HLA-DR7 predicts the response to alkylating agents in steroid-sensitive nephrotic syndrome

There is a lack of reliable predictors of the response to alkylating agents in children with idiopathic nephrotic syndrome (NS). HLA-DR7 is strongly associated with the frequency of relapses in steroid-sensitive NS before cytostatic therapy. We therefore examined retrospectively the time to the first relapse and the incidence of subsequent relapses in 54 HLA-typed children with frequently relapsing NS, after treatment with cyclophosphamide (n = 49) or chlorambucil (n = 5) for 8 or 12 weeks; 38 patients were HLA-DR7 positive and 16 negative with 80% in both groups being steroid dependent. HLA typing was performed using serological or DNA typing methods. Renal biopsy showed minimal glomerular changes. A lower proportion of HLA-DR7 positive than negative patients remained in remission after 3 years (36% vs. 81%, P<0.02) and 5 years (36% vs. 72%, P<0.03). In the first 3 years after cytostatic therapy the mean number of prednisone-treated relapses was 1.3/patient per year in HLA-DR7-positive patients compared with 0.4 in negative patients (P<0.025). There was no statistically significant difference in the proportion of relapse-free patients with and without steroid dependency. The HLA status predicts the response of NS patients to alkylating agents better than the rate of previous relapses. Received September 19, 1995; received in revised form and accepted April 16, 1996     

Indikation für eine immunsuppressive Therapie bei chronisch entzündlichen Darmerkrankungen

Zusammenfassung Der immunsuppressiven Therapie kommt bei chronischen Darmerkrankungen gro?e Bedeutung zu, insbesondere dort, wo die Standardtherapie nicht den gewünschten Erfolg zeigt. Als Therapie der ersten Wahl gelten bei Colitis ulcerosa 5-Aminosalizyls?ure-freisetzende Medikamente, bei Morbus Crohn Kortikosteroide. Innerhalb der Gruppe immunsuppressiver Pr?parate gibt es erhebliche Wirkungsunterschiede. Darüber hinaus ist die Immunsuppression auch mit ernstzunehmenden Nebenwirkungen belastet. über den Stellenwert der Immunsuppression als Erg?nzung, m?gliche oder bei Unvertr?glichkeit notwendige Substitution der Standardtherapien von Colitis ulcerosa und Morbus Crohn wird hier eingehend referiert. Auch die Behandlung dieser Erkrankungen in der Schwangerschaft wird dabei erl?utert.     

Direction-dependent amplification of the human outer ear

The transfer function of the outer ear in humans was determined by using the impulse technique. Signals were delivered from 325 or 393 positions on an imaginary sphere surrounding the experimental subject. Changes of sound pressure level in the ear canal show that certain frequency bands are amplified maximally if they impinge onto the ear from certain directions. For some frequency bands there are two directions of sound incidence that cause best amplification in the ear canal. The directionality of the human pinna appears to increase at higher frequencies. The amount of amplification by the outer ear of frequencies between 2 and 15 kHz was also determined by measuring the free-field transfer function.     

Treatment of patients with advanced colorectal cancer with cisplatin, 5-fluorouracil, and leucovorin

Based on in vitro studies that have demonstrated synergy between 5-fluorouracil (5-FU), leucovorin (LV), and cisplatin (CDDP) against human colon cancer cell lines, a clinical trial was initiated to determine the effects of this combination in patients with advanced unresectable colorectal carcinoma. Fifty-nine patients were enrolled in the study and 12 of them had received prior conventional 5-FU chemotherapy. Treatment consisted of 4 weekly courses of high-dose LV (200 mg/m2) administered by intravenous (IV) bolus, followed by 5-FU (550 mg/m2) and CDDP (20 mg/m2) each administered as a 2-hour infusion on 4 consecutive days. After a median of 5.5 treatment cycles, objective tumor response was seen in 20 of 59 patients (34%) (this included 3 complete remissions). The response rate in the 47 previously untreated patients was 38% (95% confidence limits, 26% to 53%). Stable disease occurred in 16 (27%) patients, whereas the tumor progressed in 23 (39%) patients. The median survival time was 11.5 months, with 15% of the patients alive at 2 years. The regimen was well tolerated and the primary side effects were mild and reversible gastrointestinal symptoms and myelosuppression. There was no episode of life-threatening toxicity. Eastern Cooperative Oncology Group (ECOG) Grade III adverse reactions that required 25% dose reductions occurred in only 14% of the patients. The results of this trial suggest that 5-FU, LV, and CDDP is an active, safe, and well-tolerated combination regimen in patients with advanced colorectal cancer.     

Carcinoid tumor of the ampulla of Vater. Morphology, diagnosis and therapy of a rare papilla tumor

We report on a patient with a carcinoid tumour of the ampulla of Vater and review the 33 known cases of the literature with regard to clinical presentation, morphology and therapy. As it is apparent from the location of the tumour, obstructive jaundice, pancreatitis and nonspecific upper abdominal complaints are the most frequent symptoms. The ampullary carcinoid belongs histogenetically to the APUD cell system with the ability of multiple endocrine activity. The expression of somatostatin peptide and neuron-specific enolase are the most common histopathological findings. A systemic function of these hormones, however, has not yet been shown. For diagnostic purposes in surgical pathology we found synaptophysin and chromogranin A to be important markers. For surgical treatment, partial duodenopancreatectomy remains the current therapy of choise, if the tumour exceeds two centimeters in diameter.     

Common bile duct pressure in patients with common bile duct stones with or without acute suppurative cholangitis

Resting common bile duct pressure was measured in three groups of patients: group 1, 53 patients with gallstones but without common duct stones; group 2, 35 patients with common bile duct stones unaccompanied by cholangitis; and group 3, 36 patients with common duct stones and acute suppurative cholangitis. A significantly higher pressure in the common bile duct was documented in patients with cholangitis when compared with the other two groups. Twenty-four patients with cholangitis had common duct pressure values above 20 cm H2O, the maximal values of normal. Additionally, patients with cholangitis with pressure values over 30 cm H2O (nine patients) showed absence of green bile in the extrahepatic biliary tract, suggesting cessation of bile excretion into biliary duct. In all these cases, an impacted stone at the distal end of the common bile duct was documented.     

Genetic instability in human chromosome region 3p12-p21 in renal cell carcinoma and lung cancer

contributed equally to this work     

Duplex sonography of renal arteries as a diagnostic tool in hypertensive children

Computed duplex sonography was used to examine the renal arteries in 36 hypertensive children and adolescents (ages 4–17 years) with arterial hypertension of either renal or non-renal origin. Time-averaged flow velocities, maximum blood flow velocities as well as absolute renal blood flow and renal blood flow per gram kidney weight were measured. Normal flow velocities and normal to elevated renal blood flow volume was found in patients with acute glomerulonephritis and those with signs of chronic glomerulonephritis onset. Patients having advanced stages of chronic glomerulonephritis, on the other hand, were characterized by lower levels of all parameters. Unilateral renal artery stenosis was diagnosed correctly in four patients, although one intra-renal artery stenosis escaped imaging. Scarred kidneys exhibited low-normal or reduced flow velocities and renal blood flow volumes corresponded roughly to kidney size and preservation of normal kidney structure. Hypertension in some patients with normal kidneys showed a tendency to cause higher renal blood flow without consistent acceleration of blood flow velocities. We conclude that duplex sonography is a suitable primary diagnostic tool in measuring blood flow velocities and absolute renal blood flow volume in hypertensive children, thus facilitating the choice of the next diagnostic step.