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[Indications of surgical treatment of spontaneous pneumothorax (analysis of 35 cases)].

The experiences in surgical treatment of 35 cases of spontaneous pneumothorax were reported. In 34 cases bullae or blebs were found during the operation. The operation is simple (inducing pleural adhesion by smearing pleura with iodine after local resection of bullae and blebs and with good results. No relapse occurred during 1-13 years followup. We suggest that operation should be considered for treating spontaneous pneumothorax in such cases including failure of medical management, relapse within a short time and more than two relapses. Most of the patients with impaired lung function and bilateral pneumothorax can be treated surgically as well.

Adolescent↗

Treatment approaches to major depressive disorder relapse. Part 1: dose increase.

OBJECTIVE: Although continuing antidepressant treatment after patients have responded to medication has been shown to greatly reduce the risk of relapse, this risk is not eliminated. A number of theories have been proposed to account for this apparent loss of efficacy. A common initial approach to managing relapse is to increase the dose of antidepressant. We prospectively evaluated the likelihood of response to increasing the fluoxetine doses in patients relapsing during a long-term efficacy study of two fluoxetine dosing regimens. METHOD: Patients meeting the DSM-IV criteria for major depressive disorder with modified HAMD17 scores > or =18 and CGI-severity scores > or =4 were treated for 13 weeks with open-label 20 mg/day fluoxetine in a multicenter US study. Responders (n = 501) were randomized to 20 mg fluoxetine daily, placebo, or 90 mg enteric-coated fluoxetine weekly for 25 weeks of double-blind continuation treatment. If the patients relapsed during the continuation phase, they were offered a 25-week optional rescue treatment phase during which the study medication dose was increased as follows: (1) patients on placebo had treatment with fluoxetine 20 mg/day reinitiated, (2) patients on fluoxetine 20 mg/day had their dose increased to 40 mg/day, and (3) patients on a 90-mg weekly dose had their dose increased to 90 mg twice a week. The results of the rescue phase for the latter two groups who relapsed while on continuation treatment with fluoxetine are reported. Response was defined as a 50% reduction in the modified HAMD17 score since time of relapse and a CGI-severity score < or =2. Additional efficacy analyses included HAMD and CGI-severity changes from baseline to endpoint. Safety measures included assessment of treatment-emergent adverse events, vital signs, and laboratory measures. RESULTS: Overall, patients relapsing during the continuation treatment responded to an increased dose (57% of the 40-mg-daily group and 72% of the enteric-coated 90-mg-twice-weekly group). Mean modified HAMD17 scores decreased from a mean of approximately 20 to below 8 and were maintained for up to 6 months in the responders. Thirty-five percent of patients either did not respond or initially responded but again relapsed after augmentation of medication. CONCLUSIONS: The patients relapsing after initially responding to fluoxetine can benefit from an increase in fluoxetine dose. These results also generally support increasing dose as a first-line treatment strategy for a patient who has relapsed while taking a previously effective dose of an antidepressant. Increasing enteric-coated fluoxetine 90 mg once weekly to twice weekly appeared to be as well-tolerated and effective in restoring response as increasing a daily fluoxetine dose from 20 to 40 mg.

Adult↗

Allogeneic bone marrow transplantation in patients who relapse after autologous transplantation.

Increasing numbers of patients have received autologous stem cell transplants (ASCT) for hematologic malignancies. Since only a fraction of these patients are cured, physicians are more frequently faced with the dilemma of how to manage relapse post-transplant. Potential advantages of allogeneic transplantation (alloBMT) over ASCT include lack of graft tumor contamination and presence of a graft-versus-tumor effect. For this reason, patients who relapse after ASCT are often considered candidates for allogeneic bone marrow transplantation. However, there is limited knowledge on the outcome of alloBMT in patients who relapse after ASCT. We retrospectively analyzed the outcome of 20 patients with malignant lymphoma (n = 14) and AML (n = 6) who underwent alloBMT after failing an ASCT. The median age was 30 (17-41) years and the interval from ASCT to alloBMT was 10.5 (2-25) months. Seventeen patients died between 0.3 to 11 months (median 2.0) after alloBMT, all due to BMT-related toxicities. Three patients remain alive and free of disease at 1.1, 1.2 and 2.5 years after alloBMT. Sixteen of the 18 evaluable patients (89%) developed grade II-IV acute GVHD. Patients undergoing alloBMT after ASCT have a very high treatment-related mortality and incidence of grade II-IV acute GVHD. Alternative treatments with salvage chemotherapy, radiation or investigational approaches should be considered in patients who relapse after ASCT.

Adolescent↗

Therapeutic dilemmas in the management of uterine papillary serous carcinoma.

Uterine papillary serous carcinoma (UPSC) affects 1% to 10% of patients with endometrial malignancies. UPSC is more aggressive than conventional endometrial cancer because UPSC presents with advanced disease, similar to epithelial ovarian cancer. There are several biomarkers for UPSC, which indicate that the pathogenesis of this condition is different than epithelial ovarian and conventional endometrial cancer. There are no risk factors for UPSC. Extended surgical staging is the optimal surgical approach for patients without known distant metastases. Patients with stage IA disease do not benefit from further adjuvant therapy. Adjuvant pelvic radiotherapy reduces pelvic relapse in intermediate- and high-risk patients (stage IC, II, and III disease) and extends survival rates of patients when administered with chemotherapy. In this setting, chemotherapy (with or without adjuvant radiotherapy) is a platinum-based regimen, combined with doxorubicin and cyclophosphamide. A newer regimen is paclitaxel, with or without platinum. An alternative approach for treating patients with UPSC has been to use whole abdominal radiotherapy. The results of Gynecologic Oncology Group protocol 122, which involves patients with UPSC who are being treated with chemotherapy and whole abdominal radiotherapy, are expected to reveal a minimal difference between these arms in overall survival rates. In patients experiencing distant or extensive abdominal relapse, management has been palliative, using platinum-based regimens or single-agent therapy to assess response. Treatment for patients with further relapse must be individualized because there are no studies addressing these scenarios. Palliative radiotherapy should be offered to patients needing symptom control for metastatic or progressive local disease. Many of these patients face a significant risk of treatment failure and death because of distant relapse. Therefore, the use of randomized trials to evaluate new therapies is critical.

Carcinoma, Papillary↗

Stage I-II pediatric Hodgkin's disease: long-term follow-up demonstrates equivalent survival rates following different management schemes.

The results of treatment of 171 children with stage I-II Hodgkin's disease from two institutions with differing approaches to management have been analyzed. At the Stanford University Medical Center/Children's Hospital at Stanford (SUMC/CHaS), pathologic staging followed by extended-field radiation alone or involved-field radiation plus combination chemotherapy have been cardinal to the management policy. At St Bartholomew's Hospital/The Hospital for Sick Children at Great Ormond Street (Barts/GOS), clinical staging only has been used over the last 10 years, and involved/regional-field radiotherapy used as the treatment of choice rather than extended-field radiotherapy. Some children at each institution received combined modality therapy as primary management. Relapse among children with stage I disease was a more frequent occurrence in the Barts/GOS series than in the SUMC/CHaS group. However, the survival rates from the two centers are identical, 91% at 10 years. The following scientific-philosophic question is asked: Should one maximally stage and treat all children to increase the likelihood of a high freedom from relapse (FFR; cure) rate, or is it acceptable to minimize the initial staging and treatment, realizing that a proportion of patients will fail and require salvage/rescue therapy? With the awareness of morbidity from pathologic staging and aggressive treatment, and the favorable survival data reported from specialized centers using differing approaches, treatment strategies should be directed toward the long-term goal of cure of disease with maximal quality of life. A multidisciplinary management philosophy undertaken at a center with extensive experience in pediatric Hodgkin's disease is important to achieving this goal.

Actuarial Analysis↗

Advances in the management of epithelial ovarian cancer.

Epithelial ovarian cancer (EOC) is the most lethal gynecologic malignancy in adult women. The most easily identifiable riskfactor is a strong family history of either ovarian or breast cancer; that may indicate the presence of an inherited germ-line mutation in either BRCA-1 or BRCA-2. Common symptoms, such as abdominal bloating and early satiety, indicate more advanced disease, involving the upper abdomen and present in approximately 70% of patients at the time of diagnosis. Physical examination often reveals the presence of a pelvic mass, which is best evaluated by transvaginal ultrasound (TVU) for confirmation. Exploratory laparotomy is required for histologic confirmation, staging and tumor debulking and should be performed by a surgeon trained in these aspects of ovarian cancer management. Patients with early-stage disease, limited to the ovary or pelvis (stages I and II, respectively), have survival in the 80-95% range, whereas the survival of patients with disease involving the upper abdomen or beyond (stages III and IV, respectively) is 10-30%. Because of the propensity of EOC to spread beyond the confines of the ovary, the majority of patients will require postoperative chemotherapy in an attempt to eradicate residual disease. For selected patients with early-stage disease, confined to the ovary, such as those with well-differentiated, completely encapsulated tumors (e.g., stage IA, grade 1), no further treatment is necessary in view of excellent survival after surgery alone. For patients with higher-risk early-stage disease (e.g., those with pelvic extension, capsular rupture or involvement, positive washings, ascites or high-grade lesions) and for patients with advanced-stage disease (stages III and IV), postoperative combination chemotherapy with a taxane and platinum combination is the standard of care. Such treatment is capable of inducing responses in > 70% of patients with residual EOC and is also capable of prolonging both disease-free and overall survival. Unfortunately, despite an initial response to chemotherapy in the majority of patients, relapse is afrequent problem and is often detected by a rise in the serum tumor marker CA-125 in the absence of symptoms or signs of disease by physical examination or radiographic studies. In such cases, a hormonal maneuver is oftentimes considered in order to avoid the toxic effects of chemotherapy when the patient is asymptomatic and the goal of treatment is largely palliation, although eventually the development of clinical progression mandates the institution of second-line chemotherapy. If the treatment-free interval is > 6 months from the completion of first-line treatment, rechallenge with platinum-based chemotherapy is a reasonable first step. For those patients who develop resistance to second-line platinum or who have difficulty tolerating this agent, multiple other options are available for relapse management, including liposomal doxorubicin, topotecan, gemcitabine and etoposide per os. Eventually the disease becomes resistant to multiple chemotherapy agents, and reorienting management toward supportive care and pain control is necessary. Ongoing efforts to identify more effective multiagent first-line regimens, to develop more effective strategies for early detection and to incorporate agents with novel mechanisms of action, such as antiangiogenesis compounds, hold promise.

Antineoplastic Combined Chemotherapy Protocols↗

Current status of the field: contrasting perspectives. The behavioral therapist's view.

Over the past decade, behavioral research and treatment approaches to alcohol problems have become an integral part of the alcohol field. Particularly valuable contributions have included the provision of alternative treatment methods and goals for nonaddicted problem drinkers, the development of relapse management and prevention techniques, the refinement of assessment and treatment outcome evaluation methodologies, and an overall enhancement of our understanding of the nature of alcohol problems. Viewing the progression of research studies over the last 10 years, it is evident that the behavioral perspective on alcohol problems has matured beyond ideological boundaries. The greatest strength of behavioral approaches relates to a reliance on the scientific method. Most likely, behavioral approaches will continue to contribute meaningfully to the field of alcohol studies.

Alcohol Drinking↗

Solitary eosinophilic granuloma of the pediatric skull and spine. The role of surgery.

Nine pediatric cases of solitary eosinophilic granuloma (EG) are reported. Six children harbored cranial lesions and three had spinal involvement. Plain radiographs and computed tomography scan were not always sufficient for diagnosis. Isotopic bone scan was useful to rule out multiple lesions. The authors' opinion is that surgical excision is the treatment of choice for cranial lesions, leaving radiotherapy for possible relapse. Management of EG of the spine should start with needle biopsy, followed by radiation therapy, surgery being indicated in selected patients with immediate risk of neural compression. Mean follow-up time was 4.4 years (longer than several reported series). At the time of revision all children were asymptomatic, and only one case presented a local recurrence that was managed by radiotherapy.

Child↗

[Verrucae vulgares. Treatment with 585 nm flashlamp pumped pulsed dye laser].

BACKGROUND AND OBJECTIVE: Various approaches have been taken in the management of verrucae vulgares, but a treatment of choice has not been established. PATIENTS/METHODS: Over a period of 12 months, 99 Patients with recalcitrant or untreated verrucae vulgares on their hands or feet (2:1) were treated with a 585 nm flashlamp pumped pulsed dye laser (FPDL) every 2 to 4 weeks. Laser parameters were: energy density 8 J/cm2, spot size 7 mm, pulse duration 450 microseconds. No topical measures were employed during the course of laser treatment. RESULTS: 93 patients finished the study, as 6 were lost to follow-up. Up to 8 laser treatments led to 63% total remission and 22% partial remission, 15% did not respond to this type of management. Relapses were not found in a follow-up period of 2 to 6 months. CONCLUSIONS: FPDL is efficient for the removal/reduction of verrucae vulgares and does not requires less patient compliance than other treatment options.

Adolescent↗

A behavioral-cognitive therapy program for adults who stutter: computers and counseling.

This paper evaluates the efficacy of a behavioral-cognitive treatment program for adults who stutter. The program combines a commercially available computer-assisted biofeedback program for the reduction of stuttering and a relapse management program for counseling and attitude change. Four adults who stutter, between the ages of 20 and 25 years, participated in a study with multiple baseline across individuals. The initial treatment was conducted in an intensive time block, followed by extended treatment sessions. Results show that subjects reduced their disfluencies to below 3% stuttered syllables and maintained those changes at the 6 and 12 month follow-up. Measures of attitude changes were also assessed and showed that increases in positive feelings and attitudes were maintained at follow-up.

Adult↗

An existential model for promoting life change. Confronting the disease concept.

This paper outlines an existentially based psychoeducational model for dealing with substance abuse clients' questions concerning the possibility of successful behavior change. Clients frequently misinterpret the "disease model" as meaning that they are powerless victims of addiction. Clients' readiness to change can be enhanced by providing them with a coherent method of conceptualizing the task of rehabilitation, one that explains how change is possible in spite of the "disease model" of addiction, rather than the confusing mix of self-help, "bootstrap" philosophy and "disease" talk presented in many rehabilitation programs. Productive methods of dealing with clients' guilt are presented, along with the need to develop a positive purpose in life as an essential aspect of effective relapse management.

Behavior, Addictive↗

Low dose palliative radiotherapy in low grade non-Hodgkin's lymphoma.

The clinical picture of disseminated (stage 3 and 4) low grade non-Hodgkin's lymphoma (NHL) is one of continuing relapse. Management options include observation only in asymptomatic patients, single agent chlorambucil or localised radiotherapy in patients with symptomatic nodal disease. Radiation doses of 25-40 Gray in 10-20 fractions have been the standard approach in low grade NHL, but in 1994 Ganem et al. [Hematol. Oncol. 8: 225-233, 1994] reported the use of low dose radiotherapy (LDRT)--4 Gray in 2 fractions over 3 days--for the palliation of symptomatic disease in patients with disseminated, chemoresistant low grade NHL. We describe here our early experience with this schedule.

Aged↗

Factors influencing relapse in the long-term course of schizophrenia.

Highly effective neuroleptic drugs have been available for the past 40 years, but 50% of schizophrenic patients, under normal treatment conditions, relapse within 1 year after their latest episode, frequently spending 15-20% of their time in psychiatric institutions. The term relapse usually refers to a deterioration or recurrence of positive rather than negative features, and relapses appear to impair the course of the disease. Impairment is often longer than expected for those patients who discontinue antipsychotic medication and then relapse to their prediscontinuation clinical state of function. Drug therapy is an important defense against relapse. Marked differences in relapse rate between patients receiving placebo and neuroleptic drugs have been observed (approximately 69% after 1 year for the placebo group versus 26% for the neuroleptic group). First-year relapse rates can be reduced from 75% to 15% with prophylactic treatment with neuroleptics. Follow-up studies suggest that noncompliance with medication, pharmacological factors, psychosocial factors and alcohol and drug abuse contribute to setting off new psychotic episodes. The most important of these is noncompliance with medication. The overwhelming majority of schizophrenic patients who suffered a clinical exacerbation and required hospitalization (73%) did not comply with the treatment prescribed. The effect of new antipsychotic agents should be examined in patients who relapse despite maintenance treatment with conventional neuroleptics. We have found that the rate of current drug abuse among patients with schizophrenic relapse (44%) was significantly higher than that in schizophrenic patients who regularly attended outpatient clinics. Also, the rate of alcohol and substance abuse is higher in males (79%) than in females (21%). Psychiatric units should integrate addiction treatments with psychotic-relapse management.

Antipsychotic Agents↗

Cardiomyopathy associated with clozapine.

Clozapine is an atypical antipsychotic agent that is more effective than the standard neuroleptics currently used for treating refractory schizophrenia. In addition, clozapine is a drug with few extrapyramidal side effects. However, clozapine is also associated with potentially serious adverse effects, such as cardiac complications as well as agranulocytosis. Clozapine-related cardiomyopathy has not been previously reported in East Asia. This report describes a 31-year-old Korean male patient with schizophrenia who developed dilated cardiomyopathy on treatment with clozapine. The removal of clozapine caused subsequent physical improvement. However, the readministration of clozapine for managing relapse of psychosis caused a recurrence of dilated cardiomyopathy in this patient. Therefore, this is the 1st report showing that the 2nd trial of clozapine caused recurrence of cardiomyopathy associated with clozapine. Thus, this report adds important support for a causal relation between clozapine and cardiac complications. In conclusion, this report attempts to raise awareness of clozapine-related cardiomyopathy.

Adult↗

Pseudoautologous blood stem cell transplantation for refractory chronic graft-versus-host disease.

A female patient with AML received an allogeneic BMT from her brother. She experienced two relapses managed with chemotherapy and donor leukocyte infusions. The patient subsequently developed extensive therapy-refractory chronic GVHD. Pseudoautologous blood stem cell transplantation was performed as a salvage treatment for chronic GVHD. Her blood stem cells were easily mobilized with cyclophosphamide and G-CSF. The conditioning regimen was well tolerated and consisted of 200 mg/kg cyclophosphamide and horse-derived antithymocyte globulin. A total of 4.03 x 10(6)/kg CD34+ cells were infused and hematological recovery was rapid. Chronic GVHD improved with the ability to taper steroids. Nine months post transplantation the patient died from leukemia.

Adult↗

In vitro co-stimulation with anti-CD28 synergizes with IL-12 in the generation of T cell immune responses to leukaemic cells; a strategy for ex-vivo generation of CTL for immunotherapy.

The existence of an immune based graft-versus-leukaemia (GvL) effect highlighted the prospect of managing relapsed leukaemias with T cell-based adoptive immunotherapy. Thus, various strategies have been explored for the in vitro expansion of acute myeloid leukaemia (AML)-specific T cells. In a popular approach, AML blasts have been genetically modified to express co-stimulatory molecules essential for effective T cell priming. One such tactic has been the modification of AML cells to express the B7/CD80 co-stimulatory molecule that binds to CD28 on T cells initiating events that culminate in enhanced cytokine production, proliferation and development of effector functions by T cells. The success of these strategies has been limited by difficulties in attaining sufficient transduction efficiencies and associated high levels of CD80 expression. We demonstrate that these problems can be circumvented by using anti-CD28 monoclonal antibody. Furthermore, we show that the synergistic relationship between CD80/CD28 pathway and interleukin 12 cytokine (IL-12), documented in the generation of cytotoxic T lymphocytes (CTL) for solid tumours, also applies to AML. CD28/IL-12 synergy facilitated the proliferation of allogeneic T cells in response to stimulation with primary AML blasts. The synergy also favoured generation of a Th1-type immune response, evidenced by gamma interferon (IFN-gamma) secretion and facilitated naive and memory T cell proliferation. Unlike some methods of in vitro T cell expansion, use of CD28/IL-12 synergy left T cells in the physiologically appropriate CD45RA-/CCR7- subsets known to be associated with immediate cytotoxic functions.

Acute Disease↗

Competing considerations in regional nodal treatment for early breast cancer.

The purpose of this article was to review the patterns and morbidity of regional recurrence (RR) in patients with early breast cancer, efficacy of salvage therapy for RR, and complications of regional nodal treatment. A retrospective evaluation of 1,158 patients with stage I or stage II breast cancer treated with conservative surgery and radiotherapy (RT) between 1979 and 1994 was performed. Seven hundred fifty patients underwent axillary surgery, and 229 patients received RT as their only treatment of the regional lymphatics. Regional nodal RT was given to 168 patients who also had axillary surgery. The regional lymphatics of 11 patients were not treated. The patterns and morbidity of RR, relapse management, and complications related to regional nodal treatment were reviewed from the patients' records. With a median follow-up of 88 months, a total of 31 patients (2.7%) developed a RR. Nine of 31 patients (29%) with an RR experienced significant morbidity, including pain, fungating tumor, dysphagia, dyspnoea, and/or sensory motor changes at diagnosis. Nineteen patients (61%) had symptomatic residual or progressive regional disease after salvage therapy at last follow-up or death. Six of nine patients (67%) who developed an isolated axillary recurrence and underwent salvage surgery had no further axillary recurrence. The addition of regional nodal RT to breast irradiation significantly increased the incidence of symptomatic pneumonitis (1% without regional nodal RT and 4% with regional nodal RT, p < 0.001). Combined axillary dissection and nodal irradiation resulted in a significantly higher incidence of arm edema compared with either alone (9.5% with axillary dissection, 6.1% with RT to the axilla and supraclavicular fossa, and 31% with combined modality therapy, p < 0.001). Five of 380 patients (1%) who received RT to the axilla and/or supraclavicular fossa developed a transient brachial plexus neuropathy. Although RR was uncommon in patients treated with axillary surgery and/or regional nodal irradiation, salvage therapy failed to eradicate the recurrence in approximately two thirds of the patients with a RR. Ongoing research is essential to optimize regional control with an acceptable level of risk of treatment complications. Sentinel lymph node biopsy, if validated as an accurate method of staging the axilla in patients with breast cancer, would allow selective avoidance of regional nodal treatment and hence the associated morbidity.

Adult↗

Helping individuals to help themselves.

Obesity is a serious and increasing health issue. Approximately two-thirds of adults in the UK are now overweight or obese. Recent public health reports firmly reinforce the importance of engaging individuals to look after their health, including their weight. They also spell out the need for individuals to be supported more actively, on many levels, to enable this 'engagement'. Meanwhile, national surveys indicate that approximately two-thirds of adults are concerned about weight control, with one-third actively trying to lose weight. This finding is hardly surprising considering current weight statistics, plus the plethora of popular diets on offer. Weight-loss methods include diet clubs, diet books, exercise, meal replacements, advice from healthcare professionals and following a self-styled diet. Obesity is a multi-factorial problem, and losing weight and, in particular, maintaining weight loss is difficult and often elusive. It is argued that the modern obesogenic or 'toxic' environment has essentially taken body-weight control from an instinctive 'survival' process to one that needs sustained cognitive and skill-based control. The evidence suggests that health professionals can help individuals achieve longer-term weight control by supporting them in making sustainable lifestyle changes using a range of behavioural techniques. These techniques include: assessing readiness to change; self-monitoring; realistic goal setting; dietary change; increased physical activity; stimulus control; cognitive restructuring; relapse management; establishing ongoing support. Consistently working in a client-centred way is also being increasingly advocated and incorporated into practice to help motivate and encourage, rather than hinder, the individual's progress.

Cognitive Behavioral Therapy↗