Estimating Haemophilus influenzae type b vaccine effectiveness in England and Wales by use of the screening method

In October 1992, Haemophilus influenzae type b (Hib) conjugate vaccine was introduced to infants in the United Kingdom with a "catch-up" program for those aged <4 years. Initially, the rate of invasive Hib disease decreased dramatically but has been increasing since 1999. To determine possible reasons for this increase, the effectiveness of Hib conjugate vaccine was estimated by use of the screening method. Between October 1993 and December 2001, a total of 443 cases of Hib infection occurred in children eligible for vaccination; 363 (82%) were fully vaccinated. Vaccine effectiveness was estimated to be 56.7% (95% confidence interval, 42.5-67.4). Effectiveness was lower in children vaccinated during infancy, compared with those who were vaccinated during the catch-up campaign (P=.0033), declined with time since vaccination (P=.0008), and was lower in children born during 2000-2002, compared with other children scheduled for infant vaccination (P=.0041). Use of a catch-up vaccination program enhanced the control of Hib infection in England and Wales. Since 1999, however, low effectiveness in infants, declining effectiveness with age, and the use of lower-efficacy vaccines have contributed to increased rates of Hib infection. The potential role of boosters needs to be considered.     

Feasibility study of IL-11 and granulocyte colony-stimulating factor after myelosuppressive chemotherapy to mobilize peripheral blood stem cells from heavily pretreated patients

PURPOSE: Pediatric patients with solid tumors treated with prolonged dose-intensive chemoradiotherapy are poor mobilizers of peripheral blood stem cells (PBSC). We have conducted a pilot study to mobilize PBSC in eight pediatric patients with relapsed solid tumors using ifosfamide, carboplatin, and etoposide (ICE) followed-up by IL-11 plus granulocyte colony-stimulating factor (G-CSF). PATIENTS AND METHODS: Patients received ifosfamide 1.8 g/m2 per day for 5 days, carboplatin 400 mg/m2 per day for 2 days, and etoposide 100 mg/m2 per day for 5 days. After completion of ICE chemotherapy, patients received daily subcutaneous injections of G-CSF (5 microg/kg per day) and IL-11 (50-100 microg/kg per day) until peripheral stem cell apheresis. RESULTS: The median age was 11 years. Diagnosis included three relapsed Hodgkin disease, three relapsed central nervous system tumors, one relapsed Wilms tumor, and one relapsed rhabdomyosarcoma. The median number of apheresis procedures required to obtain 5 x 10(6) CD34+ cells/kg was one. The mean +/- standard error of mean (SEM) total CD34+ cells collected was 14.0+/-2.7 x 10(6)/kg. The mean +/- SEM total CD34+/CD41+ cells collected was 4.6+/-1.9 x 10(6)/kg. Seven of the eight patients have subsequently undergone myeloablative chemotherapy with autologous PBSC transplantation and have reconstituted hematopoiesis with a median time to neutrophil recovery of 10 days and platelet recovery of 15.5 days. CONCLUSIONS: We conclude that the regimen of ICE/IL-11 plus G-CSF is successful in mobilizing large numbers of CD34+ PBSC cells with a limited number (one) of apheresis collections in patients that have previously been heavily pretreated with chemotherapy/radiotherapy.     

Uterine Preservation or Hysterectomy at Sacrospinous Colpopexy for Uterovaginal Prolapse?

This study retrospectively compared 34 women who had a sacrospinous hysteropexy and 36 who had a vaginal hysterectomy and sacrospinous fixation for symptomatic uterine prolapse. All women underwent independent review and examination, with a mean follow-up of 36 months in the hysterectomy group and 26 months in the hysteropexy group.  The subjective success rate was 86% in the hysterectomy group and 78% in the hysteropexy group (P = 0.70). The objective success rate was 72% and 74%, respectively (P = 1.00). The patient-determined satisfaction rate was 86% in the hysterectomy group and 85% in the hysteropexy group (P = 1.00). The operating time in the hysterectomy group was 91 minutes, compared to 59 minutes in the hysteropexy group (P<0.01). The mean intraoperative blood loss in the hysterectomy group was 402 ml, compared to 198 ml in the hysteropexy group (P<0.01). The sacrospinous hysteropexy is effective in the treatment of uterine prolapse. Vaginal hysterectomy may not be necessary in the surgical treatment of uterine prolapse.     

Alterations in the focal adhesion kinase/Src signal transduction pathway correlate with increased migratory capacity of prostate carcinoma cells

Focal adhesion kinase (FAK) has been implicated in the regulation of cell migration. In addition, FAK expression is increased in a number of highly metastatic tumor cell lines. Therefore, we investigated the role of FAK in regulating migration of prostate carcinoma cell lines with increasing metastatic potential. We show that highly tumorigenic PC3 and DU145 cells exhibit intrinsic migratory capacity, while poorly tumorigenic LNCaP cells require a stimulus to migrate. Increased metastatic potential of PC3 and DU145 cells correlates with increased FAK expression, overall tyrosine phosphorylation and activity, as measured by autophosphorylation of tyrosine 397. However, in PC3 and DU145 cells, FAK autophosphorylation is adhesion dependent whereas a second site of tyrosine phosphorylation, tyrosine 861, a Src specific site, is uncoupled from adhesion-dependent signaling events. Finally, inhibiting the FAK/Src signal transduction pathway by over expressing FRNK (Focal adhesion kinase-Related Non-Kinase), an inhibitor of FAK activation, or treatment with PP2, a Src family kinase inhibitor, significantly inhibited migration of prostate carcinoma cell lines, demonstrating that tumor cell migration continues to be dependent on signals emanating from this pathway.     

Group B streptococci in pharyngeal aspirates at birth and the early detection of neonatal sepsis.

The pharyngeal aspirates collected from 400 babies at the time of delivery were examined for the presence of bacteria, especially group B streptococci. Aspirates from 79 babies were found to contain viable bacteria, including 4 with group B streptococci; one of these 4 babies developed streptococcal meningitis within 24 hours. The group B streptococci were seen on a Gram-stained film of the aspirate, and were detectable by coagglutination and countercurrent immunoelectrophoresis within 4 hours and by culture after 24 hours. Examination of pharyngeal aspirates may be of value as a screening test for neonatal sepsis.     

Chronic Arsenic Poisoning From Burning High-Arsenic-Containing Coal In Guizhou, China

Optimization of a previously disclosed sorbitol dehydrogenase inhibitor (SDI, II) for potency and duration of action was achieved by replacing the metabolically labile N,N-dimethylsulfamoyl group with a variety of heterocycles. Specifically, this effort led to a series of novel, in vitro potent SDIs with longer serum half-lives and acceptable in vivo activity in acutely diabetic rats (e.g., 62, 67, and 69). However, the desired in vivo potency in chronically diabetic rats, ED90 less than or equal to 5 mg/kg/day, was achieved only through further modification of the piperazine linker. Several members of this family, including 86, showed better than the targeted potency with ED90 values of 1-2 mg/kg/day. Compound 86 was further profiled and found to be a selective inhibitor of sorbitol dehydrogenase, with excellent pharmacodynamic/pharmacokinetic properties, demonstrating normalization of sciatic nerve fructose in a chronically diabetic rat model for approximately 17 h, when administered orally at a single dose of 2 mg/kg/day.     

Production of cytokines by bone marrow cells obtained from patients with multiple myeloma

Previous work with continuously cultured multiple myeloma lines suggested that cytokine production by tumor cells may mediate some of the medical complications of this disease. To further investigate this issue, we assayed freshly obtained bone marrow (BM) cells from myeloma patients for the in vitro production of cytokines and the presence of cytokine RNA. Production of cytokine protein was assessed by bioassays with the aid of specific neutralizing anticytokine antibodies. These assays detected interleukin-1 (IL-1) and tumor necrosis factor (TNF) secretion by myeloma BM cells, which was significantly greater than secretion from similarly processed BM cells of control individuals. In contrast, lymphotoxin and interleukin-2 (IL-2) production could not be detected. The levels of IL-1 and TNF produced in vitro peaked at 24 hours of culture and correlated with stage and the presence (or absence) of extensive osteolytic bone disease. Northern blot analysis demonstrated the presence of IL-1 beta and TNF RNA in uncultured myeloma BM cells but no detectable IL-1 alpha or lymphotoxin RNA. In addition, the amount of cytokine RNA correlated with protein production, being significantly greater in patients' BM cells than in control marrow. These data suggest a role for IL-1 beta and/or TNF in the pathophysiology of multiple myeloma and argue against a role for lymphotoxin or IL-2.     

Rare detection of hepatitis B and hepatitis C virus genomes by polymerase chain reaction in seronegative donors with elevated alanine aminotransferase

BACKGROUND: Since screening for antibody to hepatitis C virus (HCV) was introduced in 1990, posttransfusion hepatitis has been reduced to nearly background levels. This has led to reconsideration of the value of testing donated blood for elevated alanine aminotransferase (ALT). The contribution of ALT testing in detecting seronegative infection was evaluated by the performance of polymerase chain reaction (PCR) for hepatitis B virus (HBV) or HCV in plasma from ALT-elevated blood units. STUDY DESIGN AND METHODS: Testing was performed on 375 units of plasma, derived from an equivalent of 47,500 blood donations, with a highly sensitive hemi-nested PCR procedure. Using a triplet of primers directed at the conserved regions of HBV DNA and 5'-noncoding regions of HCV RNA, the hemi-nested PCR assay can reliably amplify 10 viral molecules to levels detectable in ethidium bromide-stained agarose gels. Pools of plasma from groups of four donors were screened with hemi-nested PCR. For any reactive pools, the plasma from individual donors was retested twice on different aliquots. RESULTS: Two of 375 units, both with midrange ALT elevation, were repeatedly reactive in hemi-nested PCR (one each for HBV DNA and HCV RNA). However, samples from the two suspect donors tested 9 and 5 months later revealed no seroconversion, elevated ALT, or viral genomes in hemi-nested PCR. CONCLUSION: The lack of confirmed HBV or HCV infection in this study representing an estimated 47,500 voluntary blood donations suggests that routine ALT testing for further prevention of posttransfusion hepatitis after exclusion of HBV- and/or HCV-seropositive blood may be superfluous.     

Treatment of refractory adult lymphoblastic leukemia (ALL) with 4'(9- acridinylamino) methanesulfon-M-anisidide (AMSA)

Twenty-four adults with ALL were treated with AMSA alone or in combination. Twenty-two were treated at time of relapse and two patients after failing primary induction therapy. All had been treated with anthracyclines prior to receiving AMSA. Of the 22 patients with ALL in relapse, 4 achieved a complete remission. Two of these patients have relapsed while receiving maintenance chemotherapy; one died 1 mo after achieving remission due to the occurrence of cholycystitis in the setting of pancytopenia and one patient underwent bone marrow transplantation and is in remission at 8 mo after the second remission. Both patients who failed primary induction therapy remain in remission at 11 and 36 mo, respectively. The use of AMSA should be considered for patients with ALL who fail primary induction as well as those whose leukemia becomes resistant to conventional agents.