Pharmacokinetics of triamterene and its metabolite in man

The pharmacokinetic profiles of triamterene and hydroxytriamterene sulfuric acid ester, the major metabolite of triamterene, were studied in six normal male volunteers using a newly developed specific HPLC analytical method. Following a 100 mg oral dose of triamterene, the plasma concentration time course of the sulfate conjugate parallels that of triamterene in all subjects, but concentrations of the metabolite were more than 10 times higher than unchanged triamterene concentrations at identical sampling times. Interestingly, the renal clearance of the sulfate conjugate was less than that of triamterene. These characteristic features of triamterene disposition were fitted to a compartment model incorporating a first-pass metabolic process. Unbound fractions of triamterene and metabolite in plasma were 0.39 and 0.10 (mean of 6 subjects), respectively. The low unbound fraction of the metabolite in plasma most probably accounts for the low renal clearance of the sulfate conjugate as compared with triamterene.Supported in part by NIH Grant AM20884 and funds from Mylan Pharmaceuticals.     

Flow-through cytometry of meningiomas and cultured meningioma cells

Summary Flow cytometric techniques were used to compare the DNA content, size and viability of meningioma cells obtained directly from surgical specimens with the same cells after a period of culture. Cells isolated from the original meningiomas and cells in primary culture were similar with regard to size and DNA content, regardless of the histologic subclassification of tumor. The cell populations were essentially diploid with a small proportion of tetraploid cells. Viable cells were smaller and more uniform in size than the nonviable cells. An increase in the number of cells having an elevated DNA content was seen with cultures repeatedly transferred. The latter results suggest that any transfer of information from long-term cultured meningioma cells to the in vivo situation must be done with caution.     

The further investigation on the gastric acid secretion in the primary hyperparathyroidism.

The gastric acid output was studied in the 11 patients of hyperparathyroidism before and after parathyroidectomy. The gastric acid output before operation was almost equal to the normal control in our hospital. After the correction of serum calcium by parathyroidectomy, the gastric acid output and serum gastrin were decreased. The decreased gastric acid output was recovered as the days passed since operation and approached to the preoperative level. The acid output in hyperparathyroidism was less in the case whose activity of alkaline phosphatase was more, which suggested that the calcium deposition on gastric mucosa might damage the parietal cell as the result of long lasting hypercalcemia.     

A case of gastric cancer with multiple liver metastases effectively treated by hepatic arterial infusion of MMC, TS-1/CDDP therapy, and thermotherapy

A 62-year-old man was revealed to have type 2 gastric cancer with synchronous liver metastasis. We considered liver metastasis to be a prognostic factor, and performed two courses of combination thermochemotherapy consisting of hepatic arterial infusion of MMC and TS-1 and thermotherapy. Partial response was observed in the liver metastases,but the primary lesion showed no changes; therefore, we performed four courses of combination thermochemotherapy consisting of TS-1/CDDP therapy and thermotherapy. By the end of three courses of this therapy,the primary lesion had cicatrized,and endoscopic biopsy revealed no cancer cells. These results suggest that gastric cancer,in which liver metastasis is considered to be a prognostic factor,can be effectively treated by combination therapy with hepatic arterial infusion therapy, followed by thermochemotherapy for the primary lesion.     

A phase I study of TS-1 and weekly cisplatin in patients with advanced gastric cancer

This is a phase I study to determine the maximum tolerated dose (MTD) and toxicity of a combination of TS-1 and weekly cisplatin (CDDP) in advanced gastric cancer patients. TS-1 was administered orally twice daily after meals, at a standard dose of 80 mg/m2. One course consisted of 21 days' consecutive administration followed by 14 days' rest. Cisplatin (CDDP) was injected intravenously on days 8, 15 and 22 using the following dose levels: dose level 1 20 mg/m2, dose level 2 25 mg/m2, and dose level 3 30 mg/m2. Twelve patients were entered in this trial. One of the 6 patients at dose level 3 had neutropenia NCI-CTC grade 3, while another patient at dose level 3 suffered from DLT (liver function grade 3. The maximal tolerable dose (MTD) was not reached using dose level 3. Partial responses were seen in 5 (62.5%) of 8 patients with evaluable lesions. At level 2 (25 mg/m2), the response rate was 100%. We recommended dose level 2 for phase II trials from the standpoint of toxicity and response rate.     

Clinical and pathologic characteristics of dilated cardiomyopathy in hemodialysis patients

BACKGROUND: Some dialysis patients have impaired left ventricular (LV) function without coronary artery disease. The pathologic changes and prognoses of these patients have not been well described. METHODS: We performed LV endomyocardial biopsies on 40 hemodialysis patients with dilated cardiomyopathy (DCM; an ejection fraction <50% and a left ventricular end-diastolic volume index >90 mL/m(2) without coronary artery disease), and on 50 nondialysis patients with idiopathic DCM as the control group. Following LV biopsies, the patients were followed-up for a mean of 3.1 +/- 2.3 years. RESULTS: The pathologic characteristics of the dialysis group were severe myocyte hypertrophy (the mean myocyte diameter across the nucleus: 37.6 +/- 10.5 mum vs. 25.6 +/- 7.7 mum, P= 0.001), myocyte disarray (30%), and extensive fibrosis (the mean percent area of left ventricular fibrosis: 22.3 +/- 18.4% vs. 21.3 +/- 14.6%, P= NS). These pathologic characteristics resembled the dilated phase of hypertrophic cardiomyopathy. In the dialysis group, a high percent area of LV fibrosis was the only significant predictor of cardiac death by multivariate analysis (P= 0.02). The 3-year cumulative event-free survival rate for cardiac death in dialysis patients with severe fibrosis (more than 30%) was 42%, while that for patients without severe fibrosis was 82% (P= 0.03). CONCLUSION: The pathologic characteristics of the heart in dialysis patients with DCM are interstitial fibrosis and severe myocyte hypertrophy with occasional disarray. The extent of LV fibrosis is a strong predictor of cardiac death. Careful follow-up and treatment are necessary for dialysis patients with a high percent area of LV fibrosis.     

Transethmoidal meningoencephalocele in an elderly woman. Case report

A 69-year-old woman presented with a transethmoidal meningoencephalocele manifesting as gradually developing anosmia. Examinations revealed a mass in the nasal cavity associated with multiple angiomas in her lip and orbit. Neuroimaging showed meningoencephalocele extending via the ethmoid sinus to the nasal cavity. She had no history of craniofacial trauma and intranasal or intracranial operation, and no skull base tumor was detected. Frontal base reconstruction was performed with a two-layer vascularized flap to prevent cerebrospinal fluid leakage. The dural defect was repaired with the pericranial flap, and the bony defect of the cribriform plate was reconstructed using the reversed U-shaped split temporalis musculofascial flap. Transethmoidal meningoencephalocele is a rare congenital malformation and almost half of the cases are identified in the first year of life. We should be aware of this clinical pathology and avoid unexpected rhinorrhea in elderly patients. The most important aspect of the operation is watertight closure of the patent passage to the intracranial compartment. The reversed U-shaped split temporalis musculofascial flap is useful to reconstruct the midline frontal base defect.     

Renal-tissue damage induced by laparoscopic partial nephrectomy using microwave tissue coagulator

BACKGROUND AND PURPOSE: The microwave coagulator is a useful instrument that enables surgeons to perform partial nephrectomy without vascular clamping. The extent of postoperative thermal damage in surgically spared renal tissue has not been well examined. The present study was conducted to evaluate the tissue damage caused by microwave coagulation in laparoscopic partial nephrectomy (LPN) for small renal tumors. MATERIALS AND METHODS: Seven cases of LPN with a microwave tissue coagulator were entered in the present study. The median tumor diameter was 1.5 cm, and the median size of the resected specimen was 2.2 cm. Postoperative tissue damage was evaluated by contrast-enhanced CT 1 month after surgery. Surgically spared renal-tissue volume and functioning renal-tissue volume were estimated from the images by NIH Image 1.62 software. RESULTS: Postoperative CT revealed unenhanced renal tissue adjacent to the surgical margin. The median estimated volumes of surgically spared and functioning renal tissue were 96.1% (range 74.3%-99.8%) and 88.4% (range 68.0%-92.7%) of preoperative normal renal tissue, respectively. The percentile volume of functioning to surgically spared renal tissue ranged from 89.9% to 96.0% (median 92.8%). CONCLUSIONS: The microwave coagulator enables us to carry out partial nephrectomy without vascular clamping. Although 96% of normal renal tissue was surgically spared, 4% to 10% of this tissue was nonfunctioning as a result of microwave-induced thermal damage.