[A case of bilateral coronal craniosynostosis with the P250R mutation in FGFR3 gene].

Recently, the substitution of proline 250 by arginine in the fibroblast growth factor receptor 3 (FGFR3) gene, has been identified in patients with craniosynostosis and defines a new syndrome on a molecular basis. We report a 1-year-1-month-old female with bilateral coronal craniosynostosis who had the P250R mutation in FGFR3 gene detected by DNA sequencing. She had brachycephaly, temporal bossing, high and flat forehead, hypertelorism, mild proptosis, low set ears and no digital abnormalities. She underwent surgical repair at 7 months and her cosmetic problems were improved. Her development was normal up to 13 months of age. DNA analysis from her parents showed that her father had the same mutation. The phenotypes of the P250R mutation in the FGFR3 syndrome are variable even within the same family, but main characteristic clinical features are follows, 1) lateral or bilateral coronal craniosynostosis, 2) mild hand and foot anomalies, and 3) sensory deafness. In FGFR3 syndrome the diagnosis of P250R mutation by polymerase chain reaction (PCR) is very easy and important for early diagnosis and genetic counseling.

Pilot study of combined treatment with continuous infusion of 5-fluorouracil, mitomycin C, and cisplatin (FMP) in patients with inoperable advanced gastric cancer.

We investigated combined chemotherapy with 5-fluorouracil (600 mg/m2/day, day 1-5, c.i.v.), mitomycin-C (6 mg/m2, day 6), and cisplatin (60 mg/m2, day 7) for inoperable advanced gastric cancer, including those with poor performance status (PS). Overall response rates were 62.5% (20/32), 59.1% (12/22) for PS 0-2 and 70.0% (7/10) for PS 3-4. Median survival was 7.2 months, 8.7 for PS 0-2; and 6.3 for PS 3-4. There was no serious toxicity or any treatment-related death. This therapy is useful, even for poor PS.

Staging of gastric cancer with endoscopic ultrasonography and endoscopic mucosal resection.

Since it was found that the gastrointestinal wall is visualized as a five-layered structure corresponding to the histological layers of the wall, endoscopic ultrasonography (EUS) has become recognized clinically as the most accurate method for diagnosing and assessing the local staging of gastric cancer. However, some problems have remained, including how to differentiate between cancer invasion and ulcer fibrosis, how to detect microinvasion, and how to recognize malignant lymph nodes. Using the pattern analysis for depressed-type gastric cancer, it is usually possible to distinguish between cancer invasion and ulcer fibrosis, except in cases of microinvasion into ulcer fibrosis or inadequate scanning. However, the sensitivity of EUS for evaluating metastatic lymph nodes is still problematic. Endoscopic mucosal resection (EMR) for early gastric cancer has been widely accepted as a standard treatment in Japan due to its minimal invasiveness. According to our data, the overall rate of radical resection was 68.3% (168 of 246), and 31.7% of the remaining patients additionally received laser treatment, surgery, or heater-probe treatment. There were no deaths owing to gastric cancer. Some lesions in which there was microinvasion of the submucosa were incorrectly diagnosed by EUS. It may be possible to solve this problem using three-dimensional EUS (3D-EUS) in the near future.

[Prognosis in the cases with renal cell carcinoma according to clinical parameters].

BACKGROUND: The objects of this study is to evaluate the clinical prognostic factors in renal cell carcinoma. MATERIALS AND METHODS: During a 30-year period from January 1965 to December 1994, 1301 cases with renal cell carcinoma were treated at the Yokohama City University Hospital and its affiliated hospitals. In these cases, cause specific 679 cases from January 1965 to December 1990 were analyzed in a study undertaken to investigate long-term treatment results and clinical prognostic factors. RESULTS: 1. The cause specific 5-, 10-, 15-, and 20-year survival rates were 48.7%, 41.1%, 32.3%, and 26.5% respectively, indicating thus that a great number of cases had an ominous prognosis even 5 years or moreafter surgical treatment. 2. Among patients under 40 years of age (n = 29) none died more than 2 years after receiving operation, the prognosis for this particular group of cases being relatively good. 3. Female, incidentally detected cancer, small tumor size (< or = 4.0 cm), slow growing type and low stage were proven to be favourable prognostic factors in renal cell carcinoma. 4. The cause specific 5-year survival rate for the patients (n = 239) from 1965 to 1981 was 33.8%, while the rate for the patients (n = 440) from 1982 to 1990 was 56.5%. This improvement of survival rate was brought by the increase of the incidentally detected renal cell carcinoma. 5. In the incidentally detected renal cell carcinoma, the incidence of slow growing cases and the cases of less than 4.0 cm tumor size were higher than in the symptomatic renal cell carcinoma. 6. Multivariate analysis using Cox's proportional hazard model showed that stage was the most important prognostic factor. CONCLUSIONS: These results suggested that sex, age, symptom, tumor size, growing type, and stage were important prognostic factors in renal cell carcinoma.

Renal gluconeogenesis in man: comparison with rats and rabbits.

To provide evidence on renal gluconeogenesis in humans and to compare with rats and rabbits, glucose production from several substrates was determined using cortical slices of the three species. In humans, the normal parts of kidney tissue were obtained from six cases of transitional cell carcinoma of the renal pelvis and four cases of renal cell carcinoma. Renal cortical slices were incubated aerobically with or without substrates, and the glucose contents were assayed photometrically. The specificity of human kidneys was evaluated by comparison with the results obtained from rats and rabbits. The rank order of renal gluconeogenesis from various substrates was as follows: Humans: pyruvate > oxaloacetic acid > lactic acid > fructose-1,6-diphosphate > L-glutamine. Rats: pyruvate > fructose-1,6-diphosphate > oxaloacetic acid > lactic acid > L-glutamine. Rabbits: fructose-1,6-diphosphate > pyruvate > oxaloacetic acid > lactic acid >> L-glutamine = 0. In general, the human kidney can produce glucose at the lowest rate among the three species. The substrate specificity of humans was more or less similar to that of rats. These results suggest the existence of a species difference in renal gluconeogenesis both in substrate specificities and quantitative activities.

Lipid analysis of Helicobacter pylori.

Lipids from Helicobacter pylori were extracted, isolated by conventional DEAE-Sephadex and silica gel column chromatography, and then purified by preparative thin-layer chromatography. Simple and phospholipids were analyzed by HPTLC and quantitatively determined by densitometry scanning. The fatty acid compositions of simple lipids were estimated by gas-liquid chromatography. The simple lipid composition of H. pylori consisted of wax ester (2.5%), triglycerides (4.9%), free fatty acids (30.0%), cholesterol (6.9%), diacylglycerol (29.1%), and monoacylglycerol (2.6%). The neutral phospholipid composition consisted of phosphatidyl ethanolamine (79.1%), lysophosphatidyl ethanolamine (16%), and phosphatidyl choline (1.9%). That of acidic phospholipids consisted of phosphatidic acid (52.7%) and phosphatidyl serine (47.3%). The major fatty acids of crude lipid, wax, free fatty acids, triglycerides, diacylglycerides, and monoacyl glycerides were C19:1 (cyclo), C18:2, C16:0, C19:1 (cyclo), C22h:0, and C18:0, respectively. These results are new findings and suggest significant characteristics from the metabolic, physiologic, and chemotaxonomic point of view.

Menotropin stimulation after prolonged gonadotropin releasing hormone agonist pretreatment for in vitro fertilization in patients with endometriosis.

Two protocols were scheduled for in vitro fertilization and embryo transfer (IVF-ET) in patients with various stages of endometriosis who were resistant to conventional therapies. In the ultralong protocol (21 patients), gonadotropin releasing hormone agonist (Gn-RHa) was administered for at least 60 days prior to ovarian stimulation along with menotropin until human chorionic gonadotropin was injected. In the long protocol (11 patients), Gn-RHa was started at the midluteal phase and exogenous gonadotropin was commenced between the third and the seventh day of the menstrual cycle after pituitary suppression. The estradiol response and the number of retrieved oocytes, fertilized oocytes, cleaved oocytes, and transferred embryos were similar in both groups but the clinical pregnancy rate per transfer was superior in the ultralong protocol (67 vs 27%). The miscarriage rate was 14% (2/14) in the ultralong protocol. Prolonged Gn-RHa suppression of ovarian function before superovulation may overcome some causes of infertility in patients with endometriosis.

[Anesthetic management of a hemophilia A carrier for palliative operation and radical repair of a cardiac anomaly].

We experienced the anesthetic management of a hemophilia A carrier for two palliative operations (left and right unifocalization) and radical repair of cardiac anomaly. The patient was a ten-year-old girl and her father had hemophilia A. She was diagnosed as tetralogy of Fallot, major aortopulmonary collateral arteries and pulmonary atresia. Laboratory findings showed prolonged bleeding time and activated partial thromboplastin time, and decreased levels of factor VIII activity of 26%. When she was eight and nine years old, she underwent unifocalization. At both occasions, excessive bleeding tendency continued into postoperative period. This time she underwent radical repair in which her bleeding tendency was successfully controlled by use of a usual dose of concentrated factor VIII for twice.

Alterations of gluconeogenesis by ischemic renal injury in rats.

This study was designed to determine changes in one metabolic function, gluconeogenesis (GLG), after ischemic renal injury. Tubule suspensions were prepared by collagenase treatment of SD rat kidneys on 1, 3, and 7 days after left renal artery and vein occlusion for 0-90 min and incubated in Krebs-Henseleit buffer with or without 2 mM pyruvate or malate aerobically. Glucose contents were assayed photometrically. On days 1 and 3 after ischemia for longer than 60 min, serum creatinine levels rose significantly. The tendency of increase of GLG was observed on days 1 and 3 after 10-60 min of ischemia. GLG increased significantly on day 1 after 30-min ischemia. On the other hand, GLG decreased significantly on day 1 after 90-min treatment. Morphologic damage was limited to the corticomedullary region on days 1 and 3 after ischemic times of 30 and 60 min. These results suggest that renal GLG is stimulated to supply energy for ATP decrease by ischemia and for further regeneration in extraproximal segments along the nephron.

Cerebrospinal fluid cyclic adenosine 3',5'-monophosphate in cases of severe cerebral ischemia and meningitis.

The concentration of cyclic adenosine 3',5'-monophosphate (cAMP) in cerebrospinal fluid was measured in 45 samples from 45 subjects, one sample per subject. 12 of the studied persons were (control group) neurologically normal, 11 were suffering from acute cerebral ischemia with deep coma, and 22 from meningitis of different types. The mean value obtained in the control group was 21.4 +/- (SEM) 3.3 nmol/l, in the group of acute cerebral ischemic attack with deep coma it was 7.00 +/- 0.81 nmol/l and in the group of meningitis 5.5 +/- 0.4 nmol/l. These values are significantly lower than the control group (p less than 0.001). These low levels, observed in the two groups of patients, may be attributed to the altered cAMP metabolism in the central nervous system because of deep coma and bacterial infections.

Free fatty acids, central nervous system and bromazepam.

The concentrations of free fatty acids in plasma were estimated in thirty-three subjects, before and after (24 hours and 72 hours) the start of bromazepam oral administration in a daily dose of 6 mg (1.5 mg at 7 a.m., 1.5 mg at 3 p.m. and 3 mg at 11 p.m.). A fourth estimation was performed 72 hours after drug discontinuation. A control group of twelve subjects received a placebo according to the same dosage pattern. In comparison with the first estimation, the subsequent free fatty acid values showed a significant decrease (p less than 0.05, p less than 0.05 and p less than 0.001, respectively), whereas the control group showed no significant decrease (p greater than 0.05). The aim of the present article is to present the results of the three day-standard oral administration of bromazepam on free fatty acid concentration of plasma. All the samples, including the control group, were taken from a population free from any disease affecting adipose tissue metabolism.

The cerebrospinal fluid C4 complement component in different meningeal and neurological diseases.

The C4 complement component was measured in CSF from 10 patients without CNS involvement (controls) and 71 with various meningeal and neurological diseases. Serum C4 was also measured in the control group and in 46 of the 71 neurological patients. A significant increase of CSF C4 was observed in all neurological diseases with meningeal involvement independent of the causative agent. Inversely, serum C4 values were within normal limits. Increased CSF C4 with normal serum levels might indicate increased diffusion across the blood-brain barrier, decreased ability for immunocomplex production or increased local production.