Conventional Management Of Patients Research Articles

Pegylated Interferon Therapy for Patients with Philadelphia Chromosome-Negative Myeloproliferative Disorders

The conventional management of patients with high-risk Philadelphia chromosome-negative (Ph-negative) myeloproliferative disorders (MPDs) revolves around the administration of cytoreductive agents such as hydroxyurea, anagrelide, and recombinant human interferon alpha (IFN-alpha). IFN-alpha has shown significant activity in the treatment of chronic myelogenous leukemia (CML) and Ph-negative MDPs. However, the response rates of IFN-alpha therapy frequently have been hampered by high dropout rates due to side effects and inconvenient dosing schedules. Pegylated (PEG) IFN-alpha is formulated by covalently attaching polymers of ethylene glycol of large molecular weight to the native IFN-alpha molecule. Such chemical modification increases serum half-life, decreases renal excretion, and results in prolonged patient exposure to PEG-IFN-alpha, thus allowing for weekly administration while maintaining acceptable toxicity, tolerability, and activity profiles. The lack of adequate therapies for patients with MPDs and the superior pharmacokinetic and pharmacodynamic profile of PEG-IFN-alpha relative to standard IFN-alpha has prompted the investigation of the activity and safety of PEG-IFN-alpha in patients with essential thrombocythemia, polycythemia vera, and idiopathic myelofibrosis. We summarize the available data on the use of PEG-IFN-alpha in patients with Ph-negative MPDs.

Idiopathic pulmonary fibrosis--a disorder of alveolar wound repair?

Idiopathic pulmonary fibrosis (IPF) is a chronic and usually progressive lung disorder of unknown aetiology. Conventional management of patients with IPF has been primarily based on the concept that suppressing inflammation would prevent progression to fibrosis. Although the pathogenesis is incompletely understood, it is here suggested that IPF is a disease of abnormal wound repair and remodelling in the lung rather than an inflammatory disease. Therefore, treatment strategies are no longer aimed at reducing inflammation, but rather at preventing or inhibiting the fibroproliferative responses and enhancing efficient alveolar epithelial repair. So far, no cell-specific drugs for these purposes are clinically available. However, novel promising molecules or drugs are being studied in experimental models or ongoing clinical trials in patients with IPF. Evolving hypotheses on the pathogenesis of IPF are reviewed, focusing on possible implications for future therapies. A better understanding of the sequence of the pathogenic mechanisms that control the fibrotic response will hopefully lead to efficient therapies and finally a favourable outcome in patients with this disease.

Idiopathic pulmonary fibrosis--a disorder of alveolar wound repair?

Idiopathic pulmonary fibrosis (IPF) is a chronic and usually progressive lung disorder of unknown aetiology. Conventional management of patients with IPF has been primarily based on the concept that suppressing inflammation would prevent progression to fibrosis. Although the pathogenesis is incompletely understood, it is here suggested that IPF is a disease of abnormal wound repair and remodelling in the lung rather than an inflammatory disease. Therefore, treatment strategies are no longer aimed at reducing inflammation, but rather at preventing or inhibiting the fibroproliferative responses and enhancing efficient alveolar epithelial repair. So far, no cell-specific drugs for these purposes are clinically available. However, novel promising molecules or drugs are being studied in experimental models or ongoing clinical trials in patients with IPF. Evolving hypotheses on the pathogenesis of IPF are reviewed, focusing on possible implications for future therapies. A better understanding of the sequence of the pathogenic mechanisms that control the fibrotic response will hopefully lead to efficient therapies and finally a favourable outcome in patients with this disease.

Atrioventricular discordance: Results of repair in 127 patients

Objective: The conventional management of patients with atrioventricular discordance is directed at associated lesions, taking advantage of physiologic “correction”; however, the morphologic right ventricle and tricuspid valve support the systemic circulation. Questions surrounding survival using this approach led us to analyze our institutional results. Methods: All patients with atrioventricular discordance undergoing biventricular repair were analyzed (n = 127, 1959-1997), excluding those with functionally univentricular hearts. The ventriculoarterial connection associated with atrioventricular discordance varied and was most commonly discordant (87%), but occasionally concordant (6%), double-outlet right ventricle (6%), or double-outlet left ventricle (1%). At initial presentation, the most common lesions associated with atrioventricular discordance were ventricular septal defect (86%), pulmonary stenosis (64%), tricuspid regurgitation (28%), and atrioventricular block (12%). Nine patients underwent a double switch procedure to create ventriculoarterial concordance and the remainder were managed conventionally without correcting discordant connections. Results: Operative mortality was 6% and did not vary by associated lesion. Twenty years after repair, survival was 48%. Within 20 years, 56% of patients required reoperation, usually for atrioventricular valve incompetence (n = 16), pulmonary stenosis (n = 16), or both (n = 3). Pacemakers were required in 50 patients, 4 before repair, 40 within 2 months of repair, and 6 remotely after repair. In early follow-up, the double switch procedure (n = 9) had equivalent mortality and a high pacemaker requirement for atrioventricular block. Conclusions: Analysis of conventional management of atrioventricular discordance revealed cumulative increases in mortality, systemic atrioventricular valve (tricuspid) replacement, complete atrioventricular block, and incidence of reoperation. Alternative management should be examined. (J Thorac Cardiovasc Surg 1999;117:1190-203)

Conventional radiation therapy of cervical cancer.

This review of the present literature about the conventional management of patients with definitive radiotherapy for invasive carcinoma of the cervix will focus on advances in the use of external-beam radiation therapy (EBRT) as well as in the administration of low-dose-rate brachytherapy for the delivery of radiotherapy. Important concepts discussed include: techniques and dose fractionation for EBRT; newer imaging modalities for administration of EBRT; construction of the midline shield for external irradiation of the pelvic nodes following brachytherapy; the role of elective para-aortic nodal external radiotherapy; and the adequate number of brachytherapy applications needed to impact on patient outcome. Considerable attention will be given to multi-institutional clinical data (e.g., the Patterns of Care Study and the Radiation Therapy Oncology Group) to illustrate advances in radiotherapy of patients with cervical carcinoma.

Conventional radiation therapy of cervical cancer

This review of the present literature about the conventional management of patients with definitive radiotherapy for invasive carcinoma of the cervix will focus on advances in the use of external-beam radiation therapy (EBRT) as well as in the administration of low-dose-rate brachytherapy for the delivery of radiotherapy. Important concepts discussed include: techniques and dose fractionation for EBRT; newer imaging modalities for administration of EBRT; construction of the midline shield for external irradiation of the pelvic nodes following brachytherapy; the role of elective para-aortic nodal external radiotherapy; and the adequate number of brachytherapy applications needed to impact on patient outcome. Considerable attention will be given to multi-institutional clinical data (e.g., the Patterns of Care Study and the Radiation Therapy Oncology Group) to illustrate advances in radiotherapy of patients with cervical carcinoma. Semin. Surg. Oncol. 16:242–246, 1999. © 1999 Wiley-Liss, Inc.

Feeding the inflamed pancreas

See article on page 431 There is a renewed awareness of the detrimental impact of undernutrition on organ function and clinical outcome. There is also evidence that in some clinical...

Clinical results of the combination of radiation and fluoropyrimidines in the treatment of intrahepatic cancer

Radiation therapy has played a minor role in the conventional management of patients with unresectable primary hepatobiliary malignancies and liver metastases. This can be attributed to normal tissue toxicity, which has limited the dose of radiation that can be safely administered, and imaging limitations, which have prevented focal irradiation of involved regions. Trials of whole-liver irradiation with and without 5-fluorouracil (5-FU) or fluorodeoxyuridine (fur) suggest that the addition of fluoropyrimidines results in a slight increase in the median survival without an increase in radiation-induced liver disease (RILD). The development of three-dimensional radiotherapy techniques has now allowed high-dose focal irradiation to be safely delivered, which, when combined with hepatic arterial fur, produces a much higher rate of response and, in some cases, prolonged survival particularly for patients with primary hepatobiliary cancers. Further investigations into the optimal methods of combining the fluoropyrimidines and radiation to permit higher doses of both agents to be delivered as well as methods of protecting the normal liver are expected to yield significant improvement in the outcome of treatment for patients with intrahepatic malignancies.

Noninvasive Positive Pressure Ventilation for Acute Respiratory Failure: Underutilized or Overrated?

continuous positive airway pressure Noninvasive Positive Pressure Ventilation: A Positive View in Need of Supportive EvidenceCHESTVol. 111Issue 6PreviewAlthough interest in noninvasive positive pressure ventilation (NPPV) remains high, its widespread clinical application has been hampered by a lack of well-designed studies comparing it with the conventional management of patients with respiratory failure. Patient and clinician acceptance has been greatest when NPPV has been applied to individuals with chronic respiratory failure consequent upon nonobstructive conditions, such as thoracic restriction or neuromuscular disease. It has become a generally accepted management approach for such individuals and substantial experience in its use has been reported. Full-Text PDF

Extracorporeal CO2 Removal in severe adult respiratory distress syndrome.

Sixty-five per cent survival has been achieved in a group of patients with severe ARDS and a predicted mortality of 92%, by the use of Gattinoni's technique of extracorporeal CO2 removal. In patients and animals the technique has usually resulted in rapid improvement in the radiographic appearance and lung function. There are several possible mechanisms by which the technique may facilitate lung repair, including improvement of lung tissue oxygenation, the avoidance of high airway pressures and regional alkalosis in the lung, a reduction in oxygen toxicity, and the frequency observed reduction in pulmonary artery pressure. The apparent effectiveness of the technique and other associated evidence have implications which should lead us to reconsider some aspects of our conventional management of patients with severe ARDS.