Well-differentiated endometrial adenocarcinomas and poorly differentiated mixed mullerian tumors have altered ER and PR isoform expression.

Both the estrogen receptor (ER) and the progesterone receptor (PR) have two subtypes: ER-alpha and beta, and PR-A and -B, respectively. These subtypes differ in function and expression, and recent reports have correlated changes in the normal proportions of these isoforms with neoplastic states. We investigated ER and PR isoform expression in normal pre- and post-menopausal endometrium, well-differentiated endometrial adenocarcinoma, and poorly differentiated malignant mixed mullerian tumors (MMMTs). Semi-quantitative RT-PCR and immunoblotting were used to measure receptor mRNA and protein expression. Estrogen receptor-alpha/beta mRNA ratios were significantly higher in postmenopausal (27.3) compared to premenopausal endometrium (4.9) mainly as a result of lower ER-beta expression in the former. Compared to age-matched postmenopausal controls, the ER-alpha/beta ratio was reduced in both grade I adenocarcinoma and MMMT specimens (3.3 and 6.8, respectively), due to a selective loss of ER-alpha. The relative abundance of PR-A and PR-B mRNA remained unchanged between all tissue subtypes. Total PR protein, however, was significantly reduced in MMMTs compared to all other groups. Thus, sex steroid receptor expression is significantly and differentially altered in well-differentiated and poorly-differentiated endometrial cancers. Both cancers exhibit decreased ER-alpha expression and the MMMTs also demonstrate a significant loss of PR protein.

Methadone maintenance and addicts' risk of fatal heroin overdose.

An admission cohort of 296 Australian methadone maintenance patients was followed over 15 years. The relative risks of death in and out of maintenance were calculated for two age groups, 20-29 and 30-39 years. Heroin addicts in both age groups were one-quarter as likely to die while receiving methadone maintenance as addicts not in treatment. This is because they were significantly less likely to die by heroin overdose or suicide while in maintenance. Methadone maintenance had no measurable effect on the risk of death through nonheroin overdose, violence or trauma, or natural causes. A meta-analysis showed the reduction in overall mortality was consistent with the results of cohort studies conducted in the United States, Sweden, and Germany. The combined results of the five studies again indicated that methadone maintenance reduced addicts' risk of death to a quarter, RR 0.25 (95% CI 0.19 to 0.33).

Retention in methadone maintenance and heroin addicts' risk of death.

A long-term follow-up was made of a cohort of 307 heroin addicts admitted into a high-dose, Australian methadone maintenance programme in the early 1970s. Using data from clinic records, official death records and methadone treatment histories, it was found that subjects were nearly three times as likely to die outside of methadone maintenance as in it (95% CI RR 1.45 to 5.61). Data were further analyzed using Cox regression to investigate the association of maximum daily methadone dose and a change in clinic policy with retention in maintenance treatment. It is estimated that subjects given a maximum daily dose of 80 mg were nearly twice as likely to be discharged during the first three years of maintenance as those given 120 mg (95% CI RR 1.3 to 2.2). The estimated median time in maintenance for subjects given a maximum dose of 120 mg was 1150 days while for 80 mg it was 660 days. It is further estimated that the change in clinic policy from abstinence to indefinite maintenance reduced to one-third subjects' risk of leaving after three years' of treatment (95% CI RR 0.19 to 0.54). It is concluded that, in order to minimize heroin addicts' risk of death, they should be offered indefinite, high-dose methadone maintenance.

Successful use of fibrin glue during 2 years of surgery at a university medical center.

A method for producing concentrated fibrinogen, an essential component of fibrin glue, from individually stored, single-donor units of human plasma is reported. The plasma is screened for hepatitis B antigen and HIV-1 virus to reduce the risk of transmission of hepatitis and acquired immunodeficiency syndrome (AIDS). This material is routinely stocked in some operating rooms. It is thus readily available when requested by a surgeon for use in combination with topical bovine thrombin to produce fibrin glue. From April 1985 to March 1987 this material was used by surgeons from eight different surgical specialties on 413 patients with a 91 per cent success rate (376/413). Uses have included sealing vascular suture lines, reinforcing pulmonary and esophageal staple lines, closing dural cerebrospinal fluid leaks, fixing split-thickness skin grafts, reducing lymphatic leakage, and controlling bone bleeding. Additional uses include closure of bronchopleural fistulas by means of the flexible bronchoscope, reduction of perioperative hemorrhage by spraying fibrin glue on the anterior mediastinum during cardiac surgery, and reduction of bleeding during debridement of burn eschars. Careful monitoring and patient follow-up detected no cases of transmission of blood-borne diseases. Only one complication, a local wound infection, has been documented. This material has been an important adjunct for the surgical services and may be safely used at hospitals with local blood bank facilities.

The reversal of amiodarone-induced perioperative reduction in cardiac systolic reserve in dogs.

There is controversy about the myocardial depressant effects of amiodarone in patients with decreased cardiac function undergoing surgery. Some surgeons believe that these effects complicate the discontinuation of cardiopulmonary bypass. Accordingly, the hemodynamic effects of amiodarone were evaluated in two groups of anesthetized mongrel dogs that had undergone a median sternotomy. A control group of 10 dogs and an amiodarone-treated group (15 mg/kg per day for 3 weeks) of 10 dogs were studied, and serum (0.26 to 1.09 micrograms/ml) and tissue (cardiac 2.97 to 11.60 micrograms/ml) levels of amiodarone were measured by liquid chromatography. Hemodynamic measurements were made at baseline and after administration of routine therapeutic intravenous doses of dobutamine (10 micrograms/kg per min), isoproterenol (0.06 micrograms/kg per min) and epinephrine (2 micrograms/min). The amiodarone-treated dogs had a smaller increase in cardiac output compared with baseline than did control dogs. For each drug when the amiodarone-treated group was compared with the control group, increases in cardiac output (liters/min) were: dobutamine, 1.32 +/- 0.24 versus 1.73 +/- 0.31; isoproterenol, 0.84 +/- 0.26 versus 1.43 +/- 0.28; epinephrine, 0.25 +/- 0.15 versus 0.44 +/- 0.53. Amiodarone-treated dogs were also given higher doses of drugs, dobutamine (50 micrograms/kg per min), isoproterenol (1.2 micrograms/kg per min) and epinephrine (20 micrograms/min). Increases in cardiac output were 1.24 +/- 0.24, 1.62 +/- 0.25 and 2.82 +/- 0.64, respectively. All cardiac outputs were significantly increased from the baseline values (p less than 0.05) except those measured in the amiodarone group receiving the lower dose of epinephrine. Thus, amiodarone-treated dogs have a relative reduction of perioperative cardiac systolic reserve.(ABSTRACT TRUNCATED AT 250 WORDS)

Reduction of perioperative hemorrhage by anterior mediastinal spray application of fibrin glue during cardiac operations.

A variety of published techniques for the production of concentrated fibrinogen from units of screened single-donor human plasma have led to increasing clinical use of fibrin glue in the United States. We have adapted a method of applying this material with a disposable plastic sprayer. In 20 consecutively treated patients, fibrin glue was sprayed on the anterior mediastinum before closure of the median sternotomy incision. A control group of 20 patients undergoing the identical cardiac operations (13 coronary artery bypass grafting procedures [CABG], 4 valve replacements [including 1 reoperative procedure], and 3 combined valve replacements and CABG) by the same surgeon within a one-year period was chosen for comparison of chest tube outputs. Specifically, chest tube outputs were as follows for treated and untreated patients, respectively: at 12 hours, 461 +/- 40 ml (mean +/- 1 standard error of the mean versus 731 +/- 80 ml; at 24 hours, 714 +/- 73 ml versus 1,016 +/- 109 ml; and at 48 hours, 863 +/- 93 ml versus 1,187 +/- 137 ml. The differences between control and spray chest tube output are statistically significant by unpaired t test (p less than 0.05) at both 12 and 24 hours. Thus, this method can reduce perioperative hemorrhage from the anterior mediastinum after cardiac operations.

Fifty opiate addicts treated with methadone blockade. Eight-year follow up.

An extended follow up of the first 50 opiate addicts in Australasia to be treated with methadone blockade is described. At follow up, 43 patients were traced and assessed. Results show that 65% of the 43 patients completed the recommended three years of blockade therapy, with an identical proportion of patients recording no new criminal convictions; and 53.5% were reported as being drug-free, with the exception of prescribed methadone. The therapy in 28% of patients was judged as being completely successful, while 70% of patients complied with criteria of leading reasonably happy and productive lives. Methadone blockade (over 100 mg a day) offers the opiate addict an excellent opportunity for recovery and rehabilitation, provided that the treatment is properly understood, administered, and followed up.

Physician heal thyself?

Eighteen drug-dependent medical practitioners were studied, and the results of their treatment were compared with the results of the treatment of non-doctor patients of similar age. The result of this comparison lent support to the suggestion that doctors who develop a dependence on drugs tend either to become abstainers or to die.

Methadone blockade in the treatment of opiate addiction: a follow-up study.

This paper describes methadone blockade treatment of 50 opiate addicts. At follow-up, 36 patients were traced and interviewed. Results show that 89% of the 36 patients cooperated with the treatment programme, 88% had no new criminal convictions and 75% remained drug-free, apart from taking methadone during the follow-up period (mean, 12-5 months). Five of the 36 patients were free of all drug addictions, including methadone.