Laboratory data and treatment outcomes of head and neck tumor patients in the elderly.

OBJECTIVE: To elicit the factors influencing the choice of treatment and the prognosis of elderly patients, we studied the clinical and laboratory data of head and neck tumor patients. The patients were divided into two groups (group A: younger than 75, group B: 75 years of age or older) and the treatment outcomes as well as the features of the laboratory data were analyzed. METHODS: The clinical records of 1350 patients (888 males, 462 females) with head and neck tumors who received their initial treatment at our hospital were reviewed. The collected data including age, the site of the primary lesion, pre-treatment health states, pre-operative laboratory results were examined. According to the treatment policy, we grouped the patients according to whether or not they had received the standard therapy for the disease and then analyzed their treatment outcomes. RESULTS: Standard therapy was not performed in 62 (5.6%) of the 1114 patients in group A and in 43 (18.2%) of the 236 patients in group B. A further analysis performed in group B (elderly patients) revealed that standard therapy was performed in 193 patients, while 43 received non-standard therapy. The prognosis for the non-standard therapy cases was poor. The averages of the laboratory test findings between groups A and B were compared, but no marked differences were observed. However, differences were observed in the ratio of patients whose data were in the normal range between group A and group B. When the laboratory data were compared between the standard and non-standard groups of the elderly, serum albumin and CBC (especially hemoglobin) showed a close relationship to the treatment modality. CONCLUSION: The ratio of patients who did not receive standard therapy was high in the age group of 75 years or older. The prognosis of patients with head and neck tumors is therefore considered to depend on whether or not a patient receives the standard therapy against the disease. The pre-treatment clinical data and the laboratory findings vary markedly among elderly patients 75 years of age or older. Regarding the treatment of head and neck tumors in the elderly, the laboratory data and clinical conditions of each individual patient should be checked carefully and every possible means should be employed in order to allow such patients to receive the standard therapy whenever possible.

[Laser debulking surgery prior to radiotherapy for T1T2 carcinoma of the hypopharynx].

The local control rate for T1-T2 carcinomas of the hypopharynx is rather high whereas the overall survival rate is unsatisfactory, irrespective of treatment modalities. Radical radiotherapy has yielded a local control rate of 40-70% and an overall 5-year survival of 30-50%, while surgical treatment with or without postoperative radiotherapy has yielded a local control rate of 60-90% and an overall 5-year survival rate of 30-60%. Based on these reasons, for the patients with minor hypopharyngeal lesions, such as T1-T2 carcinomas, in the Kurume University Hospital radiotherapy has often been selected as a first choice instead of partial pharyngectomy. If the primary lesion is exophytic and has a large volume, laser debulking surgery has been employed prior to radiotherapy to improve the local control rate. The purpose of the present study is to describe the details of laser debulking surgery prior to radiotherapy (LDSR) for the treatment of T1-T2 carcinomas of the hypopharynx. In addition, the preliminary results for this treatment procedure will also be compared with the results of partial pharyngectomies preserving the larynx (PPPL) that were performed in the Kurume University Hospital. In this study 20 patients (T1: 4, T2: 16) who had undergone PPPL and 16 patients (T1: 4, T2: 12) who had undergone LDSR were included. For patients undergoing PPPL, the 5-year local control rate, 5-year larynx conservation rate and disease specific 5-year survival rate were 83.6%, 70.4%, and 75.0%, respectively, whereas for patients undergoing LDSR these were 87.1%, 93.8%, 87.5% respectively. Although the treatment outcomes by LDSR did not show a significant drastic improvement compared with those by PPPL, the quality of life of the patients undergoing LDSR was not aggravated. LDSR may thus be preferable to PPPL for selected cases of T1-T2 carcinomas of the hypopharynx.

[Nasopharyngeal stenosis after uvulopalatopharyngoplasty].

We report a case of nasopharyngeal stenosis after uvulopalatopharyngoplasty (UPPP). A 42-year-old man underwent UPPP because of severe snoring. Two months later, a severe nasopharyngeal stenosis was observed upon examination. The stenosis was caused by the adhesion of the soft palate to the posterior pharyngeal scar. X-ray examination of the patient's pharynx revealed that the postoperative nasopharyngeal stenosis may have also been caused by the depth of the pharynx, in addition to the morphological anomaly. To avoid velopharyngeal insufficiency and nasopharyngeal stenosis, careful examination of the pharynx prior to surgery is highly recommended.

Sublingual nifedipine in elderly patients: even a low dose induces myocardial ischaemia.

1. Low doses of sublingual nifedipine are still used for the treatment of hypertensive crises, although recent studies have raised concerns that sublingual nifedipine may cause serious dose-dependent adverse effects. The present study was performed to test the safety of low-dose sublingual nifedipine administered to elderly hypertensive patients. 2. Systemic blood pressure measurements and electrocardiographic (ECG) examinations were performed before and 45-60 min after a 5 mg dose of sublingual nifedipine in 93 consecutive hypertensive patients, 65 years of age or older, who were without coronary artery disease. In 33 patients, the effects of nifedipine on myocardial lactate metabolism were studied during cardiac catheterization. 3. In all patients, following nifedipine administration, blood pressure (BP) decreased significantly, while heart rate (HR) increased, and symptoms associated with elevated BP disappeared. However, changes consistent with myocardial ischaemia appeared on the ECG in six of 55 patients with left ventricular hypertrophy (LVH) and in one of 38 patients without LVH, although only two of these seven patients experienced angina-like precordial tightness. Sublingual nifedipine decreased myocardial lactate extraction from 52 +/- 13 to 38 +/- 19% in 20 patients with LVH (P = 0.02), but myocardial lactate extraction remained stable in 13 patients without LVH (49 +/- 7 to 50 +/- 5%; NS). The change in lactate extraction was significantly correlated with the percentage change in diastolic arterial pressure (r = 0.77, P < 0.001). 4. These results suggest that sublingual nifedipine, even at the low dose of 5 mg, may cause myocardial ischaemia in some elderly patients with LVH that is associated with a marked reduction in coronary perfusion pressure.

Clinical effects of exogenous/endogenous TNF therapy on metastatic lesions of 34 colorectal cancer patients.

BACKGROUND: We performed endogenous/exogenous TNF (EET) therapy using, as a primer, recombinant TNF-SAM2 (rTNF-S) as a premier; it has a broader anti-cancer spectrum and is less toxic than conventional TNF, and OK-432 as a trigger in patients with metastasis of colorectal cancer to the lung and/or liver. METHODS: The subjects consisted of 34 patients of whom 8 had lung metastasis, 17 liver metastasis, and 9 lung and liver metastasis. EET therapy was performed without chemotherapy in 11 patients and with anti-cancer drugs such as mitomycin-C (MMC) and 5-FU in the other 23. RESULTS: No patients showed a complete response. Partial response was observed in 10 patients (29.4%), minor response in 8 (23.5%), no change in 14 (41.2%), and progressive disease in 2 (5.8%). The response rate was 29.4%. A greater effect was observed in patients treated with EET in combination with anti-cancer drugs than those treated with EET alone. No serious side effects were observed, although all patients developed a fever above 38 degrees C, chill, and shiver. CONCLUSIONS: EET therapy with rTNF-S combined with anti cancer drugs chemotherapy may be effective, and further studies are needed to select the most suitable anticancer drugs for combination with, and to determine the effective frequency of treatment.

Usefulness of low doses of atropine to quantify the vagal stimulus-response relation in patients with congestive heart failure.

The response of low doses of atropine is reported to be attenuated in patients with congestive heart failure (CHF). Judging from the main site of action of low doses of atropine, we may be able to assess the functional state of the vagal center in the central nervous system. This study examines the clinical significance of heart rate (HR) response to a low dose of atropine in patients with CHF. Low and high doses of atropine were administered intravenously in 72 patients with CHF. HR after a low (parasympathomimetic) dose injection was assessed by the ratio Rm (minimal HR/basal HR), and after a high (parasympatholytic) dose by the ratio R1 (augmented HR/basal HR). Rm and R1 were related to indexes of CHF. Rm increased with progression of CHF (0.92 +/- 0.03 in New York Heart Association functional class I, 0.98 +/- 0.05 in class II, and 1.00 +/- 0.04 in class III). It also correlated with ejection fraction (r = -0.48, p <0.01) and more importantly, with peak oxygen uptake (r = -0.59, p <0.01). R1 exhibited weak correlation with basal HR (r = -0.33, p <0.05) and ejection fraction (r = 0.31, p <0.05), but had no correlation with other indexes. The vagal center may be already blunted in New York Heart Association class II with respect to increased Rm, which may be related to depressed exercise capacity. A low dose of atropine injection offers a simple and safe method for providing important information on the functional state of the vagal center in the central nervous system in patients with CHF.

[Study of preoperative combination therapy with UFT + CDDP in patients with gastric and colorectal cancer--concomitant effects based on the thymidylate synthase inhibitory rat].

UNLABELLED: The subjects were 39 patients with gastric cancer and 44 patients with colorectal cancer divided into a group administered 400 mg/day of UFT orally for 2 weeks preoperatively (UFT group) and a group administered 400 mg/day of UFT as well as 40 mg/m2 (i.v.) of cisplatin (CDDP) by drip infusion once concomitantly (UFT + CDDP group). The thymidylate synthase (TS) inhibitory rate was measured in resected specimens and lymph nodes, and the concomitant effects of UFT and CDDP were investigated. RESULTS: 1) The TS inhibitory rate in tumor tissue showed no significant difference between the two groups. 2) The TS inhibitory rate of metastasized lymph nodes was higher in UFT + CDDP group than in the UFT group in gastric cancer patients (p < 0.05). The TS inhibitory rate by lymph node metastasis in patients with gastric cancer or colorectal cancer was significantly higher in metastasized lymph nodes than in non-metastasized lymph nodes in the UFT + CDDP group (p < 0.05 for gastric cancer, p < 0.05 for colorectal cancer). These results indicated that concomitant use of UFT and CDDP appeared to be more effective against metastasized lymph nodes, especially in cases of gastric cancer, than against the primary tumor focus.

Intravascular ultrasonic evidence for importance of plaque distribution (eccentric vs circumferential) in determining distensibility of the left anterior descending artery.

Although previous studies have shown that coronary atherosclerosis is accompanied by impaired vessel wall compliance, few data exist regarding the regional vessel distensibility that may be important in order to gain an insight into the mechanism of atherosclerotic plaque rupture. Therefore, we analyzed 45 coronary sites of the proximal left anterior descending artery from 40 patients. Using intravascular ultrasound, luminal area in diastole (A) and in systole was measured at the diseased sites. With the ratio of luminal area changes (dA) to coronary pressure changes (dP) during a cardiac cycle, the total distensibility index was obtained by the formula: [(dA/A)/dP] x 10(3). At the sites with noncircumferential disease perimeters in diastole (L) and in systole were measured at the normal and narrowed portions. Using the changes in perimeters (dL) during a cardiac cycle, the regional distensibility index was obtained by the formula: [(dL/L)/dP] x 10(3). In 22 sites with circumferential disease, the total distensibility index was 1.03 +/- 0.61/mm Hg (mean +/- SD), and significantly lower than that from 23 sites with noncircumferential disease that showed 1.45 +/- 0.89/mm Hg (p <0.05). In noncircumferential disease, the regional distensibility index at narrowed portions was significantly lower, 0.33 +/- 0.47/mm Hg, than that at normal portion, 1.11 +/- 0.75/mm Hg (p <0.01), suggesting the heterogenous distribution of regional wall distensibility in noncircumferential lesions. These results indicate that the heterogeneous regional wall distensibility exists at the sites with noncircumferential disease where the total vessel distensibility is preserved by the presence of the compliant normal portion.

Colonic cancer in a patient with primary sclerosing cholangitis and long-standing ulcerative colitis.

A 27-year-old woman with a 9-year history of ulcerative colitis involving the entire colon was admitted to our hospital in August 1992 because of bloody stools and left lower abdominal pain. She had been treated with sulfasalazine since 1983 and the colitis had been clinically quiescent or mild for 7 years. She had also been diagnosed as having primary sclerosing cholangitis (PSC) 4 years prior to this admission, based on the clinical, laboratory, and cholangiographic findings. A barium enema and colonoscopy showed an irregular mass obstructing the bowel lumen in the distal portion of the descending colon. Biopsy specimens taken from the mass revealed moderately differentiated adenocarcinoma, and a subtotal colectomy was performed. Histologic examination of the mass lesion showed moderately differentiated adenocarcinoma invading the pericolic adipose tissue. She is currently alive 3 years after surgery. PSC has recently been reported as a risk factor for colonic neoplasia in patients with long-standing ulcerative colitis. In Japan, however, colorectal cancer associated with PSC and ulcerative colitis has rarely been reported. The present case suggests that the risk of colonic cancer is higher in patients with ulcerative colitis and PSC than in patients with ulcerative colitis alone.

Intravascular ultrasound evidence for importance of plaque distribution in the determination of regional vessel wall compliance.

Regional vessel wall distensibility was determined by measuring luminal area and pressure, using intravascular ultrasound (Sonicath; Boston-Scientific, Watertown, MA, USA; 3.5 Fr, 30 MHz) in 45 left coronary sites from 40 patients. Luminal area in diastole (A) and in systole was measured at the diseased sites. With the ratio of luminal area changes (dA) to coronary pressure changes (dP) during a cardiac cycle, the total distensibility index was calculated by the formula: [(dA/A)/dP] x 10(3). At sites with non-circumferential disease, perimeters in diastole (L) and in systole were measured at the normal and diseased portions, and the changes in perimeters (dL) during a cardiac cycle were calculated. The regional distensibility index was obtained by the formula: [(dL/L)/dP] x 10(3). In 22 sites with circumferential disease, the total distensibility index was 1.03 +/- 0.61/mmHg, significantly lower than that for 23 sites with non-circumferential disease (1.45 +/- 0.89/mmHg; P < 0.05). In non-circumferential disease, the regional distensibility index at the diseased portion was significantly lower (0.33 +/- 0.47/mmHg) than that at the normal portion (1.11 +/- 0.75/mmHg; P < 0.01). Coronary sites with residual non-circumferential disease after angioplasty also exhibited heterogeneity of regional distensibility (0.73 +/- 0.76 at disease sites versus 1.58 +/- 0.95/mmHg at normal sites, n = 10, P < 0.05). These results indicate that heterogeneous regional wall distensibility exists at sites with non-circumferential disease where the total vessel distensibility is preserved by the presence of compliant normal portion. This heterogeneity of regional wall distensibility may represent a biomechanical factor that explains the mechanism of plaque rupture that occurs mainly at the shoulder of the non-circumferential disease.

Effects of heart rate on coronary circulation and external mechanical efficiency in elderly hypertensive patients with left ventricular hypertrophy.

BACKGROUND AND HYPOTHESIS: Mechanisms of heart failure in elderly hypertensive patients with hypertrophy have not been studied sufficiently. We hypothesized that impaired increment of coronary blood flow in response to increases in heart rate could be responsible for the occurrence or aggravation of heart failure. METHODS: To test this hypothesis, we measured coronary hemodynamics and lactate balance during basal conditions and atrial pacing in 21 elderly patients aged > or = 65 years (mean 74 +/- 6 years) without coronary arterial disease: 7 normotensive control patients (Group 1), 7 hypertensive hypertrophic patients without a history of congestive heart failure (Group 2), and 7 patients with such history (Group 3). Coronary sinus blood flow (CSBF) was measured in coronary sinus using a thermodilution catheter. RESULTS: During basal conditions, heart rate did not differ among the three groups (67 +/- 3 in Group 1, 65 +/- 11 in Group 2, and 63 +/- 6 beats/ in Group 3). CSBF was significantly higher in the two hypertrophic groups than in the control group, but CSBF normalized by left ventricular mass was significantly lower in both hypertrophic groups. External mechanical efficiency (EME) obtained as left ventricular work divided by myocardial oxygen consumption did not differ among groups during basal conditions (36 +/- 9% in Group 1, 35 +/- 8% in Group 2, and 29 +/- 9% in Group 3, NS). During atrial pacing to increase heart rate by 25 +/- 5% (lower) and 54 +/- 6% (higher), the increases in CSBF were markedly limited in both hypertrophic groups, and the response in Group 3 was more depressed than that in Group 2. EME did not change in the control group or in Group 2, but did decrease to 21 +/- 5% in Group 3 during the higher pacing rate (p < 0.01 vs. basal conditions). In this group, the relationship between EME and heart rate showed a significant negative correlation (r = -0.56, p = 0.02). Lactate balance in coronary sinus blood showed a tendency to production in Group 3 during the higher pacing rate, suggesting myocardial ischemia. CONCLUSION: These findings suggest that in hypertensive hypertrophic patients with a history of heart failure, the coronary circulation system is vulnerable to increasing heart rate. In medical treatment of elderly hypertensive patients, control of heart rate in addition to blood pressure control should be considered to minimize the occurrence or aggravation of heart failure.

Intravascular ultrasound evidence of angiographically undetected left main coronary artery disease and associated trauma during interventional procedures.

To determine the clinical significance of angiographically undetected left main coronary artery (LMCA) disease, we analyzed data from 47 patients, with a mean age of 58 years, who were examined with intravascular ultrasound (3.5 Fr, 30 MHz). For assessment of atherosclerosis, the lesion area was calculated from the ultrasound images of the formula, [(total vessel area--lumen area)/total vessel areas] x 100(%). In 37 LMCA segments of patients with significant distal coronary stenosis (> 50%), the percent intima-media area (the index) was 39 +/- 11% (mean +/- SD), significantly greater than that of 10 patients without distal disease (27 +/- 4%, P < 0.01). Among those with significant coronary stenosis, the index was markedly greater in patients with multi-vessel coronary stenosis (46 +/- 12%, n = 19) than in patients with single-vessel disease (33 +/- 9%, n = 18; P < 0.01). At three LMCA sites associated with multi-vessel disease, ultrasound analysis demonstrated disruption of the intima at the site where the guiding catheter for balloon angioplasty had been positioned. These results indicate that LMCA disease is more prominent in patients with multi-vessel distal coronary disease than in those with single vessel disease, even in the absence of angiographic stenosis. We suggest that LMCA trauma can occur where the guiding catheter for angioplasty is positioned, particularly in patients with multi-vessel distal disease.

[UFT/CDDP preoperative chemotherapy for progressive gastric cancer--histological antitumor effects and thymidylate synthase inhibition rate].

Pre-operative chemotherapy with concomitant use of UFT and CDDP (UFT: oral administration of 400 mg/day for 2 weeks till one day before operation, CDDP, one intravenous drip of 40 mg/m2 one week before operation) was used for 24 untreated cases of advanced stomach cancer diagnosed as resectable pre-operatively, and the histological antitumor effect analyzed in dissected preparation and the thymidylate synthase inhibition rate (TSIR: %) in tumor tissue were examined. The average administration dose of CDDP was 61.1 mg/body, and the average total administration dose of UFT was 5.0 g/body. The histological antitumor effect was grade 0 in 8 cases (33.3%), grade 1a in 10 cases (41.7%), grade 1b in 5 cases (20.8%), and grade 2 in 1 case (4.2%). TSIR in tumor tissue was under 10% in 2 cases (9.1%); over 10% and under 20% in 4 cases (18.2 %); over 20% and under 30% in 6 cases (27.3%); over 30% and under 40% in 5 cases (22.7%); over 40% and under 50% in 3 cases (13.6%); over 50 % in 2 cases (9.1%), and not measurable in 2 cases, with the average of 29.0%. The correlation was observed between histological anti-tumor effect and TSIR in tumor tissue (p < 0.05). These results suggest the possibility that the anti-tumor effect can be estimated at the in vivo level from measurement of TSIR in tumor tissue.

Assessment of coronary artery distensibility by intravascular ultrasound. Application of simultaneous measurements of luminal area and pressure.

BACKGROUND: Atherosclerotic change in the coronary artery is associated with an impaired vessel wall distensibility. However, there are few data regarding the relation between vessel wall morphology and distensibility. Therefore, with intravascular ultrasound, we assessed coronary artery distensibility in angiographically normal coronary segments of humans. METHODS AND RESULTS: Data were analyzed at 35 angiographically normal coronary sites where circumferential or noncircumferential lesions were demonstrated by ultrasound in 22 patients (mean age, 55 years). After intracoronary injection of 500 micrograms nitroglycerin (NTG), coronary luminal area was measured with intravascular ultrasound (30 MHz, 3.5F to 4.3F, 1800 rpm). Intracoronary pressure was simultaneously measured with a 2F micromanometer-tipped catheter located at the left main coronary artery. The coronary distensibility index was calculated as 10-fold the ratio of luminal area change to intracoronary pressure change during a cardiac cycle. Another pressure-independent vascular stiffness index, beta, was derived by the following formula: beta = [ln(SBP/DBP)]/(dD/diastolic mean diameter), where SBP is systolic intracoronary pressure, DBP is diastolic intracoronary pressure, and dD is the difference between systolic and diastolic diameters. At the sites where luminal areas were measured, thickness of intima-media complex, defined as the distance between the intimal leading edge and the adventitial leading edge, was determined as an index of the severity of atherosclerosis. In seven segments, distensibility index was determined before and after NTG injection to examine the effect of NTG on coronary distensibility. In all examined sites, including circumferential and noncircumferential lesions, the luminal area was 12.6 +/- 5.0 mm2 during systole and 11.6 +/- 4.6 mm2 during diastole, and the calculated coronary distensibility index ranged from 0 to 0.83 mm2/mm Hg. The thickness of the intima-media complex ranged from 0.12 to 1.30 mm, suggesting the presence of various grades of atherosclerosis even in the absence of angiographic lesions. There was a poor inverse correlation between thickness of the intima-media complex and distensibility index (r = .19, y = -0.17x + 0.41, P = .29). However, when noncircumferential lesions were excluded for evaluation, there was a significant inverse correlation between them (r = .58, y = -0.50x + 0.72, P < .01). Under these conditions, the thickness of the intima-media complex also correlated with the value of beta (X10(-1), which ranged from 0.28 to 3.99 (r = .70). After NTG injection, coronary distensibility increased by an average of 71% in the segments with a thin intima-media complex, whereas it did not substantially change in those with a relatively thick intima-media complex. CONCLUSIONS: These results suggest that coronary distensibility is impaired in the coronary sites accompanying occult atherosclerosis, none of which can be detected by the conventional angiography. NTG can augment coronary distensibility in the segments without a markedly thickened intima-media complex. We suggest that thickness of the intima-media complex can contribute to determining the coronary distensibility in clinical settings.

[A study of preoperative administration of 5'-DFUR in patients with colo-rectal cancer].

For the purpose to assess tumor-selectivity of doxifluridine (5'-DFUR), an anticancer drug of fluorinated pyrimidine class, the authors conducted a clinical-pharmacological study with the drug. The subjects in the present study, 26 patients with colorectal cancer received surgeries, were preoperatively administered 5'-DFUR orally at either doses of 800 or 1,200 mg/day for 3 days followed by oral administration of the drug at a dose of 400 mg 4-6 hrs before operation. The tissues were collected from specimens removed at operations and we measured both the activities of pyrimidine nucleoside phosphorylase (PyNPase), an activating enzyme for 5'-DFUR, and 5-FU concentrations in the tissue samples. The PyNPase activities showed higher levels in tumor tissues and regional lymph nodes than in normal tissues adjacent to the tumors. The 5-FU concentrations were: 102.7 ng/g in tumor tissues, 12.5 ng/g in normal tissues adjacent to the tumors, 97.6 ng/g in metastatic lymph nodes, and 7.3 ng/g in normal lymph nodes. In other words, the 5-FU concentrations were significantly (p < 0.01) higher in either of tumor tissues and metastatic lymph nodes than in the rests. The 5-FU concentrations in the sera were also extremely low. The results above clearly indicate that 5'-DFUR has a high selectivity for tumors.

[The characteristic flow of the superior vena cava in cardiac tamponade: a case report].

A case of cardiac tamponade showing the characteristic flow pattern in the superior vena cava is reported. An 80-year-old man was admitted to our hospital complaining of anorexia and general fatigue. We observed a paradoxical pulse of 25 mmHg, dilatation of the jugular vein, and marked cardiomegaly on chest radiography. A two-dimensional echocardiogram demonstrated a massive pericardial effusion and collapse of the right atrial and right ventricular walls. On the basis of his echocardiograms and clinical signs, we diagnosed his condition as cardiac tamponade. Pulsed Doppler echocardiograms showed two-peaked flow in the superior vena cava in systole. To assess the diagnostic significance of this characteristic flow pattern, the superior vena cava flow was recorded simultaneously with the intrapericardial pressure and the right atrial pressure. The intrapericardial pressure was higher than the right atrial pressure in early systole. After pericardial drainage, these pressures became reversed and the two-peaked flow disappeared. The two-peaked flow is attributed to collapse of the right atrial wall caused by the higher intrapericardial pressure than the right atrial pressure. The superior vena cava flow represents the right heart filling dynamics in cardiac tamponade.

Localization of an endogenous ADP-ribose acceptor, p33, in polymorphonuclear cell granules in chicken liver interlobular connective tissue.

We investigated immunohistochemically the localization of p33, an endogenous substrate protein for an arginine-specific ADP-ribosyltransferase in chicken liver. Polymorphonuclear-pseudo-eosinophilic granulocytes (heterophils) in interlobular connective tissues of the liver were exclusively and strongly stained with the antibody against p33. Strong reactivity was associated with granules in cytoplasm of the heterophils. When the chicken liver nuclear fraction was washed, the transferase activity was released into the 600 x g supernatant fraction while a nuclear enzyme poly(ADP-ribose) synthetase was retained in the pellet fraction. These results indicate that p33 and probably also ADP-ribosyltransferase, found in the liver nuclear fraction [Tanigawa et al. (1984) J. Biol. Chem. 259, 2022-2029, Mishima et al. (1988) Eur. J. Biochem. 179, 267-273], originate from interlobular heterophils of the chicken liver.

[Study of tissue drug concentration of fluorinated pyrimidine anticancer drugs--comparison of 5'DFUR and UFT].

In order to verify the tumor-selective toxicity of fluorinated pyrimidine anticancer drugs, we conducted an investigation of the clinical pharmacology of two of these drugs, 5'DFUR and UFT. 5'DFUR was administered to 8 patients and UFT to 8 other patients in respective dosages of 800-1,000 mg/day and 400-600 mg/day an average of 6 days before the patients underwent surgery for cancer of the large bowel, and the concentrations of these drugs in tissue were then measured. No 5'DFUR whatsoever was detected in serum, the lymphnodes, normal large bowel tissue, or cancerous large bowel tissue after administration of this drug. Moreover, levels of the active substance, 5-FU, after administration of 5'-DFUR were low in serum, the lymphnodes, normal large bowel tissue (0.033 +/- 0.024 microgram/g), and cancerous large bowel tissue (0.034 +/- 0.020 microgram/g), and no difference was observed between normal and cancerous large intestine tissue. On the other hand, tegafur was detected in all of the tissues following the administration UFT, and the concentration of 5-FU was significantly high, particularly in cancerous large bowel tissue (0.108 +/- 0.057 microgram/g) compared to normal sites (0.044 +/- 0.048 microgram/g) (p less than 0.05). The above results indicate that UFT is a promising drug for use in chemotherapy for cancer of the large bowel.

Potassium-related membrane currents in the bullfrog atrial muscle differentiated in the presence of barium.

Effects of Ba on the potassium-related currents were studied on the bullfrog atrial muscle under voltage clamp with double sucrose-gap techniques. Ba, in a dose over 0.1 mM, abolished the anomalous rectification of the membrane by inhibiting the background current which reversed sign nearly at the K equilibrium potential (IK1). Ba, thus reducing the K-depletion current for hyperpolarizations, revealed the presence of funny inward current (If or Ih) in the proper atrial muscle. An increase in [K]0 increased If, and the current showed a threshold at about -80 mV and was saturated at above -160 mV in 5 mM [K]0. The delayed outward current (Ix) for depolarizations was also depressed by Ba. The depression occurred in a voltage- and time-dependent manner, manifesting an unblocking for stronger depolarizations. An analysis of the current tail, however, disclosed that low concentrations of Ba (up to 0.1 mM) inhibited the accumulation component (Ia) of the current without diminishing the next slow component of Ix (Ixs). The remaining Ixs showed a reversal potential of -82 mV, suggesting that this current is largely carried by potassium ions. These data clearly show that in the presence of Ba, If and Ixs can be differentiated from other membrane currents in the frog atrial muscle.