Annual summary of vital statistics--2003

The crude birth rate rose slightly in 2003 to 14.1 births per 1000 population, from 13.9 in 2002. The 2002 rate was the lowest ever reported for the United States. The total number of births and the fertility rate (66.1) also increased. The birth rate for teenaged mothers dropped 3% to another record low in 2003, to 41.7 per 1000 females aged 15 to 19 years. The teenage birth rate has fallen by one third since 1991. The birth rate declined for women 20 to 24 years old but rose for women aged 25 to 44 years. The number, rate, and proportion of births to unmarried women all increased in 2003. Smoking during pregnancy declined to 11%, down from 19.5% in 1989. Prenatal care utilization improved slightly for 2003; 84.1% of women began care in the first trimester of pregnancy. The cesarean delivery rate jumped 6% to 27.6% for another US high. The primary cesarean rate rose 6%, and the rate of vaginal birth after a previous cesarean delivery plummeted 16% from 2002 to 2003. The percent of infants delivered preterm continued to rise (12.3% in 2003). The preterm birth rate is up 16% since 1990. The percentage of children born at low birth weight rose slightly in 2003 to the highest level reported since 1970 (7.9%). The twinning rate increased, but the rate for triplet/+ births declined slightly between 2001 and 2002. Multiple births accounted for 3.3% of all births in 2002. The infant mortality rate rose to 7.0/1000 live births in 2002 from 6.8 in 2001, marking the first increase in this rate in >4 decades. Increases were distributed fairly widely across age, racial/ethnic groups, and geographic areas. The rise in infant mortality was attributed to increases in <750-g births in both singleton and multiple deliveries. Although the downward trend in infant mortality rates in many developed nations may have stabilized, the United States still ranked 27th among these nations in 2001. Expectation of life at birth reached a record high of 77.3 years for all gender and race groups combined in 2002. Death rates in the United States continue to decline. Between 2001 and 2002, death rates declined for the 3 leading causes of death: diseases of heart, malignant neoplasms, and cerebrovascular diseases. Death rates for children 1 to 19 years old decreased by 8% for suicide; the death rate for chronic lower respiratory diseases increased by 33% in 2002. Rates for unintentional injuries and homicide did not change significantly for children aged 1 to 19 years. A large proportion of childhood deaths continues to occur as a result of preventable injuries.     

Lung cancer audit in an Irish teaching hospital

Background Lung cancer is the most common cause of cancer-related death in Ireland. There are few complete data sets available as to the stage and cell type of lung cancers at time of presentation in Ireland. Aim To audit the lung cancers presenting to a large Dublin teaching hospital over a 12-month period. Method Prospective evaluation of all lung tumours presenting to our institution over a consecutive 12-month period. Results One hundred and ninety-eight lung cancers presented over the study period. There were 34 cases of small cell carcinoma and 150 cases of non-small cell carcinoma (NSCC). Fourteen patients were too ill or compromised at time of presentation for tissue confirmation. The most common cell type was squamous carcinoma. Eighty-four per cent of the NSCCs were either stage 3 or 4 at presentation. Conclusion Most lung cancers present late in the time course of the disease. Distribution of cell type and location are similar in Ireland and other developed countries.     

Production of genetically stable high-titer retroviral vectors that carry a human gamma-globin gene under the control of the alpha-globin locus control region

The ability to generate stable high-titer vectors that give rise to high levels of expression of transduced globin genes in erythroid cells is a prerequisite for effective retroviral-mediated globin gene therapy. The human beta-globin gene with its immediate flanking sequences does not contain all the regulatory elements necessary for regulated high-level and position-independent expression in erythroid cells. The regulatory element known as the beta-globin locus control region (BetaLCR) can provide a linked Beta-globin gene with these properties. However, addition of BetaLCR sequences to a retrovirus carrying a beta-globin gene increases its genetic instability. We have developed a new generation of retroviral vectors in which a human gamma- globin gene is placed under the control of the alphaLCR, the major regulatory element of the alpha-globin gene cluster. We demonstrate that these retroviruses are genetically stable in producer cell lines and can be produced at high titers that exceed 5 x 10(6) colony-forming units (CFU)/mL. In addition, we show that the transduced gamma-globin gene can be expressed in the adult erythroid environment of mouse erythroleukemia (MEL) cells at a level comparable to that of a single endogenous Betamaj-globin gene. These retroviruses can also transduce primary murine bone marrow progenitor cells as efficiently as retroviruses that carry the neomycin resistance (neor) gene. This new generation of globin retroviral vectors may prove useful for gene therapy of human beta-globin gene disorders such as sickle cell disease and beta-thalassemia.     

Biomarkers of periodontal inflammation in the Australian adult population

Background:  Several inflammatory biomarkers are implicated in the pathogenesis of periodontitis including interleukin-1β (IL-1β) and C-reactive protein (CRP). This study investigated the presence of these factors in gingival crevicular fluid (GCF) and their relationship to clinical and social determinants of periodontitis in the Australian population.
Methods:  Equal numbers of periodontitis cases and non-cases were sampled during oral epidemiologic examination in the National Survey of Adult Oral Health. GCF was sampled from four sites where probing pocket depth (PPD) and recession were recorded. From these, IL-1β and CRP were quantified by ELISA and the log amount of GCF IL-1β (pg) per person and the proportion of adults with detectable CRP was computed.
Results:  Periodontitis cases (n = 511) had significantly higher levels of IL-1β and CRP than non-cases (n = 562). PPD, clinical attachment loss, plaque and gingivitis indices were positively associated with elevated levels of both biomarkers. Levels of both were positively associated with age, low socio-economic position and non-Australian birth.
Conclusions:  The presence of IL-1β and CRP in GCF are associated with periodontal disease parameters within the Australian population. The levels of both biomarkers are influenced by age, education and eligibility for public dental care.     

Clonal evolution in B-lineage acute lymphoblastic leukemia by contemporaneous VH-VH gene replacements and VH-DJH gene rearrangements

B-cell acute lymphoblastic leukemia (B-ALL), more frequently than any other B-lineage neoplasm, exhibits oligoclonal Ig heavy chain (IgH) gene rearrangement in 15% to 43% of all cases studied. To study the molecular processes that promote multiple IgH rearrangements, a comprehensive sequence analysis of a B-ALL case was performed in which seven clonal IgH gene rearrangements were identified. The genetic profiles suggested that a single leukemic progenitor clone evolved into several subclones through dual processes of variable (VH) to preexisting diversity-joining (DJH) gene segment rearrangement and VH to VH gene replacement. Predominant IgH-V usage and the uniquely rearranged clonotype-specific VHDJH region gene sequences were identified using a novel DNA-based gene amplification strategy. Polymerase chain reaction (PCR) was directed by an IgH-J generic primer and a complement of family-specific IgH-V primers that defined the major B-cell IgH-V gene usage. Clonality of rearranged VHDJH bands was substantiated by high resolution denaturant gel electrophoretic analysis. Sequence patterns of the amplified VHDJH fragments segregated into two groups defined by common DJH sequences. Partial N region homology at the VHD junction as well as shared DJH sequences firmly established VH to VHDJH gene replacement as a mechanism generating clonal evolution in one group. In the second subset, oligoclonality was propagated by independent VH gene rearrangements to a common DJH precursor. The contributions of all clonal Ig-VHDJH repertoires for each group was approximately 50% and reflected a symmetric distribution of leukemic subclones generated by either process. Thus, oligoclonal rearrangements evolved by two independent, yet seemingly contemporaneous molecular genetic mechanisms. All seven clones displayed nonfunctional Ig-VHDJH recombinations. These observations may have relevance to the recombinatorial opportunities available during normal B-cell maturation.     

Fatal disseminated enterovirus infection in a patient with follicular lymphoma undergoing obinutuzumab maintenance therapy

Follicular lymphoma is the most common subtype of the indolent non‐Hodgkin lymphomas. Treatment usually consists of immuno‐chemotherapy and results in long‐lasting remissions in most cases. Progression‐free survival with the second‐generation anti‐CD20 antibody obinutuzumab was shown to be better than with rituximab when given in combination with either bendamustine or anthracycline‐based chemotherapy. Although treatment is generally well tolerated without an excessive rate of toxicities, there appear to be slightly more adverse events with obinutuzumab than with rituximab. Here, we report the case of a 45‐year‐old female patient that was diagnosed with a disseminated enterovirus infection while undergoing maintenance therapy with obinutuzumab after induction treatment with the combination of bendamustine and rituximab. Enterovirus RNA was detected in the blood, the cerebrospinal fluid, and the colon. A therapy with intravenous immunoglobulins was initiated since the patient presented with a severe treatment‐related immunosuppression indicated by hypogammaglobulinemia. Nonetheless, she eventually died from the enterovirus infection without evidence of lymphoma progression. This case underscores that clinicians should be aware of rare but potentially fatal infectious complications related to treatment protocols containing anti‐CD20 antibodies.     

Ocular MR imaging and spectroscopy: an ex vivo study

Six eyes, freshly enucleated because of choroidal melanoma, were imaged on a 1.4-T superconducting magnetic resonance (MR) imaging system, and relaxation times were calculated for various parts of the eye. Unfixed fresh tissue samples were obtained for nuclear magnetic resonance spectroscopy (NMRS) on a variable-field (0.19-1.4 T) resistive unit. Detailed ocular anatomy was demonstrated. The NMRS relaxation times correlated with the MR imaging intensity patterns. The sensitivity of MR imaging to states of hydration provides an excellent window for appreciation of ocular anatomy.