A multicenter trial of the use of the proteolytic enzyme inhibitor aprotinin in colorectal surgery

Animal studies have demonstrated the value of the proteolytic enzyme inhibitor, aprotinin, in reducing collagen breakdown and improving the healing of experimental colonic anastomoses. A double-blind, multicenter, prospective trial has evaluated the use of aprotinin in the prevention of anastomic leakage in patients. Two hundred sixteen patients undergoing colonic resection and anastomosis were studied. Patients were randomized to receive either aprotinin or placebo intravenously, peroperatively, and for the first three postoperative days. Anastomotic integrity was assessed clinically and by Hypaque^® enema on the tenth postoperative day. Although the use of aprotinin was not associated with a significant overall decrease in anastomotic leakage rates, in 95 patients undergoing anterior resection, leakage rates in those receiving aprotinin (clinical 10.8 percent; radiologic 32.4 percent) were lower than in those receiving placebo (17.2 percent and 43.1 percent, respectively). An apparent adverse association was noted, however, in patients undergoing left hemicolectomy or sigmoid colectomy who received aprotinin.     

The effects of sex steroids on thyroid C cells and trabecular bone structure in the rat model of male osteoporosis

Androgen deficiency is one of the major factors leading to the development of osteoporosis in men. Since calcitonin (CT) is a potent antiresorptive agent, in the present study we investigated the effects of androgen deficiency and subsequent testosterone and estradiol treatment on CT-producing thyroid C cells, skeletal and hormonal changes in middle-aged orchidectomized (Orx) rats. Fifteen-month-old male Wistar rats were either Orx or sham-operated (SO). One group of Orx rats received 5 mg kg⁻¹ b.w. testosterone propionate (TP) subcutaneously, while another group was injected with 0.06 mg kg⁻¹ b.w. estradiol dipropionate (EDP) once a day for 3 weeks. A peroxidase–antiperoxidase method was applied for localization of CT in the C cells. The studies included ultrastructural microscopic observation of these cells. The metaphyseal region of the proximal tibia was measured histomorphometrically using an imagej public domain image processing program. TP or EDP treatment significantly increased C cell volume (Vc), volume densities (Vv) and serum CT concentration compared with the Orx animals. Administration of both TP and EDP significantly enhanced cancellous bone area (B.Ar), trabecular thickness (Tb.Th) and trabecular number (Tb.N) and reduced trabecular separation (Tb.Sp). Serum osteocalcin (OC) and urinary Ca concentrations were significantly lower after these treatments in comparison with Orx rats. These data suggest that testosterone and estradiol treatment in Orx middle-aged rats affect calcitonin-producing thyroid C cells, which may contribute to the bone protective effects of sex hormones in the rat model of male osteoporosis.     

In vivo real-time analysis of intraperitoneal radiolabeled tumor cell movement during laparoscopy

PURPOSE: A porcine model has been developed to allow the real-time imaging of radiolabeled tumor cell movement throughout the peritoneal cavity, both at rest and during carbon dioxide insufflation. METHODS: Fifteen 30-kg domestic white female pigs were used. Under anesthesia, 15 to 20 million radiolabeled human colorectal tumor cells (LIM1215) were introduced into the peritoneal cavity under laparoscopic vision into the pelvis. Radiolabeled tumor cell movement was examined by using a 25-cm-diameter, low-energy mobile gamma camera with high resolution collimator. Tumor cell movement and distribution during two hours without insufflation was examined in four pigs. Then tumor cell movement and distribution during two hours with CO₂ insufflation was examined in four pigs. In a further four pigs, tumor cells were then mixed with blood and injected into the peritoneal cavity and the effect of no insufflationvs. insufflation was noted. A further three pigs were examined with manipulation of the intra-abdominal contents after injection of LIM1215 cells into the peritoneal cavity. Venting insufflating CO₂ was filtered for tumor cells. RESULTS: Widespread intraperitoneal distribution of tumor cells from the pelvis was identified both with CO₂ insufflation of the peritoneal cavity and without insufflation. Tumor cells dispersed throughout the peritoneal cavity at a slower rate without carbon dioxide insufflation. There was a differential rate of tumor cell movement to the left upper quadrant and right upper quadrant with insufflation and without insufflation. Blood within the peritoneal cavity and an extended contact of the laparoscopic trocars with the peritoneal cavity in this setting increased contamination of the trocars and trocar sites with tumor cells. Tumor cells were identified on laparoscopic instruments in all experiments. No evidence of aerosolization of tumor cells was found. CONCLUSION: Tumor cells move throughout the peritoneal cavity both at rest and during CO₂ insufflation. The pattern of tumor cell dispersion differs with CO₂ insufflation. The presence of blood and extended contact of trocars with peritoneal contents are a major factor in trocar and trocar site tumor cell contamination.This work was performed at The Queen Elizabeth Hospital and the Institute of Medical and Veterinary Sciences, South Australia.Supported by the National Health and Medical Research Council of Australia and the Alfred and Ferrers Scammel Scholarship, Faculty of Medicine, University of Adelaide.Material supplies provided by Johnson and Johnson Australia.Read at the meeting of The American Society of Colon and Rectal Surgeons, San Antonio, Texas, May 2 to 7, 1998.     

The phytoestrogen genistein prevents trabecular bone loss and affects thyroid follicular cells in a male rat model of osteoporosis

As a major phytoestrogen of soy, genistein effectively prevents bone loss in both humans and rat models of osteoporosis. However, although the bone‐sparing effects of genistein are achieved directly through estrogen receptors, its mode of action on bone by modulation of other endocrine functions is not entirely clear. Thus, thyroid hormones and calcitonin (CT ) have an essential influence on bone metabolism. Besides its action on bones, in this study we examined the effect of genistein on the activity of two different endocrine cell populations, thyroid follicular and C‐cells. Fifteen‐month‐old Wistar rats were either bilaterally orchidectomized (Orx) or sham‐operated (SO ). Two weeks after surgery, half of the Orx rats were treated chronically with 30 mg kg^?1 b.w. genistein (Orx + G) subcutaneously (s.c.) every day for 3 weeks, while the remaining Orx rats and the SO rats were given the same volume of sterile olive oil to serve as controls. For histomorphometrical analysis of the trabecular bone microarchitecture an ImageJ public domain image processing programme was used. Thyroid sections were analysed histologically and stereologically after visualization of follicular and C‐cells by immunohistochemical staining for thyroglobulin and CT . Thyroid follicular epithelium, interstitium, colloid and CT ‐immunopositive C‐cells were examined morphometrically. Serum concentrations of osteocalcin (OC ), triiodothyronine (T₃), thyroxine (T₄) and CT were determined as well as urinary calcium (Ca²⁺) concentrations. Genistein treatment significantly increased cancellous bone area (B.Ar), trabecular thickness (TbTh) and trabecular number (TbN) (P  < 0.05), but trabecular separation (Tb.Sp) was decreased (P  < 0.05) compared with control Orx rats. In the thyroid, genistein treatment significantly elevated the relative volume density (Vv) of the follicular cells (P  < 0.05) compared with Orx, whereas Vv of the colloid was lower (P  < 0.05) than in the Orx. Evaluation of the biochemical parameters showed significant reductions in serum OC , T₃, T₄ and urinary Ca²⁺ concentrations (P  < 0.05), compared with Orx rats. These data indicate that genistein treatment improves the trabecular microarchitecture of proximal tibia, induces histomorphometrical changes in thyroid glands, and decreases circulating thyroid hormone levels in orchidectomized rat model of male osteoporosis.     

Reproducibility of tissue Doppler parameters of asynchrony in patients with advanced LV dysfunction.

AIMS: To assess the reproducibility of tissue Doppler myocardial velocities in patients with dilated ventricles and markedly reduced systolic function (ejection fraction <35%). METHODS AND RESULTS: Forty-one patients referred for cardiac resynchronization therapy (CRT) were evaluated using tissue Doppler echocardiography. The inter and intra-individual reproducibility of peak systolic myocardial velocities and the intra-ventricular delay in three apical projections was assessed by repeated evaluation of each registered data set. Variability (measured by the coefficient of variation) ranged between 18 and 56% for the peak systolic velocities and between 32 and 117% for the time intervals. CONCLUSION: The reproducibility of the tissue Doppler echocardiography parameters (peak systolic myocardial velocity and intra-ventricular delay) was poor in our set of patients with dilated left ventricles and low ejection fraction. The most probable causes of our poor results are discussed including the missing standardization of the TDI measurements.     

Organizing treatment around the family's problems and their structural bases

One of the great challenges (and rewards) in treating children is the frequent discovery that the patient is not really sick at all, but simply reacting to pathology in the family constellation. This author conceptualizes treatment in structural terms of the family. He describes a therapeutic process in which the therapist helps members of a family system toagree on the problem they need to solve, toidentify the participants in the family structure to which the problem is related, and tomake pledges to work on changing the structural basis of the newly-clarified problem.