HLA class I and II antigen phenotypes of North American Indians from Minnesota: implications for marrow transplants using unrelated donors

As a result of an appeal for a bone marrow donor for a North American Indian (Native American) patient, 261 Native Americans from our community were typed for HLA-A,B,DR antigens, and 51 were typed for HLA-A,B antigens only. The HLA antigen frequencies of the Native Americans were compared with those of 12,881 white bone marrow donors and were found to differ markedly. To investigate the implications these differences in HLA antigen frequencies would have for the location of unrelated bone marrow donors, the HLA types of 12 Native American bone marrow transplant patients from our institution were used to search among 5389 HLA-A,B,DR-typed white donors in the National Marrow Donor Program file and the file of 261 HLA-A,B,DR-typed Native American donors. In the white donor file, at least two donors were found that matched at all HLA-A,B,DR antigen loci of one Native American patient (8%). Using the Native American donor file, which was less than one-twentieth the size of the white donor file, and HLA-A,B,DR-matched donor was also found for one (8%) of the patients. These results suggest that although donors for nonwhites can be identified in a file of HLA-typed white volunteers, the probability of finding a suitably matched donor for such individuals is enhanced if donors representing racial or ethnic minorities are included in unrelated donor registries.     

Incidence of Mycoplasma hominis and Ureaplasma urealyticum infection in pregnant women and gynaecological patients; the effectivity of doxycycline therapy

The authors report on the results of Mycoplasma hominis and Ureaplasma urealyticum cultivations performed within two and a half years in 1,421 pregnant women and gynaecological patients. Considering the obstetrical-gynaecological patients Mycoplasma hominis was identified in 7.25% and Ureaplasma urealyticum in 38.11% of cases. No significant difference was found in the incidence of Mycoplasma infection when comparing the results of cultivations of samples obtained from a clinically non-inflamed vagina or cervix with the results of cultivations of samples obtained from the female lower genital tract in the course of an inflammatory disease. In cases of endometritis, salpingitis or cophoritis Mycoplasma hominis could be isolated from the cervix significantly more frequently. The incidence of Mycoplasma hominis infection was also significantly higher in the examined 315 sterile women. The incidence of Mycoplasma hominis and Ureaplasma urealyticum infection did not differ when comparing the 267 symptom-free pregnant women to the other patients. The presence of the pathogenic organisms did not aggravate the unfavourable course of pregnancy. When examining the effectivity of Doxycycline capsule the drug proved to be effective in 78 patients for the treatment of genital Mycoplasma infections.     

Assessment of Gall Bladder Dynamics, Cholecystokinin Release and the Development of Gallstones During Octreotide Therapy for Acromegaly

The development of gallstones is a well recognized complicationof therapy with the long-acting somatostatin analogue, octreotidein patients with acromegaly. A group of nine acromegalic patientswas treated with octreotide at doses of 300–600 µgdaily for 8 months and the changes in fasting and post-prandialcholecystokinin release, and gall bladder motor function (determinedby a radiosotopic technique) were assessed at regular intervals.In addition the development of any gallstones was determinedby serial ultrasonography. Fasting cholecystokinin levels showedno significant change over 6 months, whereas the post-prandiallevels demonstrated a significant decrease (p<0.01) duringtherapy, yet remained significantly higher than fasting levels.Twenty-four hours after commencing therapy gall bladder ejectionfraction was decreased by 57±23 per cent and gall bladderejection rate decreased by 63±19 per cent compared tothe pretreatment values, whereas after 6 months, therapy a markedreduction in gall bladder ejection fraction (>35 per cent)and gall bladder ejection rate (>40 per cent) persisted inonly four of nine patients. Three of these four patients withpersistently impaired gall bladder motor function were subsequentlyshown to have developed either gallstones or biliary sludgeduring the course of therapy. We conclude that treatment with octreotide is associated withan impaired post-prandial release of cholecustokinin in allacromegalis patients, but gallstones only develop in those patientswho, in addition, have evidence of a persistently impaired gallbladder motor response to cholecyustonini.     

Comprehensive analysis of tumoral DNA content reveals clonal ploidy heterogeneity as a marker with prognostic significance in locoregional neuroblastoma

The clinical management of locoregional neuroblastoma (LR NB) is controversial. In a previous study we showed that diploidy was a strong prognostic predictor of outcome and detected the existence of clonal ploidy heterogeneity in a select group of cases. The aims of this study were (1) to assess the frequency of ploidy heterogeneity in LR NB, (2) to ascertain the best method to detect heteterogeneity, and (3) to correlate ploidy populations with clinical outcome. We undertook a comprehensive analysis of tumoral DNA content in 38 LR NBs comparing (1) flow cytometry (FCM), (2) karyotyping, (3) interphase fluorescence in situ hybridization, and (4) laser-scanning cytometry (LSC). Tumor ploidy heterogeneity was found by all methodologies. By FCM, all tumors with aneuploid peaks had detectable diploid DNA peaks. By LSC, all tumors with diploid and hyperploid peaks were GD2-positive in both, consistent with their tumoral origin. A predominant near-triploid clonal population (ratio diploid vs. triploid, <2.5) was observed in most nonprogressing LR NB tumors, and a predominant diploid clone (ratio di- vs. triploid, >2.5) in most progressing LR NB cases. Multivariate analysis was performed to evaluate the prognostic value of tumor ploidy assayed by different methods versus age, INSS (International Neuroblastoma Staging System) stage, and MYCN status. FCM was the most powerful prognostic factor related to poor prognosis (overall survival, P = 0.02; progression-free survival, P = 0.01). These results provide strong evidence for clonal ploidy heterogeneity in LR NB and clonal evolution toward diploidy in progressing LR NB.     

First-generation offspring of male mice exposed to 239Pu-citrate show no evidence of leukaemia or life shortening

The aim was to test whether male mice injected with ²³⁹Pu citrate transmit induced mutations that lead to specific causes of death, decrease longevity or both. Male CBA/Ca mice injected with ²³⁹Pu citrate solutions at nominal activities of 6 and 60 Bq g^?–?1 were mated to females (same strain) 54?–?68 days later. Absorbed doses to the testes were estimated to be approximately 0.3 and 4.0?cGy. Control males were injected with carrier only. Longevity was evaluated. All 1807 progeny were given detailed necropsies. Haematological analysis was used in an attempt to identify leukaemia. Male progeny from both treated groups lived significantly longer than those from the control, and there was no difference in longevity between the two treatments. No evidence was found of the induction of leukaemia or of any of the numerous probable causes of death. Although numerous significant differences were found in the many comparisons made between the three groups, there was no clear indication that any harmful effects were associated with paternal preconceptional plutonium exposure. This was in spite of the initial body burden (higher dose) being approximately 2800 times the maximum body burden allowed for workers when this study was initiated.     

Current state and future directions of autologous hematopoietic stem cell transplantation in systemic lupus erythematosus

Autologous haematopoietic stem cell transplantation (AHSCT) has been proposed as a treatment modality which may arrest the autoimmune disease process and lead to sustained treatment-free remissions. Since the first consensus statement in 1997, approximately 200 autologous bone marrow or haematopoietic stem cell transplantations (HSCTs) have been reported worldwide for systemic lupus erythematosus (SLE). The current state of AHSCT in SLE was reviewed at a recent meeting of the autoimmune working party of the European Group for Blood and Marrow Transplantation. There was general agreement among experts in this field that in patients with severe SLE refractory to conventional immunosuppressive treatments, AHSCT can achieve sustained clinical remissions (ranging from 50% to 70% disease-free survival at 5 years) associated with qualitative immunological changes not seen with other forms of treatment. However, this clinical benefit is associated with an increase in short-term mortality in most studies. Improving patient selection, long-term follow-up of patients after AHSCT, optimisation of induction and maintenance treatment together with detailed analysis of the immune system are identified as key areas for future research. Optimally, AHSCT should be compared with conventional treatment in randomised controlled trials. Development of stronger transplant registries, defining a core set of clinical data and standardising biological sample collections would make future collaborations and comparison of studies more feasible.     

Relationship between molecular subtype of invasive breast carcinoma and expression of gross cystic disease fluid protein 15 and mammaglobin

We investigated the expression of gross cystic disease fluid protein 15 (GCDFP) and mammaglobin (MGB) by immunohistochemical analysis in 71 invasive breast carcinomas (IBCs) subtyped into luminal (A and B), HER2, basal-like carcinoma (BLC), and unclassified triple-negative carcinoma (UTNC) by established surrogate immunohistochemical profiles. GCDFP and MGB were less likely to be expressed in BLC than in HER2 cancers (P = .000021 and P = .013, respectively) or luminal cancers (P = .00002 and P = .00008, respectively). However, the difference in GCDFP or MGB expression between HER2 and luminal cancers was not significant (P = 1.0 and P = .671, respectively). Our results suggest that luminal cancers demonstrate similar degrees of apocrine differentiation as HER2 cancers. Most BLCs and UTNCs are negative for MGB and GCDFP. Correlation with clinical findings may be needed to exclude the possibility of a metastasis to the breast when BLCs or UTNCs are encountered in a limited sample such as a core biopsy sample.