The evolving role of docetaxel in the management of androgen independent prostate cancer

PURPOSE: Androgen independent prostate cancer is an advanced disease with an extremely poor outcome. In view of this fact, a great deal of interest has recently been generated in the potential use of chemotherapeutic agents, particularly docetaxel. We reviewed the evolving role of docetaxel as a chemotherapeutic agent for the management of this disease. MATERIALS AND METHODS: The main emphasis of this review is discussion of the various clinical trials that have investigated the use of docetaxel alone or combined with other agents for androgen independent prostate cancer. RESULTS: Docetaxel, which acts primarily by inhibiting microtubular depolymerization, in combination with other agents has consistently demonstrated a palliative response, a decrease in serum prostate specific antigen levels by 50% or greater in more than 60% of patients, a decrease in measurable disease and the suggestion of improved survival. CONCLUSIONS: Docetaxel based regimens are moderately well tolerated and they have shown promising results in various phase 2 trials. The completion of ongoing phase III randomized trials are eagerly awaited since they may determine whether a definite beneficial impact on overall survival can be achieved.     

Natural killer cell cytolytic activity is necessary for in vivo antitumor activity of the dipeptide L-glutamyl-L-tryptophan

A dipeptide, L-glutamyl L-tryptophan (L-glu-L-trp), was identified in a screen for immunomodulators in the soluble fraction of the thymus. L-glu-L-trp inhibits tumor growth in mice without showing direct cellular toxicity in a variety of human tumor cell lines. L-glu-L-trp antitumor activity in vivo requires the presence of natural killer (NK) cells. Defective trafficking of cytoplasmic granules caused by the Lyst mutation also resulted in loss of antitumor activity of the dipeptide. The effect of L-glu-L-trp on tumor growth in mice with targeted gene mutations demonstrated the absolute requirement for perforin for antitumor activity. The requirement of 2 major modulators of NK cell activity, gamma interferon (IFNgamma) and interleukin (IL)-12, were also tested. L-glu-L-trp had full antitumor activity in IFNgamma knockout mice, but had significantly diminished activity in IL-12 knockout mice. These data show that L-glu-L-trp antitumor activity in mice is dependent on cytolytic cell activity of NK or NKT cells. L-glu-L-trp in vivo regulates NK cell function independent of IFNgamma but partly dependent on IL-12.     

Bone marrow transplant in Pakistan: indications and economics

Bone marrow transplant has become the treatment of choice in a number of disease and its indications are increasing every day. Until recently as it was only available in countries abroad the cost was prohibitive. For this reason majority of patients never thought about it. The facility has now become available in Pakistan at a much lower cost. Because of the limited number of transplant beds it is important that only selected patients should be advised about it. The article reviews aspects to be considered before advising a patient to undergo bone marrow transplant.     

Combination risperidone and SSRI-induced serotonin syndrome

OBJECTIVE: To report 2 cases of serotonin syndrome associated with combined therapy of risperidone and selective serotonin-reuptake inhibitors (SSRIs) in elderly patients. CASE SUMMARIES: An 86-year-old white man was admitted to the emergency department because of increased confusion and generalized weakness over the past several days. His medication history indicated paroxetine 10 mg/d and risperidone 0.25 mg/d. The patient's confusion worsened and underwent acute changes that resembled delirium. He was placed in a geri chair and he became extremely agitated. He was then treated with escalating doses of risperidone. The patient died on day 5 of admission, at which time he was being treated with risperidone 2-3 mg/d. A 78-year-old white female nursing home resident was admitted to the emergency department because of increased confusion and generalized weakness. She was being treated with paroxetine for depression and risperidone for agitation. Her risperidone dose was increased to manage agitation. The patient's agitation worsened with increasing doses of risperidone; she developed tremor, dizziness, and muscle incoordination. After psychopharmacologic consultation, the risperidone and paroxetine were discontinued and she was treated with lorazepam. The patient recovered, returned to baseline status in 2 days, and was later transferred back to the nursing home. DISCUSSION: We believe that in both cases, serotonin syndrome was precipitated by risperidone in combination with SSRI antidepressants. A literature search indicated one report of serotonin syndrome with a combination of risperidone and paroxetine. CONCLUSIONS: An objective causality assessment revealed that the adverse drug event was probable in the first patient and definite in the second patient. We caution clinicians treating elderly patients with combined risperidone and SSRIs to include serotonin syndrome in differential diagnosis if the patient is showing signs of increasing agitation with escalating doses of risperidone.     

Aeopecia areata in Kashmir: a study of 200 patients

Two hundred patients with alopecia areata who attended the Skin. O.P.D. were studied in respect to the age, sex and patterns and sites of involvement and other associated dermatoses.     

Seroprevalence of human herpesvirus-8 (HHV-8) in countries of Southeast Asia compared to the USA, the Caribbean and Africa.

Seroprevalence of HHV-8 has been studied in Malaysia, India, Sri Lanka, Thailand, Trinidad, Jamaica and the USA, in both healthy individuals and those infected with HIV. Seroprevalence was found to be low in these countries in both the healthy and the HIV-infected populations. This correlates with the fact that hardly any AIDS-related Kaposi's sarcoma has been reported in these countries. In contrast, the African countries of Ghana, Uganda and Zambia showed high seroprevalences in both healthy and HIV-infected populations. This suggests that human herpes virus-8 (HHV-8) may be either a recently introduced virus or one that has extremely low infectivity. Nasopharyngeal and oral carcinoma patients from Malaysia, Hong Kong and Sri Lanka who have very high EBV titres show that only 3/82 (3.7%) have antibody to HHV-8, demonstrating that there is little, if any, cross-reactivity between antibodies to these two gamma viruses.     

Sudden cardiac death

SCD continues to be an important cause of death and morbidity. Despite expanding insight into the mechanisms causing SCD, the population at high risk is not being effectively identified. Although there is still much to do in the management phase of SCD (predicting the efficacy of various therapies), recent clinical trials have helped define the relative risks and benefits of therapies in preventing SCD. Trials are underway to determine whether treating other patient populations, including asymptomatic patients after MI, will improve survival rate. The approach to reducing mortality rate will always be multifaceted; primary prevention of coronary artery disease and prompt salvage of jeopardized myocardium are 2 important aspects of this approach. In addition to interventions for MI, such as myocardial revascularization when indicated, simple and easily administered therapies that are likely to remain the most effective prophylactic interventions are aspirin, ACE inhibitors, beta-blockers, and cholesterol-lowering agents. However, the MADIT and AVID data clearly demonstrate a role for ICD therapy in a subgroup of patients who have VT/VF and are at risk of cardiac arrest. Even though the absolute magnitude of benefit associated with ICDs is still to be determined, the AVID study and other recent reports provide convincing evidence that patients who have VT/VF fare better with ICDs than with antiarrhythmic drug therapy. For the high-risk population described in this article, in addition to aggressive anti-ischemic and heart failure therapy, ICDs are now a mainstay of life-saving treatment. Still to be surmounted is the challenge of identifying patients who have nonischemic substrates and of providing them with the appropriate therapy. Guided by genetic studies and new insight into the mechanisms of such problems as congenital long QT syndrome, life-saving and life-enhancing therapies may soon be available for the management of SCD.