Public stem cell banks: considerations of justice in stem cell research and therapy

If stem cells fulfill their therapeutic promise, moving them from the laboratory into the clinic will raise several concerns about justice. One concern is that, for biological reasons alone, stem cell‐based therapies might not be available for every patient who needs one. Worse, depending on how we address the problem of biological access, they might benefit primarily white Americans. We can avoid this outcome—although at a cost—by carefully selecting the stem cells we make available.     

A novel dual radio- and stable-isotope method for measuring calcium absorption in humans: comparison with the whole-body radioisotope retention method

BACKGROUND: Dietary calcium absorption can be determined only with the use of isotope techniques. Currently used isotope techniques require exclusive equipment or are not true tracer approaches. OBJECTIVE: The objective was to compare a dual-isotope method combining radioisotopes and stable isotopes with a whole-body radioisotope retention method for measuring calcium absorption. DESIGN: Seven healthy adults aged 21-27 y consumed a test meal containing 63 +/- 14 (macro x +/- SD) mg Ca together with a water solution of (47)Ca (0.11 MBq). One hour after ingestion, 18 mg (44)Ca was administered intravenously. All feces and urine were collected for 5 and 6 d, respectively. Calcium absorption was estimated from whole-body retention of the radioisotope 12 times over 3 wk after ingestion and from the excretion of (47)Ca and (44)Ca in a 24-h urine sample collected on day 2. (44)Ca in urine was determined by inductively coupled plasma mass spectrometry. RESULTS: Mean (+/- SD) calcium absorption was 75 +/- 9% with the dual-isotope method and was 74 +/- 8% with the whole-body radioisotope retention method. There was a high degree of agreement between the methods. CONCLUSION: The dual-isotope method is a valid approach for measuring calcium absorption from a single meal.     

An epidemiological study of the relations between exposure to organophosphate pesticides and indices of chronic peripheral neuropathy and neuropsychological abnormalities in sheep farmers and dippers

OBJECTIVES—To investigate the hypothesis that chronic low level exposure to organophosphates (OPs) in sheep dips is related to clinically detectable measures of polyneuropathy.
METHODS—The design was a cross sectional exposure-response study of sheep dippers and other non-exposed groups. The study group consisted of 612 sheep dipping farmers, 53 farmers with no sheep dipping experience, and 107 ceramics workers. Retrospective exposure information was obtained by questionnaire based on stable and easily identifiable features of sheep dipping found during the first phase of the study; in particular, estimates of handling concentrate and splashing with dilute dip. Neurological assessments were based on a standard neuropathy symptoms questionnaire, and thermal and vibration quantitative sensory tests.
RESULTS—Adjusted for confounders there was a weak positive association between cumulative exposure to OPs and neurological symptoms, the significance of which was dependent on the inclusion of a few individual workers with extremely high exposure. There was no evidence of an association between cumulative exposure and the thermal or vibration sensory thresholds. However, separating the effects of exposure intensity and duration showed a higher prevalence of symptoms, primarily of a sensory type, among sheep dippers who handled the OP concentrate. There was also evidence that sensory and vibration thresholds were higher among concentrate handlers, the highest exposed group of dippers.
CONCLUSIONS—The findings showed a strong association between exposure to OP concentrate and neurological symptoms, but a less consistent association with sensory thresholds. There was only weak evidence of a chronic effect of low dose cumulative exposure to OPs. It is suggested that long term health effects may occur in at least some sheep dippers exposed to OPs over a working life, although the mechanisms are unclear.


Keywords: organophosphates; sheep dippers; neuropathy     

Multicenter phase II study of gemcitabine in previously untreated patients with advanced epithelial ovarian cancer

Gemcitabine has activity in advanced ovarian cancer, with responses in platinum-resistant disease. This study assessed the activity of gemcitabine in previously untreated patients with advanced epithelial ovarian cancer. All patients had histologically verified invasive epithelial ovarian cancer, International Federation of Gynecology and Obstetrics (FIGO) stage III/IV disease and no prior chemotherapy. Patients received gemcitabine 1250 mg/m(2) on days 1, 8 and 15 of a 28-day cycle. Radiological response was assessed after two cycles. Between December 1992 and October 1995, 35 patients were enrolled. Of 33 evaluable patients, there was one complete response and five partial responses, for an overall response rate of 18% (95% confidence interval 7-36%). Forty-two percent of patients had a greater than 50% decrease in their CA-125 levels. Of the 25 patients who received platinum-based chemotherapy following treatment with gemcitabine, 12 achieved an overall response rate of 48%. Toxicity was mild, with two episodes of WHO grade 4 neutropenia (not associated with fever) and two episodes of grade 4 thrombocytopenia (not associated with bleeding). Gemcitabine has single-agent activity for poor-prognosis patients with advanced ovarian cancer. Similar results with subsequent platinum-based therapy indicate a lack of cross-resistance. This, combined with gemcitabine's favorable toxicity profile, warrants testing in comparative trials.     

Acute respiratory tract infections and mannose-binding lectin insufficiency during early childhood

Context  Hospital-based studies have found that increased susceptibility to certain infections is associated with low serum levels of mannose-binding lectin (MBL) due to MBL variant alleles. However, the contribution of MBL insufficiency to incidence of common childhood infections at a population level is unknown. Objective  To investigate the effect of MBL insufficiency on risk for acute respiratory tract infection (ARI) in unselected children younger than 2 years. Design and Setting  Population-based, prospective, cohort study conducted in Sisimiut, Greenland. Participants  Two hundred fifty-two children younger than 2 years who were followed up weekly between August 1996 and August 1998 for morbidity surveillance. Main Outcome Measure  Risk of ARI, based on medical history and clinical examination, compared by MBL genotype, determined from blood samples based on presence of structural and promoter alleles. Results  A 2.08-fold (95% confidence interval [CI], 1.41-3.06) increased relative risk (RR) of ARI was found in MBL-insufficient children (n = 13) compared with MBL-sufficient children (n = 239; P<.001). The risk association was largely restricted to children aged 6 to 17 months (RR, 2.92; 95% CI, 1.78-4.79) while less effect (RR, 1.47; 95% CI, 0.45-4.82) and no effect (RR, 1.00; 95% CI, 0.42-2.37) was shown among children aged 0 to 5 months and 18 to 23 months, respectively. Conclusion  These data suggest that genetic factors such as MBL insufficiency play an important role in host defense, particularly during the vulnerable period of childhood from age 6 through 17 months, when the adaptive immune system is immature.      

Selective reduction of bone blood flow by short-term treatment with high-dose methylprednisolone. An experimental study in pigs

Treatment with corticosteroids is a risk factor for non-traumatic avascular necrosis of the femoral head, but the pathological mechanism is poorly understood. Short-term treatment with high doses of methylprednisolone is used in severe neurotrauma and after kidney and heart transplantation. We investigated the effect of such treatment on the pattern of perfusion of the femoral head and of bone in general in the pig. We allocated 15 immature pigs to treatment with high-dose methylprednisolone (20 mg/kg per day intramuscularly for three days, followed by 10 mg/kg intramuscularly for a further 11 days) and 15 to a control group. Perfusion of the systematically subdivided femoral head, proximal femur, acetabulum, humerus, and soft tissues was determined by the microsphere technique. Blood flow in bone was severely reduced in the steroid-treated group. The reduction of flow affected all the segments and the entire epiphysis of the femoral head. No changes in flow were found in non-osseous tissue. Short-term treatment with high-dose methylprednisolone causes reduction of osseous blood flow which may be the pathogenetic factor in the early stage of steroid-induced osteonecrosis.     

Smoking as a predictor of negative outcome in lumbar spinal fusion.

STUDY DESIGN: A review of the smoking habits in 426 patients who had been followed prospectively for 2 years after a lumbar spinal fusion procedure was conducted. OBJECTIVE: To analyze the effect of pre- and postoperative smoking on clinical and functional outcome after lumbar spinal fusion. SUMMARY OF BACKGROUND DATA: Several animal models have shown a negative effect of nicotine on spinal fusion. At this writing, the clinical effect of nicotine on spinal fusion has not been fully clarified. METHODS: The study comprised 426 patients who underwent lumbar spinal fusion between 1993 and 1997. These patients received a mailed questionnaire regarding their tobacco consumption before and after their surgery. All other data, including preoperative clinical and functional status, were collected prospectively during a 2-year follow-up period. To assess functional outcome, the Dallas Pain Questionnaire was used. RESULTS: The questionnaire was answered by 396 patients (93%). Of these patients, 54.5% (20% more than the background population) were smokers before the operation. Smoking of more than 10 cigarettes daily before the operation and attempted fusion at two or more levels increased the risk of nonunion: odds ratio, 2.01 (P < 0.016) and odds ratio, 3.03 (P < 0.001), respectively. Smoking cessation increased fusion rates to near those of nonsmokers. Smoking had no influence on functional outcome, as assessed by the Dallas Pain Questionnaire, but preoperative smoking predicted a negative answer to the question "Would you undergo the same treatment again, now that you know the result?" (odds ratio, 1.65; P < 0.054). CONCLUSIONS: Smoking was shown to have a negative effect on fusion and overall patient satisfaction, but no measurable influence on the functional outcome as assessed by the Dallas Pain Questionnaire.     

Occupational therapy and Colles' fractures

In this randomized trial, we enrolled 30 patients treated for a distal radius Colles' type fracture. The fractures were reduced if necessary and fixed in a below-elbow plaster cast for 5 weeks. One group consisting of 14 patients received instructions for shoulder; elbow and finger exercise and the other group consisting of 16 patients had occupational therapy. At 5 weeks, 3 and 9 months we measured the functional scores. There were no statistically significant differences between the groups at any time. It seems that for non-surgically treated patients with a distal radius fracture only instructions are necessary.     

Effects of heptachlor epoxide on components of various signal transduction pathways important in tumor promotion in mouse hepatoma cells. Determination of the most sensitive tumor promoter related effect induced by heptachlor epoxide

The effects of the organochlorine (OC) liver tumor promoter heptachlor epoxide (HE; 0, 0.1, 1, 10, and 50 μM) on several cellular tumor promoter-sensitive parameters were studied in mouse 1c1c7 hepatoma cells in an effort to identify the most sensitive biomarker for OC promoter exposure and the critical pathway and target of OC promoters. The levels of Ca²⁺ in the endoplasmic reticulum (ER) store, connexin43 (Cx43), PLCγ₁, nPKC, and AP-1 DNA binding in nucleus were studied to screen for effects induced by submicromolar HE levels. While all the parameters tested elicited effects, particulate PLCγ₁ and AP-1 DNA binding were found to be the most sensitive parameters affected by HE on both dose and temporal bases. Their levels were increased with 10- to 100-fold lower HE concentrations than were required to affect nPKC or Cx43. Further, with the lower HE dosages, particulate PLCγ₁ and nuclear AP-1 were positively modulated by HE after 1 h versus 3 or 72 h for nPKC and Cx43. Ca²⁺ store depletion was probably the third most sensitive parameter, after AP-1 and PLCγ₁. These results suggest the tyrosine kinase growth factor receptor pathway is the probable critical pathway for HE-induce tumor promotion with the critical target most likely being upstream of PLCγ₁ and AP-1. This work also demonstates that upon exposure to a tumor promoter such as HE, many hepatocellular effects or changes result, suggesting that a cellular-program shift occurs similar to that described by the resistant hepatocyte model after exposure to a carcinogen or enzyme inducer.