Non-invasive magnetic resonance imaging assessment of myocardial changes and the effects of angiotensin-converting enzyme inhibition in diabetic rats

A non-invasive cine magnetic resonance imaging (MRI) technique was developed to allow, for the first time, detection and characterization of chronic changes in myocardial tissue volume and the effects upon these of treatment by the angiotensin-converting enzyme (ACE) inhibitor captopril in streptozotocin (STZ)-diabetic male Wistar rats. Animals that had been made diabetic at the ages of 7, 10 and 13 weeks and a captopril-treated group of animals made diabetic at the age of 7 weeks were scanned. The findings were compared with the results from age-matched controls. All animal groups (n = 4 animals in each) were consistently scanned at 16 weeks. Left and right ventricular myocardial volumes were reconstructed from complete data sets of left and right ventricular transverse sections which covered systole and most of diastole using twelve equally incremented time points through the cardiac cycle. The calculated volumes remained consistent through all twelve time points of the cardiac cycle in all five experimental groups and agreed with the corresponding post-mortem determinations. These gave consistent myocardial densities whose values could additionally be corroborated by previous reports, confirming the validity of the quantitative MRI results and analysis. The myocardial volumes were conserved in animals whose diabetes was induced at 13 weeks but were significantly increased relative to body weight in animals made diabetic at 7 and 10 weeks. Captopril treatment, which was started immediately after induction of diabetes, prevented the development of this relative hypertrophy in both the left and right ventricles. We have thus introduced and validated quantitative MRI methods in a demonstration, for the first time, of chronic myocardial changes in both the right and left ventricles of STZ-diabetic rats and their prevention by the ACE inhibitor captopril.     

Deferred treatment for prostate cancer

The clinical outcome of 278 prostate cancer patients managed by a deferred treatment policy was analysed retrospectively. Following TURP or biopsy, all patients were asymptomatic and deemed suitable for management by a deferred treatment policy, i.e. hormone therapy or other forms of treatment were only initiated if and when symptomatic progression occurred. The overall 5-year survival rate was 30%; 18% of patients died from other causes without needing treatment for their prostate cancer; 11% were alive and untreated after 5 years' follow-up; 17% died from prostate cancer without further treatment. Poor tumour grade, anaemia, metastatic disease, a short history, presentation with retention, and a raised serum creatinine at presentation were associated with a poor prognosis.     

A new immune-competent animal model of mucosally derived squamous cell carcinoma.

OBJECTIVES: To develop an immune-competent animal model for mucosally derived squamous cell carcinoma (SCCA). STUDY DESIGN: Fifteen Fischer 344 rats were inoculated with 1, 2, 5, 10, or 20 x 10(6) FAT7 cells in their flanks. The animals were observed for tumor growth and metastasis. RESULTS: All animals developed tumors that grew exponentially. Pulmonary metastases developed in all animals and 13% developed lymph node metastases. CONCLUSION: The FAT7 flank tumor in Fischer 344 rats is a new animal model that closely resembles the behavior of human mucosal head and neck cancer. SIGNIFICANCE: The existence of an immune-competent, mucosally derived, and reliable animal model of SCCA that somewhat resembles human head and neck SCCA gives the opportunity to perform immune-modulating experiments on head and neck cancer in these animals. EBM rating: B-3.     

P07Reduction of Allogeneic Red Cell Transfusion using Autologous Blood Cell Salvage in Knee Arthroplasty

Recent Hospital Transfusion Committee (HTC) audit at the Royal Bournemouth Hospital (RBH) confirmed an allogeneic red cell transfusion rate of 20% for primary Total Knee Replacement (TKR). Current policy at RBH states that when blood stocks reach 67% of normal (amber alert) then surgery with a >20% likelihood of blood transfusion will be cancelled. At current transfusion rates this would include primary TKR. Recent studies have shown a reduction in allogeneic transfusion rates when autologous transfusion drains are utilized. The purpose of this study was to see whether the current rate of allogeneic transfusion could be reduced with the introduction of the CellTransTM Autologous Knee Drainage Blood Transfusion System (ABT) in TKR at RBH. Over a 3 month period all patients undergoing primary, bilateral or revision knee arthroplasty received an ABT. Demographic data was collected from the orthopaedic pre‐assessment clinic. Following surgery further data was collected relating to volume of blood loss into the drain, volume of autologous blood re‐transfused, units of allogeneic blood required and the transfusion trigger, postoperative haemoglobin levels, infection rates and length of stay in hospital. We then compared this data set with retrospective data. Of 170 patients undergoing knee arthroplasty 141 received the ABT. The data collected was compared retrospectively with 169 patients from the previous 3 month period. We demonstrated a reduction in transfusion rates of 13% for primary TKR, 42% for bilateral TKR and 57% for revision TKR with the use of the ABT. In addition we demonstrated a reduction in total allogeneic blood use (99 units to 26 units) and a reduction in mean length of stay in hospital (8.6 days to 7.5 days) with the ABT. Further analysis of the data collected showed a 46% reduction in the allogeneic transfusion rate and a reduction in total allogeneic blood usage (99 units to 9 units) of anaemic patients presenting for surgery. This study has demonstrated a dramatic reduction in allogeneic blood transfusion rates with the use of the CellTransTM Autologous Blood Transfusion System. We have also shown a reduction in length of stay in hospital. Prior to the study primary total knee replacement would have been cancelled during times of limited blood availability (amber alert). The use of the ABT is good for the patient in reducing the need for allogeneic blood, and in addition has demonstrated a significant cost saving due to the reduced blood usage and potential prevention of cancelled operation lists.     

The nigral projection to predorsal bundle cells in the superior colliculus of the rat.

Predorsal bundle cells give rise to the major efferent pathway from the superior colliculus to the premotor centers of the brainstem and spinal cord responsible for initiating orienting movements. The activity of predorsal bundle cells is profoundly influenced by an inhibitory pathway from substantia nigra pars reticulata that uses gamma aminobutyric acid (GABA) as a neurotransmitter. The present study examines the morphological basis for this influence of substantia nigra on predorsal bundle cells in the rat. In the first experiments, the laminar distributions of the nigrotectal tract terminals and the predorsal bundle cells were compared. The predorsal bundle cells were labeled by the retrograde axonal transport of horseradish peroxidase from either the decussation of the predorsal bundle or the cervical spinal cord, while the terminations of the pathway from substantia nigra pars reticulata were labeled by anterograde axonal transport from the substantia nigra. Either horseradish peroxidase, wheat germ agglutinin conjugated to horseradish peroxidase, or Phaseolus vulgaris leucoagglutinin were used as anterograde tracers. The results showed that the distributions of both the predorsal bundle cells and the nigrotectal terminals are restricted almost entirely to the intermediate grey layer and that they overlap extensively. Predorsal bundle cells varied in size. Within the areas of maximum overlap, the majority, regardless of size, was closely apposed by nigrotectal terminals. In a second series of experiments, the synaptic contacts between nigrotectal terminals and the tectospinal component of the predorsal bundle were examined in tissue in which both the terminals and the tectospinal cells were labeled for electron microscopy. In the final experiments, the distribution and fine structure of the nigrotectal terminals were compared to those of terminals that had been labeled immunocytochemically with an antibody to glutamic acid decarboxylase, the synthesizing enzyme for GABA. The results showed that nigrotectal terminals contain large numbers of mitochondria and pleomorphic vesicles, and form synaptic contacts with the somas and proximal dendrites of tectospinal cells. These synapses have modest postsynaptic densities. In both their distribution and fine structure, these terminations resemble the glutamic acid decarboxylase immunoreactive terminals that contact tectospinal cells. Taken together, these results support the view that the nigrotectal tract is an important source of GABAergic input to most, if not all, predorsal bundle cells.     

Insulin regulates the 35 kDa IGF binding protein in patients with diabetes mellitus

The serum levels of the low molecular form of insulin-like growth factor binding protein (IGFBP) was determined in 56 outpatients with diabetes mellitus by a radioimmunoassay developed for amniotic 35 kDa IGFBP. The mean level of 35 kDa IGFBP was found to be threefold higher in insulin dependent diabetes mellitus (IDDM), 112 +/- 13 ng/ml, than in age matched controls, 37 +/- 2 ng/ml, while the mean level in non-insulin dependent diabetes mellitus (NIDDM), 16 +/- 2 ng/ml, was decreased. In hospitalized IDDM patients there was a significant correlation (r = 0.91, p less than 0.01) between fasting blood-glucose and 35 kDa IGFBP levels, not found in NIDDM patients. During insulin infusion the 35 kDa IGFBP levels declined with a half-life of 60-120 min. The decline in IGFBP continued even after the establishment of steady state B-glucose at 4.7 mmol/l. In conclusion, the elevated 35 kDa IGFBP levels in IDDM can be attributed to insulin deficiency and may reflect a reduced bioavailability of the IGFs at the target cells.