Bioavailability of two clodronate formulations

Sodium clodronate is effective in the management of osteolytic lesions, hypercalcaemia and bone pain associated with skeletal metastasis. Clinical and biochemical data underpin a licensed total daily dose of 1600-3200 mg.     

Human immunodeficiency virus-associated neoplasms: epidemiology, pathogenesis, and review of current therapy

The development of cancer in the setting of human immunodeficiency virus (HIV) infection is a devastating event and highlights the role of impaired immunity in the generation of various neoplasms. Improved strategies to suppress viral replication and prevent opportunistic infections generally have enabled patients with HIV to live longer and more productively. Unfortunately, acquired immune deficiency syndrome (AIDS)-associated neoplasia is increasing. Kaposi's sarcoma (KS), primary central nervous system lymphoma, intermediate- and high-grade B-cell lymphoma, and invasive cervical carcinoma are AIDS-defining conditions and the most commonly encountered malignancies. Recent information suggests an indirect role for HIV in the pathogenesis of these tumors. Effective treatment involves addressing complex variables encountered specifically in patients with AIDS. This review focuses on the epidemiology, pathogenesis, and treatment of KS and non-Hodgkin's lymphoma.     

A new metal-binding site in photosynthetic bacterial reaction centers that modulates QA to QB electron transfer

Isolated reaction centers (RCs) from Rhodobacter sphaeroides were found to bind Zn(II) stoichiometrically and reversibly in addition to the 1 equiv of non-heme Fe(II). Metal and EPR analyses confirm that Zn(II) is ligated to a binding site that is distinct from the Fe site. When Zn(II) is bound to this site, electron transfer between the quinones QA and QB (QA-QB --> QAQB-) is slowed and the room-temperature kinetics become distributed across the microsecond to millisecond time domain. This effect of metal binding on the kinetics is similar to the more global effect of cooling RCs to 2 degreesC in the absence of Zn(II). This suggests that Zn(II) binding alters localized protein motions that are necessary for rapid QA-QB --> QAQB- electron transfer. Inspection of the RC crystal structure suggests a cluster of histidine ligands located beneath the QB binding pocket as a potential binding site.     

Induction of immunologic refractoriness in adults by meningococcal C polysaccharide vaccination

Thirty-four adults were vaccinated with 1/50 of the usual dose of meningococcal polysaccharide vaccine (1 microg of A, C, Y, and W135 polysaccharides, given intramuscularly). This dose was selected as a probe to assess B cell memory. The probe elicited meningococcal C bactericidal antibody responses in all 18 adults who had been vaccinated 4 years earlier with an investigational meningococcal A and C oligosaccharide-protein conjugate vaccine and in the majority of the 11 subjects vaccinated for the first time. In contrast, the responses of the 5 adults given a full dose of licensed polysaccharide vaccine 4 years earlier were <1/10 of those of the other 2 groups. Thus, adults previously given a full dose of meningococcal polysaccharide vaccine show evidence of immunologic refractoriness to group C polysaccharide, whereas refractoriness is not observed after conjugate vaccination. These findings have implications for the use of meningococcal polysaccharide vaccine when the risk of disease is low.     

Extragenital donovanosis of the foot

Kartagener's syndrome (KS) usually includes mirror-image dextrocardia. The incidence of congenital heart disease in KS is comparable with that in the general population. This paper reports on a case of Kartagener's syndrome associated with dextrocardia, corrected transposition of the great arteries (I,D,D), ventricular septal defect, and valvar pulmonary stenosis in an 8-year-old girl.     

Endodermal sinus tumor and embryonal carcinoma of the ovary in a 53-year-old woman

BACKGROUND: Germ cell tumors, the most common ovarian malignancies in females under the age of 21, are rare in older women. We report an unusual case of a mixed embryonal carcinoma and endodermal sinus germ cell tumor in a perimenopausal patient and review the differential diagnosis and management of these malignancies with respect to age. CASE: A 53-year-old woman complaining of irregular menses and pelvic pain was found to have a large pelvic mass and a positive pregnancy test. Subsequent investigation revealed a large left adnexal mass, and an elevated beta-HCG and alpha-AFP. At laparotomy, a mixed germ cell tumor was found. The patient was treated with multiagent chemotherapy and currently is without evidence of disease. CONCLUSION: Although rare, the diagnosis of germ cell tumor should be considered in older women presenting with a large pelvic mass. The treatment and prognosis is similar regardless of age, except that reproductive-sparing surgery is not a priority in the older patient.     

Patterns of prehistoric human mobility in polynesia indicated by mtDNA from the Pacific rat

Human settlement of Polynesia was a major event in world prehistory. Despite the vastness of the distances covered, research suggests that prehistoric Polynesian populations maintained spheres of continuing interaction for at least some period of time in some regions. A low level of genetic variation in ancestral Polynesian populations, genetic admixture (both prehistoric and post-European contact), and severe population crashes resulting from introduction of European diseases make it difficult to trace prehistoric human mobility in the region by using only human genetic and morphological markers. We focus instead on an animal that accompanied the ancestral Polynesians on their voyages. DNA phylogenies derived from mitochondrial control-region sequences of Pacific rats (Rattus exulans) from east Polynesia are presented. A range of specific hypotheses regarding the degree of interaction within Polynesia are tested. These include the issues of multiple contacts between central east Polynesia and the geographically distinct archipelagos of New Zealand and Hawaii. Results are inconsistent with models of Pacific settlement involving substantial isolation after colonization and confirm the value of genetic studies on commensal species for elucidating the history of human settlement.