FEASIBILITY OF CONDUCTING CARDIOVASCULAR OUTCOME RESEARCH IN AUSTRALIAN GENERAL PRACTICE: RESULTS FROM THE ANBP2 PILOT STUDY

1. The present study aimed to determine the feasibility of conducting a 5 year cardiovascular outcome trial of the treatment of 6000 elderly hypertensive patients in Australian general practices. 2. General practitioners (GPs) were invited to participate by mail and personal follow-up. Patient records were reviewed to identify subjects for a blood pressure (BP) screening programme. Blood pressure was measured on three occasions and eligible subjects were included if the average BP was 160 mmHg systolic or 90 mmHg diastolic if systolic BP was 140 mmHg. 3. Seven hundred and forty-one GPs were approached and 89 were enrolled in the study (12% of mail invites and 75% of those receiving a personal contact). In 16 practices where screening was completed, 82 000 records were reviewed to identify 4% patients eligible for screening. Twenty-two per cent of eligible subjects attended screening. Of 1938 subjects screened, 180 (9%) had BP 5=160/90 mmHg. Forty-seven percent of subjects (n = 916) were receiving antihypertensive therapy and 184 (20%) were withdrawn from therapy. One hundred and sixteen (63%) of these subjects had BP return to study entry levels within 6 weeks. Fifty-seven newly diagnosed and 81 previously treated subjects were randomized (7% of the screened population). 4. Based on the high participation rate of GPs, the response rate of patients to attend a BP screening programme and the 7% randomization to screening ratio for entry into the study, the ANBP2 pilot study has demonstrated that it is feasible to recruit subjects from Australian general practices to a cardiovascular outcome trial.     

Ciprofloxacin in the treatment of urinary tract infections

Twenty patients (15 males; five females) aged 11-70 years, with urinary tract infections were treated with one 250 mg tablet of ciprofloxacin every 12 h for 5-10 days. Clinical response to this treatment was the complete disappearance of symptoms in 85% of cases and the elimination of the micro-organism responsible for infection. In only three patients, who all had urinary calculus in addition to an infection, clinical failure of the therapy occurred and the causative micro-organism persisted. Tolerance to the therapy was excellent in this study, no adverse reactions connected with the treatment being reported.     

Laser irradiation and balloon dilatation in experimental transluminal angioplasty

Percutaneous transluminal balloon angioplasty (PTA) is being currently used in patients with coronary artery disease. Laser irradiation (LI) has been effective in vaporizing atherosclerotic plaques. The purpose of this work was twofold: to compare PTA and LI techniques in the recanalization of experimental obstructive arterial lesions, and to evaluate the possibility of reducing the failures and local complications and increasing the success rate of PTA by the combined use of LI. Atherosclerotic iliac stenoses were induced in 27 rabbits; lesions were evaluated angiographically before and after intervention and were studied histologically and by electron microscopy. Argon-ion LI delivered through microlens-tip optic fibers reduced the stenotic area from 64.2 +/- 21.8% to 40.3 +/- 10.7% (n = 10, P less than .01) and PTA from 60.7 +/- 15.9% to 30.4 +/- 7.7% (n = 9, P less than .01). However, percentage reduction was higher in PTA-treated stenoses (48.4 +/- 10.1% vs 34.5 +/- 13.5%, P less than .0125). In eight more rabbits, low power LI (4.55 +/- 1.25 J) was delivered after PTA in dilated segments. Post-PTA LI further decreased stenoses (from 31.2 +/- 7.8% to 29.1 +/- 8.1%, P less than .0125); laser-irradiated segments showed diffuse carbonization of the disrupted intimal layer. The normalized transtenotic pressure gradient decreased significantly in all groups: LI reduced the gradient from .40 +/- .25 to .17 +/- .07 (P = .005); PTA from .37 +/- .14 to .11 +/- .04 (P = .001); LI after PTA from .40 +/- .16 to .12 +/- .06 (P = .001). Thus, LI is effective (less than PTA) in relieving experimental atherosclerotic stenoses and seems useful when combined with PTA.     

Effects of intermittent diethylstilbestrol diphosphate administration on the R3327 rat prostatic carcinoma

Clinical trials have utilized intermittent diethylstilbestrol diphosphate (DES) therapy in advanced symptomatic prostatic carcinoma to diminish the morbidity of standard endocrine therapy. To determine the effect of intermittent DES administration on the Dunning R3327 rat prostatic adenocarcinoma 60 days following tumor implant, 6 groups were randomly assigned: control (N = 8), castrate (N = 10), high dose DES (N = 8, 1.6 micrograms/ml DES continuously in drinking water), low dose DES (N = 10, 0.4 microgram/ml continuously in drinking water), intermittent high dose DES (N = 10, 1.6 micrograms/ml DES in drinking water for 1 week, then off for 3 weeks), and intermittent low dose DES (N = 10, 0.4 microgram/ml DES for 1 week, then off for 3 weeks). Results indicate that low or high dose DES, and intermittent low or intermittent high dose DES during the week of administration were able to reduce serum testosterone to castrate levels (0.1 ng/ml). After withdrawal of intermittent DES, serum testosterone returned toward control levels (1.0 ng/ml). Initial mean tumor burden between control and treatment groups was not significantly different. All DES exposed rats had a tumor volume at death (range, 15.6-18.3 cm3) smaller than control (mean, 25.4 cm3) or castrate (mean, 40.8 cm3) rats. Despite this significant survival advantage from the time of randomization was achieved only in castrate (median survival, 331 days) or high dose DES (median survival, 359 days) groups compared to control (median survival, 225 days). Similarly, significant prolongation in tumor doubling time was achieved only by rats receiving castration or high dose DES. Intermittent DES administration controls tumor volume but does not provide a survival advantage. In this respect, intermittent DES is inferior to castration.     

Laparoscopic choledochotomy with primary closure

Background: Thirty-three patients were candidates for laparoscopic choledochotomy. The indications for this operation are described. Methods: The procedure was completed 32 times (97%). We had 29 successful common bile duct (CBD) clearances, three negative explorations, and one failed clearance which needed to be converted to laparotomy. All the completed procedures ended with primary closure of the main duct. Median duration of surgery was 180 min (range 100–300), including three associated laparoscopic procedures. Results: There were three postoperative complications (9.4%), none major. Average postoperative hospital stay was 7.1 days (range 4–14). In May–June 1995 we controlled 31 out of the 32 consecutive patients (one patient was lost to follow-up) who had a successful laparoscopic choledochotomy from October 1991 to December 1994. Median follow-up was 22 months (range 5–44). Besides clinical control, 23 patients also had ultrasound (US) controls and 24 had blood tests. Eleven had intravenous cholangiotomography. Two patients died 11 and 22 months after the operation for unrelated causes and without biliary symptoms. Two patients had umbilical hernias. One had a small residual asymptomatic stone, which was removed endoscopically. None had signs of postoperative CBD stricture. At US, CBD was ≤7 mm in 15 patients, 8–10 mm in four patients, and 10–12 mm in three patients. The last group had preoperative CBD dilation, too. We could compare preoperative and postoperative CBD diameters in 22 patients: 11 had no change; in nine it decreased; and two had a slight increase (8–10 mm). Conclusions: We conclude that laparoscopic choledochotomy with primary closure is a very good operation: It has a high success rate and low morbidity. Mortality is nil so far. Medium-term results are very positive: We had no CBD stricture and only one case of asymptomatic residual stone, which could have been avoided. Our results suggest that intraductal biliary drainage is useless, and its specific complications are well known. Received: 20 October 1995/Accepted: 28 February 1996     

Successful Treatment of Kasabach-Merritt Syndrome with Prednisone and Epsilon-Aminocaproic Acid

The Kasabach-Merritt syndrome is characterized by thrombocytopenia and localized coagulopathy associated with a hemangioma. Most techniques applied to eradicate the tumor or accelerate its involution (surgery, radiation therapy, embolization) are invasive and require transfusion of large amounts of blood products. In some cases, medical treatment is the only alternative. Efficacy of steroids and antifibronolytic agents has already been described, but even this approach is associated with the administration of blood products. We report two cases of infants with Kasabach-Merritt syndrome associated with cardiac and hepatic hemangiomas. At admission, both had signs of cardiac failure. They were successfully treated with prednisone and epsilon-aminocaproic acid (EACA). Blood products were not required once the diagnosis was made. These observations have important implications for the management of patients with Kasabach-Merritt syndrome because they show that even in severe cases blood transfusions can be avoided by the use of prednisone and EACA.     

Preparation and pharmacologic activity of amido- derivatives of 3-methyl-3,4-dihydro benzo- and pyrido-1,2,4-triazin-3-acetic acids

Thirteen amidoderivatives of 3-methyl-3,4-dihydro-6-R-benzo-1,2,4-triazin-3-yl-acetic acids and of 3-methyl-3,4-dihydro-pyrido [3,2-e]/[3,4-e]-1,2,4-triazin- 3-yl-acetic acids were prepared and submitted to a wide pharmacological screening. The dihydrobenzotriazine and dihydropyridotriazine moieties were endowed with a wide pharmacogenic capacity; in fact, several compounds exhibited high antiinflammatory [(I c), (I d), (II d), (V f), (VI f)], diuretic [(I f), (I g), (I h)] and antihypertensive activities [(I d), (III d)], as well as minor effects on the C.N.S.     

Nephrectomy during operative management of retroperitoneal sarcoma

Background: Complete resection of a retroperitoneal sarcoma often requires removal of adjacent organs. In this study we evaluated the role of nephrectomy during operation for retroperitoneal sarcoma. Methods: Between July 1982 and July 1995, 75 of the 371 (20%) patients who underwent resection of retroperitoneal sarcoma at MSKCC underwent concommitant nephrectomy. Data concerning the reasons for nephrectomy, degree of sarcomatous renal involvement, and survival were retrospectively analyzed. Results: Fifty-four patients (72%) underwent nephrectomy during the initial resection, and 21 (28%) during a resection of a recurrent or persistent tumor. The most common reason for nephrectomy was total encasement by sarcoma (n=40; 53%), followed by dense adherence of the tumor to the kidney (n=21; 28%), and the direct invasion of the kidney by tumor (n=2; 3%). Pathology demonstrated an absence of kidney invasion in the majority of cases (55 of 75; 73%). Renal capsular invasion was present in 11 of 75 (15%), renal parenchymal invasion in 7 of 75 (9%), and renal vein invasion in 2 of 75 (3%) of cases. There were no significant differences in survival based on degree of sarcoma involvement of the kidney, tumor grade, or whether the resection was for primary or recurrent disease. The 53 patients who underwent a complete gross resection of all tumor had a significantly improved long-term survival compared to the 20 patients who did not (50% versus 20% DFS at 5 years, respectively; p<0.001). Conclusions: Decisions for concomitant nephrectomy during resection of retroperitoneal sarcoma should be based on whether this maneuver will provide a complete resection of all gross tumor, in which case the long-term disease-free survival of 50% is comparable to the reported 5-year survival of all patients with retroperitoneal sarcoma who are completely resected. Presented at the 49th Annual Cancer Symposium of the Society of Surgical Oncology, Atlanta, Georgia, March 21–24, 1996.