Clinical Significance of the Champagne Bottle Neck Sign in the Extracranial Carotid Arteries of Patients with Moyamoya Disease.

BACKGROUND AND PURPOSE: The champagne bottle neck sign represents a rapid reduction in the extracranial ICA diameters and is a characteristic feature of Moyamoya disease. However, the clinical significance of the champagne bottle neck sign is unclear. We investigated the relationship between the champagne bottle neck sign and the clinical and hemodynamic stages of Moyamoya disease. MATERIALS AND METHODS: We analyzed 14 patients with Moyamoya disease before revascularization (5 men, 9 women; age, 43.2 ± 19.3 years). The ratio of the extracranial ICA and common carotid artery diameters was determined using carotid ultrasonography or cerebral angiography; a ratio of < 0.5 was considered champagne bottle neck sign-positive. The clinical disease stage was determined using the Suzuki angiographic grading system. CBF and cerebral vasoreactivity also were measured. RESULTS: The ICA/common carotid artery ratio (expressed as median [interquartile range]) decreased as the clinical stage advanced (stages I-II, 0.71 [0.60-0.77]; stages III-IV, 0.49 [0.45-0.57]; stages V-VI, 0.38 [0.34-0.47]; P < .001). Lower ICA/common carotid artery ratio tended to occur in symptomatic versus asymptomatic arteries (0.47 [0.40-0.53] versus 0.57 [0.40-0.66], respectively; P = .06). Although the ICA/common carotid artery ratio was not related to cerebral perfusion, it decreased as cerebral vasoreactivity decreased (P < .01). All champagne bottle neck sign-positive arteries were classified as Suzuki stage ≥III, 73% were symptomatic, and 89% exhibited reduced cerebral vasoreactivity. In contrast, all champagne bottle neck sign-negative arteries were Suzuki stage ≤III, 67% were asymptomatic, and all showed preserved cerebral vasoreactivity. CONCLUSIONS: The champagne bottle neck sign was related to advanced clinical stage, clinical symptoms, and impaired cerebral vasoreactivity. Thus, detection of the champagne bottle neck sign might be useful in determining the clinical and hemodynamic stages of Moyamoya disease.

A phase II trial of oral UFT plus cisplatin (CDDP) in patients with non-small cell lung cancer (NSCLC).

Based on the results of our previous pilot study, we conducted a multi-institutional phase II study of combination chemotherapy consisting of oral UFT (Taiho Pharmaceutical Co. Ltd, Tokyo) plus cisplatin (CDDP) in patients with advanced non-small cell lung cancer (NSCLC). UFT capsule containing 100 mg tegafur and 224 mg uracil was orally administered in two divided doses on days 1 through 21 making the total tegafur dose 400 mg/m(2)/day (maximum 600 mg/body). CDDP was administered by drip infusion at a dose of 20 mg/m(2) on a 5-day schedule from day 8 to 12. Treatment was repeated every 4 weeks as long as the criteria for initiation of therapy were still met. Between April 1995 and March 1997, 51 patients were entered into the study. The mean age of all 50 eligible patients was 64 years(range: 40-78). There were 21 patients with clinical stage IIIB disease and 29 patients with IV disease. Thirty-two patients had adenocarcinoma, 14 had epidermoid carcinoma, and four had large cell carcinoma. Of the 47 assessable patients, 18 achieved a partial response with an overall response rate of 38.3% (95% confidence interval: 24.4-52.2%). The median response duration was 113 days. The median survival time of the eligible patients was 12.8 months, and the 1-year survival rate was 54%. Among the 51 patients enrolled, grade 3 or 4 leukopenia developed in one patient (2%), neutropenia in six patients (11. 8%), thrombocytopenia in six patients (11. 8%), and anemia in three patients (5. 9%). Non-hematological grade 3 or 4 toxicities included anorexia in 10 patients (19.6%), nausea in ten (19.6%), vomiting in two (3.9%), and diarrhea in two (3. 9%). Grade 3 abnormal laboratory data included bilirubinemia in four (7. 8%), GPT elevation in one (2.0%), and hematuria in one (2.0%). In conclusion, combination of CDDP plus oral UFT is efficacious, with low toxicity, in the treatment of advanced NSCLC. In particular, the low hematological toxicity may warrant application of this regimen to the treatment of elderly patients and in trials of concurrent chemoradiotherapy in patients with locally advanced NSCLC.

Mortality after transurethral prostatectomy.

In 68 patients aged 80 to 94 who underwent transurethral prostatectomy between 1981 and 1987, the survival rate after the procedure was higher than that of the general population of the same age distribution. In nine patients aged 62 to 92 for whom transurethral prostatectomy was indicated but not performed because of concomitant medical problems (including cardiac problems in four, advanced cancer in two, dementia in two, and pulmonary disease in one), the survival rate was much lower, seven of the nine dying within 13 months. High mortality reported in men undergoing transurethral prostatectomy may be due to concomitant medical problems rather than aftereffects of the surgery.

Expression of inducible nitric oxide synthase in rats following subarachnoid hemorrhage.

The possible expression of the inducible isoform of nitric oxide synthase (iNOS) was examined in a rat model of subarachnoid hemorrhage (SAH). Subarachnoid hemorrhage was induced by the injection of autologous blood into the cisterna magna using stereotactic technique under general anesthesia. The rats were then killed at specific time intervals between 4 hours to 7 days after SAH. Reverse-transcriptional polymerase chain reaction (RT-PCR) revealed the expression of iNOS mRNA in the homogenate obtained from the tissue around the circle of Willis one day after SAH (Day 1). No iNOS mRNA was detected either in the sham-operated animals, or at any of the other time intervals after SAH. An immunohistochemical study was performed to examine the localization of iNOS-positive cells in the central nervous system. Inducible NOS immunoreactivity was thus observed in the mononuclear cells and polymorphonuclear cells infiltrating into the subarachnoid space of the basal cistern on Day 1. This immunoreactivity persisted faintly on Day 2, but had completely disappeared on Day 7. A vascular diameter study disclosed a vasoconstrictive change in the middle cerebral artery after SAH. Taken together, these results are thus considered to confirm the expression of iNOS in the infiltrated inflammatory cells after the insult of SAH, which may therefore play an introductory role in the development of the pathological series of events after SAH, including vasospasm.

Role of inducible nitric oxide synthase in the cerebral vasospasm after subarachnoid hemorrhage in rats.

The involvement of de novo nitric oxide synthase (NOS) induction in the development of cerebral vasospasm after subarachnoid hemorrhage (SAH) was examined using a rat model of SAH. SAH was induced by endovascular perforation with Nylon thread. The rats were killed at different time intervals, from one day to seven days after endovascular perforation. Inducible NOS messenger RNA (mRNA) expression was determined by reverse-transcription polymerase chain reaction (RT-PCR) and the distribution of iNOS positive cells was immunohistochemically examined. In the vascular tissue with a subarachnoid membrane, iNOS mRNA was expressed from one day to seven days after SAH. Inducible NOS positive cells were mainly recognized in the vascular tissue, but not in the brain parenchyma. The distribution of nitrotyrosine, an indicator of peroxynitrite production was also examined immunohistochemically and nitrotyrosine-positive cells were observed almost at the same sites of iNOS induction. To determine the role of iNOS in the development of cerebral vasospasm, we measured the diameter of the middle cerebral artery in animals either treated or not treated with aminoguanidine (AG), a selective inhibitor of iNOS. AG ameliorated the vasoconstrictive change after SAH. These results are thus considered to provide molecular and immunohistochemical evidence showing that iNOS expression following SAH and NO produced by iNOS can develop cerebral vasospasm after SAH.

High incidence of hyponatremia in patients with ruptured anterior communicating artery aneurysms.

We studied the incidence and timing of hyponatremia (Na < 135 mEq l-1) after subarachnoid hemorrhage (SAH) with special reference to ruptured anterior communicating artery (A-com) aneurysms. Hunt and Kosnik (HK) grading, symptomatic vasospasm in A-com aneurysm, and hydrocephalus were analyzed for connections to hyponatremia in 55 patients with ruptured A-com aneurysms, 65 with ruptured internal cerebral artery (ICA) aneurysms, and 49 with ruptured middle cerebral artery (MCA) aneurysms. Hyponatremia occurred in 28 (51%) of 55 patients with A-com aneurysms and in nine (18%) of 49 patients with MCA aneurysms. Severe hyponatremia (Na < 130 mEq l-1) occurred in 16 patients (29%) in the A-com group, four patients (6%) in the ICA group, and three patients (6%) in the MCA group. The A-com aneurysm group had a significantly higher incidence of mild hyponatremia (p < 0.01) and severe hyponatremia (p < 0.001) than other groups. Among A-com cases, hyponatremia occurred significantly more often in HK grade III and IV cases (p < 0.05), in cases with vasospasm (p < 0.001), and in cases with hydrocephalus (p < 0.01). Respective days of onset for symptomatic vasospasm and for hyponatremia were day 7.6 +/- 4.4 and day 10.6 +/- 5.8 following SAH, representing a 3-day delay for hyponatremia (p < 0.05). In most patients hyponatremia resolved within 28 days following SAH. Hyponatremia occurred more often with A-com aneurysms, possibly because of vasospasm around the A-com or hydrocephalus causing hypothalamic dysfunction. Since hypervolemic therapy can cause hyponatremia, particularly careful observation is required during such therapy in patients with A-com aneurysm.

Effect of intracarotid bradykinin infusion on cerebral blood flow in dogs.

We examined whether intracarotid infusion of bradykinin altered circulation in the normal canine brain. Twenty-four anesthetized dogs were divided into four groups receiving different doses of bradykinin (1, 2.5, 5, and 10 micrograms kg-1 min-1). Regional cerebral blood flow (rCBF) was measured continuously using laser Doppler flowmetry through a burr hole in the frontal bone. Systemic blood pressure (SBP) and heart rate (HR) were monitored simultaneously. Higher doses of bradykinin significantly but temporarily decreased rCBF and SBP immediately after the start of infusion; these parameters rapidly recovered and then were stable through the rest of the infusion. During this period, percent change in rCBF and SBP was small, and differences between groups were not significant. On the other hand, HR increased during infusion and remained high. SBP, rCBF, and HR returned to pre-infusion levels after bradykinin was stopped. The results suggest that intracarotid infusion of bradykinin for treatment of brain tumors would be safe in terms of circulation to the uninvolved brain.

[Incidence of infection after transurethral prostatectomy].

The incidence of preoperative and postoperative infections among 46 patients who underwent transurethral prostatectomy (TUR-P) was studied. Perioperative antibacterial schedule was as follows: one gram of cefotaxime (CTX) was intravenously injected just before the beginning of TUR-P, One gram of the antibiotic was intravenously infused once more on the day after TUR-P, twice on the next day, and once during each of the succeeding 2 days. Thirteen cases out of 46 (28.3%) had significant preoperative bacteriuria (greater than or equal to 1 X 10(4)/ml), but the postoperative eradication of the bacteria was observed for 10 of the 13 cases (76.9%). Among the 33 cases that did not have significant preoperative bacteriuria, only one case developed significant bacteriuria. In this case, a non-significant bacterial contamination of the urine had been observed before TUR-P.

[Fundamental study of imipenem/cilastatin sodium in obstetrics and gynecology].

Following results were obtained from drip intravenous administration of imipenem/cilastatin sodium (MK-0787/MK-0791) (500 mg/500 mg) by measuring concentration of MK-0787 in uterine arterial plasma, cubital venous plasma, oviduct, ovary and several sites in uterine tissue in cases of simple hysterectomy, and pelvic cavity fluid in cases of radical operation. Cervix uteri, portio vaginalis, myometrium showed higher concentration among various uterine tissues in any time after the end of administration. In cases of radical operation, the pelvic cavity fluid showed 6.6 approximately 7.8 micrograms/ml at 5 hours after the end of administration. In the field of obstetrics and gynecology, it was considered that MK-0787/MK-0791 has good efficacy in infections especially caused by Gram-positive aerobic bacteria.

[A pharmacokinetic study of antibiotics in patients with benign prostatic hypertrophy].

Twenty cases intravenously received 1 g of cefotetan before the transurethral prostatectomy. High serum and prostatic concentrations were obtained and half-lives were 298 minutes for serum and 250 minutes for the prostate. The mean value of their creatinine clearance was as low as 46.6 ml/min and it was found to be the reason why the serum half-life time was longer than that reported for normal volunteers.

[The duration of antibacterial treatment following transurethral prostatectomy].

Forty-three cases were studied to determine the most optimal timing to discontinue an oral antibacterial agent for preventing urinary tract infection after transurethral prostatectomy. On the 5th postoperative day intravenous antibiotic treatment was replaced by oral medication of 1.5 g talampicillin hydrochloride (TAPC, Yamacillin), which was tapered and discontinued depending on the urinary findings. Nine out of 15 cases who discontinued the medication within 2 weeks failed to keep the urine sterile. It may be advisable to continue the medication at least 3 weeks and to discontinue thereafter when pyuria has vanished. All 24 cases who followed this principle became sterile within 8 weeks. Medication continued over 8 weeks seemed to have no additional benefit. Four cases dropped out from this treatment mainly because of gastrointestinal symptoms.

[Disappearance of bacteriuria after transurethral prostatectomy with special reference to the sensitivity to the used antimicrobials].

From 333 patients who underwent transurethral prostatectomy between May 1983 and April 1987, 123 strains of bacteria were isolated before surgery. Although all of the cocci which were sensitive to the used antimicrobials disappeared after surgery, significant difference was not observed between the disappearance rates of sensitive and non-sensitive gram-negative bacilli (disappearance rates were 86.4% and 77.8%). About two-third (34/57) of postoperative bacteria were those not isolated before surgery and patients with preoperatively infected urine had more chance than patients with sterile urine to develop infection by bacteria which was not pre-operatively detected. Precise preoperative condition is not known at the time of surgery and the sensitivity of preoperatively reported bacteria is, although important, not a sufficient information. We can only guess bacteria which might become apparent after prostatectomy.

[Stone burden on extracorporeal shock wave lithotripsy].

Based on the 89 stones treated by ESWL therapy alone, the factors which influence the number of ESWL shots were analyzed. Stone volume was calculated by summing up the value "length x short axis" for each stone. The value correlated well with the number of shots needed to disintegrate the stone (p less than 0.01). The stones below the pelvis-ureteral junction needed twice shots compared with stones in the pelvis and calyces (80.3: 40.2, p less than 0.005). Stones formed by a single component of cystine or calcium oxalate were hard to be disintegrated (53.2: 31.6, compared with other complex stones). The radiological figure could not predict the fragility.

[A case of posterior fossa hypertrophic pachymeningitis with hydrocephalus].

A 52-year-old woman was admitted to our hospital because of nausea, headache, ataxic gait, and memory disturbance. CT scans and MRI showed a markedly enhanced lesion in the dura mater of the posterior fossa, edema in the right cerebellar hemisphere, occlusion of the transverse sinus, and hydrocephalus, suggesting hypertrophic pachymeningitis. Chronic otitis media and mastoiditis were also noted. Subjective complaints diminished after steroid administration. The patient underwent right suboccipital craniectomy and biopsy. The dura mater was markedly thickened, and the cerebellar surface was edematous. Histological examination revealed the thickened dura mater to be infiltrated by chronic inflammatory cells of forming lymphatic follicles and accompanied by Langhans giant cells. Inflammatory cells were not found in the cerebellar parenchyma, but were present in the subarachnoid space. Acid-fast stain, PAS and Grocott stain were negative. The cause of the hypertrophic pachymeningitis in this patient, may have been related to the chronic otitis media, but the patient's clinical course suggested that it might represent so-called "idiopathic hypertrophic pachymeningitis".

[Relationship between cardiac natriuretic peptide (ANP/BNP) and fluid intake in patients with subarachnoid hemorrhage].

Several authors described elevated natriuretic peptides, atrial natriuretic peptide(ANP) and brain natriuretic peptide (BNP), in patients with subarachnoid hemorrhage(SAH), which were account for inappropriate antidiuretic hormone(SIADH) or cerebral salt wasting syndrome(CSW). Although the secretion of natriuretic peptide depends on the total blood volume, central venous pressure, and cardiac output volume, the volume of fluid intake in patients with SAH had not been taken in consideration in previous report. We here examined the relationship between fluid intake and the natriuretic peptides in two cases without cardiac failure. ANP elevated 2 or 3 days after SAH and remained in normal range for 2 weeks. BNP elevated when the volume of fluid intake was increased, and BNP did not elevate during the periods with lower fluid intake. Several authors proposed the possibility of iatrogenic factor in natriuresis after SAH and these results supported this opinion.

[Laparoscopic nephrectomy. Animal experiment and clinical application].

Laparoscopic nephrectomy was carried out on 6 sows in order to develop the procedures of clinical laparoscopic nephrectomy and the equipment necessary for this operation. Based on the animal experiments, it was shown that (1) retroperitoneal approach was difficult due to narrow space. (2) there must be at least 5 cm distance between each trocar and 4 or 5 trocar 1 cm in diameter were basically required. (3) The procedure consisted of incision and dissection of the peritoneum around the kidney, cutting and ligation of the ureter, dissection along the medial side of the ureter to approach the renal pedicle and clipping and cutting of the renal vessels. (4) The equipment required for this surgery must be functionally equivalent to those used in the open surgery. (5) In addition, the specifically designed equipment, such as a morcellator and an instrument to ligate renal vessels are necessary. The first clinical case of laparoscopic nephrectomy was a 34 years old man with a right non-functioning hydronephrosis due to ureteropelvic junction stricture. The surgery was successfully performed with a 110 ml blood loss. It took 7 and half hours because of abundant peri-renal fatty tissue and large extra-renal pelvis. The convalescence was uneventful. Laparoscopic nephrectomy can be applied on selected cases and the development of equipment will make the surgery more popular.

[Comparisons of factors affecting voiding disorders between patients with benign prostate hyperplasia and volunteers].

PURPOSE: The prostate size and motivation to visit clinics were investigated in patients with prostate hyperplasia. OBJECTS AND METHODS: One hundred ninety-five patients who had urinary symptoms and visited our outpatient clinic between September 1994 and October 1999 and 268 age-matched volunteers in Mitaka City who underwent a medical examination of the prostate in June 1997 were compared. International Prostate Symptom Score (IPSS), Quality Of Life Score (QOL score), residual urine volume, prostate volume and urinary flow rate were measured. RESULTS: The prostate volume of the volunteers was 20-25 cm3 irrespective of the age. The prostate size of the outpatients was larger than that of the volunteers for every age group. IPSS and QOL score were significantly higher in the outpatients than in the volunteers. Diurnal urinary frequency and sense of residual urine contributed to the discrimination index of the two groups more significantly than the other scores. There was a significant correlation between prostate volume and residual urine volume. The score of weak urinary steam was inversely and significantly correlated with peak urinary flow rate. CONCLUSIONS: There was no age-related enlargement of the prostate gland. The prostate gland was significantly larger in the patients than in the volunteers even in those in their fifties. Urinary frequency and sense of residual urine are important factors for men to seek and receive medical care.

[The significance of early detection for prostate cancer in mass screening].

PURPOSE: In Mitaka city, mass screening for prostate cancer was conducted for 3 years from 1995 to 1997. Clinical stages were compared between patients found by screening and those diagnosed at our clinic during the same time. The significance of serum-free prostate specific antigen (PSA) in mass screening for prostate cancer was examined. MATERIAL AND METHODS: A prospective clinical trial was conducted on men aged 50 years or older. The primary examination consisted of taking the international prostate symptom score, quality of life score, PSA (Tandem-R) and digital rectal examination (DRE). If PSA was greater than 4.0 ng./ml and/or if DRE suggested cancer, transrectal ultrasound-guided sextant prostate biopsies were indicated. RESULTS: Of the men screened, 23.2% (320/1375) had serum PSA greater than 4.0 ng./ml. and/or suspicious findings on DRE. Biopsy was performed in 199 of 320 (62.1%). Cancer was detected in 21 (1.5%, 21/1375). Prostate cancer was found in one case among 154 males (0.65%, 1/154) who were screened twice or more. The cancer stage found by screening was significantly earlier than that diagnosed at the outpatient clinic (Wilcoxon's rank-sum test: p = 0.0047). Receiver operating characteristics analysis showed that the optimal free PSA-to-PSA ratio was 12%. Positive predictive value increased from 18% to 50% when free PSA-to-PSA ratio was combined with PSA. CONCLUSION: 1. Cancer detection rate was 1.5% in the mass screening in Mitaka City. 2. Cancer stage found by screening was significantly earlier than that diagnosed at the outpatient clinic. 3. Free PSA determination might eliminate unnecessary biopsies in men with PSA above 4.0 ng./ml with minimal loss of cancer detection.

[Effect of etoposide for pulmonary metastases from urogenital tract cancer].

Seven cases with pulmonary metastases from the urogenital tract were treated with VP-16 in either oral doses of 200 mg or intravenous doses of 100 mg for 5 days. Two of 4 cases with transitional cell cancer from the urinary bladder and a case with prostatic adenocarcinoma responded to the treatment. Another 2 cases with adenocarcinoma arising from the kidney showed no response. Leucopenia, thrombocytopenia and alopecia were outstanding side effect.

[A trial of hormonochemotherapy of prostate cancer].

Four hundred mg of UFT and 100 mg of cyclophosphamide were orally administered to patients with prostate cancer, additional to conventional hormone therapy. Four cases are presented here, all of whom showed good response to the therapy.