Phenytoin-induced cerebral thrombosis in rats: cerebral ultrastructure, water content and ischaemic volume in the acute phase

A new rat model for multifocal cerebral thrombosis has recently been reported (Tani et al. , 1994; 1995). Ultrastructural changes in the cerebral neocortex in the acute phase were investigated in order to characterize the early pathological events in this model. A bolus injection of alkaline phenytoin solution (pH 10.8) into one internal carotid artery in the rat caused severe endothelial injury accompanied by thrombosis in the cerebral vasculature within 5 minutes, and severe oedema of the ipsilateral hemisphere within an hour. Cerebral water content was measured by the simple dry–wet method, and cerebral surface area and the surface area and volume of the ischaemic zone were measured using computer-aided image analysis. Good correlations were demonstrated between cerebral water content and cerebral surface area, and between the surface area and volume of the ischaemic zone. We report here that quantitative evaluation of acute cerebral damage induced by phenytoin solution is possible with high reliability using simple image analysis.     

Weber-Christian disease with benign cytophagic histiocytes in the skin lesion

We describe an 8 year old female with Weber-Christian disease who manifested erythema on her legs and an intermittent high fever. A wedge skin biopsy revealed lobular panniculitis and bean-bag cells, which were characteristic to cytophagic histiocytic panniculitis (CHP). However, she showed no evidence of liver dysfunction, hyperlipidemia, or coagulation disorders usually seen in CHP. Moreover, she responded well to oral corticosteroids therapy with resultant advanced subcutaneous fat atrophy.     

The diagnostic value of kappa/lambda ratios determined by flow cytometric analysis of biopsy specimens in B‐cell lymphoma

Flow cytometry (FC) is widely utilized in the diagnosis of lymphoma and the light chain ratio (LCR) is especially useful in the diagnosis of B‐cell malignancy. In this study we analysed, retrospectively, the predictive value of the LCR in the diagnosis of B‐cell lymphoma in 105 consecutive patients with persistent lymph node enlargement or extranodal masses who underwent biopsy. We used a receiver‐operating characteristic curve to establish a LCR threshold value of 2.0. The specificity, sensitivity, positive and negative predictive values were 92.3%, 73.1%, 90% and 77%, respectively. We concluded that determination of LCR is a useful adjunct to pathological diagnosis.     

Usefulness of the [13C]-urea breath test for detection of Helicobacter pylori infection in fasting patients

Most of the reported [¹³C]-urea breath test procedures use a test meal, which is believed to assist in the spread of the [¹³C]-urea solution into the entire stomach, as results without a test meal may mainly reflect urease activity in the antrum. Yet, procedures for the [¹³C]-urea breath test and interpretation of the obtained ¹³C excess value have not been well established. We carried out the present study to validate the usefulness of the [¹³C]-urea breath test in fasting subjects and to establish cut-off values. [¹³C]-Urea breath tests were performed on 258 Helicobacter pylori-positive and 151 -negative subjects (247 H. pylori positive and 26 negative prior to any H. pylori cure treatment and 125 H. pylori negative and 11 positive after undergoing H. pylori cure treatment). The breath test procedure was performed under the following conditions: an 8 h fast, mouth washing before and after dosing, administration of 100 mg [¹³C]-urea, collection of breath sample in a plastic bag, a baseline and a 20 min sampling point and subject in a sitting position. Delta-¹³C at the 20 min sampling point in H. pylori-positive and -negative subjects was 31.0 ± 1.25 and 1.6 ± 0.11%o, respectively. Although the mean Δ¹³C value was greatest in duodenal ulcer or ulcer scar patients, there were no significant differences among mean Δ¹³C values in the various diseases. From Receiver Operator Characteristic curves and calculation of accuracy of the test, a cut-off value of 5.0%o is considered to be appropriate for diagnosis of H. pylori infection, which provides 96.7% specificity and 96.5% sensitivity, suggesting that the [¹³C]-urea breath test in the fasting state is as effective in detecting the presence of H. pylori as other reported methods.     

Effects of genetic defects in the CYP2C19 gene on the N-demethylation of imipramine, and clinical outcome of imipramine therapy

Abstract  The relationship between the genetic polymorphism of S-mephenytoin 4'-hydroxylation catalyzed by CYP2C19 and the N-demethylation of imipramine was examined in 10 Japanese depressed patients. Five patients, who were poor metabolizers of S-mephenytoin, were determined to be either homozygous for a mutation in exon 5 or heterozygous for mutations in exon 4 and exon 5 of the CYP2C19 gene. In contrast, five patients, who were extensive metabolizers, had no mutations. The demethylation index (the desipramine/imipramine ratio) was significantly lower in patients with genetic defects. Plasma levels of imipramine and 2-hydroxyimipramine normalized by the daily dose (mg) per weight (kg) were significantly higher in patients with genetic defects. This suggests that the N-demethylation of imipramine is impaired in patients with genetic defects in the CYP2C19 gene, and that genotype determination may be useful in preventing side effects induced by unexpectedly elevated levels of imipramine.     

Up-titration of vardenafil dose from 10 mg to 20 mg improved erectile function in men with spinal cord injury

AIM: Vardenafil is a highly selective phosphodiesterase type-5 inhibitor for the treatment of erectile dysfunction (ED). Efficacy of vardenafil has been demonstrated in various ED populations, but that in Japanese patients with spinal cord injury (SCI) has not been assessed. METHODS: This was an open-label, multicenter, flexible dose, 12-week study in patients with ED due to SCI. Following a 4-week observation period, patients received vardenafil 10 mg for 4 weeks, and based on efficacy, tolerability and patient preference, doses for the remaining 8 weeks were decided by investigators. The primary efficacy parameter was erectile function domain score of the International Index of Erectile Function. RESULTS: Ten patients took 10 mg all through the study, while 22 patients took 20 mg after completing 4 weeks' treatment with 10 mg. The erectile function domain score increased from 12.2 at baseline to 25.0 at Last Observation Carried Forward (LOCF) in the former group and from 10.3 to 22.5 in the latter group, respectively. Importantly, there was a 5.0 point increase in erectile function domain score after up-titration in the latter group. Drug-related adverse events were observed in 22% of patients including hot flushes (9%) and headache (6%), but these were transient and mild in intensity. Serious adverse events and adverse events leading to discontinuation of the study drug were not reported. CONCLUSIONS: Vardenafil 10 and 20 mg was well tolerated and improved erectile function in patients with SCI. Of interest, erectile function was further improved by 20 mg in patients who were not sufficiently treated with 10 mg.     

Serum amino acids as indicators of cerebrospinal neuronal activity in patients with micturition disorders

OBJECTIVE: Our previous study showed that the spinal glycine level in rats was changed by spinal injury or bladder outlet obstruction, and this change was reflected by serum glycine levels. Therefore, we measured the serum glutamate and glycine levels in healthy volunteers and patients with cerebrospinal damage or benign prostatic hyperplasia (BPH) to confirm whether the change of serum amino acid levels was obtained from these patients as well as the animal experiment. METHODS: We measured the serum glutamate and glycine levels in 170 healthy controls, 57 patients with cerebrovascular disease (CVD), 68 patients with spinal cord injury (SCI), and 70 patients with BPH. Amino acid levels were compared between the controls and patients, according to gender, level of spinal injury and the type of bladder activity. RESULTS: In the healthy controls, glutamate levels were higher and glycine levels were lower in men than in women. On group comparison of each gender, there were no differences of glutamate levels. However, glycine levels were lower in male and female SCI patients and BPH patients than in controls. According to the level of spinal injury or the pattern of bladder activity and amino acid levels, there were no relationships among them. CONCLUSIONS: Serum glutamate and glycine levels were not related to the spinal injury level or bladder activity. However, serum glycine levels changed in patients with SCI or BPH patients, so it may be possible to use it as an indicator of spinal glycinergic neuronal activity.     

Clinically isolated cerebellar metastasis of renal pelvic urothelial cancer

A 70-year-old man who had undergone radical surgery for renal pelvic transitional cell carcinoma 9 months previously developed solitary cerebellar metastasis. Despite neurosurgical removal, the patient died and post-mortem pathological examination revealed microscopic metastatic lesions within microvessels of the lung. No other lesion, including local residual cancer, was detected.