A single-center population-based consecutive series of 1500 cytogenetically investigated adult hematological malignancies: karyotypic features in relation to morphology, age and gender

During the 18-yr period 1976-93, a population-based series of 1586 adults with suspected or confirmed hematological malignancies were successfully cytogenetically investigated at a single center. Eighty-six cases were excluded due to unretrievable medical records or if analyzed only in remission or at relapse. The remaining 1500 medical records were reviewed regarding morphology and clinical parameters in order to investigate possible associations between karyotypic pattern (normal, 1, 2 or complex anomalies; specific abnormalities) and gender, age and morphological subgroups. The impact of time-period, i.e. 1976-87 vs. 1988-93, and referring center on cytogenetic findings was also studied. A total of 372 acute myeloid leukemias (AML), 389 myelodysplastic syndromes (MDS), 64 acute lymphoblastic leukemias (ALL) and 262 chronic myeloid leukemias (CML) were identified, altogether 1087 cases. Patients with other (n=261) or no hematological malignancies (n = 152) were excluded from the present analysis. Cytogenetic abnormalities were detected in 52% AML, 51 % MDS, 68% ALL and 97% CML, frequencies that did not differ significantly between the 2 time periods or referring centers. No significant age- or gender-related differences in karyotypic patterns were discerned in AML, MDS, ALL or CML, whereas the karyotypic patterns varied among the FAB groups in both AML (p= 0.001) and MDS (p < 0.001). The specific abnormalities t(8;21), t(15;17) and inv(16) were more common (p < 0.001) in younger AML patients and 5q- was more frequent in females with MDS (p<0.001). These findings indicate, in contrast to previous series, that neoplasia-associated karyotypic aberrations are not more common among older patients or in males.     

The role of Raf-1 kinase inhibitor protein in the regulation of pancreatic beta cell proliferation in mice

Aims/hypothesis

Manoeuvres aimed at increasing beta cell mass have been proposed as regenerative medicine strategies for diabetes treatment. Raf-1 kinase inhibitor protein 1 (RKIP1) is a common regulatory node of the mitogen-activated protein kinase (MAPK) and nuclear factor κB (NF-κB) pathways and therefore may be involved in regulation of beta cell homeostasis. The aim of this study was to investigate the involvement of RKIP1 in the control of beta cell mass and function.

Methods

Rkip1 (also known as Pebp1) knockout (Rkip1 ^?/?) mice were characterised in terms of pancreatic and glucose homeostasis, including morphological and functional analysis. Glucose tolerance and insulin sensitivity were examined, followed by assessment of glucose-induced insulin secretion in isolated islets and beta cell mass quantification through morphometry. Further characterisation included determination of endocrine and exocrine proliferation, apoptosis, MAPK activation and whole genome gene expression assays. Capacity to reverse a diabetic phenotype was assessed in adult Rkip1 ^?/? mice after streptozotocin treatment.

Results

Rkip1 ^?/? mice exhibit a moderately larger pancreas and increased beta cell mass and pancreatic insulin content, which correlate with an overall improvement in whole body glucose tolerance. This phenotype is established in young postnatal stages and involves enhanced cellular proliferation without significant alterations in cell death. Importantly, adult Rkip1 ^?/? mice exhibit rapid reversal of streptozotocin-induced diabetes compared with control mice.

Conclusions/interpretation

These data implicate RKIP1 in the regulation of pancreatic growth and beta cell expansion, thus revealing RKIP1 as a potential pharmacological target to promote beta cell regeneration.     

The necessity of a test reading after 1 week to detect late positive patch test reactions in patients with oral lichen lesions

Objectives

Establishing the clinical relevance of contact allergy to dental materials in patients with oral lichen lesions (OLL) may be difficult, and tests are often read only on day 3 or day 4; also, concentration of the tested allergens may vary. Several studies on dermatitis patients have shown that additional positive patch test reactions can be found after day 4. Therefore, the aim of the present study was to analyse the frequency of late positive reactions to potential allergens in patients with OLL.

Material and methods

Eighty-three of 96 consecutive patients with biopsy-verified OLL were patch-tested with a recently developed lichen series. The patches were removed after 48 h and reactions read 3 and 7 days after application.

Results

A total of 129 contact allergies were found, and 26 (20.2 %) of the allergic reactions in 23 patients were seen on day 7 only. The 25.2 % increase in positive test reactions with an additional reading on day 7 in addition to day 3 was statistically significant. Metals were the substances with the highest frequency of late positive reactions.

Conclusions

Patients with OLL cannot be considered properly investigated with regard to contact allergy, unless the testing has been performed with mandatory readings on day 3 (or day 4) and day 7.

Clinical relevance

Late patch test readings are crucial in order to elucidate the role of contact allergy to dental materials in the aetiology of OLL.     

Inverted papilloma: a follow-up study including primarily unacknowledged cases

Inverted papillomas (IPs) in the nose or the paranasal sinuses exhibit a tendency for rapid growth with bone destruction, a high recurrence rate, and an association with malignancy, requiring early diagnosis and aggressive surgical therapy. A number of operative approaches have been reported in the literature, with greatly varying results. Furthermore, the incidence of IP and the association with carcinoma are not well-established. In this study, we present a series of 42 patients with IP. Drawing from the resources of two institutes of pathology, we reviewed all specimens of nasal cavity or paranasal sinus tissue taken between the years 1975 and 1986, and performed a thorough follow-up of all IP patients. The incidence was found to be 0.6 cases per 100,000 inhabitants per year in a well-defined representative geographic region. Two patients had concomitant carcinoma. When the initial surgical approach was lateral rhinotomy, the recurrence rate was 50%. This was not significantly different from that noted following excision through a sinusectomy (62%) or simple endonasal excision (43%). However, initial procedures were selected individually, mainly on the basis of tumor size and location. Accordingly, a limited procedure is considered justified even in cases with lateral lesions, if the tumor is sufficiently visible and confined. In other cases, lateral rhinotomy is required. Septal IPs are often detected at an early stage and are therefore often amenable to local excision.     

Ectopic pregnancy and antibodies to Chlamydia trachomatis

Ectopic pregnancy is one of the most serious sequelae to acute salpingitis. Chlamydia trachomatis seems to be the most common etiologic agent of acute salpingitis. In the present study, we tested whether women with ectopic pregnancy had serologic evidence of a current or past chlamydial infection. Sixty-five percent of the women with ectopic pregnancy had IgG serum antibodies to C. trachomatis, and 21% of women pregnant in utero had such antibodies. Eleven percent of women with infertile husbands, 42% of women with cervicitis, and 69% of women with salpingitis had IgG serum antibodies to C. trachomatis. In women with ectopic pregnancy, there was a correlation between the occurrence of IgG antibodies and a history of salpingitis or gross evidence of a previous tubal inflammation. We conclude that previous chlamydial salpingitis may be a major etiologic factor leading to ectopic pregnancy.     

Serum bilirubin subfractions in patients with alcohol abuse during detoxication

Sera were obtained from 41 alcohol abusers consecutively admitted for detoxication. Blood samples were withdrawn on the second, fourth and seventh days of abstention. Initial bilirubin values were moderately elevated in 10 patients. Determination of the bilirubin subfractions by high performance liquid chromatography showed elevated values of unconjugated (alpha), monoconjugated (beta), diconjugated (gamma) and albumin-bound (delta) bilirubin, in 8, 15, 4 and 15 patients, respectively. During abstention, the total bilirubin value normalized rapidly, only three patients still had values above the upper reference limit after 7 days. In patients with initially elevated values of bilirubin subfractions, only a few had elevated beta and gamma levels on the seventh day, whereas delta levels decreased at a slower rate and remained virtually unchanged. On admission, 27 patients exhibited elevated levels of serum bile acids; these values decreased during abstention and after 7 days only six patients had slightly elevated values. Only five patients had initially elevated levels of alkaline phosphatase (ALP). These became normalized in all but two patients during abstention. The results suggest that mild cholestasis is common among alcohol-abusers without clinically evident liver disease and that these changes are reversible on abstention.     

Glomerular filtration rate up to 10 years after urinary diversion of different types. A comparative study of ileal and colonic conduit, refluxing and antirefluxing ureteral anastomosis and continent caecal reservoir

To evaluate the influence of conduit type (ileal or colonic) and method of ureterointestinal anastomosis (refluxing or antirefluxing) on renal function in patients with urinary diversion, a prospective randomized trial was conducted in 1977-1984. During these years urinary diversion via a continent caecal reservoir emerged as an alternative to conduit diversion at our hospital, and these patients with continent reservoir were also included in the study. Total and separate glomerular filtration rate (GFR) were measured, the latter with scintillation camera renography, preoperatively and at follow-up in 70 patients. Measurements 2-10 years postoperatively showed slight to moderate decrease of GFR in all groups, with no significant difference between values according to conduit type or caecal reservoir or between refluxing and antirefluxing ureterointestinal anastomosis. Almost all of the anastomotic strictures involved the ureter that had been brought beneath the sigmoid mesentery, indicating that ischemia secondary to extensive ureteral mobilization is a likely cause of stricture in these cases.     

A Phase II trial of high-dose intravenous interferon alpha-2 in advanced colorectal cancer

Twenty-one patients with metastatic colorectal cancer were treated with high-dose intravenous interferon alpha-2 (30-50 X 10(6) units/m2) administered daily for 5 consecutive days. Courses of therapy were repeated every 2 to 3 weeks. No tumor responses were seen among 15 evaluable patients. In two subjects, disease remained stable for 3 and 7 months, respectively. Toxicity was substantial and a de-escalation of dose was frequently required. Fevers, gastrointestinal symptoms, fatigue, leukopenia, and elevated serum transaminases were common. High-dose interferon was found to be ineffective in the treatment of metastatic colorectal cancer. A daily dose of 50 X 10(6) units/m2 was greater than the maximum tolerated dose in this group of patients.