Skewed X chromosome inactivation in fraternal female twins results in moderately severe and mild haemophilia B

Summary. Female carriers of haemophilia B are usually asymptomatic; however, the disease resulting from different pathophysiological mechanisms has rarely been documented in females. In this study, we investigated the mechanisms responsible for haemophilia B in fraternal female twins. We sequenced the factor IX gene (F9) of the propositus, her father, a severe haemophilia B patient and the other family members. X chromosome inactivation was assessed by the methylation‐sensitive HpaII‐PCR assay using X‐linked polymorphisms in human phosphoglycerate kinase 1 gene (PGK1) and glutamate receptor ionotropic AMPA 3 gene (GRIA3). The twins were found to be heterozygotes with a nonsense mutation (p.Arg384X) inherited from their father. The propositus, more severely affected twin, exhibited a significantly higher percentage of inactivation in the maternally derived X chromosome carrying a normal F9. The other twin also showed a skewed maternal X inactivation, resulting in a patient with mild haemophilia B. Thus, the degree of skewing of maternal X inactivation is closely correlated with the coagulation parameters and the clinical phenotypes of the twins. Furthermore, we identified a crossing‐over in the Xq25–26 region of the maternal X chromosome of the more severely affected twin. This crossing‐over was absent in the other twin, consistent with their fraternal state. Differently skewed X inactivation in the fraternal female twins might cause moderately severe and mild haemophilia B phenotypes, respectively.     

Kinetic Evidence for Facilitated Peritoneal Transport of Benzoic acid in Rats

To evaluate the dose dependency in apparent peritoneal permeability (P_d) of benzoic acid as a model compound for a monocarboxylic acid transport system, a kinetic model, which involves changes in the volume and osmolality of the dialysate as well as the diffusion and convection of drugs across the peritoneum, was applied. We compared the P_d value of benzoic acid to that of phenobarbital which is a more lipophilic drug than benzoic acid. The concentration-time courses of phenobarbital in both peritoneal cavity and serum after the intraperitoneal administration with various doses were parallel according to dose, whereas those of benzoic acid varied in a dose-dependent manner. Using the values of unbound fraction (f_u), the value of P_d for unbound drugs was estimated. The P_d values of benzoic acid at 20 μg mL^?1 was three times the value determined at 1000 μg mL^?1. We suggest that certain facilitated transport systems constitute the mechanism of enhanced peritoneal membrane permeability of benzoic acid.     

Radiofrequency Catheter Ablation of Left Ventricular Outflow Tract Tachycardia:

Left Ventricular Outflow Tract Tachycardia. Idiopathic ventricular tachycardia (VT) originating from the left ventricular outflow tract (LVOT) is rare. We report two patients whose QRS configuration during VT commonly showed an inferior axis and monophasic R waves in all the precordial leads. The mechanism of these VTs appeared to be triggered activity. From mapping and ablation, the origin of these VTs was determined to be in the most posterior LVOT, corresponding to the aortomitral continuity (left fibrous trigone).     

Alveolar soft-part sarcoma of the retroperitoneum

A 33-year-old woman was referred to Iida Municipal Hospital because of left back pain. Computed tomography showed a tumor (17 x 11 x 10 cm) in the left retroperitoneal space. T1- and T2-weighted magnetic resonance imaging showed an inhomogeneous mass with marginal blood vessels. The tumor was resected via lumbar oblique incision with the thoraco-abdominal approach. The tumor weighed 1800 g and consisted of nests of 5-100 large, loosely arranged, polygonal cells, surrounded by capillaries, resembling alveoli. The tumor cells were rich in cytoplasm, containing periodic acid-Schiff- and diastase-positive granules and typical crystals. The pathological diagnosis was alveolar soft-part sarcoma (ASPS). Alveolar soft-part sarcoma is a rare soft-tissue tumor that accounts for approximately 0.5-1% of soft-tissue sarcomas. Such tumors originating in the retroperitoneal space are extremely rare. Herein is reported a case of ASPS of the retroperitoneum with radiological and pathological findings.     

Epithelial stromal tumor of the seminal vesicle

Primary tumors of the seminal vesicles are rare neoplasms; there have been only 69 accepted cases. The histologic features are usually adenocarcinoma; however, there are rarely reported epithelial stromal tumors of the seminal vesicles. We report a case of a 70-year-old man with an epithelial stromal tumor of the seminal vesicle who presented without symptoms of bladder outlet obstruction. The patient underwent radical cystoprostatectomy. No signs of tumor recurrence were noted within 14 months of surgery. To our knowledge, 13 cases of epithelial stromal tumors of the seminal vesicle have been previously reported.     

Assessment of a protocol for prophylactic antibiotics to prevent perioperative infection in urological surgery: A preliminary study

BACKGROUND: The aim of the present study was to assess the usability and efficacy of our new protocol of prophylactic antibiotic use to prevent perioperative infection in urological surgery. METHODS: We prospectively investigated 339 cases of typical urological surgery in our department between April 2001 and March 2002 (group I). We classified surgical procedures into four categories by invasiveness and contamination levels: category A, clean less invasive or endoscopic surgery; category B, clean invasive or clean contaminated surgery; category C, urinary tract diversion using the intestine; and category D, infected surgery. Antibiotics were administrated intravenously according to our protocol: category A, first or second generation cephems or penicillins during the operative day only; category B, first and second generation cephems or penicillins for 3 days; and category C, second or third generation cephems for 4 days. Category D was excluded from the analysis. To judge perioperative infections, the wound condition and general conditions were evaluated in terms of the surgical site infection (SSI) as well as remote infection (RI) up to postoperative day (POD) 14. We retrospectively reviewed 308 patients who underwent urological surgery between April 2000 and March 2001 (group II) as reference cases that were administered antibiotics without any restriction. RESULTS: Perioperative infection rates (SSI + RI) in group I and group II were 25 of 339 (7.4%) and 35 of 308 (11.4%), respectively. Surgical site infection rates of categories A, B, and C in group I were 1.8%, 7.6%, and 30.0%, respectively, while those in group II were 2.0%, 7.4%, and 46.2%, respectively. There was no significant difference in infection rates in terms of RI and SSI between group I and group II. The amounts, as well as the prices, for intravenously administrated antibiotics and oral antibiotics decreased to approximately half and one-fifth, respectively. CONCLUSION: Our protocol effectively decreased the amount of antibiotics used without increasing perioperative infection rates. Thus, our protocol of prophylactic antibiotic therapy would be recommended as an appropriate method for preventing perioperative infection in urological surgery.     

Mechanism of the Pancreas-parotid Gland Interaction

In order to elucidate the mechanism of interaction between the pancreas and parotid gland, male Wistar rats of tlie same litters were used to produce parabiotic pairs. Six pairs which survived tlie procedure more than 30 days were available for experimentation. In one of each pair of rats, acute pancreatitis was induced. Amylase concentration in the sera, pancreas and parotid glands in these rats was estimated and histocytological studies of these organs were performed. The following results were obtained: 1. The serum amylase level was elevated in the rats with experimentally induced pancreatitis. It was slightly elevated in the rats without pancreatitis. 2. Organ amylase concentration in the pancreas and parotid gland was reduced in the rats with and without pancreatitis. The reduction of pancreas tissue amylase in the rats without pancreatitis was slight and insignificant. 3. In hght microscopy, the pancreas in the rats without pancreatitis was not significantly altered compared to that of the control rats. The parotid gland in the rats without pancreatitis showed apparent atrophie degenerative changes, which were less severe than in the rats with pancreatitis. Electron microscopy revealed that the pancreas in rats without pancreatitis showed similar findings with those of the control rats. In the parotid gland, the findings in the rats without pancreatitis were less severe, but similar to those in the rats with pancreatitis. A humoral transmission mechanism is participating in the development of an interactive response between the pancreas and parotid gland.     

A New Diagnostic Test for Pancreatic Disorders by Examination of Parotid Saliva

The parotid saliva test was performed in 146 subjects, including 48 patients with pancreatic disorders, 82 with nonpancreatic disorders and 16 healthy persons. The following results were obtained: 1. The salivary output as well as the maximum bicarbonate concentration and amylase content in the parotid saliva of patients with pancreatic disorders were significantly less than those of patients with nonpancreatic disorders. 2. An abnormal saliva test was found in 83.3% of the patients with the pancreatic disorders. 3. Comparison was made of the parotid saliva test with the pancreozyminsecretin test in regard to diagnostic reliability in 44 subjects, including 22 with pancreatic disorders and 22 with nonpancreatic disorders. The data indicated that, in this series, an abnormal parotid saliva test was 88.6% accurate in diagnosing pancreatic disorders, whereas positive pancreozyminsecretin was only 65.9%.     

Severe, widespread vasculopathy in late-onset group B streptococcal meningitis

Although improvements in antimicrobial therapy during the last few decades have decreased mortality in childhood bacterial meningitis, some patients are left with neurologic sequelae. Cerebrovascular complications are often associated with unfavorable clinical outcome of the disease. We report a 36-day-old infant with severe, widespread cerebrovascular complications due to group B streptococcal meningitis. Magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA) contributed to a non-invasive demonstration of meningeal inflammatory changes and vascular lesions with the meningitis in this patient.