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Spontaneous renal allograft rupture attributed to acute tubular necrosis.

A renal allograft recipient receiving triple immunosuppressive therapy developed spontaneous allograft rupture 5 days after her second cadaveric renal transplantation. Renal biopsy showed interstitial edema with severe acute tubular necrosis (ATN). There was no evidence of acute rejection or renal vein thrombosis. The ruptured renal graft was salvaged by an aggressive fluid resuscitation therapy and surgical hemostasis. The renal function was satisfactory on discharge. We conclude that renal allograft rupture can be the result of interstitial edema solely attributed to ATN in the absence of graft rejection. The ruptured graft kidney is potentially salvageable for those patients whose hemodynamic status can be stabilized by appropriate supportive therapy.

Adult↗

Incidence and risk factors for immune reconstitution inflammatory syndrome during highly active antiretroviral therapy.

BACKGROUND: There is little systematic information regarding the immune reconstitution inflammatory syndrome (IRIS). OBJECTIVE: To determine the incidence, risk factors, and long-term outcome of IRIS in HIV-infected patients receiving highly active antiretroviral therapy (HAART) who were coinfected with one of three common opportunistic pathogens. DESIGN: A retrospective cohort identified through a city-wide prospective surveillance program. METHODS: A retrospective chart review was performed for 180 HIV-infected patients who received HAART and were coinfected with Mycobacterium tuberculosis, Mycobacterium avium complex, or Cryptococcus neoformans between 1997 and 2000. Medical records were reviewed for baseline demographics, receipt and type of HAART, response to antiretroviral therapy, development of IRIS, and long-term outcome. RESULTS: In this cohort, 31.7% of patients who received HAART developed IRIS. Patients with IRIS were more likely to have initiated HAART nearer to the time of diagnosis of their opportunistic infection (P < 0.001), to have been antiretroviral naive at time of diagnosis of their opportunistic infection (P < 0.001), and to have a more rapid initial fall in HIV-1 RNA level in response to HAART (P < 0.001). CONCLUSIONS: IRIS is common among HIV-infected persons coinfected with M. tuberculosis, M. avium complex, or C. neoformans. Antiretroviral drug-naive patients who start HAART in close proximity to the diagnosis of an opportunistic infection and have a rapid decline in HIV-1 RNA level should be monitored for development of this disorder.

AIDS-Related Opportunistic Infections↗

The magic bullet?

The promise of gene therapy has yet to be realised and a recent death has cast a long shadow over clinical trials. Will gene therapy develop into the magic bullet of the 21st Century or is it a technology too complicated to succeed?

Clinical Trials as Topic↗

[The current approaches to organizing the combined treatment of neurotic patients].

Today the study of the pathogenetic mechanisms of the origin and development of neuroses has demonstrated the high effectiveness of a comprehensive approach to their treatment. The staged-reconstructive and prophylactic approach to the treatment of neurotic pathology designed at the Clinic of Neuroses is based on the territorial and administrative unity and close interrelation of all 8 components of the system. An individual approach, comprehensive use of the treatment methods, drug-free therapy developed at the Clinic of Neuroses are based on a profound study of the neurohormonal, immunological and psychological status of patients.

Combined Modality Therapy↗

Rescue therapy with tacrolimus and mycophenolate mofetil does not prevent deterioration of graft function in C4d-positive chronic allograft nephropathy.

BACKGROUND: Humoral alloresponses may contribute to chronic allograft nephropathy (CAN) in a subset of kidney transplant recipients. For chronic humoral rejection, the efficacy of rescue therapy with tacrolimus and mycophenolate mofetil has been suggested. METHODS: Eleven recipients with C4d-positive CAN (index biopsy performed after a median of 3 years posttransplantation), who had been on cyclosporine A-based immunosuppression, were converted to tacrolimus, and if not part of basal therapy, to mycophenolate mofetil. We evaluated the effect of this tacrolimus/mycophenolate mofetil rescue therapy on clinical outcomes and on alloantibody formation detected with flow cytometric testing of panel-reactive antibody. RESULTS: Tacrolimus/mycophenolate mofetil rescue therapy (plus anti-rejection treatment in six recipients with additional signs of acute cellular rejection) failed to prevent progressive deterioration of graft function. Four patients returned to dialysis after 4 to 18 months. Serial post-transplant serology detected HLA class I and/or II reactivity in seven recipients. Tacrolimus/mycophenolate mofetil therapy did not affect the time course of alloantibody levels. One patient with C4d-positive transplant glomerulopathy, who did not respond to tacrolimus/mycophenolate mofetil rescue therapy, developed nephrotic-range proteinuria associated with a rapid decline of allograft function. Despite considerable reduction in alloantibody levels and nearly complete clearance of C4d deposits, immunoadsorption failed to prevent graft failure in this patient. CONCLUSION: Our data argue against the efficacy of tacrolimus/mycophenolate mofetil rescue therapy in established C4d-positive chronic allograft dysfunction. Prospective trials are needed to evaluate whether early initiation of this or other antihumoral strategies are capable of effectively preventing alloantibody-mediated chronic graft injury.

Adult↗

[Rheumatic pain].

RA is a chronic inflammatory arthropathy that characterized by joint destruction with invasive proliferation of synovial cells in articular cartilage. Inflammatory cytokines like TNF-alpha, IL-1 and IL-6 are overproduced and play an important role in the process. In order to relief patient's chronic pain and to prevent of joint destruction, NSAIDs, steroids and DMARDs are common. Recently, anti-cytokine therapy develop and neutralizing antibody to TNF-alpha (infliximab) and TNF-alpha receptor/IgG fusion protein(etanercept) are already used in U.S.A. and in Europe. In Japan, these medicines are now on clinical trial and will be available in a few years. Other anti-cytokine therapy like IL-1 receptor antagonist and anti-IL-6 receptor antibody is also on clinical trial.

Anti-Inflammatory Agents↗

Enhancing patient compliance with tuberculosis therapy.

A major determinant of the outcome of tuberculosis treatment is patient compliance; nevertheless, 20 to 50 per cent of patients fail to complete therapy. The consequences of failure to complete therapy include prolonged communicability, relapse, prolonged and more expensive therapy, development of drug resistance, and death. Noncompliance is a significant factor leading to the persistence of tuberculosis in the United States. Although one-to-one counseling offers the greatest impact for improving compliance, other strategies, such as the use of enablers, incentives, and directly observed therapy, are important as well.

Antitubercular Agents↗

Sinonasal small cell neoplasm developing after radiation therapy for retinoblastoma: an immunohistologic, ultrastructural, and cytogenetic study.

Patients with retinoblastoma have an increased risk of developing second primary tumors. Only a few examples of sinonasal small cell neoplasms developing after radiation therapy for retinoblastoma have been reported. We report one such case that developed 18 years after treatment for retinoblastoma. Histologic examination revealed a small, blue, round cell tumor without rosettes or cytoplasmic glycogen. Immunohistochemically, the tumor cells were positive for neuron-specific enolase, synaptophysin, and S-100 protein, but negative for epithelial and mesenchymal markers, suggesting that this was a primitive neuroectodermal tumor. Cytogenetic studies of this tumor failed to reveal the chromosome 13 abnormality typical of retinoblastoma and the t(11:22) translocation typical of the group of peripheral neuroepitheliomas.

Adult↗

Future directions in the management of ovarian cancer.

As investigators at the bench define the oncogenic pathways involved in ovarian cancer growth and invasion, clinical scientists will develop therapies to target these important pathways. The approach to the treatment of ovarian cancer will change to focus on strategies designed to eliminate minimal residual disease after primary therapy and in this way cure the disease. Concepts of consolidation after standard adjuvant chemotherapy and maintenance regimens will start to be evaluated for clinical efficacy. In addition, the focus on recurrent disease may change from repeated cytotoxic approaches to regimens chosen to prevent invasion or the development of drug resistance, changing the approach to ovarian cancer recurrence to a treatment plan of managing a chronic, but not imminently terminal, disease.

Antineoplastic Combined Chemotherapy Protocols↗

Laryngeal epidermoid carcinoma associated with juvenile laryngeal papillomatosis.

The speculation whether juvenile laryngeal papillomatosis may transform into or be associated with epidermoid carcinoma is explored. We document a case of invasive laryngeal carcinoma arising in preexisting juvenile laryngeal papillomatosis. After multiple childhood laryngoscopies and a tracheotomy, a 54-year-old, 30-pack per year smoker, who had never received radiation therapy, developed a florid exophytic transglottic squamous cell carcinoma. Histologically, the invasive epidermoid carcinoma was surrounded by a field of papillomata with varying degrees of atypical changes. After total laryngectomy, isolated papillomata were found in the lower trachea. There were no cervical lymph node metastases. No postoperative radiation therapy was given. Persistent squamous papillomata in the tracheostomy site, the lower trachea, and the posterior pharynx were treated with the CO2 laser. We emphasize the need to maintain a high index of suspicion for malignancy. In addition, we review the problem of benign papillomata in the aerodigestive tract following laryngectomy.

Carcinoma, Squamous Cell↗

Functional outcome scales in traumatic brain injury: a comparison of the Glasgow Outcome Scale (Extended) and the Functional Status Examination.

Clinical trials aimed at developing therapies for traumatic brain injury (TBI) require outcome measures that are reliable, validated, and easily administered. The most widely used of these measures, the Glasgow Outcome Scale (GOS) and the GOS-Extended (GOS-E), have been criticized as suffering from ceiling effects. In an attempt to develop a more useful and dynamic outcome measure, the Functional Status Examination (FSE) was developed, which grades outcome across 10 functional domains. The FSE has been demonstrated to be reliable and sensitive in monitoring recovery after TBI. This manuscript compares FSE with GOS-E in a cohort of patients with a wide range of injury severities. 177 individuals who survived at least 6 months after TBI were studied. The FSE and GOS-E were administered 6-12 months after injury. FSE and GOS-E scores correlated well with each other. FSE scores were distributed throughout the range, indicating that ceiling and floor effects were not present. Physiologic measures of injury severity (Glasgow Coma Score [GCS]) did not correlate with anatomic measures (Abbreviated Injury Scale [AIS] and Injury Severity Score [ISS]). GCS correlated weakly with both outcome measures, but AIS/ISS did not. We conclude that FSE and GOS-E are reliable outcome measures for TBI survivors, and FSE may offer some advantages over GOS-E due its ability to provide a more detailed description of deficits. The majority of the variance in outcome is not accounted for by currently available measures of injury severity.

Abbreviated Injury Scale↗

Management strategies for osteoarthritis, ankylosing spondylitis, and gouty arthritis.

Rheumatic diseases are among the most frequent causes of pain and disability. Effective management of rheumatic diseases including osteoarthritis (OA), ankylosing spondylitis (AS), and gouty arthritis requires an understanding of the underlying disease mechanisms.Symptoms of OA result from both mechanical factors and elements of inflammation. Current management strategies target both of these factors and generally consist of nonpharmacologic and pharmacologic interventions, including use of nonspecific nonsteroidal antiinflammatory drugs (NSAIDs) and cyclooxygenase-2-specific inhibitors (coxibs), which have analgesic and antiinflammatory properties. Other approaches include intraarticular hyaluronate and the use of alternative therapies under investigation such as acupuncture or glucosamine.Disease mechanisms in AS involve enthesitis, an inflammation at the site of insertion of ligaments, tendons, or joint capsules to bone. Posture and exercise are important nonpharmacologic strategies that may be made easier with the use of NSAIDs or coxibs. Recently developed therapies, including tumor necrosis factor inhibitors, target the underlying disease mechanisms and have demonstrated dramatic symptomatic effects. Disease-modifying effects still need to be established.In gout, hyperuricemia leads to crystal-induced inflammation in some patients. Etoricoxib, one of the newer coxibs, has shown promise in treating acute gout, with efficacy similar to indomethacin, the current standard NSAID often used in these patients. Oral or intraarticular steroids can also be considered. For chronic care uricosurics can be beneficial if renal function is normal and excretion is not excessive, but allopurinol is used most often. Nonpharmacologic modalities, such as rest and cold applications, are useful for acute episodes, and lifestyle modification in the form of diet can also play a role in chronic disease management.

Journal Article↗

The use of Fas Ligand, TRAIL and Bax in gene therapy of prostate cancer.

Prostate cancer is the second leading cause of cancer death in the United States. Treatment options for confined disease are generally successful in prolonging life but long-term cures (10-15 years) are elusive for the majority of patients. The prognosis for advanced extra-capsular prostate cancer is grim. However, we are now entering the era of gene therapy options for treatment of prostate cancer. The human genome project coupled with genomics and protemics are providing information that will lead to selection of genes for treatment of prostate cancer. The problem is the science of delivery lags behind knowledge of gene function. Thus, it is important to develop therapies that do not require delivery to 100% of tumor cells but which nevertheless kills the entire cancer by virtue of the bystander effect or other means. This review covers the use, in gene therapy, of apoptotic inducing molecules such as Fas Ligand, and TRAIL which are believed to induce bystander killing activity and Bax which also may function in a similar way.

Adenoviridae↗

[Modern treatment methods for multiple myeloma: guidelines from the Dutch Haemato-Oncology Association (HOVON)].

The treatment for multiple myeloma has undergone many changes over the past decade. Intensive therapy with autologous stem-cell support has improved the clinical outcome significantly in younger patients. Reduced intensity conditioning regimens have lowered the high treatment-related mortality of myeloablative allogeneic transplantation. New effective anti-myeloma drugs such as bortezomib and thalidomide analogues have become available. These new developments have made it necessary to formulate recommendations to facilitate decisions concerning the management of myeloma patients. The Myeloma Working Party of the Dutch Haemato-Oncology Association (Stichting Haemato-Oncologie voor Volwassenen Nederland) has developed therapy guidelines based on phase-II and phase-III studies as well as the expertise of the working party. These include upfront induction therapy followed by autologous transplantation for patients aged up to 65 years and oral melphalanprednisone treatment for patients with severe co-morbidities and patients over the age of 65 years. Patients under the age of 66 with an HLA-identical (family) donor are candidates for non-myeloablative stem-cell transplantation following autologous stem-cell transplantation. For second-line treatment, thalidomide, combined with dexamethasone is recommended. Younger patients responding to second-line treatment are candidates for a second autologous transplant. Bortezomib is indicated for those patients refractory to the previous two lines of treatment. All patients should receive long-term bisphosphonates. Erythropoietin may be considered in symptomatic anaemia as well as antibiotic prophylaxis during induction therapy which includes dexamethasone.

Antineoplastic Combined Chemotherapy Protocols↗

Psychotherapy of panic syndrome: focusing on ecological aspects of relationships.

Cognitive Behavioral Therapy (CBT) has been shown to be an effective symptomatic treatment for panic attacks; however, this paper recommends complementing it with an approach based on an interactive ecological model. The approach is based on the thesis that a panic syndrome can occur if patients block an impending and/or already initiated development of their relationships, especially involving partners or work. The case may be that, over a period of years, phobic attitudes and behavior described further in the text have enabled patients to maintain a socially positive shaping of their personal niches. Later, phobic avoidance behavior is no longer adequate due to the requirements of the new stage of life. Unconsciously, patients configure an outer relationship situation that demands of them the realization of the impending step in development. Therapy should utilize this relationship configuration.

Adult↗

Evaluation of the effective drugs for the prevention of nausea and vomiting induced by morphine used for postoperative pain: a quantitative systematic review.

Postoperative nausea and vomiting (PONV) with morphine therapy develops in more than 60% of patients after surgery, markedly reducing patient QOL. The prophylactic effect of several antiemetics has already been studied, but evaluations, and even those using the same drug, are not uniform. The present research involved a meta-analysis of randomized controlled trials on prophylactic drug therapy for PONV in patients receiving morphine for the treatment of postoperative pain. The efficacy of the prophylactic administration of the drugs was examined. As a result, meta-analysis of five drugs was possible and the evidence of efficacy was shown for three drugs ranked in order of an increasing odds ratio (OR) and confidence interval (CI): dexamethasone (OR: 0.23, 95% CI: 0.15-0.35, p < 0.00001), droperidol (OR: 0.27, 95% CI: 0.21-0.34, p < 0.00001), and metoclopramide (OR: 0.48, 95% CI: 0.30-0.75, p < 0.001). These results suggest that the three drugs are effective in prophylactic treatment for PONV. Of them, dexamethasone used as a prophylactic drug for PONV provided the best results. Dexamethasone was shown to reduce the incidence of PONV from 66-80% to 16-50% with a dose of 1.25 to 10 mg and to be suitable as a first drug of choice.

Antiemetics↗

Treatment options for newly diagnosed patients with adult acute lymphoblastic leukemia.

The treatment of adults with acute lymphoblastic leukemia (ALL) has been modeled on therapy developed for childhood ALL. The similarity between childhood and adult forms of this disease allows for inferences to be drawn from experience in the pediatric population. However, adults with ALL have far poorer outcome when compared to children. Some of this difference can be attributed in ability to tolerate intensive therapy coupled with an increased incidence of unfavorable cytogenetic subgroups and a decreased incidence of favorable cytogenetic subgroups. Treatment of adult ALL is typically divided into four broad categories: induction, consolidation, maintenance, and central nervous system prophylaxis. Despite three decades of clinical investigation for devising improved treatment programs for adults with ALL, no single program has emerged as the standard. Here we review classification, prognostic features, current treatment programs, and new advances as applied to adult patients with newly diagnosed ALL.

Adult↗

[Non-toxic nodular goiter: treatment and follow-up].

Between 1982 and 1993, 224 patients (196 females and 28 males) with benign lesion of the thyroid underwent surgery. This group included: 1) 210 pts with p multinodular goiter or solitary nodule with normal serum levels of T3, T4, FT3, FT4, TSH (Thyroid stimulating hormone; 2) 14 pts with a hyper-functioning goiter; 3) 12 pts with recurrent nodules following surgery which had been carried out in another hospital. In this study only those pts with solid cold (hypofunctioning) nodules which had not been treated previously were evaluated. The minimal follow-up was 18 months. It consisted of serologic studies (86 cases), ultrasonography (70 cases) and ultrasonography and scintigraphy (5 cases). We performed isthmusectomy in 2 cases, total lobectomy in 42 cases and subtotal thyroidectomy in 42 cases. Out of the 86 pts evaluated, 70 (81.3%) were treated with post-surgical hormone suppressive therapy (Levothyroxin 100 gamma daily). The endogenous thyroid stimulating hormone (TSH) was suppressed in 50 cases (71%), while 20 pts (28.5%) remained within the norm. Thyroid ultrasonography demonstrated recurrent nodules in 14 out of the 86 evaluated (16.2%). All these pts received thyroxine therapy. Among the 50 pts who had been treated with an adequate dose of thyroid hormone, 5 had recurrences (10%), as compared to 3 out of the 20 cases (15%) who had been administered thyroxine dosage not high enough to suppress THS and to 6 pts out of the 16 (33.5%) who had not been administered thyroid hormone. One out of the 20 pts (5%) who had undergone total lobectomy and post-surgical suppressive hormone therapy developed recurrence as compared to 6 out of the 24 pts (25%) who had under gone lobectomy and had been administered a hormone dosage which was not high enough to suppress TSH. Four out of the cases (13.3%) who had under gone subtotal thyroidectomy and post-surgical suppressive hormone therapy had recurrence as compared to 3 out of the 12 (25%) who had undergone subtotal thyroidectomy without TSH suppression. We conclude that treatment with thyroid hormone decreases the risk of benign recurrences only when undergone a long thyroxine therapy in doses high enough to suppress endogenous TSH.

Aged↗