Clinical analysis of pulmonary <Emphasis Type="Italic">Mycobacterium avium</Emphasis> complex disease in association with corticosteroid treatment

We studied the clinical characteristics of nine patients with pulmonary Mycobacterium avium complex disease occurring in association with corticosteroid drugs collected from our associated hospitals during the past 6 years. The average age of the nine patients was 62.2 years and the male/female ratio was 3 : 6. Regarding underlying disease, respiratory diseases existed in four of the patients and nonrespiratory diseases in the other five patients. The duration of corticosteroid treatment ranged from 5 months to 5 years, and the total dose of corticosteroid drugs ranged from 1.78 to 43.20 g. Pulmonary Mycobacterium avium complex disease was detected by clinical symptoms during corticosteroid treatment in six patients, and purified protein derivative was positive in three of eight patients tested. Radiological findings showed an infiltration shadow without cavity and bronchiectasis in the lower lung field. Microbiological examination was smear-positive in three patients, and the isolated mycobacterium was Mycobacterium intracellulare in five patients and Mycobacterium avium in four. Tolerance was shown to all antituberculous drugs, except for clarithromycin, in all patients. Although treatment including clarithromycin was performed for seven patients, the sputum conversion rate was 33% and an improved clinical effect was noted in only one patient. No change occurred in four and worsening occurred in four. Attention should be paid to the clinical symptoms and radiological findings of patients who have received corticosteroid drugs over a long period of time, because pulmonary Mycobacterium avium complex is characterized by atypical radiographic findings with no relationship to the total dose or duration of the administered corticosteroid drugs. Received: August 22, 2002 / Accepted: October 21, 2002     

Clinical characteristics of spontaneous isolated visceral artery dissection

Objective

Spontaneous isolated visceral artery dissection (SIVAD) involving the celiac artery or superior mesenteric artery is rare, but it can be fatal. Given its rare incidence, the clinical characteristics of SIVAD are not fully understood. Therefore, the aim of this study was to investigate the clinical characteristics and prognosis of SIVAD.

The Charlson Comorbidity Index as an Independent Prognostic Factor in Older Colorectal Cancer Patients

High-age patients have higher rates of comorbidity that are associated with a poor prognosis. It is important to correctly evaluate their preoperative status to avoid mortality. The aim of this study was to clarify whether the Charlson comorbidity index (CCI) was useful for predicting postoperative outcomes. This retrospective study collected data from 250 consecutive patients over 75 years of age. The CCI takes into account 19 comorbid conditions. Inflammation-based scores, including the Glasgow prognostic score (GPS) and the platelet to lymphocyte ratio (PLR), are other preoperative scoring systems. The relationships among these scores and postoperative outcomes were evaluated. The patients were classified according to their vital status (dead, n = 30 or alive, n = 220). Comorbidities, the presence of double cancer, and lymph node metastases were significantly different between the groups (p < 0.01, p = 0.01, and p < 0.01). In regard to the scoring systems, the CCI, GPS, and PLR were significantly different (p = 0.02, p = 0.03, and p = 0.05). Multivariate analysis identified CCI ≥ 2 (hazard ratio (HR) = 5.24, 95 % confidence interval (CI) = 1.30–12.1, p = 0.01) as a significant determinant of postoperative outcome (p < 0.01). The overall survival tended to be lower in patients with high CCI scores group (p = 0.03). The CCI was useful to predict postoperative outcomes in high-age colorectal cancer patients.     

CAR-dependent and CAR-independent pathways of adenovirus vector-mediated gene transfer and expression in human fibroblasts

Primary fibroblasts are not efficiently transduced by subgroup C adenovirus (Ad) vectors because they express low levels of the high-affinity Coxsackie virus and adenovirus receptor (CAR). In the present study, we have used primary human dermal fibroblasts as a model to explore strategies by which Ad vectors can be designed to enter cells deficient in CAR. Using an Ad vector expressing the human CAR cDNA (AdCAR) at high multiplicity of infection, primary fibroblasts were converted from being CAR deficient to CAR sufficient. Efficiency of subsequent gene transfer by standard Ad5-based vectors and Ad5-based vectors with alterations in penton and fiber was evaluated. Marked enhancement of binding and transgene expression by standard Ad5 vectors was achieved in CAR-sufficient fibroblasts. Expression by AdDeltaRGDbetagal, an Ad5-based vector lacking the arginine-glycine-aspartate (RGD) alphaV integrin recognition site from its penton base, was achieved in CAR-sufficient, but not CAR-deficient, cells. Fiber-altered Ad5-based vectors, including (a) AdF(pK7)betagal (bearing seven lysines on the end of fiber) (b) AdF(RGD)betagal (bearing a high-affinity RGD sequence on the end of fiber), and (c) AdF9sK betagal (bearing a short fiber and Ad9 knob), demonstrated enhanced gene transfer in CAR-deficient fibroblasts, with no further enhancement in CAR-sufficient fibroblasts. Together, these observations demonstrate that CAR deficiency on Ad targets can be circumvented either by supplying CAR or by modifying the Ad fiber to bind to other cell-surface receptors.     

Intracranial invasive aspergillosis originating in the sphenoid sinus: a successful treatment with high-dose itraconazole in three cases

We report three cases of intracranial aspergillosis originating in the sphenoid sinus in immunocompetent patients. The patients presented with an orbital apex syndrome in that a unilateral loss of vision and cranial nerve III palsy were seen in all cases and a contralateral involvement was also seen in one case. Despite the initial treatment with a conventional dose of itraconazole (ITCZ, 200 mg/day), the neurological deficits failed to improve and the granulomatous inflammation was not suppressed. Therefore, we treated with a combination of a high dose of ITCZ at 500-1000 mg/day (16-24 mg/kg/day) and amphotericin B (AMPH-B) at 0.5 mg/kg/day, in conjunction with a pulse dose of methylprednisolone at 1000 mg/day. Two cases responded favorably in that the ocular movements completely recovered, and their maximum serum concentrations of the hydroxy ITCZ were 7816 ng/ml and 5370 ng/ml. However, the other case worsened, despite ITCZ treatment at 16 mg/kg/day, and the serum concentration of the hydroxy ITCZ was 3863 ng/ml. The surgical decompression of the cavernous sinus via an extradural approach was performed, and the dose of ITCZ was increased to 24 mg/kg/day. The resulting serum concentration of the hydroxy ITCZ was 4753 ng/ml, and the outcome of this case has been favorable. These results suggest that a high blood level of the hydroxy ITCZ (more than 4500 ng/ml) is a prerequisite for the successful treatment of intracranial aspergillosis and that the combination treatment of ITCZ with AMPH-B would be preferred. The concomitant use of steroid and/or surgical decompression should be considered, if the invasiveness is not well-controlled in spite of intensive medical therapy.     

Diagnosis of Helicobacter pylori infection

Peptic ulcer in elderly patients may be associated with Helicobacter pylori infection. Diagnosis for H. pylori infection should be needed in these patients. The test may be resulted in false negative in case of invasive diagnostic methods based gastric biopsy, because atrophic gastritis and intestinal metaplasia developed in patients may not be able to detect scarce infection of the bacterium. Urea breath test or stool antigen test are recommended for diagnosis of H. pylori infection in patients. It is suitable for patients, because of the non invasive nature of these diagnostic tests.     

Modulatory effect of roxithromycin on human neutrophil function

Neutrophils are thought to play a key role in tissue injury. We investigated the effect of roxithromycin, a 14-membered ring macrolide, on human neutrophil functions. The drug inhibitedN-formyl-methionyl-leucyl-phenylalanine (fMLP)-induced superoxide (O ₂ ^? ) production and Ca²⁺ influx of human neutrophils. The inhibition was overcome by adding an inhibitor of cyclic AMP-dependent protein kinase (PKA), H-89. These results suggest that the drug affects O ₂ ^? production and intracellular Ca²⁺ concentration of neutrophils via the action of PKA. Moreover, roxithromycin ameliorated endothelial cell injury induced by neutrophils, which may be, in part, due to the effect of the drug on neutrophils. Thus, roxithromycin may contribute to the treatment of diseases worsened by the excessive action of neutrophils.