Prospective randomized trial of chemoembolization versus intra-arterial injection of 131I-labeled-iodized oil in the treatment of hepatocellular carcinoma

Intra-arterial injection of radioactive Lipiodol has shown promising results in patients with hepatocellular carcinoma (HCC) and portal obstruction. The aim of this prospective, randomized trial was to compare the efficacy and tolerance of 131I-labeled Lipiodol and chemoembolization for the treatment of patients with HCC. From September 1990 to September 1993, 142 patients (135 men, 7 women; age: 65 +/- 6.6 years) were randomly assigned to treatment groups and given either intra-arterial injections of 131I-labeled Lipiodol (60 mCi; 2.2 GBq) (n = 73) or chemoembolization (70 mg cisplatin) (n = 69). Subsequent injections were given at 2, 5, 8, 12, and 18 months. Tumor response was assessed on the basis of tumor size and serum alpha-fetoprotein levels. Patient tolerance was assessed clinically and angiographically. Survival rate was the main end-point. A total of 129 patients (65 in the 131I-labeled Lipiodol group and 64 in the chemoembolization group) were available for analysis; 13 were excluded, mainly because of portal vein thrombosis. The two groups were comparable. Actuarial survival curves were not significantly different between the two groups. Overall survival rates at 6 months, 1, 2, 3, and 4 years were 69%, 38%, 22%, 14%, and 10%, and 66%, 42%, 22%, 3%, and 0% in the 131I-labeled Lipiodol and chemoembolization groups, respectively. Reduction in tumor size was similar for the two groups, with complete response in 1 and 0 patients and partial response in 15 and 16 patients in the 131I-labeled Lipiodol and chemoembolization groups, respectively. Tolerance was significantly better in the 131I-labeled Lipiodol group both clinically (3 severe side effects vs. 29 in the chemoembolization group; P < .001) and angiographically (1 arterial thrombosis vs. 10 in the chemoembolization group; P < .01). In terms of patient survival and tumor response, radioactive 131I-labeled Lipiodol and chemoembolization were equally effective in the treatment of HCC, but tolerance to 131I-labeled Lipiodol was significantly better.     

Noradrenaline-assisted selective chemoembolization of hepatocellular carcinoma

Despite the postulated tumour affinity of Lipiodol is liver dysfunction after chemoembolization of hepatic malignancies common. Vasoconstricting action of noradrenaline to protect non malignant tissue was studied. 70 patients with unresectable HCCs (UICC IV: 61%) were treated via percutaneous catheter. After noradrenaline (0.1-0.8 mg) induced and documented vessel constriction a suspension of Lipiodol (5-8 ml) and Mitomycin C (10-20 mg) was injected. In addition minced dehydrated dura suspended in Lipiodol occluded the major tumour feeding vessels. 120 (73%) of a total of 164 chemoembolizations were performed after intrahepatic noradrenaline (0.1-0.8 mg) bolus injection. Arterial perfusion of non malignant liver parenchyma was significantly reduced in 95%. 24 hours later selective tumor retention of lipiodol was noticed in 67%. Side effects were fever (79%), thoracoabdominal pain (67%), nausea and emesis (43%) and tachycardia (15%). There were two treatment related deaths: one each from liver failure and cardiac arrest. By WHO response criteria there were 17 (23%) partial remissions (PR), 34 (49%) stable diseases (SD) and 20 (28%) patients had progression (PD). The median survival time from initiation of treatment was 312 days. Bilobal and multiple tumors reduced survival time (90 days). These findings suggest that noradrenaline guided chemoembolization is feasible in Europe and even in patients with pylethrombosis well tolerated.     

Interventional radiology in the treatment of primary and metastatic liver cancer

The data available in the literature and the authors' own treatment outcomes in 600 patients with primary and metastatic carcinoma of the liver (in 1983-1996) were analyzed. Systemic or intravascular therapy as regional drug infusion, embolization, chemoembolization of the hepatic artery (CEHA) and portal vein (CEPV) was performed in unresectable cases. Whether pre- and postoperative chemoembolization was evaluated in resectable tumors. It is concluded that X-ray endovascular interventions play an important role in the treatment of malignant hepatic tumors. Transcatheter CEHA alone and in combination with CEPV is the most effective current treatments of unresectable carcinoma of the liver. In some patients, preoperative CEHA makes it possible to remove the tumor previously considered to be unresectable. Resection in combination with adjuvant CEHA and CEPV reduces the incidence of postoperative recurrences. The combined approach to treating malignant hepatic neoplasms expands the possibilities of delivering care to patients and improving late outcomes.     

Important microsatellite markers in the investigation of replication errors (RER) in colorectal carcinomas

PURPOSE: Our purpose was to assess the value of monitoring serum P and inhibin A to determine how values might improve the clinical monitoring of natural cycle in vitro fertilization (IVF)-embryo transfer (ET) patients. METHODS: All patients (n = 26) who underwent natural-cycle IVF-ET (n = 35) were analyzed. Groups were evaluated according to patients who had a spontaneous luteinizing hormone (LH) surge (group I) and women receiving human chorionic gonadotropin (hCG) who underwent subsequent oocyte aspiration (group II). Group II was further evaluated according to women who did (n = 10) and did not (n = 7) have an ET. All cycles were evaluated with serial transvaginal ultrasonography and serum estradiol, progesterone, and inhibin A. When follicle maturity was achieved, hCG, 10,000 IU, was administered intramuscularly if a LH surge was not detected. Transvaginal ultrasound-guided aspiration was performed 34-36 hr after hCG administration followed by a 48-hr transcervical ET. RESULTS: No differences were seen in cycles the day prior to (d-1) and the day of a spontaneous LH surge, (n = 18) or hCG (d-0)(n = 17) in group I or group II with respect to lead follicular diameter (d-1, 15.3 +/- 0.6 vs. 14.2 +/- 0.9 mm; d-0, 17.4 +/- 0.8 vs. 17.8 +/- 0.6 mm) and serum estradiol (d-1, 148 +/- 15 vs. 150 +/- 15 pg/ml; d-0, 218 +/- 15 vs. 199 +/- 16 pg/ml), respectively. However, serum progesterone was significantly elevated in group I compared with group II on d-1 (0.82 +/- 0.6 vs. 0.48 +/- 0.04 ng/ml; P < 0.05) and d-0 (1.1 +/- 0.12 vs. 0.63 +/- 0.08 ng/ml; P < 0.05). Inhibin A was significantly greater on d-1 in group I (24 +/- 2.5 vs. 15 +/- 2.2 pg/ml; P < 0.05). In group II, cycles that resulted in an ET (n = 10) compared with group II cycles that did not (n = 7) revealed a significant difference in serum progesterone (0.51 +/- 0.05 vs. 0.7 +/- 0.07 ng/ml; P < 0.05) and inhibin A (15 +/- 2.5 vs. 37.3 +/- 5 pg/ml; P < 0.05) the day of hCG. CONCLUSIONS: The possible application of serum progesterone and inhibin A in managing natural-cycle IVF-ET is suggested. These assays may predict women who should be set up for egg retrieval, while cancelling others in spite of the absence of an LH surge.     

Cerebral hemodynamic response to CO2 after severe head injury: clinical and prognostic implications

PURPOSE: To evaluate the efficacy and safety of transcatheter oily chemoembolization therapy (TOCE) via the inferior phrenic artery (IPA) in hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Fifty patients with HCC underwent a total of 82 procedures of TOCE of the IPA, as well as of the hepatic artery. In 16 patients, additional extrahepatic collaterals were depicted and were also embolized in 10 patients. TOCE was performed with an emulsion of iodized oil and doxorubicin hydrochloride, and gelatin sponge particle embolization was added in 32 patients. RESULTS: Initial response showed complete or partial remission of the tumor in 31 patients. The cumulative survival rates after combined TOCE of the hepatic artery, IPA, and other extrahepatic arteries were 89% (6 months), 78% (1 year), 46% (2 year), and 30% (3 year), when calculated from the time of IPA chemoembolization. Liver abscess and empyema developed in one case of combined IPA and multiple intercostal artery chemoembolization. There were no serious complications after IPA chemoembolization alone. CONCLUSION: TOCE of the IPA has a potential therapeutic role as a safe adjunct to TOCE of the hepatic artery in the management of HCC supplied by the IPA.     

Sequential step-up and step-down dose regimen: an alternative method for ovulation induction with follicle-stimulating hormone in polycystic ovarian syndrome

This study was designed to compare both the effectiveness and safety of two low-dose gonadotrophin regimens (step-up versus sequential step-up and step-down) for ovulation induction in polycystic ovarian syndrome (PCOS) patients. In all, 56 infertile clomiphene citrate-resistant PCOS patients were included in this prospective randomized study. A total of 38 cycles were conducted with a classic step-up protocol, whereas for 35 cycles the follicle-stimulating hormone (FSH) threshold dose was reduced by half when the leading follicle reached 14 mm in diameter (sequential protocol). Serum oestradiol, progesterone and luteinizing hormone concentrations and follicular growth rate were evaluated during the cycle. At the time of human chorionic gonadotrophin administration, cycles treated with sequential protocol exhibited significantly lower oestradiol concentrations [434 +/- 45 versus 593 +/- 67 pg/ml (mean +/- SEM)] and the number of medium-sized (14-15 mm) follicles was significantly reduced (0.3 +/- 0.1 versus 0.8 +/- 0.2) compared with cycles treated with the classic step-up protocol. Moreover, in these cycles serum luteal oestradiol concentrations were decreased significantly (350 +/- 77 versus 657 +/- 104 pg/ ml) compared with the classic step-up protocol. A sequential step-up and step-down protocol seems to be a safe and effective regimen for ovulation induction in PCOS patients. Decreasing the FSH dose following step-up follicular selection may be an alternative method to avoid multifollicular development.     

Value of pre-operative embolization in surgery for nasopharyngeal angiofibroma

The value of embolization in surgery for nasopharyngeal angiofibroma is a controversial matter. We analysed retrospectively the results of surgical treatment in ten patients with a nasopharyngeal angiofibroma, the last five of whom underwent pre-operative embolization with Gelfoam. Embolization reduced the intraoperative blood loss at primary surgery from an average of 1510 ml in the non-embolized patients to 510 ml in the embolized patients and transfusions from an average of 4.4 units to none. Seven reoperations were performed on four non-embolized patients on account of tumour recurrence, while no recurrences were diagnosed among the pre-operatively embolized patients. Blood loss in the reoperations averaged 4065 ml, and transfusions 7.1 units. The results indicate that embolization is effective in reducing intraoperative blood loss and contributes to improved surgical results. We recommend it as a routine pre-operative adjunct to surgery for nasopharyngeal angiofibroma.     

Plasma concentration of oestradiol-17beta in premature thelarche and in different types of sexual precocity

Plasma Oe2 concentration was measured by radioimmunoassay in patients with premature thelarche, with precocious puberty and in 29 normal controls. The mean plasma Oe2 was 1.5 pg/ml (0-7.2) in normal prepubertal girls, 23.8 +/- 17.8 (SD) in pubertal girls, 50.2 (+/- 19.4) in the follicular phase, and 94.2 (+/- 19.5) in the luteal phase of normal adult females. Ten girls with premature thelarche had a mean of 7.7 +/- 6.6 pg/ml. Three of them showed higher values than the other 7, suggesting that in these cases, elevated levels of plasma Oe2 might have played a role in the development of breast tissue. Ten untreated girls with idiopathic precocious sexual development had a mean of 51.6 +/- 42.9 pg/ml while 6 patients treated with 150 mg per week of medroxyprogesterone acetate had a mean of 11.4 +/- 2.5 pg/ml. Two patients with Down's syndrome, hypothyroidism and sexual precocity had plasma Oe2 of 144 and 31.5 which fell to 24.7 and 8 pg/ml, respectively, after thyroid replacement. One girl with a granulosa cell tumour had a basal value of 304 pg/ml and a concentration of 27 pg/ml after surgery.     

The graft flow and 201Tl-myocardial scintigram in patients with saphenous vein graft or left internal thoracic artery graft

To evaluate myocardial perfusion in patients with saphenous vein graft (SVG) or internal thoracic artery graft (ITA-G), we studied 38 patients (14: SVG, 10 males and 4 females, mean age 66 +/- 9 y-o; 24: ITA-G, 18 males and 6 females, mean age 64 +/- 7 y-o) by digital subtraction angiography (DSA) of ITA-G or SVG, and thallium-201 myocardial perfusion scintigraphy on exercise or dipyridamole stress. The grafting sites were left anterior descending artery (LAD) in all patients. Normal controls (n = 22) were defined by normal coronary angiogram and no evidence of myocardial ischemia. The graft flow and flow reserve on dipyridamole were measured by Rutishauser's formula. The basal blood flow of native normal ITA, SVG and ITA-G were respectively 72 +/- 24 ml/min, 51 +/- 23 ml/min, and 36 +/- 20 ml/min. The basal ITA-G flow was significantly lower than SVG-flow (p < 0.05). The flow reserves of SVG and ITA-G were respectively 2.32 +/- 0.65 and 1.78 +/- 0.59 (p < 0.02). The incidence of moderate hypoperfusion of thallium-201 SPECT was 14.3% in SVG and 12.5% in ITA-G on exercise stress, and 35% in SVG and 50% in ITA-G on dipyridamole stress. The incidence of reversible myocardial ischemia on dipyridamole stress was significant. The graft flow in patients with normal and abnormal thallium-201 SPECT were respectively 61 +/- 21 ml/min and 33 +/- 15 ml/min in SVG (p < 0.01), 46 +/- 19 ml/min and 27 +/- 16 ml/min in ITA-G (p < 0.02). The graft flow reserve were respectively 2.69 +/- 0.38 and 1.65 +/- 0.49 in SVG (p < 0.001), 2.25 +/- 0.40 and 1.31 +/- 0.28 in ITA-G (p < 0.001). We concluded that the basal blood flow and flow reserve of ITA-G were significantly lower than those of SVG. The myocardial ischemia was occasionally documented by the thallium-201 myocardial SPECT on dipyridamole stress in patients with patent ITA-G.     

Hypothalamic-pituitary-adrenal axis function in patients with active rheumatoid arthritis: a controlled study using insulin hypoglycemia stress test and prolactin stimulation

OBJECTIVE: To study the response of cortisol and of prolactin (PRL) to specific stimuli in rheumatoid arthritis (RA). METHODS: We measured the response of cortisol to insulin induced hypoglycemia and of PRL to thyrotropin releasing hormone (TRH) in 10 patients with active RA and in 10 paired control subjects. All were women with regular menstrual cycles. They had never received corticosteroids before the study. The PRL concentration was assessed by chemiluminescence immune assay and the cortisol concentration by radioimmunoassay. RESULTS: The basal serum levels of cortisol (14.47+/-2.5 microg/dl) and PRL (10.1+/-1.3 ng/ml) in the RA group were not significantly different from those of the control group (12.3+/-1.1 microg/dl and 13.7+/-2.4 ng/ml, respectively). The peak value of cortisol after hypoglycemia was comparable in both groups (25.5+/-2.4 microg/dl in RA vs. 26.0+/-1.5 ng/ml in controls). The integrated cortisol response to hypoglycemia expressed as area under the response curve (AUC) did not differ significantly in either group (1927+/-196 in RA vs. 1828+/-84 in controls). The interval-specific "delta" cortisol response was significantly higher for the 30 to 45 min interval in controls compared to patients with RA (9.8+/-0.9 microg/dl vs. 6.1+/-1.1 microg/dl; p = 0.02). The peak of PRL after TRH did not differ significantly in both groups (56.4+/-6.4 ng/ml in RA vs. 66.3+/-7.7 ng/ml in controls) and the AUC of PRL secretion after TRH was comparable in both groups (3245+/-321 vs. 4128+/-541). CONCLUSION: Our findings suggest that active RA is associated with subtle dysfunction of the hypothalamic-pituitary-adrenal glucocorticoid function and normal PRL secretion.     

Leukocytes in the cervix: a quantitative evaluation of cervicitis

OBJECTIVE: To quantify the numbers of leukocytes in the normal cervix and relate these numbers to the diagnosis of cervicitis. METHODS: Isolated cell suspensions were prepared from cervical tissue recovered at hysterectomy from 37 women who had no obvious cervical disease. The percentages of CD45+ cells (leukocytes) in these preparations were determined using immunofluorescence-based flow cytometric analysis. These percentages were compared with the pathologist's assessment of cervicitis. RESULTS: Leukocytes were present in all cervical samples tested. For endocervical samples, the mean (+/- standard error of the mean [SEM]) percentage of CD45+ cells was 12.4 +/- 1.9% of cells in patients with a diagnosis of cervicitis (n = 16) and 9.1 +/- 1.1% in patients without cervicitis (n = 17). For ectocervical samples, the mean (+/- SEM) percentage was 14.8 +/- 3.0% in those with cervicitis (n = 16) and 9.5 +/- 1.6% in those without cervicitis (n = 19). The differences between samples from patients with cervicitis and those without cervicitis were not statistically significant at the .05 level. Intra- and interassay variabilities were 5.7 +/- 1.2% and 7.3 +/- 1.6%, respectively. CONCLUSION: Our study demonstrates there is a resident population of leukocytes in the cervix. Leukocyte number did not relate clearly and consistently to the diagnosis of cervicitis made by the pathologist. We suggest that the resident population of leukocytes, in the absence of other indicators of infection, may confuse determinations of cervicitis.     

Regeneration of defects in articular cartilage with callus and cortical bone grafts. An experimental study

Luteal-phase estrogen and progesterone concentrations were measured every other day and used to monitor the corpus luteum activity. The patterns of estrogen and progesterone concentrations were compared relative to the day of endogenous human chorionic gonadotropin (hCG) detection (defined as the day of implantation). The relationship between estrogen and progesterone and hCG concentrations was studied in 71 viable pregnancies, 12 clinical abortions, five preclinical abortions and 84 non-pregnant cycles after IVF/ET. Although all patients received luteal-phase progesterone support (25-50 mg/ml), low late luteal-phase progesterone concentrations of < 30 ng/ml from day + 11 to day + 15 were found in 64 patients (17% of viable pregnancies, 33.3% of clinical abortions, 60% of preclinical abortions and 53.6% of non-pregnant cycles) day + 1 was the day of retrieval). Implantation always occurred before or on day + 13 and 86% of pregnant cycles implanted on day + 8 to day + 11. Viable pregnancies had significantly higher mean progesterone concentrations on day + 3 to day + 7 (pre-implantation) and on day + 9 to day + 15 (postimplantation) than those of non-pregnant cycles or abortions. On the day of implantation, the mean +/- standard of deviation of estrogen (pg/ml) and progesterone (ng/ml) levels for viable pregnancies, clinical abortion and preclinical abortions were 314 +/- 210, 40.5 +/- 25; 226.7 +/- 246, 48.7 +/- 31; and 39.6 +/- 24.5, 28.6 +/- 24.5, respectively. On the same day, 73.2% of viable pregnancies, 41.7% of clinical abortions, and 20% preclinical abortions had a progesterone concentration > 30 ng/ml; 73.2% of viable pregnancies, 41.7% of clinical abortions and 20% of preclinical abortions had an estrogen concentration > 100 pg/ml. Although not precluding implantation completely, late luteal-phase hormonal deficiencies may impair endometrial growth and might ultimately lead to failure or abnormal implantation. A viable pregnancy requires not only a functional corpus luteum in the early luteal phase to develop a receptive endometrium, but also a responsive corpus luteum in the late luteal phase to support pregnancy. The time of implantation is critical. Implantation that occurs before the demise of the corpus luteum will facilitate a normal pregnancy.     

Propranolol serum levels during twenty-four hours

Propranolol serum levels during a 24-hr period were determined every 2 hr in 9 hospitalized patients with angina pectoris after oral administration of 40 mg of propranolol 3 times a day. After the first, second, and third tablets the mean maximum serum propranolol concentrations averaged 118 +/- 71 ng/ml, 134 +/- 97 ng/ml, and 118 +/- 94 ng/ml and the mean minimum concentrations averaged 21 +/- 18 ng/ml, 45 +/- 25 ng/ml, and 54 +/- 34 ng/ml (+/-SD), respectively. These data show a very wide inter- and intraindividual variation in serum propranolol levels. No relationship was found between serum level and blood pressure or dose (related to body weight).     

First-pass radionuclide angiography during bicycle and treadmill exercise

BACKGROUND: Treadmill testing is usually preferred over cycle ergometry because of the greater sensitivity in diagnosing coronary artery disease. Treadmill testing has only recently been used with radionuclide angiography (RNA) because patient motion makes RNA imaging difficult. In this study we evaluate the comparability of treadmill and cycle exercise RNA with a dual isotope motion correction technique. METHODS AND RESULTS: Volunteer patients (n = 27) performed first-pass RNA during maximal exercise using both cycle ergometer and treadmill. Exercise capacity was greater during treadmill exercise (8.1 +/- 2.4 vs 7.5 +/- 2.2 METs). Twenty-three of 27 treadmill and all cycle ergometer exercise studies were technically adequate. Maximal heart rate was greater during treadmill exercise (150 +/- 24 vs 143 +/- 25 beats * min-l), however, systolic blood pressure was greater during cycle ergometry (174 +/- 23 vs 188 +/- 25 mmHg), resulting in no difference in heart rate times systolic blood pressure (25.7 +/- 7.2 vs 26.9 +/- 6.0). There were no differences between treadmill and cycle ergometer for peak exercise left ventricular ejection fraction (56% +/- 13% vs 57% +/- 14%) (r = 0.89). Calculated left ventricular end-diastolic volume was not different at rest (183 +/- 42 ml vs 176 +/- 44 ml) but differed significantly at peak exercise (282 +/- 75 ml vs 231 +/- 60 ml). The clinical impression, based on wall motion and left ventricular ejection fraction was very similar between treadmill and cycle ergometer. CONCLUSION: Treadmill exercise RNA is feasible, with about 85% of studies likely to be technically adequate. The overall clinical results are very similar to cycle exercise RNA, although the ordinarily expected advantages of treadmill exercise were largely absent.     

Treatment of the survivors from the Nagoya air crash

Sixteen multiparous nonpregnant lactating Holstein cows (each weighing 662 +/- 65 kg in 150.4 +/- 40 day of lactation) were confined to wooden metabolic cages with 12:12 h light:dark cycle during the experiment. The cows were divided into two sequences of eight cows each and exposed to electric and magnetic fields (EMF) in an exposure chamber. This chamber produced a vertical electric field of 10 kV/m and a uniform horizontal magnetic field of 30 microT at 60 Hz. One sequence was exposed for three estrous cycles of 24 to 27 days. During the first estrous cycle, the electric and magnetic fields were off; during the second estrous cycle, they were on; and during the third estrous cycle, they were off. The second sequence was also exposed for three 24 to 26 days estrous cycles, but the exposure to the fields was reversed (first estrous cycle, on; second estrous cycle, off; third estrous cycle, on). The length of each exposure period (21 to 27 days) varied according to the estrous cycle length. No differences were detected in plasma progesterone concentrations and area under the progesterone curve during estrous cycles between EMF nonexposed and exposed periods (2.28 +/- 0.17 and 2.25 +/- 0.17; and 24.5 +/- 1.9 vs. 26.4 +/- 1.9 ng/ml, respectively). However, estrous cycle length, determined by the presence of a functional corpus luteum detected by concentrations of progesterone equal to or more than 1 ng/ml plasma, was shorter in nonexposed cows than when they were exposed to EMF (22.0 +/- 0.9 vs. 25.3 +/- 1.4 days).     

Skeletal muscle lactate accumulation and creatine phosphate depletion during heavy exercise in congestive heart failure. Cause of limited exercise capacity?

OBJECTIVE: To study the mechanisms of limited exercise capacity and skeletal muscle energy production in male patients with congestive heart failure. DESIGN: Muscle biopsy study. PATIENTS: Skeletal muscle metabolic response to maximal bicycle exercise was studied in 10 patients with chronic congestive heart failure (ejection fraction 0.22 +/- 0.05; peak oxygen consumption, VO2 15.1 +/- 4.9 ml.min-1.kg-1) and in nine healthy subjects (peak VO2 33.5 +/- 6.7 ml.min-1.kg-1). Activities of skeletal muscle enzymes were measured from the vastus lateralis muscle of 48 patients (ejection fraction 0.24 +/- 0.06, peak VO2 17.4 +/- 5.4 ml.min-1.kg-1) and 36 healthy subjects (peak VO2 38.3 +/- 8.4 ml.min-1.kg-1). RESULTS: Although blood lactate levels were lower in patients than in healthy subjects (2.2 +/- 0.3 vs 5.2 +/- 0.6 mmol.l-1; P < 0.001) at peak exercise (96 +/- 11 W for patients and 273 +/- 14 W for controls), skeletal muscle lactate was similarly elevated (25.6 +/- 3.2 vs 22.7 +/- 2.7 mmol.kg-1) and creatine phosphate was equally depressed (P < 0.02) to low levels (7.0 +/- 1.9 vs 6.7 +/- 0.9 mmol.kg-1). The muscle ATP decreased by 21% (P < 0.05) and 8% (P < 0.01) in the patients and controls, respectively. Activities of rate limiting enzymes of the citric acid cycle (alpha-ketoglutarate dehydrogenase) and oxidation of free fatty acids (carnitine palmitoyltransferase II) were 48% and 21% lower than in controls, but the mean phosphofructokinase activity was unchanged in congestive heart failure. CONCLUSIONS: It seems that the main limiting factor of exercise performance during heavy exercise is the same in congestive heart failure and healthy subjects, a high rate of skeletal muscle lactate accumulation and high-energy phosphate depletion. In congestive heart failure, the low activity of aerobic enzymes is likely to impair energy production and lead to lactate acidosis at low workloads.     

The significance of the occlusion in making dentures

PURPOSE: Multivariate analysis was used to study the effectiveness and optimum dose level of Lipiodol (LP) in transcatheter arterial embolization (TAE) of hepatocellular carcinoma (HCC). METHODS: A total of 219 cases of nodular type HCC, with a tumor diameter less than 7 cm, were studied. TAE was performed using both Gelfoam sponge (GS) and LP in 158 cases; in the remaining 61 cases only GS was used. RESULTS: Statistical stepwise variable selection revealed that only LP had a negative T-value, suggesting that LP is a useful factor for prognosis. The most favorable effect on patient prognosis was obtained with an LP dose level (expressed in mm) of 1-1.5 times the absolute value of the tumor diameter (expressed in cm). CONCLUSION: A significant difference (p < 0.01, log-rank test) in survival was found between the GS with LP group and the GS only group, using Cox's proportional hazard model.     

Dose released and absolute bioavailability of nicotine from a nicotine vapor inhaler

In an open, randomized, three-way crossover study, 14 healthy smokers used one type of nicotine vapor inhaler intensely for 20 minutes every hour for 11 hours (12 administrations). Two different inhalation techniques were applied, shallow frequent sucking (buccal mode) and deep inhalations (pulmonary mode). The determination of nicotine was performed by capillary gas chromatography after single-step liquid-liquid extraction of the plasma sample. Nicotine was detected by means of a nitrogen-sensitive detector, giving high selectivity and sensitivity. The mean (+/- SD) nicotine dose released from each nicotine vapor inhaler unit was estimated at 4.00 +/- 0.60 mg (buccal mode) and 3.87 +/- 0.75 mg (pulmonary mode), inhaled with approximately 15 L of air. Mean (+/- SD) peak plasma level of the last dosing interval was 32.0 +/- 8.7 ng/ml and 34.2 +/- 8.9 ng/ml for the buccal and the pulmonary technique, respectively, achieved after 0.33 and 0.50 (median) hour, respectively. The mean (95% confidence interval [CI]) absolute bioavailability of nicotine was 51 (95% CI, 40 to 65) and 56 (95% CI, 47 to 67) when the buccal and pulmonary techniques were used, respectively. A significant correlation was found between systemically available dose and average steady-state nicotine plasma concentration. Based on the achievement of similar nicotine plasma levels, it may be concluded that the two modes of inhalation appear to be clinically equivalent.     

Endotoxin induces biphasic alterations in small intestinal myoelectric activity in fasted newborn piglets

Previous studies have shown that i.v. endotoxin infusion causes gastrointestinal dysfunction and intestinal injury in piglets. The aim of this study was to investigate the effects of endotoxin on intestinal myoelectric activity in newborn swine and to correlate this with gastrointestinal and hemodynamic events. Three pairs of electrodes were implanted in the jejunal wall of piglets, and after recovery, intestinal myoelectric activity was continuously recorded in the conscious, fasted condition. The intestinal myoelectric activity on the control day showed regular, repeating migrating myoelectric complex (MMC) cycles, each of which was composed of the classic phases I, II, and III. Mean cycle duration was 67.0 +/- 18.7 min (+/- SD), and phase III comprised 9.1 +/- 2.2% of each cycle. On the next day, infusion of 30 micrograms/kg endotoxin caused an initial, prolonged quiescent period and delayed the appearance of the first postendotoxin phase III complex. After the quiescent period, there was a period of irregular spiking activity followed by several shortened MMC cycles (47.9 +/- 22.7 min, p < 0.01 versus control) with a prolongation of the percentage of time spent in phase III (15.4 +/- 11.3%, p < 0.01). Endotoxin thus produced biphasic alterations in intestinal myoelectric activity characterized by an initial quiescence followed by increased gastrointestinal smooth muscle activity. Animals developed diarrhea, hypotension, and tachycardia about 1 h after endotoxin infusion in temporal association with increased spiking activity and MMC cycling. These studies are the first to show this biphasic response to endotoxin.     

Rapid and simple chromatographic method for the determination of diazepam and its major metabolites in human plasma and urine

A simple, rapid, sensitive and selective HPLC method has been developed for the analysis of diazepam (DZP) and its major metabolites, N-desmethyldiazepam (DMDZP), temazepam (TZP) and oxazepam (OZP), in plasma and urine, using clonazepam (CZP) as the internal standard and chloroform as the extracting solvent, with a 10 ng/ml limit of quantitation for the four assayed drugs, and an average (+/-S.D.) recovery of 87.7+/-6.46%, 92.9+/-5.31%, 91.4+/-4.01% and 91.7+/-2.68% for DZP, DMDZP, TZP and OZP, respectively (from plasma), and 89.6+/-2.26%, 90+/-4.24%, 87.45+/-0.64% and 94.50+/-0.71% for DZP, DMDZP, TZP and OZP, respectively (from urine). The method has also proved to be selective and reproducible.