In vivo effects of some histamine H1-receptor antagonists on monoamine metabolism in the mouse brain

Summary The in vivo effects of four Hr-antagonists, diphenhydramine, chlorpheniramine, mepyramine, and promethazine, on the metabolism of noradrenaline (NA), dopamine (DA), and 5-hydroxytryptamine (5-HT) were investigated in the whole mouse brain. Diphenhydramine and chlorpheniramine had no significant effect on levels of NA, 3-methoxy-4-hydroxyphenylethyleneglycol (MHPG), DA, and 5-HT, but they significantly decreased levels of 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), and 5-hydroxyindoleacetic acid (5-HIAA). In particular chlorpheniramine markedly decreased 5-HIAA levels at doses as low as 1 mg/kg, i. p. Mepyramine significantly decreased 5-HIAA levels but not those of other substances. High doses of promethazine significantly decreased NA levels but markedly increased those of MHPG, DOPAC, HVA, 5-HT, and 5-HIAA. The DA reduction induced by -methyl-p-tyrosine (-MT) was significantly inhibited by diphenhydramine, chlorpheniramine, and promethazine, but the -MT-induced NA decrease was significantly enhanced by promethazine. The 5-HIAA accumulations induced by probenecid were significantly inhibited by chlorpheniramine and mepyramine. These results suggest: (1) Diphenhydramine and chlorpheniramine inhibit the turnover of both DA and 5-HT by blocking their neuronal uptake. (2) Promethazine and mepyramine inhibit DA and 5-HT turnover, respectively, as a result of the inhibition of the uptake mechanism. (3) Promethazine increases NA turnover by enhancing NA release. The discriminative effects of these drugs on the monoamine systems may be related to some differences in their CNS actions. Send offprint requests to K. Saeki at the above address     

Pediatric myositis ossificans mimicking osteosarcoma

Myositis ossificans (MO) is a rare benign cause of heterotopic bone formation in soft tissue that most commonly affects young adults, typically following trauma. We report the case of an 11‐year‐old girl who developed MO mimicking osteosarcoma in her right shoulder. Plain radiography and computed tomography showed poorly defined flocculated densities in the soft tissue and a periosteal reaction along the proximal humerus. On magnetic resonance imaging, the mass displayed an ill‐defined margin and inhomogeneous signal change. Histologically, the mass had a pseudosarcomatous appearance. Based on these findings, the patient was initially misdiagnosed with osteosarcoma at another hospital. The diagnosis was difficult because the patient was 11 years old and had no trauma history, with atypical radiographic changes and a predilection for the site of origin for osteosarcomas. We finally made the correct diagnosis of MO by carefully reviewing and reflecting on the pathological differences between stages.     

Transient swelling of peripheral nerves in a case of neurosarcoidosis

We present a case of neurosarcoidosis showing bilateral carpal tunnel syndrome which disappeared without any medication. This patient was also suffering from motor and sensory disturbance caused by peripheral neuropathy of the four extremities. Magnetic resonance image showed transient swelling of the median nerve, and subperineurial edema was unexpectedly observed in some fascicles in sural nerve biopsy. We hypothesize that the carpal tunnel syndrome in this case was induced by the intercanal high pressure due to edema inside the tunnel, which might be related to the high level of serum IL-2.     

Improvement in physiological outcomes and health-related quality of life following cardiac rehabilitation in patients with acute myocardial infarction.

BACKGROUND: The present study examined the impact of an 8-week cardiac rehabilitation (CR) program on physiological outcomes and health-related quality of life (HRQOL) of patients with acute myocardial infarction (AMI). METHODS AND RESULTS: A total of 124 consecutive AMI patients were divided into a supervised outpatient CR group (n=82) and a non-CR group as a control (n=42). Peak oxygen uptake, handgrip strength, and knee extension muscular strength were used as physiological outcome measures. HRQOL outcomes were assessed by the Medical Outcome Study Short Form 36 (SF-36). CR group patients performed both aerobic exercise and moderate resistance training from 1 month (T1) to 3 months (T2) after AMI onset. Age, sex, body mass index, medications, and ejection fraction were similar in both groups. Significantly greater increases in overall physiological outcomes from T1 to T2 were measured in the CR group compared with those of the non-CR group. There were also significantly greater improvements in 4 of the 8 SF-36 health status subscales (physical functioning, role-physical, general health, and vitality) in the CR group compared with the non-CR group. CONCLUSIONS: Eight weeks of exercise training have specific effects on improvement in HRQOL and physiological outcomes in Japanese patients.     

Usefulness of autotaxin for the complications of liver cirrhosis

BACKGROUND Autotaxin(ATX) has been reported as a direct biomarker for estimating the evaluation of liver fibrosis. But available data on ATX as a useful biomarker for the complications of liver cirrhosis(LC) are scant.AIM To assess the clinical usefulness of ATX for assessing the complications of LC.METHODS This multicenter, retrospective study was conducted at six locations in Japan. We include patients with LC, n = 400. The ATX level was evaluated separately in men and women because of its high level in female patients. To assess the clinical usefulness of ATX for the complications of LC, the area under the curve(AUC) of ATX assessing for the severe complications was analyzed in comparison with the model for end-stage liver disease score, albumin-bilirubin(ALBI) score, fibrosis-4 index, and aspartate aminotransferase-to-platelet ratio index.RESULTS The mean age was 68.4 ± 11.4 years, 240 patients(60.0%) were male. A total of 213(53.3%) and 187(46.8%) patients were compensated and decompensated,respectively. The numbers of patients with varix rupture, hepatic ascites, and hepatic encephalopathy were 35(8.8%), 131(32.8%), and 103(25.8%),respectively. The AUCs of ATX in men for hepatic encephalopathy, hepatic ascites, and varix ruptures were 0.853, 0.816, and 0.706, respectively. The AUCs of ATX in women for hepatic encephalopathy, hepatic ascites, and varix rupture were 0.759, 0.717, and 0.697, respectively. The AUCs of ATX in men were higher than those in women, as were all the other biomarkers used to detect encephalopathy and varix ruptures. However, for detecting ascites, the AUC of ALBI in men was more effective than using ATX.CONCLUSION ATX in men was more effective than any other biomarkers for detecting hepatic encephalopathy and varix ruptures.     

A newly designed bioabsorbable substitute for the treatment of diaphragmatic defects

Purpose

Earlier studies have investigated the suitability of various materials and autologous grafts for the repair of diaphragmatic defects. Our group investigated the feasibility of using an artificial diaphragm (AD) to repair wide diaphragmatic defects.

Methods

Twelve pigs were laparotomized and, in each pig, a defect was fashioned by resecting a round 8-cm diameter hole in the left diaphragm. Next, the defect was repaired by implanting an AD. The animals were relaparotomized 8 or 24 weeks after implantation for gross, histological and radiological observation of the implanted sites.

Results

All recipient animals survived until killing for evaluation. Chest X-ray examinations showed no differences between the preoperative diaphragms and the grafted diaphragms at 8 and 24 weeks after implantation. At 8 weeks after implantation, the implanted sites exhibited fibrous adhesions to the liver and lungs without deformities or penetrations. Parts of the surface tissue at the graft sites had a varnished appearance similar to those of the native diaphragm. Histology performed at 8 weeks detected no trace of the ADs in the graft sites; however, numerous inflammatory cells and profuse fibrous connective tissue were observed. At 24 weeks after implantation, no differences were found in the thorax between the areas with the grafts and the unaffected areas. Histology of the graft sites in the thorax confirmed growth of mesothelial cells similar to that observed in the native diaphragm.

Conclusions

Artificial diaphragms can be a novel substitute for diaphragmatic repair.     

Differences in cerebral metabolic impairment between early and late onset types of Alzheimer's disease

Hypercortisolemia is thought to be a marker of the stress response following stroke. The aim of this study was to investigate the prevalence and prognostic significance of hypercortisolemia. The circadian variation of cortisol level and the relationship between serum cortisol levels and other stress, inflammatory, and haemostatic markers were also investigated. Seventy consecutive patients with their first ischemic stroke and 24 age- and sex-matched controls were included in the study. Serum cortisol levels (at 6:00 AM, 10:00 AM, 6:00 PM, and 10:00 PM), 24-h urine catecholamine excretion, beta-thromboglobulin levels, and other standard biochemical and haematological parameters were measured on the first day of hospitalisation and in control subjects. Outcome measures used the Barthel Index at Day 30, as well as 30- and 90-day mortality rates. Hypercortisolemia, defined as at least two of the four measurements above the normal range of serum cortisol levels (i.e. >618 nmol/l from the morning samples and >460 nmol/l from the evening samples) was found in 25 (35.7%) of the acute stroke patients and in 3 (12.5%) of the controls (p<0.05). Hypercortisolemia was associated with older age, greater severity of neurological deficit, larger ischemic lesions on CT, and worse prognoses (p<0.05). The study did not find a correlation between serum cortisol levels and other markers of the stress response such as catecholamines excretion and glucose levels. A significant correlation between serum cortisol levels and some markers of the inflammatory response, such as fever, fibrinogen level, white blood cell (WBC) count, and beta-thromboglobulin level, was established in stroke patients. Prognostic significance of hypercortisolemia in acute stroke patients seems to be related to the inflammatory response rather than to the stress response.     

Latent addition in human motor and sensory axons: different site-dependent changes across the carpal tunnel related to persistent Na+ currents.

OBJECTIVE: To compare site-dependent changes across the carpal tunnel in axonal persistent Na+ conductances in motor and sensory axons. Positive sensory symptoms are prominent features in carpal tunnel syndrome, and a persistent Na+ current is a major determinant of axonal excitability. METHODS: The technique of latent addition was used to estimate persistent Na+ currents in median motor and sensory axons at the wrist and palm of 10 normal subjects. Brief hyperpolarizing conditioning current pulses were delivered, and threshold change at the conditioning-test interval of 0.2 ms was measured as an indicator of persistent Na+ currents. RESULTS: Threshold changes at 0.2 ms were greater in sensory than in motor axons at both the wrist and palm. In motor axons, the threshold changes were significantly smaller at the palm (mean, 4.9%) than at the wrist (10.0%). By contrast, the threshold changes were similar at the two sites of sensory axons (12.6 and 13.1%). The passive membrane time constant was similar for motor and sensory axons at the palm and wrist. CONCLUSIONS: Nodal persistent Na+ conductances have substantial site-dependent changes decreasing distally across the carpal tunnel in median motor axons, but not in sensory axons. SIGNIFICANCE: Whereas sensory axons generally have higher excitability than motor axons, the sensory-motor differences become more prominent across, and possibly at the carpal tunnel than the nerve trunk, and it is suggested that this contributes to the predominance of positive sensory symptoms in carpal tunnel syndrome.