Clinical pilot studies on pre-operative hyperthermic tumour ablation for advanced breast carcinoma using an 8 MHz radiofrequency heating device.

The multimodality treatment approach for advanced breast cancer provides survival advantages with decreased locoregional and distant recurrences, but these intensive anti-tumour treatments cause severe myelosuppression. Thus, in this study, the usefulness of pre-operative anti-tumour treatment without myelosuppression was investigated. Nine patients with advanced breast carcinoma underwent pre-operative hyperthermic tumour ablation (HTA) using an 8 MHz radiofrequency (RF) heating device (Thermotron RF-8) combined with a grounded needle electrode. The patients had a mean age of 58.3+/-13.9 years and included four patients with stage IIIA, two with stage IIIB and three with stage IV cancer. The target temperature was over 50 degrees C. They tolerated pre-operative HTA therapy well with no early or late complications. The initial mean tumour size was 122.1+/-71.5 cm3 and the post-HTA tumour size was 82.2+/-63.4 cm3; the reduction rate was significant (p = 0.000 293). After the pre-operative HTA, all patients underwent surgery with Level III nodal extirpation. Post-operatively, no locoregional recurrence was observed. Microscopic examination of the primary focus showed complete coagulation necrosis expanding for a diameter of 3.5-5.0 cm. Taken together, the pre-operative HTA was a safe, well-tolerated and effective treatment, achieving tumour reduction as well as complete coagulation necrosis that resulted in a large volume of destruction in breast cancer tissue.

Synthesis and bronchodilatory activity of four new derivatives of deoxyvasicine.

As part of a continuing effort aimed at the development of efficacious antihistaminic and bronchodilator agents for the treatment of asthma and related respiratory diseases, a series of novel trisubstituted deoxyvasicine derivatives was designed and synthesized. Bronchodilatory activity of pure samples of ligands 17a-d, and DL-8-chlorovasicine hydrochloride is investigated and compared with isoprenaline and aminophylline. These studies confirm the activity of ligands 17a-d and the potentiating effect of 17c on aminophylline.

Secondary carnitine deficiency in handicapped patients receiving valproic acid and/or elemental diet.

We examined serum-free carnitine (SFC) concentrations and serum acylcarnitine (SAC)/SFC ratios in 40 severely handicapped patients, aged 2 to 36 years, and 69 age-matched control subjects. SFC levels in the patients treated with valproic acid (VPA) and/or receiving carnitine-deficient elemental diets (ED) were significantly lower, and their SAC/SFC ratios were significantly higher than in the other patients or in control subjects. There were 6 patients whose SFC levels were less than the -2SD level (15.8 +/- 6.7 microM, range 6.3-25.5) of those in control subjects (52.1 +/- 11.5 microM). They had no clinical symptoms of carnitine deficiency such as non-ketotic hypoglycemia, hepatomegaly, muscle weakness or cardiac function impairment, and showed normal transaminase, lipid and ammonia levels. In two cases (SFC = 11.0, 13.4 microM), the ketogenic responses to intravenous administration of fat-emulsion were impaired, but they were restored after D-,L-carnitine supplementation (30 mg/kg/day, po) for 1 month. However, in one case with the lowest SFC level (6.3 microM), the ketogenic responses to fat-emulsion infusion or fasting were normal, and dicarboxylic aciduria was not detected. These results indicate that 1) SFC levels are reduced in handicapped patients receiving VPA and/or ED, although clinical symptoms of carnitine deficiency do not easily develop, 2) some of these hypocarnitinemic cases show a subclinical impairment of hepatic fatty acid metabolism, not always correlated with the degree of SFC reduction, which can be restored by exogenous carnitine supplements, and therefore 3) in patients with acquired hypocarnitinemia, carnitine therapy should be considered, although a low SFC level alone may not imply an immediate indication.

[The effects of nifedipine on blood pressure and renal function].

The effects of nifedipine (NIF) on blood pressure and renal function were examined in control spontaneously hypertensive rats (SHR) (group A), SHR with moderate renal dysfunction (group B), and those with severe renal dysfunction (group C). The hypotensive effect of NIF administration was greater in SHR with severe renal dysfunction, and this might relate with pharmacokinetics of NIF, decreased sensitivity of baroreflex and low plasma renin activity in SHR with reduced renal function. When mean arterial blood pressure (MAP) was reduced by about 30% in these three groups, the baseline renal function was maintained and natriuresis was observed in group A and B, whereas the renal function and urine volume decreased transiently, and urinary sodium excretion tended to decrease in group C. In hypertensive patients with normal renal function (group I), moderate renal dysfunction (group II), and severe renal dysfunction (group III), 5 or 10 mg NIF was orally administered. In these three groups, MAP was reduced by about 20%. In group I, glomerular filtration rate tended to increase, renal plasma flow increased and natriuresis was observed. In group II and III, renal function didn't decrease with few exception, but when MAP was reduced by about 30%, renal function decreased in three of five cases. Also on long-term administration of NIF in hypertensive patients, renal function improved. The results suggests that NIF by single administration or long-term administration is effective on hypertensive patients with renal dysfunction, but we should be cautious to decide the dose of NIF and the rate of blood pressure reduction.