Cytogenetic studies in malignant fibrous histiocytoma.

Among soft tissue sarcomas, malignant fibrous histiocytoma is considered to be the most commonly encountered tumor-type of late adult life. Cytogenetic data are, however, sparse and contradictory, without any specific anomalies. We are describing the results of cytogenetic studies in 20 malignant fibrous histiocytomas of various subtypes and gradings. Although we saw two single and therefore possibly primary rearrangements, t(13;14) and t(5;7), most tumors had complex rearrangements without sharing any characteristic aberrations. In our opinion, the heterogeneity of these findings supports the concept that malignant fibrous histiocytoma is not a distinctive entity but merely a name for a group of as yet poorly defined sarcomas.

Lansoprazole versus omeprazole: influence on meal-stimulated gastric acid secretion.

AIMS: To investigate, by means of meal-stimulated acid secretion, the extent to which differences in plasma half-life, bioavailability and the recommended therapeutic dose can influence the antisecretory potency of lansoprazole and omeprazole. METHODS: In this double-blind, placebo-controlled, crossover study, 10 healthy male volunteers received 15 mg or 30 mg lansoprazole, 20 mg or 40 mg omeprazole or placebo for 5 days, in a randomized order. Meal-stimulated acid secretion was determined by means of a homogenized test meal and intragastric titration. RESULTS: On day 1, meal-stimulated acid secretion was decreased by 35% and 45% after administration of 15 mg or 30 mg lansoprazole, and by 16% and 42% after 20 mg or 40 mg omeprazole. After 3 and 5 days of dosing the decreases were 53% and 48% with 15 mg lansoprazole, 82% and 82% with 30 mg lansoprazole, 43% and 39% with 20 mg omeprazole, and 76% and 83% with 40 mg omeprazole. At all measuring points during the 5-day dosing periods, lansoprazole 15 mg and 30 mg proved superior to 20 mg omeprazole in inhibiting meal-stimulated gastric acid secretion, but the differences were only statistically significant for the lansoprazole 30 mg dose, 30 mg lansoprazole and 40 mg omeprazole proved equipotent. On day 1 only 30 mg lansoprazole was significantly better than placebo. CONCLUSION: This study demonstrated the following order of antisecretory potency: 30 mg lansoprazole = 40 mg omeprazole > 15 mg lansoprazole approximately 20 mg omeprazole.

Increasing the yield of harvested bone marrow cells by raising room temperature during marrow collection.

The time it takes to harvest bone marrow before transplantation could be reduced significantly by increasing the temperature of the operating room by 8-10 degrees C, to about 28-30 degrees C. In healthy donors, the collected volume of marrow was increased from 22.45 to 36.31 mL/min; in patients who received chemotherapy previously, from 21.67 to 29.98 mL/min. The time to collect a volume of 1200 mL marrow could be reduced significantly, from 57.78 to 38.25 minutes in healthy donors and from 71.07 to 43.36 minutes in patients who received chemotherapy previously, without any loss of quality of the sampled marrow. Operation time and thereby time of anesthesia could be reduced significantly by heating the operating room to a temperature of 28-30 degrees C. Harvesting at higher room temperature did not result in any adverse side effects for the patients. The procedure to increase the body temperature could be simplified by using electric blankets and aluminum foils for wrapping to avoid heat emission.

Efficacy of continuous therapy for peptic ulcer in controlled clinical trials.

Long-term studies have confirmed unequivocally the clinical efficacy of continuous therapy with H2-receptor antagonists in reducing the incidence of ulcer recurrence. However, studies have also reported varying relapse rates as a result of differences in study design, particularly the frequency of endoscopy and hence the detection of asymptomatic ulcer relapse. Risk factors for ulcer relapse include smoking, stress, previous history of frequent ulcer relapses, duration of disease for more than 10 years and concomitant administration of non-steroidal anti-inflammatory drugs. In the prevention of relapse with H2-receptor antagonists, choice of agents also may influence the rate of relapse. A meta-analysis of data from direct comparative trials indicates that recurrence rates of duodenal ulcer are significantly lower after one year of treatment with ranitidine (150 mg nocte) than with cimetidine (400 mg nocte). It has been claimed that patients with peptic ulcer disease can be successfully managed by intermittent courses of treatment with H2-receptor antagonists which are taken in response to the development of symptoms. However, high relapse rates (64-100%) have been reported during the first year of follow-up of patients who were receiving intermittent treatment with H2-receptor antagonists. High complication rates (haemorrhage 11.4%, perforation 1.2%) have also been reported over a seven-year follow-up, while continuous treatment with H2-receptor antagonists significantly decreases the risk of haemorrhage in the event of ulcer recurrence.

Atypical chronic myelogenous leukemia in a patient with trisomy 8 mosaicism syndrome.

A 17-year-old woman was admitted for bone marrow transplantation with the diagnosis of atypical Philadelphia-negative chronic myelogenous leukemia (aCML), cytogenetically characterized by trisomy 8 as the sole chromosome aberration. A striking feature was a congenital opacity of the right cornea. Chromosomal analysis of skin fibroblasts were performed and revealed a mosaic for trisomy 8. Commonly, a distinct clinical picture leads to the diagnosis of trisomy 8 mosaicism syndrome (T8ms), but an extreme phenotypic variability has been observed. To our knowledge the development of an aCML in a patient with T8ms has not been reported. A review of the literature revealed that an association to other hematological disorders had been described in two cases. The question of whether our patient's aCML was a random event or not is discussed. The patient is now 24 months post transplant and shows no evidence of disease. Her Karnofsky score is 100%. We conclude that it might be worthwhile to look for an associated constitutional trisomy 8 mosaicism in all patients with trisomy 8 leukemia.

Cytogenetics in multiple myeloma and plasma cell leukemia: simultaneous cytogenetic and cytologic studies in 51 patients.

Cytogenetic studies in patients with multiple myeloma (MM) and plasma cell leukemia (PCL) have in general been largely unsuccessful. The investigation of mitoses of nonmalignant hematopoietic precursor cells, rather than mitoses of malignant plasma cells might account for the low percentage of pathological genetic findings. We investigated bone marrow (BM) cells of 51 patients both cytogenetically and cytologically. In patients with a normal karyotype (n = 39) nearly all mitoses examined cytologically (107/117) derived from granulopoietic or erythropoietic cell lineages. In contrast, 20/27 metaphases in patients with a pathological karyotype (n = 12) were found to be plasma cell mitoses. These findings may explain the low rate of chromosomal rearrangements in MM and may suggest that the real abnormality rate is considerably higher.

A case of adult ALL with +i(13q) as the sole anomaly.

A case of ALL with +i(13q) as the sole anomaly in a 77-year-old patient is reported. The clinical and cytogenetic findings are discussed.

Clinical and prognostic significance of the Philadelphia chromosome in adult patients with acute lymphoblastic leukemia.

Between 1983 and 1991 the Philadelphia chromosome (Ph1) was found in bone marrow and/or peripheral blood cells of 25 adult patients with acute lymphoblastic leukemia (ALL). The Ph1 as sole anomaly was seen in 13 patients, while six patients had additional structural and another six structural and numerical aberrations. Most patients (23/25) received combination chemotherapy according to the BMFT protocols 1/81, 2/84, 3/87, and 4/89. For 25 evaluable patients two early deaths, two treatment failures, two partial remissions (PR), and 19 complete remissions (CR) after phase 1 or 2 of the induction regimen were recorded. Two of these 19 patients who achieved CR are presently disease free, whereas 17 have relapsed after a median duration of remission of 9 months. Actuarial median survival for all patients was 13 months. The probability of continuous complete remission (CCR) after 39 months, as well as that of survival after 40 months, is only 6%. Our results confirm that the presence of the Ph1 is associated with a poor prognosis in adult-ALL patients. Therefore, whenever first CR is obtained and an HLA-identical donor is available, allogeneic bone marrow transplantation (BMT) should be performed at once, the more so, since transplantation in second CR seems to offer no cure. Future studies will have to show whether an intensified cytotoxic therapy can improve the prognosis of Ph1(+)-ALL.

Treatment of metastatic gastric carcinoma with a modified FAMTX chemotherapy regimen.

Fifty patients with locally far advanced or metastasizing gastric carcinoma were treated with 5-fluorouracil, adriamycin and methotrexate using a slightly modified FAMTX protocol. Complete remission was achieved in four (8%) patients, confirmed operatively, partial remission in 13 (26%) patients, two of these going into complete remission after operative removal of residual tumor. Median duration of remission for the six patients in complete remission was 21 months, for those in partial remission five months. Median survival for all 50 patients was seven months, for those in complete and partial remission 12 months, and for those without remission four months. These results indicate the possibility of a further improvement of treatment results in patients with metastasizing gastric carcinoma using this protocol of combined operation and chemotherapy.

Apparent duplication of inv(3)(q21q26) in one of five cases with inv (3) in myelodysplastic syndromes and acute leukemia.

Rearrangements affecting the long arm of chromosome 3 have been linked to abnormalities of platelet production and morphology in hematologic disorders. We present five patients with myelodysplastic syndromes or acute leukemia in whom inv(3)(q21q26) was seen. One of the patients showed an inversion of both homologs involving precisely the same breakpoints, suggesting apparent duplication of the abnormal chromosome 3 and loss of the normal homolog. To our knowledge this is the first report detailing such a condition.

The cytogenetics of renal tumors. Where do we stand, where do we go?

In this review an attempt is made to give an overview of the present status of cytogenetic research in tumors of the kidney. The results of numerous studies in renal cell carcinoma and adenoma, transitional cell carcinoma, and renal oncocytoma are presented, and the findings from the literature, together with 52 current observations, are analyzed and evaluated with respect to their significance for the understanding of renal malignancies.

inv(12)(p11.2q13) in an endometrial polyp.

A benign endometrial polyp from a 50-year-old postmenopausal woman has been cytogenetically investigated. A single clonal karyotypic anomaly, inv(12)(p11.2q13), was found in about 30% of cells analyzed after short-term culture. This finding contributes further to the hypothesis that the chromosomal segment 12q13-q14, which is also involved in chromosomal rearrangements in uterine leiomyomas, pleomorphic adenomas of the salivary glands, lipomas, and myxoid liposarcomas, contains a gene or genes that are related to cellular proliferation rather than to malignant transformation.

Translocation t(9;11)(p23;q12): a primary chromosomal change in renal oncocytoma.

We report the cytogenetic, clinical, radiological and pathological features of a renal oncocytoma, diagnosed accidentally in a 50-year-old man who originally presented with symptoms related to prostatic hyperplasia. All metaphases examined showed a structural chromosomal rearrangement t(9;11)(p23;q12) as the only change. The constitutional karyotype was established as 46XY. We believe that this karyotypic anomaly may represent a primary and possibly specific change characterizing this uncommon and generally benign type of tumor.

Loss of heterozygosity on 3p in a renal cell carcinoma in von Hippel-Lindau syndrome.

A renal cell carcinoma with an unbalanced t(X;3) in a patient with von Hippel-Lindau (VHL) syndrome has previously been reported. This rearrangement suggested loss of genetic material from the short arm of chromosome 3, which we are now able to confirm by restriction fragment length polymorphism analysis of tumor DNA using polymorphic probes derived from 3p. The VHL gene has recently been mapped to 3p, therefore loss of this region in this VHL-related renal cell carcinoma may have cogent significance for tumor development in this interesting cancer-predisposing syndrome.

3p involvement in a renal cell carcinoma in von Hippel-Lindau syndrome. Region of tumor breakpoint clustering on 3p?

The cytogenetic findings in a renal cell carcinoma from a patient with von Hippel-Lindau syndrome are reported. Of the two consistent changes, one was a dicentric chromosome evolving from an unbalanced translocation between the proximal part of the short arm of chromosome 3 and the distal segment of the long arm of the X chromosome.

Inversion of chromosome 5 long arm in region of cell growth gene cluster in hematologic disorders.

Inversions of the long (q) arm of chromosome #5 are reported in five cases with hematologic disorders. Inversion of 5q with breakpoints in bands 5q13 and 5q33 was found in two cases with lymphoid malignancy and in two cases of myeloid hematologic malignancy. Because an inversion of 5q with breakpoints in 5q22 and 5q33 was also found in a case with myeloproliferative syndrome, the common denominator in these five cases was band 5q33. An extraordinary cluster of genes affecting cell growth and differentiation is present on 5q and may be altered by the chromosome rearrangement of 5q in hematologic disorders.

The 24-hour acid suppression profile of nizatidine.

To determine the antisecretory potency of bedtime doses of the new thiazole H2-receptor antagonist nizatidine in the suppression of nocturnal acid secretion, this randomized, cross-over, single-blind study was performed in 10 healthy male subjects. The actions of a single bedtime (2100 h) dose of the H2-receptor antagonist nizatidine (150 mg and 300 mg), ranitidine (300 mg), cimetidine (800 mg), and famotidine (40 mg), as well as placebo on nocturnal gastric acid and volume secretion (2400 to 0600 h) and on overall 24 h H+-ion concentration were studied. Compared with placebo, night-time (2300 to 0700 h) H+ ion concentration was reduced by 70, 79, 95, 75, and 89% (p less than 0.05 to p less than 0.01). Nocturnal acid secretion, too, was significantly lower for the H2-blockers than for placebo (p less than 0.01). A significant reduction in total night-time gastric volume secretion was observed (p less than 0.01). Nizatidine 300 mg nocte, ranitidine, cimetidine and famotidine had no significant carry-over effects on daytime acidity (0800 to 1800 h). No significant pharmacodynamic differences between nizatidine 300 mg nocte, ranitidine 300 mg nocte, cimetidine 800 mg nocte and famotidine 40 mg nocte were observed. Thus, it may be concluded that these four H2-blockers will be equally effective in accelerating peptic ulcer healing and pain relief.