Proliferation kinetics of subpopulations of human marrow cells determined by quantifying in vivo incorporation of [2H2]-glucose into DNA of S-phase cells

This report investigated in vivo turnover kinetics of marrow hematopoietic progenitors and precursors using a recently developed stable isotope-mass spectrometric technique (SIMST). Human subjects were administered a 2-day infusion of 6,6-[2H2]-glucose, a nontoxic stable isotope-labeled form of glucose, which becomes incorporated into DNA of all S-phase cells. The percent [2H2]-glucose incorporated into DNA in the form of [2H2]-deoxyadenosine (%[2H2]-dA enrichment) was determined by gas chromatography-mass spectrometry. The rate constant of replacement of unlabeled by labeled DNA strands (labeling kinetics) was used to calculate population turnover kinetics of CD34+ cells, CD133+ cells, and CD133-CD34+ cells. The observed mean replacement half-life (t1/2) was 2.6 days for CD34+ cells, 2.5 days for CD133-CD34+ cells, and 6.2 days for CD133+ cells. Results from the estimated rate constant of replacement of labeled by unlabeled DNA (delabeling kinetics) also demonstrated slower turnover rates for CD133+ cells than for CD133-CD34+ cells. Although there was a relatively rapid initial decrease in the %[2H2]-dA enrichment, low levels of labeled DNA persisted in CD34+ cells for at least 4 weeks. The results indicate the presence of subpopulations of CD34+ cells with relatively rapid turnover rates and subpopulations with a slower t1/2 of 28 days. Results also demonstrate that in vivo [2H2]-glucose-SIMST is sensitive enough to detect differences in turnover kinetics between erythroid and megakaryocyte lineage cells. These studies are the first to demonstrate the use of in vivo [2H2]-glucose-SIMST to measure in vivo turnover kinetics of subpopulations of CD34+ cells and precursors in healthy human subjects.     

T-cell depletion and graft survival induced by anti-human CD3 immunotoxins in human CD3epsilon transgenic mice

BACKGROUND: Anti-CD3 immunotoxins are broad-spectrum immunosuppressive agents in a wide range of organ transplantation animal models with potential use in eliciting antigen-specific tolerance. However, the anti-CD3 immunotoxins used in animal studies do not cross-react with human T cells, limiting extrapolation to humans and hindering clinical development. METHODS: Three anti-human CD3-directed immunotoxins, DT389-scFv(UCHT1), scFv(UCHT1)-PE38, and UCHT1-CRM9, were compared in vitro and in transgenic mice, tg(epsilon)600+/-, that have T cells expressing both human and murine CD3epsilon antigens. RESULTS: These immunotoxins were extraordinarily potent in vitro against human or transgenic mouse T cells, with IC50 values in cellular assays ranging from pM to fM. Systemic administration of these immunotoxins dose-dependently depleted >99% of tg(epsilon)600+/- lymph node and spleen T cells in vivo. Depletion was specific for T cells. The loss of the concanavalin A-induced, but not the lipopolysaccharide-induced, splenic proliferative response from immunotoxin-treated animals further demonstrated specific loss of T-cell function. Immunotoxin treatment prolonged fully allogeneic skin graft survival in tg(epsilon)600+/- recipients to 25 days from 10 days in untreated animals. T-cells recovered to approximately 50% of normal levels after approximately 22 days in animals with or without skin grafts; T-cell recovery correlated with skin graft rejection. All three immunotoxins elicited >100 day median survival of fully allogeneic heterotopic heart grafts. By 100 days, T cells recovered to normal numbers in these animals, but the grafts showed chronic rejection. CONCLUSION: These immunotoxins profoundly deplete T cells in vivo and effectively prolong allogeneic graft survival.     

Primary hepatic leiomyosarcoma in a woman after renal transplantation: report of a case

In contrast to malignant lymphomas or skin cancer, smooth muscle tumors including leiomyosarcoma are rarely associated with transplant recipients. We herein present a 33-year-old woman with end-stage renal disease who received a transplant at 27 years of age. Four years after the transplantation, at age 31, she underwent a mastectomy because of primary right breast cancer, which was found to be a 5-mm-sized mucinous carcinoma with no regional lymph node metastasis. Six years after the transplantation, a liver tumor was unexpectedly discovered. An explorative laparotomy revealed a well-encapsulated tumor occupying the posterior portion of the right lobe of the liver. The patient underwent a posterior segmentectomy. Histologically, the tumor possessed intermingling fascicles of spindle cells with eosinophilic cytoplasm and elongated nuclei. Based on an immunohistochemical examination, the tumor cells were positive for the muscle-associated antibody. In addition, RNA probes for Epstein-Barr virus were negative based on in situ hybridization. The histologic, immunohistochemical findings were considered to be diagnostic for leiomyosarcoma, which is a low-grade malignancy. Two years after surgery, the patient is doing well with no recurrence of liver tumors or breast cancer. Received: April 16, 2001 / Accepted: September 11, 2001     

Lateral thrust of anterior cruciate ligament-insufficient knees and posterior cruciate ligament-insufficient knees

Leaving anterior cruciate ligament (ACL) insufficiency and posterior cruciate ligament (PCL) insufficiency untreated frequently leads to osteoarthritis (OA). The purpose of this study was to evaluate dynamically the lateral thrust of ACL-insufficient knees and PCL-insufficient knees, and from the findings investigate the relationship between cruciate ligament insufficiency and OA occurrence. An acceleration sensor was attached to the affected and control anterior tibial tubercles, acting in medial-lateral and perpendicular directions. The lateral thrust immediately after heel strike was measured continuously by a telemeter under stabilised walking conditions. When compared to the contralateral healthy knee, the peak value of lateral acceleration immediately after heel strike was significantly larger in the ACL-insufficient knee; and lateral thrust was increased, but not significantly, in the PCL-insufficient knee. Given that lateral thrust of the knee during walking increases due to ACL or PCL injury, it may be a principal contributor to OA progression.     

Natural orifice surgery: initial US experience utilizing the StomaphyXTM device to reduce gastric pouches after Roux-en-Y gastric bypass

Introduction

Weight gain after gastric bypass can occur in up to 10% of patients 5 years following and in about 20% of patients 10 years following surgery. The nadir weight is usually reached within the first 2 years after bypass surgery. However, weight may slowly be regained for numerous reasons. This phenomenon has been studied extensively, but there is often no one reason this occurs. Once psychological and dietary reasons have been investigated, revisional surgery may be the only alternative for treatment. Revisional gastric bypass surgery is associated with a much higher morbidity and mortality when compared with a primary gastric bypass procedure.

Patients and methods

Thirty-nine patients underwent endoluminal gastric pouch reduction with the StomaphyX^TM device after informed consent. The StomaphyX^TM device is a sterile, single-use device for use in endoluminal transoral tissue approximation and ligation in the gastrointestinal (GI) tract.

Results

Average age was 47.8 (29–64) years, and 36/39 (92.3%) patients were female. Average body mass index (BMI) and weight prior to the StomaphyX^TM procedure were 39.8 (22.7–63.2) kg/m² and 108.0 kg (65.90–172.2 kg). The average preprocedure excess body weight was 51.1 kg. Weight loss at 2 weeks (n = 39) was 3.8 kg (7.4% excess body weight loss, EBWL), at 1 month (n = 34) was 5.4 kg (10.6% EBWL), at 2 months (n = 26) was 6.7 kg (13.1% EBWL), at 3 months (n = 15) was 6.7 kg (13.1% EBWL), at 6 months (n = 14) was 8.7 kg (17.0% EBWL), and at 1 year (n = 6) was 10.0 kg (19.5% EBWL). No major complications were observed. The minor complications that were seen included a sore throat lasting less than 48 h in 34/39 patients (87.1%) and epigastric pain that lasted for a few days in 30/39 patients (76.9%). Three patients with chronic diarrhea had their symptoms resolved after the procedure. Eight patients with gastroesophageal reflux disease reported improvement in their symptoms post procedure.

Conclusions

Endoluminal revision of gastric bypass patients with weight gain using the StomaphyX^TM procedure may offer an alternative to open or laparoscopic revisional bariatric surgery.     

Associations among everyday stress, critical life events, and sexual problems

This study addresses the question of how stress is linked to sexual problems among women and men in close relationships. Psychological symptoms, relationship quality, internal daily stress (i.e., originating within the couple such as conflicts, worry for the partner), external daily stress (i.e., stress arising outside the couple such as job stress, stressful relatives, and so forth), and critical life events were examined with regard to their association with different sexual problems. The results support the hypotheses that (1) there is an incremental effect of stress on sexual problems after controlling for psychological symptoms and relationship quality, and that (2) it is primarily internal daily stress and in some cases critical life events rather than external daily stress that are related to sexual problems, particularly hypoactive sexual desire in women and men, sexual aversion in women, vaginismus in women, and premature ejaculation in men. Our findings indicate that the treatment of these sexual problems should address relationship issues and include a focus on helping individuals improve their stress management skills within their couple relationship.     

The optimal timing to resect pulmonary metastasis

OBJECTIVE: There is no criterion for the timing of surgical resection of pulmonary metastasis. In this study, we investigated the optimal period for pulmonary metastasectomy. METHODS: Between 2000 and 2005, 68 patients underwent complete pulmonary resection of metastatic cancer. Clinical prognostic factor in multivariate analysis was examined. RESULTS: The interval from pulmonary metastasectomy until subsequent recurrence and the interval from detection of pulmonary metastasis until pulmonary metastasectomy were independent prognostic factors. To investigate the relationship between the two characteristics, the 68 patients were divided into two groups according to the interval from lung metastasectomy until subsequent recurrence. Nineteen patients relapsed within 1 year after pulmonary metastasectomy (group A), while 49 patients did not relapse within 1 year (group B). The interval from detection of pulmonary metastasis until pulmonary metastasectomy was significantly shorter in group A than in group B (2.9 months vs 7.1 months, p=0.01). Based on these results, we divided the patients into two different groups and survival was compared. Significantly shorter survival was observed in the patients who underwent pulmonary metastasectomy within 3 months after detection of pulmonary metastasis (group X, n=35) than in those who underwent the surgery beyond 3 months (group Y, n=33). CONCLUSIONS: There were many cases of early relapse after metastasectomy when the interval from detection of pulmonary metastasis until pulmonary metastasectomy was short. Performing metastasectomy at least three months after detection of pulmonary metastasis may significantly improve the prognosis of patients.     

Diffusion-weighted magnetic resonance imaging of normal and degenerative lumbar intervertebral discs: a new method to potentially quantify the physiologic effect of physical therapy intervention

STUDY DESIGN: Observational, repeated measures design. OBJECTIVES: To determine the reliability of the apparent diffusion coefficient (ADC) calculated from diffusion-weighted magnetic resonance images (MRI) of the nuclear region of lumbar intervertebral discs (IVDs), to investigate the differences in the ADC based upon T2-signal intensity, and to examine the test-retest variation in these measures obtained from subjects undergoing serial, diffusion-weighted MRI scans. BACKGROUND: Impaired diffusion of water within the lumbar IVD is a central characteristic of degenerative disc disease. Diffusion-weighted MRI scans can provide quantitative estimates of water diffusion and may be useful to evaluate the physiologic effects of healing or the change in hydration related to interventions such as traction, manual therapy, or exercise on normal and degenerative lumbar IVDs. METHODS AND MEASURES: Thirty subjects underwent T2 -weighted and diffusion-weighted lumbar MRI scans. Twenty-one of these subjects underwent a second diffusion-weighted MRI scan 4 to 7 weeks after the initial scan. The ADC was calculated from midsagittal diffusion-weighted images for the IVDs of L1-2 to L5-S1. To assess reliability, repeated measures of the ADC were performed on the first 16 scans. The T2-signal of the nuclear region of each disc was classified as hyperintense, intermediate, or hypointense, and its relationship to the mean ADC of the nuclear region was determined. Test-retest variation in the ADC was described using the coefficient of variation (CV), plus or minus the width of the 95% confidence interval of the standard error of measurement (SEM). RESULTS: Intraclass correlation coefficients for estimates of intrarater and interrater reliability ranged from 0.95 to 0.99 and the SEM ranged from 0.006 to 0.026 X 10-3 mm2/s. The mean ADC was significantly greater for hyperintense IVDs compared to intermediate and hypointense IVDs. The CV plus or minus the 95% CI of the SEM between scans ranged from 9.0% to 13.6% for all discs, 6.1% to 10.1% for hyperintense discs, and 13.1% to 23.7% for intermediate discs. The prevalence of hypointense discs was too low to make meaningful judgments about their normal degree of variation over time. CONCLUSION: The ADC of the nuclear region of the lumbar IVDs may be reliably measured from diffusion-weighted images. Degenerative discs had lower mean ADC values than normal discs but demonstrated greater variation between scans. Diffusion-weighted imaging may be a useful procedure to assess change in diffusion of water in lumbar discs that occurs over time.     

Arthroscopic findings in Maisonneuve fractures

Background A Maisonneuve fracture consists of a proximal fibular fracture with associated syndesmotic ligament disruption and injury to the medial ankle structures. The treatment outcome is good in most cases, although poor results have also been reported. The purpose of this study was to investigate intra-articular lesions in Maisonneuve fractures. Methods The subjects consisted of four patients (four ankle joints) who had suffered a Maisonneuve fracture and had undergone surgical treatment between June 2005 and November 2005. The mean age was 24. 2 years. At the time of surgery, we performed ankle arthroscopy and determined the presence of tibiofibular syndesmosis disruption, cartilaginous damage, and ligament damage. Lesions of the articular cartilage were graded by depth as determined by inspection and probing. Results All four of the cases had cartilaginous damage to the medial section of the talar dome. Lateral lesions were not observed. Chondral debris and hemarthrosis were noted in virtually all cases, and each ankle had a tear on the anterior inferior tibiofibular ligament and interosseous tibiofibular ligament. No patients had a tear of the posterior inferior tibiofibular ligament. Conclusions Arthroscopy was useful in identifying associated intra-articular lesions in Maisonneuve fractures.     

Association between height loss and bone loss, cumulative incidence of vertebral fractures and future quality of life: the Miyama study

Introduction The study aimed to clarify associations between height loss, bone loss and the quality of life (QOL) score among general inhabitants of Miyama, a rural Japanese community. This population-based epidemiological study was conducted in Miyama, a village located in a mountain area in Wakayama Prefecture, Japan. Methods A list of all inhabitants comprising 1,543 inhabitants (716 men, 827 women) born in this village between 1910–1949 was compiled. From the above whole cohort, a subcohort to measure bone mineral density (BMD) was recruited, consisting of 400 participants, divided into four groups of 50 men and 50 women each, and stratified into age decades by decade of birth-year (1910–1919, 1920–1929, 1930–1939 or 1940–1949). BMD measurement, physical measurements of height (cm) and body weight (kg) were taken, and body mass index (BMI; kg/m²) were calculated. BMD and anthropometric measurements were repeated on the same participants at 3, 7 and 10 years after baseline measurement (1993, 1997 and 2000). Results and discussion Among 299 of 400 participants, changes in height over 10 years for men in their 40s, 50s, 60s and 70s were −0.7 cm, −0.5 cm, −1.2 cm and −1.5 cm, respectively, compared with −0.7 cm, −1.4 cm, −2.1 cm and −3.7 cm in women, respectively. No significant relationships between change in height and rate of change in BMD at the lumbar spine and femoral neck after adjustment for age in men (lumbar spine, β = 0.058, standard error of the mean (SE) = 0.031, P = 0.501, R² = 0.038; femoral neck, β = 0.100, SE = 0.038, P = 0.228, R² = 0.121) were identified. By contrast, among women, a significant positive association was identified between height change and change rate of BMD at the lumbar spine after adjusting for age (β = 0.221, SE = 0.039, P = 0.012, R² = 0.069), while no significant relationship was found between height change and change rate at the femoral neck (β = 0.107, SE = 0.039, P = 0.229, R² = 0.048). No significant relationship was noted between vertebral fractures (VFx) and height at baseline in men and women (men: odds ratio (OR) 0.93, 95% confidence interval (CI) 0.81–1.05, P = 0.24; women: OR 0.97, 95% CI 0.87–1.08, P = 0.58) or between VFx and height loss (men: OR 1.31, 95% CI 1.00–1.71, P = 0.051; women: OR 1.20, 95% CI 0.94–1.53, P = 0.14). In both men and women, no significant relationship was identified between utility of the EuroQol EQ5D questionnaire and height at baseline (men: β = −0.148, SE = 0.003, P = 0.202, R² = 0.076; women: β = 0.127, SE = 0.004, P = 0.235, R² = 0.048), and height change (men: β = −0.078, SE = 0.008, P = 0.452, R² = 0.065; women: β = 0.053, SE = 0.010, P = 0.608, R² = 0.038).