Topical corticosteroid therapy for the prevention of acute radiation dermatitis: a systematic review of randomized controlled trials

Acute radiation dermatitis (ARD) is a common side effect of radiation therapy and is characterized by erythema, dry desquamation or moist desquamation. This wet desquamation is a very painful condition for the patient and often leads to interruption of radiotherapy. The objective of this article is to assess the efficacy of topical corticosteroids in the prevention of ARD compared with placebo, other topical medication or no treatment. The prophylactic application of topical corticosteroid among patients undergoing radiotherapy appears to significantly reduce the incidence of ARD, specifically moist desquamation, compared with other treatments. Future trials with a more standardized measure of radiation dermatitis grading are recommended. Further research may also be conducted to determine if a mildly potent, midpotent or super potent topical steroid will be more effective in preventing ARD.     

Cortical petechial hemorrhage,subarachnoid hemorrhage and corticosteroid-responsive leukoencephalopathy in a patient with cerebral amyloid angiopathy

We describe a 69-year-old woman who developed subacute onset cognitive decline after hitting the left side of her head. Cerebral spinal fluid showed yellowish discoloration with highly elevated protein content. FLAIR MRI revealed diffuse high signal intensity in all cortical sulci, and leptomeningeal enhancement in the left cerebral hemisphere was seen in the T1 image after contrast administration. She was treated with a corticosteroid. Consciousness disturbance was temporarily relieved but again worsened, resulting in an apathetic state due to communicating hydrocephalus. A shunt tube was placed in her right lateral ventricle. A brain biopsy disclosed multiple cortical microbleeds and heavy deposition of Aβ-immuoreactive amyloid on vascular walls. Inflammatory mononuclear cells surrounded a few leptomeningeal vessels. After the operation her condition further deteriorated and she fell into a coma. MRI showed diffuse swelling of the right cerebral white matter. She again received high-dose corticosteroid and gradually recovered during the following 2 months. On MRI the vast majority of abnormal signals in the right cerebral white matter disappeared. An initial manifestation of this patient was possibly caused by multiple microhemorrhages from fragile cortical and subarachnoid vessels with Aβ-amyloid deposition, which was triggered by head trauma. CAA-related inflammation possibly worsened this condition. Additionally, surgical intervention for communicating hydrocephalus might have induced cerebral amyloid angiopathy (CAA)-related leukoencephalopathy in her right cerebral hemisphere. These CAA-derived manifestations are unusual and high-dose corticosteroids seems to be useful for vascular events in CAA patients.     

Prospective study of corticosteroid as an adjunct in the treatment of endobronchial tuberculosis in adults

Abstract Although endobronchial tuberculosis frequently causes bronchial stenosis, there are no specific therapies to prevent the sequelae. The use of corticosteroids remains controversial and there have been no prospective comparative studies about the effectiveness of corticosteroids. This study was undertaken in order to determine the effectiveness of corticosteroids in the prevention of complications of endobronchial tuberculosis. Thirty-four patients with endobronchial tuberculosis who were admitted to Chung-Ang University hospital from March 1991 to December 1995 were evaluated prospectively to determine the effect of corticosteroid in the treatment of endobronchial tuberculosis. All patients were randomly divided into two groups: group 1 ( n =17, anti-tuberculosis chemotherapy only) and group 2 ( n = 17, combining anti-tuberculosis chemotherapy with oral corticosteroid). Serial bronchoscopies, pulmonary function tests and chest roentgenograms were analyzed every 2 months until the complete resolution of endobronchial tuberculosis. Before treatment commenced there were no significant differences between the two groups with respect to sex, mean age, pulmonary function, chest roentgenogram and morphologic patterns of endobronchial lesion. After treatment, the healing rate of bronchoscopic findings and changes in pulmonary function showed no significant differences between the two groups. Radiologic improvements were observed in all eight patients (five in group 1 and three in group 2) with segmental atelectasis on chest roentgenograms after 2 months of treatment. This study suggests that corticosteroid therapy would not influence the outcome of endobronchial tuberculosis and that prompt treatment with early diagnosis, before formation of fibrosis would be necessary to prevent complications of endobronchial tuberculosis, such as bronchostenosis.     

Multifocal spinal and extra-spinal Mycobacterium chelonae osteomyelitis in a renal transplant recipient

Only localized cases of Mycobacterium chelonae osteomyelitis have been reported. In this article, a 55-year-old immunosuppressed man with M. chelonae osteomyelitis and multiple spinal and extra-spinal involvement is presented. The patient had nodule-pustular skin lesions, spondylodiscitis at multiple levels, and osteolytic lesions at extra-spinal locations. Biopsy and cultures of the osseous lesions showed M. chelonae osteomyelitis. The patient started antimycobacterial chemotherapy with ciprofloxacin and clarithromycin. Progressive cervical kyphosis associated with anterior wedged deformity of the C5 vertebra and posterior C5-C6 spondylolisthesis resulted in compression of the spinal cord and neurological impairment. The patient underwent anterior decompression and C4-C6 arthrodesis using a titanium mesh cage and cervical plate. About 15 months after the initiation of chemotherapy and 5 months after surgery, the patient was pain free, with significant improvement of his neurological function. In the presence of immunosuppression, the physician should be alert for unusual or opportunistic pathogens of osteomyelitis. Long-term antimicrobial chemotherapy and surgical intervention is the cornerstone of successful treatment of multifocal bone M. chelonae infection.     

Corticosteroid receptor genetic polymorphisms and stress responsivity

A fundamental question in the neuroendocrinology of stress-related psychopathology is why some individuals florish and others perish under similar adverse conditions. In this contribution we focus on the variants of mineralocorticorticoid (MR) and glucocorticoid receptors (GR) that operate in balance and coordinate behavioral, autonomic, and neuroendocrine response patterns involved in homeostasis and health. In the GR-gene, three single nucleotide polymorphism (SNPs) have been associated with changes in metabolic profile and cardiovascular parameters: the ER22/23EK with a favorable and the N363S and the Bcl1 with a more adverse profile. Importantly, the N363S and the Bcl1 are found to increase cortisol responses to a psychosocial stressor. As a result, the whole body will suffer from overexposure with possible adverse effects on metabolism, cardiovascular control, immune function, and behavior. Also in the MR gene, variants are being identified that are associated with dysregulated autonomic, behavioral, and neuroendocrine responses. The data suggest that these MR and GR variants contribute to individual differences in resilience and vulnerability to stressors, and that these receptors therefore are potential drug targets for recovery of homeostasis and health.     

Technical interventions to increase adenoma detection rate in colonoscopy

Introduction: Adenoma detection rate (ADR) is the most robust colonoscopy quality metric and clinical studies have adopted it as the ideal method to assess the impact of technical interventions.

Areas covered: We reviewed papers focusing on the impact of colonoscopy technical issues on ADR, including withdrawal time and technique, second evaluation of the right colon, patient positional changes, gastrointestinal assistant participation during colonoscopy, water-aided technique, optimization of bowel preparation and antispasmodic administration.

Expert commentary: Overall, technical interventions are inexpensive, available worldwide and easy to implement. Some of them, such as the adoption of split dose regimen and slow scope withdrawal to allow a careful inspection, have been demonstrated to significantly improve ADR. Emerging data support the use of water-exchange colonoscopy. According to published studies, other technical interventions seem to provide only marginal benefit to ADR. Unfortunately, the available evidence has methodological limitations, such as small sample sizes, the inclusion of expert endoscopists only and the evaluation of single technical interventions. Additionally, larger studies are needed to clarify whether these interventions might have a higher benefit on low adenoma detectors and whether the implementation of a bundle of them, instead of a single technical maneuver, might have a greater impact on ADR.     

Chronic daily ethanol and withdrawal: 4. Long-term changes in plasma testosterone regulation, but no effect on GnRH gene expression or plasma LH concentrations

Although ethanol has been repeatedly demonstrated to inhibit the hypothalamo-pituitary-testes axis by multiple mechanisms, plasma testosterone levels can be normal in alcoholics who do not exhibit severely compromised liver function and even increased in some abstinent alcoholics, suggesting that adaptive changes to chronic alcohol abuse may alter these regulatory mechanisms. To address this variability, we have investigated the effects of chronic ethanol and withdrawal on rat testosterone regulation using a well-characterized liquid diet model that we have previously demonstrated to (1) provide daily oral ethanol consumption that produces behaviorally relevant plasma ethanol levels during the active (awake) stage of the photoperiod; (2) establish physical dependence on ethanol; and (3) produce not only hypothalamo-pituitary-adrenal axis, but also behavioral (anxiety-like behavior, response to novelty, sucrose preference) changes consistent with those of actively drinking and subsequently abstinent alcoholics. The results demonstrate that chronic daily episodes of ethanol consumption and withdrawal by male Sprague-Dawley rats decreased (p<0.01) plasma testosterone levels late in the afternoon (by 70% relative to ad libitum-fed controls and 63% relative to pair-fed controls), but not in the morning. During gradual cessation of daily ethanol consumption, morning plasma testosterone levels increased, and this 90–115% (p<0.05) increase was maintained for 3 d after complete cessation of ethanol consumption. Three weeks after cessation of ethanol consumption, plasma testosterone levels were again increased by approx 100% (p<0.01). Plasma luteinizing hormone (LH) concentrations and anterior hypothalamus/preoptic area gonadotropin-releasing hormone (GnRH) mRNA levels were not altered at any of these time points. Thus, chronic daily ethanol consumption and daily withdrawal induced changes in circulating testosterone regulation that (a) were time of day dependent and (b) included adaptive changes persisting long after consumption of ethanol ceased. Accordingly, resolution of changes in testosterone regulation and their potential roles in alcohol abuse and relapse will require evaluating changes throughout the circadian cycle during, shortly after, and long after active alcohol abuse.     

Cardiac sarcoidosis: Diagnostic, prognostic, and therapeutic considerations

Summary Cardiac involvement in patients with sarcoidosis is an important consideration for those who are concerned with this strange disease. Sarcoidosis is not an acute malignant disease but may be noticed at the time of sudden, unexpected death as fatal myocardial sarcoidosis at autopsy. Even with modern advances in our ability to diagnose heart disease, cardiac sarcoidosis is still often overlooked because of its subclinical disease progression. In view of this, an extensive review of previously published literature and of our own case analyses has been carried out because of the authors' long-term experience with performing Konno's endomyocardial biopsy, which was originally developed in 1962 at the author's institution. However, the sensitivity of endomyocardial biopsy in detecting sarcoid granuloma is low (20–30%), and, instead, various kinds of nongranulomatous pathologies are often seen. During the course of our research it was found that there might exist a racial difference in cardiac sarcoidosis. Cardiac death was much more frequent in Japanese patients. The possibility that heart disease in sarcoidosis is caused by cor pulmonale due to advanced pulmonary fibrosis should be reevaluated because only a limited amount of background data is available. The authors' review clarified the fact that cardiac sarcoidosis is caused by myocardial or pericardial involvement, resulting in various kinds of bradyarrhythmias or tachyarrhythmias and/or congestive heart failure. Electrocardiographic (ECG) and Holter monitor readings provide a simple and effective method for early detection of this disease. The incidence of ECG abnormalities in a total of 963 sarcoidosis patients was 22.1%, which was more frequent than that of the sex- and age-matched healthy control subjects (17.9%; p < 0.025). Echocardiography and radionuclide studies also provide useful clinical information. Careful follow-up and early corticosteroid administration followed by small maintenance doses may prevent the progression of the disease and improve prognosis. Owing to the progress in antiarrhythmic drugs and pacemaker implantation, the primary cause of death in cardiac sarcoidosis has changed from sudden death (1976 report) to congestive heart failure (1985 report).     

Abrupt withdrawal of isosorbide-5-mononitrate in Durules(R) (Imdur(R)) after long term treatment in patients with stable angina pectoris

In a single-blind study of 6 weeks' duration, 32 patients withstable angina pectoris, who hadbeen receiving controlled-release,Durules®, isosorbide-5-monoitrate (Imdur®) 60 to 180mg daily for at least 1 year, were assessed after abrupt withdrawalof the nitrate. After 2 weeks of placebo treatment nitrate therapywas re-instituted, and the patients followed for antoher 2 weeks.The possibility of developemnt of tolerance and rebound phenomenawas also investigated. Three patietns experienced severe anginal symptoms necessitatinghospitalization when controlled-release isosorbide-5-monoitratewas withdrawn abruptly. Patients complained of more severe anginalsymptoms during the placebo period, experienced more frequentanginal attacks and used more glyceryl trinitrate tablets thanduring active treatment. ST segment changes during exercisewere more pronounced with placebo. After controlled-releaseisosorbide-5-mononitrate was re-introduced, these variablesindicated significant improvement. On the other hand, no deteriorationoccurred in exercise performance during the placebo phase. Responsivenessto glyceryl trinitrate was maintained, as shown by comoparisonsof exercise tests performed after the long term treatment andduring the placebo phase. Controlled-release isosorbide-5-mononitrate retains a beneficialeffect in patients with angina pectoris during prolonged use,although some attenuation of the effect is seen. Abrupt withdrawarlof the drug is not recommended because of the possibility ofsevere exacerbation of anginal symptoms, although no clearcutrebound phenomena were seen.