Clinical evaluation of norfloxacin in gonococcal urethritis

Norfloxacin, a new quinolinecarboxylic acid derivative, was administered to 30 male patients with gonococcal urethritis at a daily dose of 600 mg for 7-21 days. The clinical response was evaluated after administration of 7 days as excellent; Negative culture of N. gonorrhoeae. WBC less than 3/hpf in first voided urine sediment, good; Negative culture, WBC greater than or equal to 3/hpf, and poor; Positive culture. The result was excellent in 14 cases and good in 16 cases. No subjective side effects were observed. The minimum inhibitory concentration (MIC) distribution against the clinically isolated 30 strains of N. gonorrhoeae ranged from 0.0096 micrograms/ml to 0.34 micrograms/ml. Seven of thirty strains were resistant to ABPC. The MIC of these 7 strains ranged from 0.018 micrograms/ml to 0.18 micrograms/ml. Seven cases with ABPC resistant strains had a similar clinical response to other cases. Twelve patients (40%) developed post gonococcal urethritis for 7-14 days after treatment. Clinical observation of this series suggests that a 7 day therapy of Norfloxacin for the patients with gonococcal urethritis is sufficiently effective and that treatment should be changed to other antibacterial agents in the case of post gonococcal urethritis, since continuous administration for more than 7 days of Norfloxacin is not so effective.     

ENDOSCOPIC OBSERVATION OF MUCOSAL SPREAD LESION OF CHOLANGIOCARCINOMA USING PERORAL CHOLANGIOSCOPY WITH NARROW BAND IMAGING

A 69‐year‐old man was admitted to Toho University Omori Medical Center complaining of icterus. Abdominal computed tomography, magnetic resonance cholangiopancreatography and endoscopic retrograde cholangiopancreatography were suspicious of cholangioma of inferior bile duct. Peroral cholangioscopy using narrow band imaging (NBI) was performed and it was possible to diagnose the mucosal spread lesions of cholangioma. Histological findings reflected the endoscopic findings. Mucosal spread lesions of cholangiocarcinoma were successfully diagnosed using the CHF‐B260 for NBI.     

Long-term results of first-line sequential high-dose carboplatin, etoposide and ifosfamide chemotherapy with peripheral blood stem cell support for patients with advanced testicular germ cell tumor

OBJECTIVE: Standard chemotherapy shows relatively low long-term survival in patients with poor-risk testicular germ cell tumor (GCT). First-line high-dose chemotherapy (HD-CT) may improve the result. High-dose carboplatin, etoposide, ifosfamide chemotherapy followed by autologous peripheral blood stem cell transplantation (PBSCT) was investigated as first-line chemotherapy in patients with advanced testicular GCT. METHODS: Fifty-five previously untreated testicular GCT patients with Indiana 'advanced disease' criteria received three cycles of bleomycin, etoposide and cisplatin (BEP) followed by one cycle of HD-CT plus PBSCT, if elevated serum tumor markers were observed after three cycles of the BEP regimen. RESULTS: Thirty patients were treated with BEP alone, because the tumor marker(s) declined to normal range. Twenty-five patients received BEP and HD-CT. One patient died of rhabdomyolysis due to HD-CT. Three and six (13% and 25%) out of 24 patients treated with BEP and HD-CT achieved marker-negative and marker-positive partial responses, respectively. The other patients achieved no change. Fifteen (63%) are alive and 14 (58%) are free of disease at a median follow-up time of 54 months. Severe toxicity included treatment-related death (4%). CONCLUSIONS: HD-CT with peripheral stem cell support can be successfully applied in a multicenter setting. HD-CT demonstrated modest anticancer activity for Japanese patients with advanced testicular GCT and was well tolerated. This regimen might be examined for further investigation in randomized trials in first-line chemotherapy for patients with poor-risk testicular GCT.     

A case of constrictive pericarditis due to traumatic pericardial hematoma

Although the cause varies widely, we recently experienced a case of constrictive pericarditis of which cause seemed to be traumatic as described below. The patient was a 62-year-old man having a history of epigastric trauma about 20 years ago. Since then, palpitation appeared and he was recently hospitalized in our department for the purpose of receiving an operation under the diagnosis of constrictive pericarditis. At operation, a hematoma was found in the pericardial region, which was considered to have been caused by trauma in the past. Less reports have so far been available concerning trauma-induced constrictive pericarditis and this case thus seemed to be of rarity as well.     

Accumulation of cyanide and thiocyanate in haemodialysis patients.

BACKGROUND: Cyanide is a toxic agent, and its detoxification product, thiocyanate, may be a major pathogenetic substance in uraemia. Recent studies examining the myeloperoxidase(MPO)/thiocyanate system have suggested a link between thiocyanate and atherosclerosis. However, inaccuracies in conventional assays for cyanide and thiocyanate have limited the understanding of their metabolism in haemodialysis (HD) patients. METHODS: We used high-performance liquid chromatography to measure cyanide in erythrocytes and thiocyanate in plasma in 43 HD patients and in a group of 46 healthy controls that included 15 current smokers. To clarify the metabolic conversion of cyanide to thiocyanate in uraemic patients, we also measured cysteine and sulfate. We then used stepwise regression analysis to analyse factors that determine erythrocyte cyanide and plasma thiocyanate. RESULTS: Mean cyanide and thiocyanate were significantly greater in HD patients than in non-smoking controls. However, cyanide was far below lethal concentrations in dialysis patients. Thiocyanate was six to seven times greater in HD patients than in non-smoking controls, and decreases in thiocyanate following dialysis were only 19.3+/-3.5%. Multiple regression analysis showed a positive correlation between cyanide and thiocyanate in controls, but a negative correlation in HD patients. In patients, an inverse relationship between thiocyanate and BUN was also observed. CONCLUSIONS: The elevation of thiocyanate in patients undergoing dialysis probably is secondary to both limited efficiency of HD and deranged metabolism of cyanide and thiocyanate. Because thiocyanate is a preferred substrate for MPO, it may play a role in uraemic complications including cardiovascular events.     

Glycogen synthase kinase-3beta is involved in the process of myocardial hypertrophy stimulated by insulin-like growth factor-1.

BACKGROUND: Glycogen synthase kinase-3 beta (GSK-3beta) is involved in many cellular processes, such as metabolism, apoptosis, differentiation and proliferation. Insulin-like growth factor-1 (IGF-1), which is well known to have a hypertrophic effect on cardiomyocytes, inactivates (phosphorylates) GSK-3beta in some cell types. The role of GSK-3beta in cardiomyocytes as a negative regulator of cardiac hypertrophy has been recently reported and the present study investigated the role of GSK-3beta in the cardiac hypertrophy of cultivated neonatal rat cardiomyocytes induced by IGF-1. METHODS AND RESULTS: First, the IGF-1 induced signal transduction leading to GSK-3beta in neonatal rat cardiomyocytes was examined. The phosphatidylinositol (PI) 3-kinase/Akt/GSK-3 beta signaling induced by IGF-1 was investigated using inhibitors of PI 3-kinase and Ad AktAA, a dominant negative form of Akt. Furthermore, using Ad MEK DN, a dominant negative form of MEK, it was found that MEK negatively regulates Akt phosphorylation upon IGF-1 stimulation. Next, it was examined whether GSK-3beta acts as a negative regulator in the cardiac hypertrophy induced by IGF-1. Sustained stimulation by IGF-1 caused cardiac hypertrophy in protein synthesis and cellular morphology, and overexpression of unphosphorylatable GSK-3beta (Ad GSK-3beta S9A) repressed these hypertrophic effects of IGF-1. CONCLUSIONS: GSK-3beta may play an important role as a negative regulator of cardiac hypertrophy induced by IGF-1.     

Association of the GNAS1 gene variant with hypertension is dependent on alcohol consumption.

The beta-adrenoceptor (beta-AR)-stimulatory guanine nucleotide-binding (Gs) protein system has been shown to play important roles in the cardiovascular system. The gene encoding the alpha-subunit of Gs proteins (GNAS1) is a candidate genetic determinant for hypertension. Because alcohol consumption is known to affect blood pressure partly through the beta-AR-Gs protein system, we examined the possible interaction between GNAS1 T393C polymorphism and drinking status in the association with hypertension in the present study. As a result, a non-significant but reasonable trend supporting the presence of an interaction was shown (p = 0.076). In line with this trend, the T393C polymorphism significantly interacted with drinking status in the association with systolic blood pressure (p = 0.028). Moreover, supporting the presence of an interaction, T allele carriers consistently had a higher probability of hypertension, higher systolic blood pressure, and higher diastolic blood pressure than CC homozygotes in non-drinkers and light drinkers. In contrast, CC homozygotes consistently had a higher probability of hypertension, higher systolic blood pressure, and higher diastolic blood pressure than T allele carriers in moderate to heavy drinkers. The present study also showed a significant interaction between the T393C polymorphism and drinking status in the association with pulse pressure (p = 0.026), reflected by a significant association between the T393C polymorphism and pulse pressure in moderate to heavy drinkers (p = 0.026). These findings may be helpful in conducting further molecular and biological studies on the relationship among the effects of alcohol, the beta-AR-Gs protein system, and hypertension.     

Traumatic degeneration of transected myelinated fibers of the mouse sciatic nerve.

Traumatic degeneration of myelinated fibers was studied by electron microscopy over 5 days following transection of mouse sciatic nerve. Special attention was paid to the mechanism which separates the degenerating part, while preserving the viable part of the axon. Immediately after transection, the opened end of the proximal stump revealed extensive subcellular changes including the disorganization of neurofilaments, and disruption of mitochondria and axonal endoplasmic reticulum (SER). Subsequently, vesicles of round and tubular profiles filled up the whole area of the stump end, and proximal to it appeared a neurofilament-predominant area characterized by randomly oriented neurofilaments and normally appearing mitochondria and SER. Characteristic membranous demarcations occurred in early periods at the border between the vesicle accumulation and the neurofilament-predominant areas, and later also within these areas. The demarcation membranes formed both by invagination of the surface plasma membrane and, probably, by fusion of the large vesicles. These became prominent with time, dividing the axoplasm into compartments of varying sizes, which gradually underwent degeneration and were liberated from the parent axon. Occurrence of autophagic vacuoles was characteristic of the degenerating portions of the parent axon. Thus, by the function of demarcation membranes, the parent axon to be preserved could remain membrane-bound, while the degenerating parts were shed off.