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PubMed1997

Presence of circulating prostate cells in the bone marrow of patients undergoing radical prostatectomy is predictive of disease-free survival.

PURPOSE: To determine whether the presence of circulating prostate cells in the bone marrow is associated with disease-free survival in patients undergoing radical prostatectomy. MATERIALS AND METHODS: We evaluated the bone marrow of 86 patients with clinically localized prostate cancer treated by radical prostatectomy for the presence of circulating prostate cells using reverse-transcriptase polymerase chain reaction (RT-PCR) amplification of prostate-specific antigen (PSA) mRNA. Follow-up duration ranged from 1 to 43 months (mean, 15.4). RESULTS: Two of 47 patients (4%) with negative RT-PCR PSA results and 10 of 39 patients (26%) with positive RT-PCR PSA results have had disease recurrence. Patients whose RT-PCR PSA results were positive had a significantly shorter disease-free survival period than those patients with negative RT-PCR PSA results (P = .004). RT-PCR status correlated significantly with serum PSA level (P = .001) and pathologic stage (P = .003). Based on Cox's proportional hazards models, RT-PCR status was found to be a significant predictor of disease-free survival. However, after controlling for PSA level, RT-PCR status was not significant in predicting disease-free survival. CONCLUSION: RT-PCR PSA of bone marrow may be a useful pretreatment prognostic test for patients undergoing radical prostatectomy. Currently, this test should not be used to determine if patients receive definitive local therapy.

Adenocarcinoma↗
PubMed2006

Transcarboxylase mRNA: a marker which evidences P. freudenreichii survival and metabolic activity during its transit in the human gut.

Dairy propionibacteria have recently been considered as probiotics which may beneficially modulate the intestinal ecosystem. However, appropriate vectors (food matrices containing the probiotic) which preserve their viability and offer good tolerance towards digestive stresses need to be developed. In addition, the development of efficient non-invasive methods which specifically monitor Propionibacterium freudenreichii concentration and activity within the human gut is required. To address this latter need, an enzyme involved in propionic fermentation, transcarboxylase, was evaluated in this study as molecular marker in P. freudenreichii. In vitro, the three transcarboxylase subunits were shown to be encoded by an operon and their expression regulated. It occurred during propionic fermentation, ceased in starved cells and was not affected by digestive stresses. The 5S subunit gene of transcarboxylase allowed specific detection of P. freudenreichii by real time PCR in the complex human faecal microbiota. A dairy vector harbouring P. freudenreichii was developed and afforded elevated probiotic faecal concentrations in humans. In vivo, this PCR method allowed rapid quantification of faecal P. freudenreichii in agreement with the cultural method (cfu counting). Moreover, real time Reverse Transcription (RT) -PCR evidenced transcription of the 5S subunit gene during transit through the human digestive tract. This work constitutes a methodological advance for survival and activity evaluation in human trials of the probiotics belonging to the P. freudenreichii species. It strongly suggests that this bacterium not only survives but remains metabolically active in the human gut.

Base Sequence↗
PubMed2006

A survival study and prognostic factors analysis on acute promyelocytic leukemia at a single center.

This study was aimed to investigate the factors influencing long-term survival on patients with acute promyelocytic leukemia. Here, we present a single center retrospective study with long-term follow-up to explore the prognostic factors and a rationale of the using of ATRA, chemotherapy and As(2)O(3) in the treatment of newly diagnosed APL patients. In total, 222 patients, 184 achieved complete remission (CR) with the CR rate of 82.88% and 22 patients died during early induction therapy with the early-death-rate of 10%. Total 171 newly diagnosed APL patients entering CR were retrospectively analyzed from November 1989 to December 2004,with a median follow-up of 36 months (6-185 months). Univariate and multivariate analysis of eight factors potentially influencing survival and prognosis were carried out with Log-Rank and Cox regression method, including sex, age, initial WBC count, the level of lactic dehydrogenase (LDH), first induction regimen, days from induction therapy to CR, post-remission therapy and the status of PML-RAR alpha fusion gene by reverse transcription-polymerase chain reaction (RT-PCR). The results showed that the estimated 5-year overall survival (OS) and relapse-free survival (RFS) were 80.9+/-4.0 and 71.0+/-4.0%, respectively. Univariate analyses showed that initial WBC count, first induction regimen, days from induction therapy to CR, post-remission therapy regimen and the status of PML-RAR alpha in remission were important prognostic factors for long-term survival. Multivariate study showed that only post-remission therapy regimen was associated with RFS and OS. It is concluded that the post-remission treatment combining ATRA, As(2)O(3) and chemotherapy would significantly improve the long-term survival of APL patients achieving CR(1).

Adolescent↗
PubMed2002

Safety and antiretroviral activity of chronic subcutaneous administration of T-20 in human immunodeficiency virus 1-infected children.

BACKGROUND: Entry inhibitors, a new class of antiretroviral agents, interfere with the attachment, coreceptor interaction or fusion of HIV-1 with host target cells. The fusion inhibitor T-20 is the first in this new class, and the present study is the first to examine chronic s.c. administration of T-20 to HIV-1-infected children. METHODS: Fourteen children, 4 to 12 years of age, with incompletely suppressed HIV-1 were studied. The median plasma viral load at baseline was 26,866 copies/ml (4.4 log10), and the median CD4 count was 523 cells/mm3. T-20 was administered twice daily by s.c. injection at 30 or 60 mg per m2 of body surface area per dose. For 7 days T-20 was added to the patients' background antiretroviral regimens; at Day 7 each subject's background therapy was changed to a regimen that was predicted to be virologically active, while T-20 was continued. Results are presented for the first 24 weeks of chronic T-20 dosing. RESULTS: T-20 was generally well-tolerated. One child discontinued the drug because of aversion to injections, but no child discontinued because of adverse events. Eleven (79%) of 14 children had local injection site reactions at some time during the chronic T-20 dosing. Eleven of 14 subjects achieved the protocol-specified milestone of at least a 0.7-log10 reduction in plasma HIV-1 RNA by Day 7. In 10 subjects (71%) virologic suppression of 1.0 log10 or greater was achieved at 24 weeks; 6 subjects (43%) had viral loads <400 copies/ml and 3 (21%) had fewer than 50 copies/ml at 24 weeks. CONCLUSIONS: These results indicate that a 24-week regimen of twice daily s.c. dosing of T-20 in HIV-1-infected children is safe and tolerable and that it is associated with suppression of HIV-1 replication during 24 weeks of administration.

Child↗
PubMed2001

[Antisense oligodeoxynucleotide of telomerase gene enhances cisplatin-induced apoptosis in acute myeloid leukemia and chronic myeloid leukemia cells].

OBJECTIVE: To explore the effect of human telomerase reverse transcriptase(hTERT) gene antisense oligodeoxynucleotide (ASODN) on cisplatin-induced apoptosis in cultured primary acute myeloid leukemia (AML) and chronic myeloid leukemia (CML) cells. METHODS: Cell surviving fraction was determined using the trypan blue dye exclusion assay. Apoptosis was detected by DNA gel electrophoresis and flow cytomertric cell cycle analysis. RESULTS: Treatment with cisplatin after 24 hours of exposure of the cells to ASODN significantly reduced the number of viable AML and CML cells. However, there was no difference on AML and CML cells survival between those treated with sense oligodeoxynucleotide (SODN)/cisplatin combination and cisplatin alone. Agarose gel electrophoresis of genomic DNA from the blasts of AML and CML treated with ASODN and cisplatin combination for 72 hours showed typical DNA "ladder", but DNA from AML or CML cells treated with SODN plus cisplatin or cisplatin alone did not. The percentage of apoptotic AML and CML cells treated with cisplatin for 48 or 72 hours after 24 hours of exposure to ASODN (42.68%, 35.72%) was significantly different with that of apoptotic cells treated with SODN plus cisplatin (29.02%, 23.84%) or cisplatin alone (27.53%, 21.02%). CONCLUSION: hTERT ASODN could enhance the cisplatin-induced apoptosis of AML and CML cells.

Acute Disease↗
PubMed2002

Mycobacterium tuberculosis genes induced during infection of human macrophages.

We identified Mycobacterium tuberculosis genes preferentially expressed during infection of human macrophages using a promoter trap adapted for this pathogen. inhA encodes an enoyl-acyl carrier protein reductase that is required for mycolic acid biosynthesis (A. Quemard et al., Biochemistry 34:8235-8241, 1995) and is a major target for isoniazid (INH) in mycobacterial species (A. Banerjee et al., Science 263:227-230, 1994). Since overexpression of inhA confers INH resistance in Mycobacterium smegmatis (Banerjee et al., Science 263:227-230, 1994), we designed a promoter trap based on this gene. A library of clones, containing small fragments of M. tuberculosis DNA cloned upstream of inhA in a plasmid vector, was electroporated into M. tuberculosis, and the resulting culture was used to infect the human monocytic THP-1 cell line. Selection was made for clones surviving INH treatment during infection but retaining INH sensitivity on plates. The DNA upstream of inhA was sequenced in each clone to identify the promoter driving inhA expression. Thirteen genes identified by this method were analyzed by quantitative reverse transcription-PCR (R. Manganelli et al., Mol. Microbiol. 31:715-724, 1999), and eight of them were found to be differentially expressed from cultures grown in macrophages compared with broth-grown cultures. Several of these genes are presumed to be involved in fatty acid metabolism; one potentially codes for a unique DNA binding protein, one codes for a possible potassium channel protein, and the others code for proteins of unknown function. Genes which are induced during infection are likely to be significant for survival and growth of the pathogen; our results lend support to the view that fatty acid metabolism is essential for the virulence of M. tuberculosis.

Bacterial Proteins↗
PubMed2003

Sterilization failure, sterilization reversal, and pregnancy after sterilization reversal in Quebec.

OBJECTIVE: 1). To determine the likelihood of sterilization reversal and of subsequent sterilization after sterilization reversal among men and women and 2). to examine the likelihood of pregnancy after sterilization (contraceptive failure) and of pregnancy after sterilization reversal. METHODS: Payment data from the Quebec provincial health insurance system were obtained for each person undergoing vasectomy or female sterilization from January 1, 1980 to December 31, 1999 and linked through a unique identifying number for each person. Using standard techniques of survival analysis, we computed the cumulative probability of experiencing each of six events. RESULTS: Among women, 0.9% (of 311960) experienced a pregnancy after sterilization, 1.8% (of 321929) obtained a reversal after sterilization, 61% (of 4369) achieved a pregnancy after sterilization reversal and 48% achieved a delivery; 23% (of 4677) obtained a subsequent sterilization after reversal. Among men, 2.4% (of 310827) obtained a reversal after vasectomy and 18% (of 6694) obtained a subsequent vasectomy after reversal. All of these risks were much higher among those in the youngest age groups. CONCLUSION: Sterilization reversal and pregnancy after sterilization are not rare. Relatively high rates of reversal among the youngest age groups suggest a need for better counseling about alternative contraceptive strategies.

Adolescent↗
PubMed2001

The clinical significance of tenascin-C splice variant expression in chondrosarcoma.

OBJECTIVES: Tenascin-C (TNC) is an oligomeric glycoprotein of the extracellular matrix that is prominently expressed in malignant tumors. The purpose of this study was: (1) to determine the in vitro TNC splicing pattern in cultured human chondrocytes and chondrosarcoma cells, (2) to determine the in vivo TNC splicing pattern in clinical chondrosarcoma specimens, and (3) to perform survival analysis based on the TNC splicing pattern of the tumor specimens. METHODS: Human articular chondrocytes and chondrosarcoma cells (cell line JJ012) were grown in a three-dimensional alginate bead system and harvested at two time points. Semiquantitative reverse transcription polymerase chain reaction (RT-PCR) was used to determine the in vitro TNC splicing pattern for the two cell types. Clinical chondrosarcoma specimens were obtained intra-operatively and underwent RT-PCR to determine the in vivo TNC splicing pattern. Specific immunohistochemical staining for the large TNC splice variant was performed on the clinical specimens. Survival analysis was used to determine the association between the specific TNC splicing pattern and survival. RESULTS: The in vitro mRNA expression pattern of TNC in normal human articular chondrocytes was characterized by a high ratio of the small to the large splice variant (TNC(small):TNC(large)), whereas the in vitro mRNA expression pattern for cultured chondrosarcoma cells was characterized by a low TNC(small):TNC(large) ratio. Clinical chondrosarcoma specimens with a lower TNC(small):TNC(large) ratio showed a trend towards decreased survival. The TNC splicing pattern of these specimens was verified through specific immunohistochemical staining for the large TNC isoform. CONCLUSIONS: The specific TNC splicing pattern may have clinical significance in chondrosarcoma. TNC expression may therefore play a future role in objective tumor grading and novel therapeutic approaches to this malignancy.

Adult↗
PubMed1993

Anoxia-tolerant hepatocytes: model system for study of reversible metabolic suppression.

Chrysemys picta bellii is well known for its ability to survive extended anoxic periods and has been widely used as a model system to study anoxic metabolism. Described here is a method for the isolation of anoxia-tolerant hepatocytes from this species. Freshly isolated hepatocytes were determined to be viable based on trypan blue exclusion, gluconeogenic capacity from [14C]lactate, responsiveness to epinephrine and glucagon, and maintenance of cellular adenylate concentrations. Under anoxic conditions for 10 h there was no significant increase in cell staining and no decrease in cellular ATP concentration. Furthermore, the addition of cyanide at the 5-h mark did not result in any significant differences in these parameters; however, iodoacetate added at this time caused trypan blue staining to increase and ATP concentrations to fall. The rate of glucose production from the cells was threefold greater under anoxic than normoxic conditions, underscoring the important role of the liver in supplying substrate during anoxia. From the rate of O2 consumption and rate of lactate production under anaerobic conditions, ATP turnover rates were calculated to be 68.4 +/- 7.2 and 6.5 +/- 0.43 mumol ATP.g-1.h-1, respectively; this corresponds to a 90% decrease in metabolic rate during anoxia. Within a cellular system such as this the more complex regulatory mechanisms involved in a large coordinated reduction in metabolism can be probed.

Adaptation, Physiological↗
PubMed2005

Reevaluation of surgery for the treatment of brain metastases: review of 208 patients with single or multiple brain metastases treated at one institution with modern neurosurgical techniques.

OBJECTIVE: Patients with brain metastases were analyzed retrospectively to assess the risks and benefits of surgery with modern neurosurgical techniques, including image guidance coupled as indicated with corticography. METHODS: We retrospectively analyzed charts of patients treated surgically for brain metastases. We identified patients with single or multiple brain metastases who underwent craniotomies to reverse associated neurological symptoms or establish a diagnosis. We assessed patients according to recursive partitioning analysis (RPA) prognostic groups as well as functional grades of tumor location (eloquent versus noneloquent, Grades I-III). Perioperative complications, neurological outcomes after surgery, survival, and prognostic factors were analyzed. Statistical analysis of survival was performed with the Kaplan-Meier method. A P value of <0.05 was considered statistically significant. RESULTS: Two hundred eight patients were treated between March 1995 and December 2002. Patient age ranged from 31 to 82 years (median, 59 yr). One lesion was resected in 191 patients, and of 76 patients with multiple lesions, two or more metastases were resected in 17 patients. Tumors were located in eloquent cortex in 27 patients and near eloquent cortex in 124 patients. Four patients died within 30 days after surgery for a mortality rate of 1.9%. Neurological deterioration was noted in 13 patients (6%) after surgery for Grade I and II tumors and in 5 patients (19%) of 27 patients with Grade III tumors. Karnofsky Performance Scale scores were improved (68 patients) or unchanged (124 patients) in 192 patients and worse in 16 patients after surgery. The median survival time (MST) from the date of surgery was 8 months for all patients and 9 months for 163 patients who did not undergo prior whole-brain radiation therapy. There was no difference in survival between patients operated for single metastasis (MST, 8 mo) versus patients with two or three metastases (MST, 9 mo; P = 0.9364). By both univariate and multivariate analysis, variables significantly affecting outcome included a high Karnofsky Performance Scale score and RPA Class I assignment. By univariate analysis, significant treatment variables included postoperative radiotherapy and postoperative chemotherapy. The MSTs of RPA Class I, II, and III patients were 16.1 months, 7.2 months, and 1.4 months, respectively (P < 0.001, log-rank test). These survival data compare favorably with the stereotactic radiosurgery boost arm of the recently published Radiation Therapy Oncology Group 9508 trial. CONCLUSION: In most patients with single or multiple brain metastases, surgical resection reversed or stabilized neurological symptoms with therapeutic benefit, conveying a notable survival advantage without apparent increased risk, particularly in RPA Class I patients. In patients with Grade III single metastasis or RPA Class II multiple metastasis, surgical judgment should be exercised, and stereotactic radiosurgery boost treatment may be preferable. An algorithm for treatment of brain metastases is proposed.

Adult↗
PubMed1993

Spermicidal and antiviral properties of cholic acid: contraceptive efficacy of a new vaginal sponge (Protectaid) containing sodium cholate.

Cholic acid (sodium cholate) exhibits a strong spermicidal and antiviral [anti-human immunodeficiency virus (HIV)-1] activity. The same effects are observed for F-5 Gel, the active mixture of a new contraceptive sponge (Protectaid), which contains sodium cholate in association with low concentrations (0.5%) of nonoxynol-9 and benzalkonium chloride. Both cholic acid and the F-5 Gel exert a dose-dependent, in-vitro inhibitory effect (i) on the activity of HIV-1 associated reverse transcriptase in an acellular system and (ii) on the potential of HIV-1 efficiently to infect human lymphocytes. During 12 months use, the contraceptive efficacy of the 'Protectaid' sponge was 100% in 20 young women who had chosen this method for reasons of both contraception and anti-sexually transmitted disease. No side-effects were recorded throughout this period. Cervical cultures at 6-month intervals showed the presence of Mycoplasma hominis and Candida albicans in one or two cases. The combined spermicidal and anti-HIV properties of cholic acid reported in this paper and used in the 'Protectaid' sponge offer a new and modern protective method of contraception.

Adult↗
PubMed2004

J. Maxwell Chamberlain Memorial Paper. Early fundoplication prevents chronic allograft dysfunction in patients with gastroesophageal reflux disease.

BACKGROUND: Chronic allograft dysfunction limits the long-term success of lung transplantation. Increasing evidence suggests nonimmune mediated injury such as due to reflux contributes to the development of bronchiolitis obliterans syndrome. We have previously demonstrated that fundoplication can reverse bronchiolitis obliterans syndrome in some lung transplant recipients with reflux. We hypothesized that treatment of reflux with early fundoplication would prevent bronchiolitis obliterans syndrome and improve survival. METHODS: A retrospective analysis of 457 patients who underwent lung transplantation from April 1992 through July 2003 was conducted. Patients were stratified into four groups: no history of reflux, history of reflux, history of reflux and early (< 90 days) fundoplication and history of reflux and late fundoplication. RESULTS: Incidence of postoperative reflux was 76% (127 of 167 patients) in pH confirmed subgroups. In 14 patients with early fundoplication, actuarial survival was 100% at 1 and 3 years when compared with those with reflux and no intervention (92% +/- 3.3, 76% +/- 5.8; p < 0.02). Further, those who underwent early fundoplication had improved freedom from bronchiolitis obliterans syndrome at 1 and 3 years (100%, 100%) when compared with no fundoplication in patients with reflux (96% +/- 2.5, 60% +/- 7.5; p < 0.01). CONCLUSIONS: Reflux is a frequent medical complication after lung transplantation. Although the number of patients undergoing early fundoplication is small, our results suggest early aggressive surgical treatment of reflux results in improved rates of bronchiolitis obliterans syndrome and survival. Further research into the mechanisms and treatment of nonalloimmune mediated lung allograft injury is needed to reduce rates of chronic lung failure.

Adult↗
PubMed2005

Reverse obliquity and transverse fractures of the trochanteric region of the femur; a review of 101 cases.

BACKGROUND: Reverse obliquity and transverse fractures of the proximal femur represent a distinct fracture pattern in which the mechanical forces displace the femur medially thus increasing the risk of fixation failure. There is a paucity of published literature in this area of trauma. This study constitutes the largest series of such fractures. METHODS: Using a retrospective analysis of prospectively collected data from a single institution, 101 reverse obliquity and transverse fracture patterns were identified from 3336 consecutive hip fractures. All surviving patients were followed up for 1 year. RESULTS: Of 100 patients treated operatively, 59 were treated with 135 degrees sliding hip screws (SHS), 19 with a Medoff plates modification of the SHS, three with a sliding hip screw and trochanteric stabilising plate and 19 with intramedullary sliding hip screw devices. Nine fracture fixation-healing complications occurred, with cut-out being the commonest complication (seven cases). Cut-out of the implant was associated with femoral medialisation and a larger tip to apex distance. CONCLUSION: This fracture pattern is a challenge for the orthopaedic surgeon with a high risk of fracture healing complications. The 135 degrees SHS and the intramedullary devices had similar failure rates.

Adult↗
PubMed2006

An easy, non-destructive, probabilistic method to evaluate the imposex response of gastropod populations.

Endocrine disruption in marine populations is a growing concern. One of the best documented examples is imposex, the development of male characteristics in female gastropods, including the development of a penis and/or vas deferens, by exposure to organotins, mainly tributyltin. This syndrome has been an effective and widely used biomarker of organic tin contamination for almost 20 years. However, established imposex evaluation protocols sacrifice all the animals and repeated assessments can result in depletion of populations. To preserve animal lives as much as possible and to have a fast screening of areas subjected to organotin impacts, a non-destructive approach was tested. This approach uses reversible narcotization and a statistical criterion to evaluate the extent of imposex in the populations, instead of imposex indexes, which are based on evaluation of sacrificed, fixed animals. The data consist of two categories: males plus masculinized females in one category and normal females in another. The probability is then calculated that this sample could have been drawn from a normal population. This new method was tested in two contrasting areas of Brazil and with two different species, and the results compared to the conventional evaluation. Narcotization was completely reversed with a survival rate of 98%. Impacted sites could be identified with this technique in the same way as with the conventional one. The only limitation was that female sterility could not be verified. This disadvantage could well be compensated by the minimal mortality in the studied populations.

Animals↗
PubMed2004

Focal adhesion kinase gene silencing promotes anoikis and suppresses metastasis of human pancreatic adenocarcinoma cells.

BACKGROUND: Inadequate or inappropriate cell-substrate contact triggers a subset of apoptotic cell death, termed anoikis. Resistance to anoikis is a characteristic of malignant cells that is associated with increased tumorigenesis and metastasis. Focal adhesion kinase (FAK) is an important regulator of cell survival and migration and cell cycle progression. We tested the hypothesis that FAK gene silencing would promote anoikis and reverse acquired anoikis resistance in human pancreatic adenocarcinoma cells. METHODS: FAK expression was assessed by Northern and Western blot analysis. Anoikis was induced in PANC1, BxPC3, MiaPaCa2, and Mia(AR) (an anoikis-resistant derivative of MiaPaCa2) with the use of polyHEMA culture. FAK expression was suppressed by RNA interference. Anoikis was detected by YO-PRO-1/propidium iodide staining and flow cytometry. Fluorometric caspase profiling was performed. Metastasis was assayed in a nude mouse orthotopic xenograft model. RESULTS: The cell lines that were tested showed marked variation in their anoikis resistance, greater resistance being associated with higher levels of FAK expression. FAK gene silencing promoted anoikis in all cell lines and reversed acquired anoikis resistance in Mia(AR), which was associated with increased caspase activation. Suppression of FAK expression also inhibited metastasis in the nude mouse model. CONCLUSION: FAK gene silencing suppresses anoikis resistance in pancreatic adenocarcinoma cells. FAK represents a potential target for novel antimetastatic therapies.

Adenocarcinoma↗
PubMed1988

Use of a brief steroid trial before initiating OKT3 therapy for renal allograft rejection.

OKT3 (Ortho Pharmaceutical, Raritan, NJ) has been employed in a protocol where all patients received cyclosporine as part of their baseline immunosuppressive regimen and, after the diagnosis of rejection was established, were treated with up to three pulses of methylprednisolone before monoclonal antibody therapy was initiated. Use of this protocol has allowed 46% of rejection episodes encountered to be treated on an outpatient basis without resorting to inpatient use of OKT3, but has avoided delaying OKT3 therapy until after all other methods of rejection treatment were found to be ineffective. Of 83 rejection episodes treated with OKT3 between March 1985 and May 1987, 78 (94%) were reversed. Overall graft survival is 84% and patient survival is 96% in OKT3-treated patients. Of the 17 rejection episodes where OKT3 treatment was a second or third exposure to the drug, rejection was successfully reversed in 15 (88%). In cadaver donor allograft recipients transplanted between March 1985 and May 1986, actual 1-year graft survival is 80% for 30 patients requiring no rejection therapy, 80% for 20 patients with rejection episodes responding quickly to steroids, and 82% for 28 patients with OKT3-treated, steroid-insensitive rejections. Mean serum creatinine at 1 year posttransplant is 1.5 +/- 0.5; 1.9 +/- 0.7; and 2.1 +/- 0.8, respectively, for these groups of patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Monoclonal↗
PubMed2005

Association of morbid obesity and weight change over time with cardiovascular survival in hemodialysis population.

BACKGROUND: In maintenance hemodialysis (MHD) outpatients, a reverse epidemiology is described, ie, baseline obesity appears paradoxically associated with improved survival. However, the association between changes in weight over time and prospective mortality is not known. METHODS: Using time-dependent Cox models and adjusting for changes in laboratory values over time, the relation of quarterly-varying 3-month averaged body mass index (BMI) to all-cause and cardiovascular mortality was examined in a 2-year cohort of 54,535 MHD patients from virtually all DaVita dialysis clinics in the United States. RESULTS: Patients, aged 61.7 +/- 15.5 (SD) years, included 54% men and 45% with diabetes. Time-dependent unadjusted and multivariate-adjusted models, based on quarterly-averaged BMI controlled for case-mix and available time-varying laboratory surrogates of nutritional status, were calculated in 11 categories of BMI. Obesity, including morbid obesity, was associated with better survival and reduced cardiovascular death, even after accounting for changes in BMI and laboratory values over time. Survival advantages of obesity were maintained for dichotomized BMI cutoff values of 25, 30, and 35 kg/m2 across almost all strata of age, race, sex, dialysis dose, protein intake, and serum albumin level. Examining the regression slope of change in weight over time, progressively worsening weight loss was associated with poor survival, whereas weight gain showed a tendency toward decreased cardiovascular death. CONCLUSION: Weight gain and both baseline and time-varying obesity may be associated with reduced cardiovascular mortality in MHD patients independent of laboratory surrogates of nutritional status and their changes over time. Morbidly obese patients have the lowest mortality. Clinical trials need to verify these observational findings.

Adult↗
PubMed1982

Effects of repeated, small aliquot, same donor transfusions of HL-A defined blood on prospective recipients.

A series of HL-A defined, nonrelated blood transfusions given in small aliquots from the same donor to prospective cadaveric and living-related donor recipients has been presented. The results to date show 100% kidney survival in this small series over a relatively short period of time. The rejections noted have been very mild, and easily reversed. Nonspecific antibodies appear to be produced by the recipients in response to the blood, and these antibodies seem to have no negative effect upon kidney survival. This method of small aliquot transfusion to produce the desired effect is cheaper, wastes less blood, is less likely to lead to a CMV or HAA infestation in the transfusion recipient, and appears to be a highly efficient method of producing the desired effect.

Blood Transfusion↗