Optimising Hormone Therapy in Advanced Disease

Although most prostate cancer (PCa) patients nowadays are diagnosed at an early stage of disease, unfortunately still a significant number of patients will develop advanced PCa or will be diagnosed at an advanced (or metastatic) stage of disease. The group of patients showing the highest increase in incidence are those with rising prostate specific antigen (PSA) after radical therapy.In the last quarter of 2004, a Medline search has been performed targeting publications on patients diagnosed with advanced PCa, as well as with PSA relapse after previous radical therapy. This review aims at providing guidance to optimise hormone therapy in those selected groups of patients by addressing three pivotal questions; (i) who should receive hormonal treatment, (ii) what type of hormonal therapy should the patient be offered and (iii) what is the best timing of starting hormonal treatment.In patients relapsing after radical therapy, the PSA doubling time (PSA DT) has become a critical instrument to distinguish patients to have innocuous PSA evolution from patients at high risk for disease progression. A PSA DT of 3 months seems to be the cut-off point for identifying patients at risk. Therefore patients with a PSA DT of less than 3 months should be advised to initiate hormonal therapy. Antiandrogen monotherapy may be considered in this setting as it has been shown to delay progression; however, significant survival data are not yet available. Whether luteinising hormone releasing hormone (LHRH) agonists should be given continuously or intermittently (IHT) remains subject of debate.Surgical castration has been the standard of care in patients diagnosed with advanced PCa. Currently, LHRH agonists have become the preferred way of suppressing testosterone.Combination of an antiandrogen and a LHRH agonist (CAB) shows a modest benefit over LHRH agonist monotherapy. As CAB leads to increased side effects and costs, LHRH agonist monotherapy is preferred in the majority of patients.Conflicting data have been published concerning the optimal timing of LHRH agonist therapy. So it is not clear whether LHRH agonist therapy should be started immediately or deferred until appearance of symptoms. When initiating continuous hormone therapy, patients should be carefully monitored for the risk of long term androgen deprivation (anaemia, osteopenia and osteoporosis).     

Participation in patient self‐management programs

Objective

Participation in evidenced‐based arthritis self‐management programs (SMPs) has not been well documented. The purpose of this study was to investigate the participation rate and participant characteristics in a closed cohort of subjects in a geographic region where arthritis SMPs have been offered multiple times and continuously for 2 decades.

Methods

Data were from osteoarthritis (OA) and rheumatoid arthritis subjects participating in the Arthritis, Rheumatism, and Aging Medical Information System (ARAMIS) who resided in the San Francisco (SF) Bay area who had responded to questions about ever participating in an SMP. Differences between participants and nonparticipants were examined by t‐tests and chi‐square tests.

Results

Questions added to the Health Assessment Questionnaire were returned by 1,176 patients; 618 resided in the SF Bay area. Of the SF Bay area sample, 41.9% had participated in an SMP. Small group SMPs, which had been offered multiple times, in diverse settings, continuously over the past 2 decades, were attended by the highest proportion (28%) of participants. Characteristics of participants and nonparticipants in the SF Bay area were similar (～70 years old, 15 years of education, and the majority had OA [～72%]). However, a higher proportion of participants were white (88% versus 82%; P = 0.046) and female (82% versus 73%; P < 0.05).

Conclusion

When arthritis SMPs were offered multiple times in diverse settings and continuously over many years, >40% of the cohort was reached. More research is needed with larger samples and different geographic regions to identify participation rates in more diverse populations.     

Physiological pharmacokinetics of solutes in the isolated perfused rat hindlimb: Characterization of the physiology with changing perfusate flow,protein content,and temperature using statistical moment analysis

Distribution of Evans Blue (EB), sucrose, and water into the isolated perfused rat hindlimb was studied under various conditions using the multiple indicator dilution (MID) technique. Statistical moment analyses of the outflow profiles for the EB, sucrose, and water were used to define the vascular, extravascular, and total water spaces, respectively. The varied perfusion conditions included albumin content (2, 4.7, and 7%), temperature (25, 37, and 42 C), perfusate flow rate (2, 4, 8, and 12 ml/min) and the presence/absence of red blood cells. The range of studies undertaken were chosen to represent the variety of conditions used in the preparation of both isolated animal and human limbs, the latter being particularly important in cytotoxic therapy for recurrent malignant melanoma. The distribution volumes of EB, sucrose, and water were dependent on the flow rate and the albumin content of perfusate. The normalized variances (CV ² ) of the markers were of the following order: sucrose (2.18) > water (1.58) > EB (0.68), indicating that some disequilibrium occurs during the capillary exchange of water and sucrose. It is suggested that a Krebs-Henseleit buffer containing 2% BSA is a suitable perfusate for most studies of the isolated rat hindlimb perfusion. The effect of albumin concentration manifests itself only at higher flows.We acknowledge the support of the National Heart Foundation (Queensland) and the Mayne Bequest Foundation. This study was conducted while the investigator (Z.Y. Wu) was in receipt of a WHO Research Training Grant. Professor M. S. Roberts also acknowledges the support of the Queensland and Northern New South Wales Lions Kidney & Medical Research Foundation.     

First analysis of the proteome in two nematomorph species, Paragordius tricuspidatus (Chordodidae) and Spinochordodes tellinii (Spinochordodidae).

The proteome of most parasite species is currently unknown. Hairworms (Nematomorpha), 300 species distributed around the world, are parasitic in arthropods (mainly terrestrial species) when juveniles, but they are free-living in aquatic environments when adult. Most aspects of their systematics and biology are currently unknown. The aim of this paper was (i) to report a novel and reproducible protocol for the analysis of the proteome of hairworms using two-dimensional gel electrophoresis (2-DGE) and mass spectrometry (matrix laser desorption ionization-time of flight mass spectrometry (MALDI-TOF)) and (ii) to determine the level of proteomic divergence between two sympatric but taxonomically unrelated nematomorph species in the adult stage, Paragordius tricuspidatus Dufour (Nematomorpha, Gordiidae) and Spinochordodes tellinii Camerano (Nematomorpha, Gordiidae). In total, 689 protein spots were observed for P. tricuspidatus, 575 for S. tellinii. Only 36.2% spots were shared between the two species. Quantitative analysis of the proteins which are common to both parasite species reveals substantial differences in the pattern of protein expression. These results suggest a rapid evolutionary divergence between these two nematomorph families. Also, to test the value of our MALDI-TOF protocol, we used Actin-2 (Act-2), a protein highly conserved in the course of evolution. Peptide mass fingerprint (PMF) data obtained for Act-2 of P. tricuspidatus and S. tellinii suggest a very high homology with Act-2 of different worms species belonging to the Bilateria phylum (Annelida and Nematoda) and more specifically to Lumbricus terrestris (Annelida, Lumbricidae) and Caenorhabditis elegans (Nematoda, Rhabditidae). We discuss our results in relationship with current ideas concerning the use of proteomics in systematics.     

Reoperative coronary surgery. Comparative analysis of 6591 patients undergoing primary bypass and 508 patients undergoing reoperative coronary artery bypass

During an 18-year period a consecutive series of 6591 patients underwent primary coronary bypass grafting and 508 patients underwent reoperative bypass. The mean patient age for the reoperative group was identical to that of the primary group, 59.8 years, but the mean age at initial operation for the reoperative group was 55.2 years. Mammary grafts were done at initial operation in 59% of patients who have had one operation versus only 46% of patients who subsequently required reoperation (p less than 0.001). The overall operative mortality rate was 2.0% (134/6591) for primary coronary bypass versus 6.9% (35/508) for reoperations (p less than 0.001). Patients with a reoperative interval of 1 to 10 years had a 6.0% (18/312) mortality rate, compared with 17.6% (13/74) for those in whom the interval between operations was greater than 10 years (p less than 0.01). Ventricular arrhythmias, excessive bleeding, prolonged ventilatory support, intraaortic balloon pump insertion (all p less than 0.05), and perioperative myocardial infarction (p less than 0.001) were all more prevalent after reoperations. Including perioperative mortality, the actuarial survival rate at 5 years was 80% for reoperations versus 90% for primary operations. The corresponding figures at 10 years were 65% and 75%. The probability of undergoing reoperation within 5 and 10 years was 0.034 +/- 0.003 and 0.055 +/- 0.005, respectively. Ten years postoperatively, 36% of patients having the initial operation had recurrent angina whereas 58% of the reoperative group had significant recurrent angina. Ten years after reoperation, 30% of operative survivors were free of heart-related morbidity and mortality compared with 50% of patients having a primary operation. Univariate analysis of factors increasing the probability of reoperation include the absence of a mammary graft and younger age at operation. Patients undergoing a second bypass operation represent a substantially higher risk subgroup than patients undergoing initial operation in terms of perioperative morbidity, mortality, decreased long-term survival, and decreased relief of recurrent cardiac morbidity.     

Different clinical types of degenerative aphasia

The authors report 3 cases of slowly progressive aphasia with different language disturbances: anomia, pure word deafness and Broca's aphasia. All patients were independent in daily life activities. Insight, judgement and overall behaviour were intact. There was no major disturbance of other cognitive functions, but psychometric tests showed mild deficits suggesting widespread involvement. CT scans and magnetic resonance imaging showed focal dilatation of the left sylvian fissure. A positron emission tomographic study showed left perisylvian hypometabolism. A review of the literature yielded an increasing number of cases of this degenerative syndrome affecting dominant hemisphere language areas. Our cases confirm the clinical heterogeneity of degenerative aphasia. Postmortem neuropathological examinations are rare and many causes are found: Pick's disease, Alzheimer's disease or aspecific gliosis.     

Anatomic variations of the spermatic vein and endovascular treatment of left varicoceles: a pediatric series]

OBJECTIVE: To report on the high incidence of anatomical variants of the origin and course of the internal spermatic vein (ISV) discovered at the time of percutaneous embolization of left varicoceles in a pediatric population. METHODS: We reviewed retrospectively the 65 cases of left varicocele treated by percutaneous embolization (grade II and III) in our institution between 1990 and 2000. The course of the left renal vein (LRV), the origin of the ISV, and the number of ISVs and their pathway were recorded in all cases, according to the B?hren classification. RESULTS: In 37/65 (57%), the ISV was single and arose from a normal LRV (type I). The following variants were encountered: type V--circumaortic LRV 9/65 (14%); type IVb--intrarenal origin of ISV 8/65 (12%); type II--multiple ISV 5/65 (8%); and pelvic collaterals 6/65 (9%). CONCLUSION: Venous anatomical variants are frequently encountered (43%) at the time of left varicocele embolization in children. Such variants often impose some adjustments to the technique of embolization and, at times, hamper the procedure.