Aspergillus endocarditis in chronic granulomatous disease

We report the first case, to our knowledge, of Aspergillus endocarditis in chronic granulomatous disease in a patient who also had an atrial septal defect. A diagnosis was made on culture of the organism from the mass despite extensive prior investigation. The presence of distinctive skin lesions as a diagnostic clue of fungaemia is highlighted. Possible advances in diagnosis by detection of fungal cell wall components and in prophylaxis by use of itraconazole are referred to. We conclude that fungal endocarditis should be considered in this condition, especially in the presence of a structural heart defect.     

IMPAIRED LYMPHOCYTE TRANSFORMATION AND CHROMOSOMAL ABNORMALITIES IN FATAL GRANULOMATOUS DISEASE OF CHILDHOOD

A previously described case of fatal granulomatous disease of childhood is presented here as certain previous findings could not be confirmed and since two unusual features were noted. Upon the basis of impaired leucocyte function in the father of this patient a new mode of genetic transmission for the disease was proposed meanwhile we have been unable to confirm these original findings (11). This case in itself was interesting since, firstly an impaired in vitro lymphocyte transformation was noted and this later related to the presence of a serum inhibitory factor. Secondly, chromosomal abnormalities were recorded in peripheral blood cells of both patient and his mother and this might be considered evidence to favour a sex-linked transmission of the disease in this case.     

In-field and out-of-field effects in partial volume lung irradiation in rodents: possible correlation between early dna damage and functional endpoints

Purpose: Recent observations have shown that there are regional variations in radiation response in mouse lung as measured by functional assays. Furthermore, there are both in-field and out-of-field effects in radiation-induced lung damage as observed by DNA assay in rats. The purpose of this work is: (a) to examine mice lethality data following partial volume lung irradiation to assess the possibility of directional or regional effects, (b) to evaluate the correlation between mice lethality data and DNA damage assayed by micronuclei production in rat lung, and (c) to re-interpret mice lethality considering the existence of directional effects in lung cellular response to partial volume irradiation.

Methods and Materials: The lethality data for mice, generated at the M. D. Anderson Cancer Center, Houston, and micronuclei yield data for rats obtained at Princess Margaret Hospital, Toronto, were used. A radiobiological model that allows for out-of-field and in-field effects for lung cell damage and lung response was developed. This model is based on the observation of DNA damage in shielded parts of rat lung that was assumed relevant to cell lethality and consequently overall lung response.

Results: While the experimental data indicated directional or regional volume effects, the applicability of dose and volume as sole predictors of lung response to radiation was found to be unreliable for lower lung (base) irradiation in mice. This conforms well to rat lung response where micronuclei were observed in shielded apical parts of lung following base irradiation. The radiobiological model, which was specifically developed to account for the lung response outside of primary irradiated volume, provides a good fit to mice lethality data, using parameters inferred from rat micronuclei data.

Conclusion: Response to lung irradiation in rodents, in particular, elevated sensitivity to base irradiation, can be interpreted with a hypothesis of in-field and out-of-field effects for cellular response. If the existence of these effects for lung is subsequently proven in humans, it will require the incorporation of geometrical and directional information in normal tissue complication probability calculations for lung. These considerations are ignored in present approaches based only on conventional dose-volume histograms.     

Cytomegalovirus interstitial pneumonitis following allogeneic peripheral blood stem cell transplantation

Objective： To explore the risk factors and prophylaxis and treatment of cytomegalovirus interstitial pneumonitis （CMV-IP） after allogeneic peripheral blood stem cell transplantation （allo-PBSCT）. Methods： 43 patients who received allo-PBSCT were allocated to either a Gancyclovir（GCV）-prophylaxis group （n=19） or a non-GCV prophylaxis group （n=24）. A comparison was made of the incidence of CMV-IP in patients given or not given prophylactic gancyclovir. Results： 9 patients in non-GCV prophylaxis group developed late CMV-IP （P〈0.05）. Graft-versus-host-disease （GVHD） may be associated with a high risk of CMV-IP. 5 cases of CMV-IP were successfully treated with GCV, but 3 cases died of CMV-IP. The most common adverse event of GCV was neutropenia, but was reversible. Conclusion： CMV infection was a major cause of interstitial pneumonitis after allo-PBSCT, which correlated strongly with the severity of GVHD. Gancyclovir was shown to be effective in both prophylaxis and treatment of CMV-IP.     

Sirolimus-associated interstitial pneumonitis in solid organ transplant recipients

Sirolimus is a potent immunosuppressive agent used with increasing frequency in solid organ transplantation (SOT). However, it has been associated with rare but devastating pulmonary toxicity. We describe a case of pulmonary toxicity associated with the use of sirolimus in a 64-yr-old heart transplant recipient. We also review all reported cases of sirolimus-associated lung toxicity among SOT recipients in an effort to better understand the pathophysiology, risk factors, and outcomes of this rare but serious complication. A total of 64 cases have been reported since January 2000 including the present case. These consisted of 52 kidney, four lung, three liver, three heart, one heart-lung and one islet cell transplants. In most cases, patients presented with a constellation of symptoms consisting of fever, dyspnea, fatigue, cough, and occasionally hemoptysis. Although the risk factors for this association have not been clearly established, high dose, late exposure to the drug and male gender have been noticed among most. In almost all of the reported cases, sirolimus was added later in the course of immunosuppressive therapy, usually in an effort to attenuate the nephrotoxic effects of a previous regimen containing a calcineurin inhibitor. There were three deaths (4.8%) among 62 patients with known status at follow up; all deaths were among heart transplant recipients. Most patients (95%) resolved their clinical and radiographic findings with discontinuation or dose-reduction of the drug. Sirolimus-induced pulmonary toxicity is a rare but serious entity that should be considered in the differential diagnosis of a transplant recipient presenting with respiratory compromise. Dose-reduction or discontinuation of the drug can be life saving.     

Outpatient treatment with corticosteroids and antibiotics for acalculous cholecystitis in chronic granulomatous disease

We report the outpatient management of acalculous colecistitis in an 18-y-old male with X-linked chronic granulomatous disease. The patient complained of abdominal pain and the initial ultrasound showed a gallbladder with a thickened wall.CONCLUSION: In chronic granulomatous disease, pain from a thickened gallbladder disappears after oral treatment with glucocorticoids and antibiotics.     

Amantadine in chronic granulomatous disease

Chronic granulomatous disease (CGD) is a rare genetically determined immunodeficiency. Neutrophils from CGD patients show a defective killing of phagocytosed fungi and bacteria, due not only to an impairment in oxidative burst, but also to absence of normal pH value within phagocytic vacuole following phagocytosis. Because a weak base such as amantadine could potentially reverse these pH abnormalities, the authors used this drug to treat 2 CGD patients. They observed modifications of both phagosomal pH and killing activity on their neutrophils compared to those of healthy controls. Since the drug has been employed, the patients have not developed new infections, suggesting a role of amantadine as a part of CGD prophylactic regimen. These results suggest the opportunity of testing the drug in larger studies.     

Microscopic colitis with granulomatous inflammation

AIMS: To present four cases in which the clinical and endoscopic findings were consistent with microscopic colitis, but the inflammatory infiltrate included a conspicuous granulomatous reaction. Microscopic colitis is defined as a syndrome of chronic watery diarrhoea with a chronic inflammatory cell infiltrate in the colonic mucosa and without significant abnormalities at colonoscopy. It encompasses both collagenous and lymphocytic colitis. METHODS AND RESULTS: In all cases the clinical course and endoscopic findings were unlike Crohn's disease and no infectious agents were identified. In all cases the main symptom was frequent watery diarrhoea, all were female and there were no endoscopic findings apart from mild mucosal erythema. Histologically, an active chronic inflammatory infiltrate was accompanied by scattered non-necrotizing granulomas, often closely associated with crypt epithelium (cryptolytic or pericryptal granulomas). In three of the patients the symptoms began after antibiotic use or had worsened with antibiotic use. Two of the patients were on allopurinol at the time of the onset of symptoms. In two of the patients symptoms have continued for more than 10 years. One patient died as a result of medical complications relating to severe diarrhoea and dehydration. CONCLUSIONS: Microscopic colitis rarely may be characterized by granulomatous inflammation. Such patients should not be regarded as having Crohn's disease.