Mutations in SOX2 cause anophthalmia-esophageal-genital (AEG) syndrome

Table 1     

A prospective study of tobacco use and multiple myeloma: evidence against an association

The relationship between the use of cigarettes and other tobacco products and the risk of multiple myeloma was examined in a cohort of nearly 250,000 American veterans followed prospectively for 26 years. Compared with men who had never used tobacco, the risk of death from myeloma was not increased among current (relative risk [RR]=0.9, 95 percent confidence interval [CI]=0.8–1.2) or former (RR=1.0, CI=0.8–1.3) cigarette smokers, nor among users of chewing tobacco or snuff (RR=1.0, CI=0.4–2.3). Risk was only slightly and nonsignificantly increased among pipe or cigar smokers (RR=1.2, CI=0.9–1.5). There was no indication of increasing risk with amount of tobacco used or earlier age at first use. With over 90 percent power to detect a 30 percent increased risk of this tumor occuring among current cigarette smokers, this study provides the strongest evidence to date against an association of cigarette smoking with multiple myeloma.Epidemiology and Biometry Program, Division of Cancer Etiology, National Cancer Institute. Westat, Inc. Rockville, MD. National Cancer Institute, 6130 Executive Blvd, Room 418, Rockville, MD 20892, USA.     

A simple cardiac contractility computer

A single-purpose analogue-computing device is described for the online assessment of the contractile state of the human myocardium from the left ventricular pressure (P_lv) data available during routine cardiac catheterisation. Due attention has been paid to the design of the computer circuits so that they will not process pressure phenomena outside the isovolumic contractile period. Either a \(\left( {\frac{1}{{P_{lv} }}\frac{{dP_{lv} }}{{dt}}} \right)_{max} \) or a plain \(\left( {\frac{{dP_{lv} }}{{dt}}} \right)_{max} \) index is presented on a digitalvoltmeter display, thus obviating the need for any graphical extrapolation or additional computation.     

Influence of Various Immunomodulators on the Induction of Experimental Autoimmune Encephalomyelitis in Lewis Rats

The effect of various immunomodulators on the induction of experimental autoimmune encephalomyelitis (EAE) is evaluated in the Lewis rat. Bordetella pertussis (BP) is the optimal inductor of EAE in this rat strain. Treatment of the animals with BP either before or after or simultaneously with guinea-pig spinal cord preparation (GpSC) resulted in an EAE about two weeks thereafter. Additional injection of living BCG, of CFA, IFA (incomplete Freund's adjuvant) or Vibrio cholerae neuraminidase (VCN) did not augment or mitigate the effect induced by BP or GpSC. Living BCG, IFA, VCN or Corynebacterium parvum (CP) did not induce EAE when given in combination with GpSC but without BP. CFA combined with GpSC only occasionally induced EAE. However, EAE could be induced by the combination of CFA and GpSC or IFA and GpSC in a part of the animals tested if they had been pretreated or simultaneously been injected with living BCG by intravenous route. EAE could not be enhanced by the additional injection of VCN. Surprisingly, most of the animals peracutely died after injection of CFA and BP in combination with GpSC when they had been pretreated with CP. This effect was most pronounced when pretreatment was done on day -4. No acute effect could be seen when CP was given simultaneously to CFA, BP and GpSC. Animals which did not peracutely succumb developed EAE similarly as those in the positive control groups. CP treatment simultaneously with BP but without CFA resulted in a reduction of the EAE specific mortality. This reduction could not be seen if treatment with CP was done after injection of GpSC and BP.     

Apoptosis of Merkel cells in neurotrophin-3 null mice

Postnatal mice lacking neurotrophin-3 (NT3) are deficient in Merkel cells of touch domes and whisker follicles. We examined the mechanism of Merkel cell loss by immunocytochemistry and electron microscopy. Merkel cell of whisker follicles of NT3 null newborns exhibited decreased immunoreactivity for cytokeratin 8 and contained apoptotic bodies that were positive for cleaved caspase-3, a marker of active apoptosis. By electron microscopy, the Merkel cells displayed aggregation of chromatin along the nuclear membrane, with the marginated chromatin forming caps at the periphery of the nucleus. Ribosomes aggregated in the cytoplasm, while dense core granules characteristic of Merkel cells were still discernible. Finally, the Merkel cells and their nuclei fragmented into apoptotic bodies. None of the apoptotic Merkel cells were contacted by nerve fibers, and their desmosomal contacts with surrounding keratinocytes disappeared. After postnatal day 6 apoptotic Merkel cells were no longer observed, and the number of surviving Merkel cells was severely reduced. They were flat and contained few osmiophilic granules. We conclude that perinatal apoptosis is responsible for the loss of Merkel cells lacking innervation in NT3 null mice.     

Prolongation of graft survival in allogeneic islet transplantation by (−) 15-deoxyspergualin in the rat

Summary The effect of 15-Deoxyspergualin, a novel drug which has been described to have anti-tumour activity, on allogeneic graft survival (Dark Agouti Lewis rats) after pancreatic islet transplantation was tested. A marked prolongation of graft survival could be shown using doses of 1.0, 2.5 and 5.0mg Deoxyspergualin/kg on day 0 until day +9 post transplantation. A maximum of 55.6 days (average) survival time was observed using 2.5mg/kg Deoxyspergualin compared to 5.2±0.6 days without immunosuppression. Using the chemiluminescence reaction of recipient monocytes after islet transplantation, a marked suppression of the monocyte system exceeding the treatment period could be observed. Since, in contrast to cyclosporin, B-cell toxicity could not be shown, the new drug seems to be a hopeful step towards successful allogeneic islet transplantation for treatment of diabetes.     

Laparoscopic surgical staging for uterine malignancies using harmonic shears (UltraCision) in comparison to electrosurgery: operative technique, feasibility and complications

This retrospective study assesses and compares perioperative parameters in two groups of patients treated by different operative techniques of laparoscopic surgical staging (LASS) for uterine cancer. Between April 1996 and May 2005, 119 consecutively selected women with cervical cancer (n=30) or clinical stage I endometrial cancer (n=89) underwent laparoscopic assisted vaginal hysterectomy (LAVH), total laparoscopic hysterectomy (TLH) or radical laparoscopic assisted vaginal hysterectomy (RALVH) plus bilateral salpingo-oophorectomy (BSO) and/or lymph node dissection (LND) during a primary surgical procedure using an electrosurgery (ELC, n=37) or ultrasonic (US, n=82) operative technique (harmonic shears, UltraCision). The UltraCision was used as a primary method of dissection and hemostasis from 1999. We were unable to perform prompt and thorough hemostasis in 2 patients from the US group (successful procedure rate 97.5%) because of ineffective post-ultrasonic coagulation of venous paravaginal varices (RALVH procedure) and of vena ovarica varices (LAVH, BSO procedure). The UltraCision was effective in all cases of lymphadenectomy. Successful procedure rate of the ELC operative technique was 100%. There were no statistically significant differences between the groups with regard to operation time, blood loss, hospital stay, and complications. There was a significant difference (P<0.001) in the number of lymph nodes harvested: a mean of 18.1 in the US group and 13.7 in the ELC group. We think that the difference was influenced by an increase in experience with laparoscopic lymph node dissection. The UltraCision operative technique ensures efficient dissection, coagulation, cutting, and grasping for LASS in women with cervical and endometrial cancer.     

Effects of Alendronate and Calcitonin on Bone Mineral Density in Postmenopausal Osteoporotic Women. An Observational Study

Objective: Alendronate and calcitonin are antiresorptive drugs that were used for the treatment of postmenopausal osteoporosis and were shown to increase bone mineral density (BMD). However, the effect of both drugs in daily clinical practice may differ from that observed in clinical trials.Method: About 50 postmenopausal osteoporotic women were observed during their first year of treatment. Among them, 32 patients used alendronate and 18 used calcitonin. Lumbar spine and femoral neck BMD were measured by dual energy X-ray absorptiometry (DXA) at baseline and after 1 year of therapy. Biochemical markers (B-ALP – bone-specific alkaline phosphatase, OTC – osteocalcin and DPD/UCr – deoxypyridinoline/creatinine ratio) of bone metabolism were measured at baseline and 6 months later. Patient compliance was assumed by tablet counting and verified at interview. Each patient was further questioned about her attitude towards the treatment, as well as her dairy product intake, physical activity, use of other medications, smoking and social status.Main outcome measure: (1) Annual percent change in BMD in lumbar spine and femoral neck after the one-year treatment with either alendronate or calcitonin. (2) The change in biochemical markers of bone turnover.Results: The lumbar spine BMD significantly increased by 7.0% (P < 0.001), the femoral neck BMD by 4.3% (P < 0.01). OTC, B-ALP and DPD/UCr decreased significantly during the therapy with alendronate. Compliance with therapy was 79% (95% CI 68–90%). In the calcitonin-treated group, the lumbar spine BMD significantly increased by 3.1 % (P < 0.05), while the femoral neck BMD remained unchanged. OTC, B-ALP and DPD/UCr did not change significantly during the treatment with calcitonin. Compliance with calcitonin therapy was 87% (95% CI 63–110%). The annual change of BMD in both treatment groups was independent on all questioned factors.Conclusion: In daily practice, alendronate enhanced significantly BMD both in lumbar spine and femoral neck. Calcitonin showed increase only in the lumbar spine BMD.