Golgi study on brain of macular mutant mouse as a model of Menkes kinky hair disease

Summary This study was undertaken to elucidate, using the Golgi method, the neuropathological change in the brain of the macular mutant mouse, whose hemizygote (Ml/y) is considered to be a model of Menkes kinky hair disease (MKHD). The hemizygote mice gradually lost weight after 10 days of age and died with emaciation and seizure around day 15. The normal littermate (+/y) was well developed. In the cerebrum, the arborization of pyramidal neurons in the layer V of the Ml/y was the same as that in the +/y on day 10. However, development of arborization in the Ml/y was delayed in comparison with that in the +/y on days 12 and 14. Purkinje cells with several somal sprouts were observed in the cerebellum in both the Ml/y and +/y on day 7. The somal sprouts in the +/y had regressed gradually by day 12, while they were still in the anterior and middle lobes of the Ml/y on day 14. Additionally, the trunks of Ml/y stem dendrites became thicker and a cactus formation was recognized on the branching portion of the dendrites on day 14. Arborization of these abnormal Purkinje cells was distinctly poor compared with that in the +/y. These results suggest that the growth of the neurons is delayed in the Ml/y and simultaneously their cytoskeletal developments are disturbed, especially in the Purkinje cells. There is a close similarity in many respects to the neuropathological change in MKHD.     

Spectral characteristics of early receptor potential in congenital red-green color blindness

The spectral response curve (amplitude versus wavelength) of the R₂ of the early receptor potential (ERP) was studied in normal, protan, and deutan subjects. The R₂ amplitude peaked at 520nm in most normal subjects. The R₂ at long wavelengths was smaller than normal in protans and larger than normal in deutans when the maximum amplitudes were normalized to 100% at the peak. The ratio of the R₂ amplitude at 460 nm to that at 600 nm clearly differed between protans and deutans. The ERP and the rapid off-response, which is mainly due to the cessation of the late receptor potential, were recorded in the same subjects. The ratio of the sensitivity of the rapid off-response at 500 nm to that at 600 nm was correlated with the ratio of the R₂ amplitude at 460 nm to that at 600nm (correlation coefficient, 0.823, p < 0.001). This study, in conjunction with our previous study, indicates that the abnormality is in the outer segments of the cones in protans and deutans.     

Hypoxia‐inducible factor 1α may be a marker for vasculitic neuropathy

Neuromuscular biopsy is still an essential method for diagnosing vasculitic neuropathy, although its diagnostic sensitivity is at most 60%. Our objective was to examine the expression of hypoxia‐inducible factor 1α (HIF‐1α) in peripheral nerves and to evaluate its usefulness in diagnosing vasculitic neuropathy, especially for discrimination from other axonal neuropathies. Forty‐one patients with vasculitic neuropathy consisting of 20 definite, 14 probable and seven possible diagnoses, 15 patients with metabolic neuropathy, five with motor neuron disease and six with chronic inflammatory demyelinating polyneuropathy were included. Nerve biopsy specimens were immunohistochemically examined for HIF‐1α and various cell markers. Distinct immunoreactivity (IR) was observed in nuclei of endoneurial cells in 54% (22/41) of vasculitic patients, while specimens from metabolic neuropathies showed less nuclear IR and the difference of mean density of HIF‐1α‐positive nuclei was significant. Two patients with possible vasculitis who showed HIF‐1α‐positive nuclei in endoneurium, were later confirmed to have vasculitis by skin biopsies. Most of the cells expressing HIF were demonstrated to be Schwann cells. There was a trend in the vasculitic patients with early phase nerve damage to display higher endoneurial HIF‐1α‐IR. HIF‐1α may be an immunohistochemical marker for vasculitic neuropathy, especially when the observed section contains no vasculitic lesions.     

Predictive factors of etiologic agents of community-acquired pneumonia presenting at a district general hospital]

Community-acquired pneumonia is one of the major respiratory diseases causing hospital admission in previously healthy patients. Prompt and appropriate antibiotic selection is essential for recovery. The authors tried to determine the distribution of the etiologic agents of community-acquired pneumonias and to analyze predictive factors. Out of 188 cases of community-acquired pneumonia presenting to our hospital, etiologic agents were determined in 106 cases (56%). Twenty-nine cases were due to Streptococcus pneumoniae, 27 cases due to Mycoplasma, 17 cases due to Haemophilus influenzae and 21 cases due to Mycobacterium tuberculosis. M. tuberculosis was the cause in 11% of all cases and the importance of pulmonary tuberculosis must be emphasized as a community-acquired pneumonia. Out of 58 cases under 50 years old, Mycoplasma pneumoniae was the etiologic agent in 23 cases (40%) and S. pneumoniae in 7 cases (12%). Out of 62 cases not less than 70 years old. M. tuberculosis was the most common etiologic agent (15 cases, 24%). S. pneumoniae followed, being causative in 13 cases (21%). M. tuberculosis was the cause in 10 cases out of 31 cases who did not complain of fever at presentation. In 86 cases who did not show leukocytosis on admission, 21 cases were due to Mycoplasma (24%) and 15 cases were due to M. tuberculosis (17%). In particular 17 cases were due to Mycoplasma among 28 cases under 50 years old without leukocytosis (61%), and 11 cases were due to M. tuberculosis in the 27 cases no less than 70 years old without leukocytosis (41%).(ABSTRACT TRUNCATED AT 250 WORDS)     

Magnetic resonance imaging of osteonecrosis in divers: comparison with plain radiographs

Objective. To assess the diagnostic value of magnetic resonance imaging (MRI) as compared with radiographic findings in osteonecrosis in divers. Design and patients. MRI scans and conventional radiographs of the shoulder, hip and knee joints of 23 professional male scuba divers were reviewed together with their clinical findings and personal histories. Correlations between the MRI findings and the radiographic evaluation, clinical symptoms, and personal history were then investigated. Results and conclusions. Lesions found on MRI in 23 divers included 27 in 39 proximal humeri, 17 in 36 proximal femora, 13 in 32 distal femora, and 12 in 32 proximal tibiae. Diffuse, marginated, or irregular patterns were observed. No lesions were seen in epiphyses of the distal femur or proximal tibia. We tried to classify these MRI findings by location and appearance. MRI showed no patients with only one affected bone. A close correlation between the MRI findings and maximum diving depth was observed in the proximal humerus. MRI depicted bone lesions that could not be detected on the radiographs. A routine MRI investigation of the hip joints should be performed in every diver in whom osteonecrosis is diagnosed at another site, for early detection of femoral head osteonecrosis. MRI of the shoulder joint is also the best surveillance in divers who dive deeper than 15?m.     

Synthesis, pharmacological activity and biopharmaceutical characteristics of alpha,2-dimethyl-5H-[1]benzopyrano[2,3-b]pyridine-7-acetates

The pro-drugs of alpha,2-dimethyl-5H-[1]benzopyrano[2,3-b]pyridine-7-acetic acid(I) with a potent anti-inflammatory activity were synthesized in order to reduce its gastrointestinal side effects. Various esters synthesized were evaluated for their anti-inflammatory activity and ulcerogenicity. Among the compounds maintaining a potent activity of I, N,N-dimethylcarbamoylmethyl alpha,2-dimethyl-5H-[1]benzopyrano[2,3-b]pyridine-7-acetate (II-18) showed excellent biopharmaceutical characteristics. The ulcerogenic effect of II-18 on the rat gastric mucosa was about 3 times less than that of I. It was suggested that II-18 may be an useful biolabile pro-drug for I among the compounds tested.     

Species differences in platelet aggregation induced by platelet-activating factor (PAF).

Species differences in platelet aggregation induced by platelet-activating factor (PAF) were investigated by using the same procedure of platelet preparation and biological assay. Washed platelets of six different species (horses, dogs, rats, rabbits, sheep and guinea pigs) were prepared employing the same method and platelet aggregation was induced by C16-PAF. Horse platelets were most sensitive to PAF (8.0 x 10(-12) M) and rabbit platelets activated by 5.0 x 10(-11) M PAF were also sensitive enough to detect PAF in clinical samples.     

Mortality among children with Kawasaki disease in Japan.

BACKGROUND AND METHODS. It is not certain whether patients with Kawasaki disease have a higher death rate than the age-matched healthy population. We therefore undertook a study to investigate this question. Between July 1982 and December 1988, 53 collaborating treatment centers collected data on all patients who had an unequivocal new diagnosis of Kawasaki disease; patients who had recurrent disease or whose first visit to the treatment center occurred more than 14 days after the onset of symptoms were excluded. Patients were followed from the time of the first visit to the treatment center until December 31, 1989, or until death, whichever occurred first. The expected number of deaths was calculated from Japanese vital-statistics data and compared with the number observed. RESULTS. Of 4676 patients who met the eligibility criteria, 4608 (98.5 percent) were followed through either the end of the study or the date of death. Thirteen patients (10 boys and 3 girls) died during the study period. The number of deaths expected was 7.61 (ratio of observed to expected deaths, 1.71; 95 percent confidence interval, 0.91 to 2.92). The ratio was 2.04 (95 percent confidence interval, 0.98 to 3.76) for boys and 1.11 (95 percent confidence interval, 0.23 to 3.23) for girls. During the acute phase of the disease (the first two months after onset), the ratios of observed to expected deaths were higher: 9.86 overall (95 percent confidence interval, 3.95 to 20.31), 13.33 for boys (95 percent confidence interval, 4.89 to 29.07), and 3.85 for girls (95 percent confidence interval, 0.10 to 21.42). After the acute phase, however, both sexes had ratios of observed to expected deaths that were lower than 1, and the difference from the control population was not statistically significant. CONCLUSIONS. The mortality rate among boys with Kawasaki disease in Japan is twice that among healthy boys of the same age, and most deaths occur within two months of diagnosis. The mortality rate among girls with the disease appears similar to that among healthy girls, although the numbers are very small.     

Intraocular kinetics of ceftazidime (Modacin).

The concentration of ceftazidime was determined in the aqueous humor and the vitreous body of normal, vitrectomized and aphakic/vitrectomized eyes and in the serum of albino rabbits 1 h after intravenous injection of 100 mg/kg ceftazidime. The intravitreal ceftazidime concentration was low (0.1-0.2 microgram/ml) in normal eyes 1 h after intravenous injection, and high (8.7 +/- 8.5 micrograms/ml) in vitrectomized and aphakic/vitrectomized eyes when injected immediately after surgery. The ceftazidime concentration was also determined in the aqueous humor and the vitreous body of normal eyes and in the serum of albino rabbits 3, 6, 12, 24 and 48 h after intravitreal injection of 200 micrograms. The intravitreal ceftazidime concentration after intravitreal injection decreased exponentially for 12 h (half-life about 7.4 h). It decreased more slowly thereafter and remained at 13.0 micrograms/ml (mean) even 48 h after injection. This concentration exceeded the minimum inhibitory concentrations against common gram-positive and gram-negative organisms causing endophthalmitis.