Incidence and clinical predictors of infections in patients treated with severe systemic ANCA-associated vasculitis.

BACKGROUND: Immunosuppressive therapy has improved the outcome of ANCA-associated vasculitis (AAV), but infectious morbidity and mortality remained high. Recognizing its risk factors seems crucial for prevention, aiming to increase survival of these patients. METHODS: We investigated the incidence and types of infections and assessed predictive factors in 132 patients with severe systemic AAV. RESULTS: Patients with lower than median incidence of total infections/patient-year during induction had lower baseline serum creatinine, dialysis requirement and Charlson comorbidity index (CCI), compared to those with higher than median incidence (P = 0.037; P = 0.024; P = 0.001; respectively). In subgroups with below and above than median number of severe infections/patient-year during induction, differences were found in baseline creatinine (P = 0.002) and dialysis requirement (P = 0.001); comparing the same cohorts during maintenance immunosuppression, baseline dialysis requirement, diabetes, CCI, and dose of cyclophosphamide (CYC) administered as induction therapy differed significantly (P = 0.019; P = 0.015; P = 0.001; P = 0.015, respectively). Severe infections were predicted by baseline serum creatinine (OR 1.002 [CI 1.001-1.003]) and pulmonary manifestation (OR 2.153 [CI 1.017-4.560]) during induction immunosuppression. In multivariable Cox regression model all-cause mortality was independently predicted by severe infection (HR 1.998 [CI 1.214-3.287]). Among the 168 positive cultures Gram-negative bacteria were responsible for blood stream infections in 33%, and respiratory tract infections in 72%. CONCLUSIONS: Advanced renal failure, pulmonary involvement and high degree of comorbidities increase the risk of infection in AAV. Those who suffer infection during induction immunosuppression have worse long-term survival. Our findings indicate the need for high vigilance for infections and close follow-up of comorbidities when treating AAV.

Nephrotic syndrome with focal segmental glomerulosclerosis after an insect bite.

AIMS AND METHODS: Focal segmental glomerulosclerosis (FSGS) is a glomerular disease defined by a characteristic histologic pattern that occurs either as a primary kidney disease (primary FSGS) or as a result of a systemic illness (secondary FSGS). Proteinuria, often in the nephrotic range, is the hallmark of FSGS. The occurrence of nephrotic syndrome after an insect sting is rarely reported in the literature. We present a case of nephrotic syndrome with focal segmental glomerulosclerosis with a glomerular tip lesion developing after an insect bite. RESULTS: A 51-year-old Caucasian female was bitten by an insect on her left leg, which immediately became swollen. Generalized edema developed and she was admitted for further investigations. Urinary 24-h protein excretion was 7 g. Percutaneous renal biopsy was performed and showed focal segmental glomerulosclerosis of the tip variant. Nephrotic syndrome was steroid-resistant, and when we added cyclophosphamide for 8 weeks complete remission was achieved. There was no relapse of the disease during the 2-month follow-up. CONCLUSIONS: This report demonstrates the useful role of cyclophosphamide in the treatment of steroid-resistant nephrotic syndrome due to FSGS with glomerular tip lesion. A causal relationship between the insect bite and the nephrotic syndrome is suggested and an immune response could be responsible for the nephrotic syndrome.

Changes in apoptotic and mitotic index, bcl2, and p53 expression in rectum carcinomas after short-term cytostatic treatment.

Twenty patients with rectal adenocarcinoma were endoscopically biopsied and given short-term cytostatic therapy [5-fluorouracil (5-FU) (600 mg/m(2)) and Ca-folinate (60 mg/m(2)) for 2 days]. Seven days later, the tumor was resected or a second biopsy was performed. Apoptotic and mitotic indices as well as (mutant) p53 and bcl(2) expression were determined in the tumor tissue before and after the short-term chemotherapy. The patients were treated thereafter with long-term, intermittent 5-FU administration and followed up clinically for 7-26 months. Six patients showed progression of the disease and died, whereas 14 improved or showed no tumor progression. Significant increase of the apoptotic index and nonsignificant decrease of the mitotic index after the short-term cytostatic treatment were seen in the tumor tissue of responder cases. Nonresponders showed no change in both mitotic activity and apoptotic activity. Both survivors and deceased showed high mutant p53 expression, and the changes after short-term 5-FU treatment were not significant. Expression of bcl(2) was present in only 5 cases, with the postchemotherapy changes being not significant. These findings suggest that apoptotic response to short-term cytostatic therapy may be an additional predictive factor in rectal adenocarcinoma.

Changes in apoptosis, mitosis, Her-2, p53 and Bcl2 expression in breast carcinomas after short-term tamoxifen treatment.

The short-term (7 days) effect of tamoxifen on apoptosis and mitosis index, p53, Bcl2 and Her-2/neu/c-erb2 expression in invasive ductal mammary carcinoma was studied histologically in the diagnostic biopsy and surgically removed tumor tissue of 10 patients. Following tamoxifen treatment expression of HER-2 and p53 decreased but Bcl2 remained unchanged. Mitotic activity decreased slightly, but not significantly. Apoptotic activity increased in six cases in the second sample compared to the values measured of the first biopsy. These changes may be attributed to the effect of antiestrogen therapy.

Changes in apoptotic and mitotic activity in rectal carcinoma after short-term cytostatic therapy as possible predictive factors.

Fifteen patients with rectal adenocarcinoma were endoscopically biopsied and given short-term [5 fluorouracil (5FU) (600 mg/m2) and Ca-Folinate (60 mg/m2) for two days] cytostatic therapy. Seven days later the tumor was resected or a second biopsy was performed. Apoptotic and mitotic indices were determined in the tumor tissue before and after the short-term chemotherapy. The patients were treated thereafter with long-term, intermittent 5 FU administration and followed up clinically for 4-13 months. Three patients showed progression of the disease, twelve improved or showed no tumor progression. An increase of the apoptotic index and decrease of the mitotic index after the short-term cytostatic treatment were seen in the tumor tissue of responder cases. Non-responders showed increase or no change in mitotic activity, and decrease or no change in apoptotic activity. These findings suggest that apoptotic and mitotic response to short-term cytostatic therapy may be additional predictive factor in rectal adenocarcinoma.

[Ganglioneuroma of the adrenal gland]. / Mellékvese ganglioneuromák.

149 patients with adrenal incidentalomas were examined. Sixty-eight cases were histologically confirmed, five of them had ganglioneuromas. On the basis of these patients history current knowledge of this benign tumour was summarized. Histological and pathological characteristics of one tumour suggest that ganglioneuromas may develop by maturing of malignant neuroblastic tumours. The clinical symptoms (abdominal pain, meteorism) were local. In 2 of 5 cases mildly elevated levels of urinary vanillylmandelic acid and catecholamine could be measured. One patient had persisting hypertension after surgery. In an other patient previous diarrhoea stopped after the removal of tumour. On the basis of ultrasound and computertomographic features, the size and origin of a tumour and its relation to the surrounding organs can be well characterized. One patient was inoperable because of an infiltratively spreading tumour, but during five years of follow-up no tumour progression could be observed with computertomography. After surgery we could follow only 2 of 4 patients. Until now no recurrence of tumour were detected.

Diagnosis from thyroid aspirates. Is the cytopathologist handicapped if not fully informed about the patient?

OBJECTIVE: When fine needle aspiration cytology (FNA) of the thyroid is performed as a first-line test, the cytopathologist cannot be fully informed about the patient's data. The authors investigated whether this decreases the accuracy of FNA and results in consequences for the patient. STUDY DESIGN: FNA smears of 202 patients, 190 with benign and 12 with malignant thyroid disease, were reevaluated, supplying the cytopathologist first with only information from the case history known already at the initial admission, and subsequently with full data. RESULTS: The FNA diagnoses were corrected in 13 cases; in 8/13 they showed a more serious finding. The therapeutic modality was changed in only one case. No corrections were made in the ultimately malignant cases. CONCLUSION: In several cases the cytopathologist may be handicapped by receiving only partial information about the patient, but in our patients this had no demonstrable adverse consequences. Thus, FNA can be performed upon patient's admission.

IgE lambda monoclonal gammopathy and amyloidosis.

The prevalence of IgE myeloma is 0.01% in all plasmocytomas. Although signs and symptoms are similar, it is generally accepted that IgE myeloma has a more malignant clinical course than other forms of plasmocytoma with monoclonal gammopathy. The disease has widely variable presentation. Most of the reported cases were accompanied by complications that are rarely seen with other types of myeloma. So far only one idiopathic (benign?) IgE monoclonal gammopathy has been reported. This case report is the first recorded IgE myeloma in Hungary with a rather unusual clinical presentation and diagnostic process. It is of particular interest that a monoclonal chain was detected in the urine of the patient several years prior to diagnosis.

Low dehydroepiandrosterone sulfate (DHEA-S) level is not a good predictor of hormonal activity in nonselected patients with incidentally detected adrenal tumors.

To assess its differential diagnostic value, dehydroepiandrosterone sulfate (DHEA-S) was measured in a nonselected cohort of 84 patients with incidentally detected adrenal tumors (incidentaloma). Of the 38 histologically confirmed cases, 6 of 12 patients with primary or metastatic malignant tumor of the adrenals and 7 of 14 patients with benign cortical adenoma had low DHEA-S levels. Thus, the sensitivity, specificity, and predictive value of a low DHEA-S level to indicate a benign adrenal tumor were 0.35, 0.50, and 0.60, and the values to indicate a cortical adenoma were 0.50, 0.67, and 0.47, respectively. Of the 14 cases of histologically confirmed benign cortical adenoma, 10 had signs of hormonal activity, but DHEA-S was suppressed in only 7 cases. Thus, the sensitivity, specificity, and predictive value of a low DHEA-S level to indicate clinically significant hormonal activity of a benign cortical adenoma were 0.60, 0.75, and 0.86, respectively. For comparison, 5 of 5 males and 2 of 5 females with metastatic carcinomatosis, but without involvement of the adrenals, also had low DHEA-S levels. The data clearly show that in nonselected cases of incidentaloma a suppressed DHEA-S level is not a good predictor of hormonal activity and that DHEA-S measurement may be valuable only after having ascertained the cortical origin and benign feature of the tumor.

Incidentally detected adrenal tumours (incidentalomas): histological heterogeneity and differentiated therapeutic approach.

OBJECTIVES: To find a differentiated therapeutical approach to incidentalomas. DESIGN: Prospective study of incidentalomas: their histology, hormonal activity, and growth if primarily non-operated. SETTING: Admissions to an academic tertiary care centre because of incidentaloma. PATIENTS: Thirty-eight female, 25 male, 27-85 years old. INTERVENTIONS: Ultrasound, computed tomography and adrenal scintigraphy when appropriate; investigations to exclude malignancy giving metastasis into the adrenal gland; ACTH, cortisol, aldosterone, renin activity, androgene, catecholamine measurements; surgery or follow-up. MAIN OUTCOME MEASURES: Rate of malignancy; linkage of tumour size to probability of malignancy; prevalence of tumours with subtle hormone excess. RESULTS: Cortical adenomas occurred in 13/31, metastases in 7/31 of the histologically confirmed cases. In 10/31 cases, the computed tomography indicated a size that was smaller than the pathological size (mean = 20 mm). 20.6% of all incidentalomas and 61.5% of the 13 operated corticol adenomas showed subtle hormonal activity. Twenty-seven incidentalomas < 30 mm were followed-up (3-41 months; mean 18 months) and showed growth in only one case. Sensitivity, specificity, and predictive value (PV) of a tumour > or = 30 mm to indicate malignancy were: 1.0, 0.56 and 0.27, respectively. The PV of a < 30 mm tumour to exclude malignancy was 1.0. CONCLUSIONS: Oncological screening tests are necessary in all incidentalomas. Tumours > or = 30 mm should be operated but smaller ones can be followed-up, because they are usually benign and rarely show progressive growth. Cortical adenomas with subtle hormonal overproduction and hypertension, diabetes or osteoporosis should be operated, irrespective of their size, but in the absence of relevant clinical symptoms they can be followed-up.

[Unity of diagnostic pathology, continuing education and research at our institute]. / A diagnosztikus pathológiai, továbbképzö és kutató munka egységéröl intézetünkben.

Authors give a brief view on the activity in Institute of Pathology and Histopathology of Post-graduate University of Medicine. In its frame, close relation of diagnostic, post-graduate education and research activity is illustrated by examples of different fields (intestinal, cardiac, vascular system, respiratory tract, organ of locomotion, urological diseases, electronmicroscopic tumor diagnostics, endocrinology). Importance of modern morphological methods and their place both in practical and scientific activity are dealt with.

Lp(a) lipoprotein concentration in serum of patients with heavy proteinuria of different origin.

We measured serum cholesterol, triglyceride, and lipoprotein Lp(a) concentrations in serum of 37 patients with massive proteinuria of different origin, comparing values with those for age- and sex-matched controls and finding significantly increased Lp(a) concentration in the total group of patients compared with controls. Lp(a) concentration was not correlated with serum cholesterol, triglyceride, serum creatinine, daily urinary protein loss, or selectivity index. Selecting the patients according to their histological diagnosis obtained by renal needle biopsy, we found divergent results in seven patients with minimal change disease (MCD) compared with 11 patients with membranoproliferative glomerulonephritis. Lp(a) in MCD patients did not differ from that controls (101 +/- 102 and 90 +/- 115 mg/L) and correlated positively with total daily urinary protein loss (r = 0.7962, P less than 0.05). In contrast, the patients with membranoproliferative glomerulonephritis had significantly higher Lp(a) values than the controls (219 +/- 222 mg/L), and Lp(a) concentrations correlated negatively with the daily protein loss in urine (r = -0.6545, P less than 0.05). The most surprising results were the marked Lp(a) concentrations in serum of three patients with primary amyloidosis and nephrosis syndrome. Our results indicate a regulatory role of the kidney in the metabolism of Lp(a) and different effects on the serum Lp(a) concentration, depending on the type of damage to renal tissue.

[Functional morphology of Peyer's patches. Lymphocyte activation in Peyer's patches]. / A Peyer-plakkok funkcionális morfológiája. Lymphocyta aktiválódás patkányok Peyer-plakkjaiban.

Peyer plaques of rats were studied by morphological methods in order to compare the structure of these organs with the present theories on their function. It was established that near to the follicules of plaques folds perpendicular to the intestinal passage are formed, which are able to direct a part of the bowel-contents into the direction of the follicules. Between the surface of the follicules and large intestinal villi recesses are formed, in which stagnation of the intestinal content takes place. As a result of this antigens and mitogens containing in the intestinal lumen can contact lymphoid cells of through the special epithelial cells the Peyer-plaques. The latter were recently studied by polarized light too, since earlier studies of the authors have shown that birefringence of these cells depends on their functional state. Authors disclosed that birefringence of the cells of the Peyer-plaques is significantly stronger, than that of the cells of spleen, lymph nodes, and thymus. Cells with increased birefringence are situated on the epithelial side of the capsule of follicules. Reported studies evidence, that Peyer-plaques are structures specialized for incorporation of antigens. Lymphoid cells of Peyer-plaques are activated by effects coming from the intestinal lumen.

Cross-resistance of transformed mouse cells to some drugs.

The Colcemid-resistant L--53 cell strain was examined for cross-resistance to metaphase inhibotors (Vincristine, Vinblastine, estradiol-17beta), an antitumor antibiotic (Rubomycin C) and an alkylating agent (Lycurim), compared with the Colcemid-sensitive L cells. The L-53 cells proved to be resistant besides colchicine to Vincristine, Vinblastine and estradiol-17beta concerning their antimitotic effect. The comparison of the viability of L and L-53 cells in the presence of Rubomycin C and Lycurim showed a resistance of the L-53 cells to Rubomycin C, while the effect of Lycurim was the same on both cell lines. The chromosome-mutagenic action of Lycurim was also equal on both cell lines.