High-dose chemotherapy followed by autologous stem cell transplantation for relapsed or refractory Hodgkin lymphoma: prognostic features and outcomes

Between January 1990 and April 2001, 115 patients received high-dose chemotherapy (HDT) followed by autologous stem cell transplantation (ASCT) for relapsed or refractory Hodgkin lymphoma (HL). With a median follow-up of 58 months (range, 1 - 175 months), 5-year progression-free survival (PFS) and overall survival (OS) were 46% and 58%, respectively. Twelve patients with primary refractory disease had a 5-year PFS of 41% and OS of 58%, not significantly different from those of the remaining cohort. Early and overall regimen related mortality were 7% and 16%, respectively. Male gender (P = 0.04) and a time to relapse (TTR) < 12 months (P = 0.03) were associated with decreased OS by univariate analysis. In multivariate analysis, TTR < 12 months remained statistically significant (P = 0.04). We have confirmed that HDT and ASCT result in long-term survival for a proportion of patients with relapsed or refractory HL. All patients, including those with primary refractory disease, benefited from HDT and ASCT.     

25-Hydroxyvitamin D3 1alpha-hydroxylase splice variants in breast cell lines MCF-7 and MCF-10

BACKGROUND: It is known that 25(OH)D3 can be metabolized to 1,25(OH)2 D3 by 1alpha-OHase in breast tissue. This tissue-specific expression of 1alpha-OHase may act as the pivotal link between vitamin D status (25(OH)D3 levels) and the anticancer effects of 1,25(OH)2 D3. Alternative splicing frequently occurs in breast cancer cells; different splice variants of a given protein can display different biological functions and may cause tissue-specific variations. With this study it is the first time that expression and alternative splicing of 1alpha-OHase in the human breast cancer cell line MCF-7 and thebenign breast cell line MCF-10A are described. MATERIALS AND METHODS: Expression of 1alpha-OHase RNA and protein was assessed using a real-time polymerase chain reaction (RT-PCR). The expression of 1alpha-OHase splice variants was detected by a highly specific PCR that combines nested and touchdown PCR. To determine which variants are translated in protein western blot analysis was carried out. RESULTS: The expression of 1alpha-OHase was found to be 1.25-fold higher in MCF-7 compared to MCF-10A cells. In MCF-10A cells, at least 6 splice variants were detected whereas MCF-7 showed no or marginal expression levels of these variants. In MCF-7 cells the antibody detected a signal at 56 kDa corresponding to the size of normal 1alpha-OHase protein. In MCF-10A cells this signal was weaker. In western blot analysis at least two smaller variants at 45 kDa were found in MCF-7 cells. In MCF-10A cells at least 6 proteins between 37 and 56 kDa were detected with an only faint signal. CONCLUSION: We propose that alternative splicing of 1alpha-OHase can regulate the level of active enzyme. Splice variants may lead to a reduction of the protein. The significance of the smaller variants in MCF-7 cells has not been clarified either, but it is known that they are not able to use 25(OH)D3 as a substrate to generate 1,25(OH)D3. In MCF10A cells, more splice variants were identified, it may be that malignant cells contain inactive variants. How far they show a reduced activity remains unclear as no activity measurements were performed.     

Renal transplantation in elderly patients older than 70 years of age: results from the Scientific Registry of Transplant Recipients

BACKGROUND: Elderly patients (ages 70 yr and older) are among the fastest-growing group starting renal-replacement therapy in the United States. The outcomes of elderly patients who receive a kidney transplant have not been well studied compared with those of their peers on the waiting list. METHODS: Using the Scientific Registry of Transplant Recipients, we analyzed data from 5667 elderly renal transplant candidates who initially were wait-listed from January 1, 1990 to December 31, 2004. Of these candidates, 2078 received a deceased donor transplant, and 360 received a living donor transplant by 31 December 2005. Time-to-death was studied using Cox regression models with transplant as a time-dependent covariate. Mortality hazard ratios (RRs) of transplant versus waiting list were adjusted for recipient age, sex, race, ethnicity, blood type, panel reactive antibody, year of placement on the waiting list, dialysis modality, comorbidities, donation service area, and time from first dialysis to first placement on the waiting list. RESULTS: Elderly transplant recipients had a 41% lower overall risk of death compared with wait-listed candidates (RR=0.59; P<0.0001). Recipients of nonstandard, that is, expanded criteria donor, kidneys also had a significantly lower mortality risk (RR=0.75; P<0.0001). Elderly patients with diabetes and those with hypertension as a cause of end-stage renal disease also experienced a large benefit. CONCLUSIONS: Transplantation offers a significant reduction in mortality compared with dialysis in the wait-listed elderly population with end-stage renal disease.     

Hospitalization patterns before and after liver transplantation

BACKGROUND: Mortality among patients with chronic liver failure is significantly reduced upon liver transplantation. However, decreases in mortality may not be accompanied by decreases in morbidity metrics, such as hospitalization rates. We compared pre- and posttransplant hospitalization rates for liver transplant recipients. METHODS: Statewide hospitalization data were analyzed among 215 adult chronic liver failure patients in Pennsylvania who received a deceased donor transplant from September 2001 to December 2002. Generalized estimating equation (GEE) models were fitted to compare covariate-adjusted pre- and posttransplant hospital admission rates and mean length of stay per admission. The study minimized biases by calculating pre- and posttransplant morbidity in a cohort restricted to patients who received a transplant and were compared to themselves. RESULTS: Liver transplant recipients experienced a significant 70% reduction in hospitalization rates (P<0.0001) posttransplant versus pretransplant. The decline, which occurred for all Model for End-Stage Liver Disease (MELD) subgroups, was significant for patients transplanted at all MELD scores except 6-9. However, even patients with MELD 6-9 experienced a significant decrease in mean length of stay, post versus pretransplant. Higher MELD scores at transplant were generally associated with a greater reduction in hospitalization rates. Also, patients transplanted with lower MELD scores appeared to receive lower quality livers. CONCLUSIONS: Our results indicate that the benefit of transplantation extends beyond patient survival and that an important reduction in hospitalization rates is experienced by transplanted patients. Further study is required to determine whether these results are generalizable to the entire United States and to evaluate the donor liver quality used for recipients of different MELD scores.     

Telemedizinische Anwendungen in der diabetologischen Schwerpunktpraxis

Die Diabetologie - Die digitale Sprechstunde und Onlineschulung entwickelten sich seit den COVID-Pandemie-bedingten (COVID: ?coronavirus disease“) Einschränkungen zu einem festen...     

The Hong Kong Society of Rheumatology consensus recommendations for the management of gout

Clinical Rheumatology - Gout is one of the most common noncommunicable diseases in Hong Kong. Although effective treatment options are readily available, the management of gout in Hong Kong remains...     

Differentially expressed genes in neurofibromatosis 1-associated neurofibromas and malignant peripheral nerve sheath tumors

Neurofibromas represent one of the hallmarks of neurofibromatosis 1 (NF1) patients. Tumor progression of neurofibromas to malignant peripheral nerve sheath tumors (MPNST) is a frequent and life threatening complication. To learn more about processes involved in malignant transformation, we evaluated differential gene expression in plexiform neurofibroma and MPNST from the same NF1 patient. Suppression subtractive hybridization (SSH) yielded 133 differentially expressed genes confirmed by reverse Northern blotting. Virtual Northern blots were employed to validate 23 genes. To independently verify differential expression, immunohistochemical analyses with antibodies to matrix metalloproteinase 13 (MMP13), platelet-derived growth factor receptor alpha (PDGFRA) and fibronectin (FN1) were performed on 9 dermal and 9 plexiform neurofibromas and 16 MPNST from 19 NF1 patients. All three proteins proved to be up-regulated in MPNST. MMP13 expression was observed in 44% of MPNST but was absent in neurofibromas. PDGFRA was expressed in all tumors, but the number of cells expressing it was below 30% in neurofibromas and over 50% in MPNST. Likewise, FN1 was expressed in all tumors, but less than 30% of the cells in neurofibromas and more than 70% of the cells in MPNST exhibited antibody binding. Our data point to several genes not previously recognized to be differentially expressed, and provide a framework for future studies on progression-associated gene expression in low- and high-grade nerve sheath tumors.     

Expression of cyclooxygenase isozymes during morphogenesis and cycling of pelage hair follicles in mouse skin: precocious onset of the first catagen phase and alopecia upon cyclooxygenase-2 overexpression

Cyclooxygenase (COX)-1 and -2 catalyze the key reaction in prostaglandin biosynthesis. Whereas COX-1 is found in most tissues, COX-2, with a few exceptions, is not expressed in normal tissues but becomes transiently induced in the course of inflammatory reactions. In many neoplastic epithelia, COX-2 is constitutively overexpressed. Here we show that COX isozymes are spatiotemporally expressed during morphogenesis of dorsal skin epithelium of NMRI mice. COX-1 and COX-2 mRNA and protein were detected in embryonic and postnatal epidermal tissue by RT-PCR, northern blot, and immunoblot analysis indicating that both isoforms may contribute to prostaglandin production. Being barely detectable in interfollicular epidermis and resting hair follicles of adult mice, COX-2 protein appeared in embryonic skin first in epidermal precursor cells and later on in the basal cells and the peridermal layer of the stratified epidermis. In the course of pelage hair follicle morphogenesis, COX-2 remained expressed in the basal interfollicular compartment and, in addition, became apparent in elongated hair germs and hair pegs and later on in the outer root sheath cells of the distal and proximal hair follicles as well as in basal sebaceous gland cells. During the subsequent synchronous phases of hair cycling, COX-2 expression declined in catagen, was barely detectable in telogen, and was reinduced in the basal outer root sheath and basal sebaceous gland cells of anagen hair follicles. COX-1 immunosignals were detected predominantly in the interfollicular spinous and granular layers of the developing, neonatal, and adult epidermis but not in follicular epithelial cells of developing or cycling hair follicles. Dendritic cells in the interfollicular epidermis and distal hair follicles were also COX-1-positive. Transgenic overexpression of COX-2 under the control of a keratin 5 promoter in basal cells of the interfollicular and follicular epidermis induced a precocious entry into the first catagen stage of postnatal hair follicle cycling and a subsequent disturbance of hair follicle phasing. Furthermore, transgenic mice developed an alopecia. Inhibition of transgenic COX-2 activity by feeding the specific COX-2 inhibitor valdecoxib suppressed the development of alopecia, indicating that COX-2-mediated prostaglandin synthesis is involved in hair follicle biology.     

Descemet membrane endothelial keratoplasty: analysis of clinical outcomes of patients with 8–10 years follow-up

International Ophthalmology - This study aimed to evaluate the clinical outcomes up to 10&nbsp;years after Descemet membrane endothelial keratoplasty (DMEK). In this retrospective, consecutive,...