigated 4 patients with SARS who had concomitant neuromuscular problems. A diagnosis of SARS was based on the demonstration of serum coronavirus antibodies. Clinical presentations, laboratory results, electrophysiologic findings, and follow-up conditions were determined. RESULTS: Patients developed neuromuscular problems approximately 3 weeks after the onset of SARS. Two women experienced motor-predominant peripheral nerve disorders. A man developed myopathy and a third woman experienced neuropathy and myopathy. Cerebrospinal fluid obtained from 2 patients with neuropathy disclosed normal protein content and the absence of pleocytosis and SARS coronavirus antibodies. Both patients with myopathy had elevated serum creatine kinase levels. A rapid clinical and electrophysiologic improvement was evident during follow-up examinations, with a good prognosis. CONCLUSIONS: The neuromuscular problems in patients with SARS are considered to be critical-illness polyneuropathy or myopathy, possibly coexistent. Further pathological and microbiological studies are necessary to determine the relationship between SARS coronavirus and neuromuscular problems.     

Characterization of bone and soft-tissue tumors with in vivo 1H MR spectroscopy: initial results

PURPOSE: To determine if in vivo detection of choline by using hydrogen 1 (1H) magnetic resonance (MR) spectroscopy with dynamic contrast material-enhanced MR imaging can help differentiate between benign and malignant musculoskeletal tumors. MATERIALS AND METHODS: MR imaging was performed in 36 consecutive patients with bone and soft-tissue tumors larger than 1.5 cm in diameter. Examinations were performed at 1.5 T with a surface coil appropriate for the location of the lesions. Single-voxel 1H MR spectroscopy was performed by using a point-resolved spectroscopic sequence with echo times of 40, 135, and 270 msec. The volume of interest within lesions was positioned on the areas of early enhancement (<8 seconds after arterial enhancement) according to the findings of dynamic contrast-enhanced MR imaging with subtraction. The criterion for determining whether choline was present in a lesion was a clearly identifiable peak at 3.2 ppm in at least two of the three spectra acquired at echo times. MR spectroscopic results and histopathologic findings were determined in blinded fashion and compared with kappa statistics. P <.001 was considered to indicate a significant difference. RESULTS: Choline was detected in 18 of 19 patients with malignant tumors and in three of 17 patients with benign lesions. The three benign lesions included one perineurioma, one giant cell tumor, and one abscess. Choline was not detected in 14 patients with benign lesions nor in one patient with a densely ossifying low-grade parosteal osteosarcoma. In vivo 1H MR spectroscopy characterized bone and soft-tissue tumors, resulting in a sensitivity of 95%, specificity of 82%, and accuracy of 89% (P <.001). CONCLUSION: Choline can be reliably detected in large malignant bone and soft-tissue tumors by using a multiecho point-resolved spectroscopic protocol. 1H MR spectroscopy can help differentiate malignant from benign musculoskeletal tumors by revealing the presence or absence of water-soluble choline metabolites.     

A hematology surveillance study of petrochemical workers exposed to benzene

Historically, complete blood counts (CBCs) have been recognized as an easy and readily available screen for hematotoxicity following occupational exposure to benzene. The purpose of this study is to evaluate hematology data from employees who have ever participated in the Shell Benzene Medical Surveillance Program (BMSP) compared to employees who have not participated and to examine the sensitivity of CBCs to detect hematological changes in a low-exposure occupational setting. This large study included 1200 employees who participated in the BMSP, with mean benzene exposure (TWA-8) of 0.60 ppm from 1977 to 1988 and 0.14 ppm since 1988, and 3227 comparison employees. The comparison group included employees not enrolled in either the benzene or butadiene surveillance programs. Abnormality of six CBC parameters and the adjusted mean values of these parameters in the exposed group were compared with that of the comparison group. We found no increased abnormality for any hematology parameter among exposed employees. The adjusted mean values (adjusted for age, sex, race, length of time between first and last exam, and current smoking status) of the exposed employees were similar to those in the comparison group. At current occupational exposure levels for benzene, no evidence of adverse hematological effects was observed in this study. These results raise the question of whether annual CBC surveillance for benzene-exposed workers has adequate sensitivity to detect meaningful hematological changes due to low-level exposures.     

Development and validation of an HPLC method for AG331 bulk drug substance and lyophilized powder for injection

AG331 is a water soluble glucuronate salt of a novel antitumor compound synthesized by protein structure based drug design. A lyophilized powder for injection was developed for clinical studies. During HPLC assay development, AG331 showed an inherent tailing problem due to an amino group in the structure. An optimized reverse-phase gradient HPLC method was developed to minimize the tailing and separate AG331 from its synthetic intermediates (I-1, I-2, I-3, I-4, I-5, I-6, I-8), other impurities and degradation compounds. The method was shown to be linear, precise, accurate, rugged and stability-indicating.     

Optimization of sustained-release propranolol dosage form using factorial design and response surface methodology

The purpose of this study was to develop propranolol extended release formulations containing hydroxypropylmethylcellulose (HPMC). The results indicate that the drug release from the tablet form containing a high amount of HPMC was incomplete, and avicel addition could increase the release percent at a later stage. In order to readily obtain an optimal formulation, response surface methodology and multiple response optimization utilizing a quadratic polynomial equation was used. The model formulations were prepared according to a factorial design. The effects of causal factors including the HPMC/drug ratio (X1) and avicel level (X2), on drug release were also measured. The drug release percentage at 1.5, 4, 8, 14 and 24 h were the target response and were restricted to not more than 25%, 35-50%, 55-70%, 75-90%, and 95-110%, respectively. The results showed that the optimized formulation provided a dissolution pattern equivalent to the predicted curve, which indicated that the optimal formulation could be obtained using response surface methodology. The mechanism of drug release from HMPC matrices tablets followed quasi-Fickian diffusion.