Fracture risk in monoclonal gammopathy of undetermined significance.

To assess fractures in monoclonal gammopathy of undetermined significance (MGUS), the precursor of multiple myeloma, we followed 488 Olmsted County, MN, residents with MGUS in a retrospective cohort study. There was a 2.7-fold increase in the risk of axial fractures but no increase in limb fractures. The pathophysiologic basis for the increased axial fractures should be determined. INTRODUCTION: Multiple myeloma is often preceded by monoclonal gammopathy of undetermined significance (MGUS). Fractures are common in myeloma as a result of lytic bone lesions, generalized bone loss, and elevated bone turnover from excessive cytokine production. Whether fractures are also increased in MGUS is unknown. MATERIALS AND METHODS: In a population-based retrospective cohort study, 488 Olmsted County, MN, residents with MGUS first diagnosed in 1960-1994 (52% men; mean age, 71.4 +/- 12.8 years) were followed for 3901 person-years; follow-up was censored at progression to myeloma. The relative risk of fractures was assessed by standardized incidence ratios (SIRs), and risk factors were evaluated in proportional hazards models. RESULTS AND CONCLUSIONS: Altogether, 200 patients experienced 385 fractures. Compared with expected rates in the community, statistically significant increases were seen for fractures at most axial sites, for example, vertebrae (SIR, 6.3; 95% CI, 5.2-7.5). There was a slight increase in hip (SIR, 1.6; 95% CI, 1.2-2.2) but not distal forearm fractures (SIR, 0.8; 95% CI, 0.4-1.5). The relative risk (SIR) of any axial fracture was 2.7 (95% CI, 2.3-3.1) compared with only 1.1 (95% CI, 0.9-1.4) for all limb fractures combined. In a multivariate analysis, the independent predictors of any subsequent fracture were age (hazard ratio [HR] per 10-year increase, 1.4; 95% CI, 1.2-1.6) and corticosteroid use (HR, 1.8; 95% CI, 1.2-2.6); greater weight at diagnosis (HR per 10 kg, 0.8; 95% CI, 0.8-0.9), and IgG monoclonal protein (HR, 0.7; 95% CI, 0.5-0.97) were protective. Baseline monoclonal protein level, a determinant of myeloma progression, did not predict fracture risk. Thus, the risk of axial, but not peripheral, fractures is increased among MGUS patients even before progression to myeloma. The pathophysiologic basis for this should be determined because elevated bone turnover, for example, might be treatable.     

Status of Women and Infants in Complex Humanitarian Emergencies

Women and children bear the greatest burden in the midst of war and long‐term disasters. Complex humanitarian emergencies are characterized by social disruption, armed conflict, population displacement, collapse of public health infrastructure, and food shortages. Humanitarian assistance for refugees and internally displaced populations requires particular attention to the common issues affecting morbidity and mortality in women and infants. Gender‐based violence and reproductive health concerns are discussed within the context of populations affected by conflict and forced migration. Recommendations for midwives and women's health care providers engaging in care for women and children in complex humanitarian emergencies are discussed.     

Effect of Early Corticosteroid Therapy for Landau-Kleffner Syndrome

Four children treated for seizures between 1980 and 1986 were diagnosed as having Landau-Kleffner syndrome (acquired aphasia with convulsive disorder), following the onset of aphasia. They received early and prolonged ACTH or corticosteroid therapy, with high initial doses. In all four cases the EEG promptly became normal, with subsequent long-lasting remission of the aphasia and improvement of seizure control. Three to six years after discontinuation of hormone therapy the children are off medication and free from seizures and language disability.     

Transarterial embolization of vein of Galen aneurysmal malformation after unsuccessful stereotactic radiosurgery

The authors present three cases of vein of Galen aneurysmal malformations (VGAMs) diagnosed in infancy and submitted by the referring teams for stereotactic radiosurgery as the initial therapy (therapeutic doses ranging between 20–25 Gy and 40–50 Gy to the peak dose). After the conventional follow-up of 18–24 months, no change could be detected in the angioarchitecture of the lesions. All three cases were then referred for endovascular treatment and underwent embolization by the transarterial route using liquid adhesives (N-butyl cyanoacrylate). This resulted in complete anatomical exclusion of the lesion. Regardless of the theoretical efficiency of radiosurgery in the management of brain arteriovenous malformations, the present authors believe that transarterial embolization remains the treatment of choice in VGAMs. It offers a high rate of morphological cure and the best chances for normal neurocognitive development. The time required by radiosurgery to achieve a significant result is too long for developing and maturing brain and may not prevent the negative effects of the lesion, mainly in regard to hemo- and hydrodynamic disorders (atrophy, subcortical calcifications, etc.) created by the VGAM, thus leading to irreversible mental retardation.     

Benign osteoblastoma of the parietal bone

A 5-year-old girl presented with a 1-year history of a subcutaneous swelling in the right parietal region. There were no cerebral symptoms or signs. Plain X-ray of the skull showed a lytic bony lesion with sclerotic margin. Computed tomography showed a hypodense, osteolytic lesion with thinned and bulged inner and outer skull tables with intact continuity. There was no intracranial lesion. At operation, the mass was found to be pink and granular, and was totally enucleated. Histology revealed it to be a benign osteoblastoma.     

Research letter: How should abridged scientific articles be presented in journals? A survey of readers and authors

SEVERAL SCIENTIFIC AND GENERAL MEDICAL JOURNALS publish full-length articles on their Web sites and abridged versions in their print journals. We surveyed a stratified random sample of BMJ readers and authors to elicit their preferred format for the abridged print version. Each participant received a research paper abridged in 3 different formats: conventional abridged version, journalistic version and enhanced-abstract version. Overall, 45% (95% confidence interval [CI] 42%–48%) of the respondents said they liked the conventional version most, 31% (95% CI 28%–34%) preferred the journalistic version and 25% (95% CI 22%–27%) preferred the enhanced-abstract version. Twenty-eight percent (95% CI 25%–32%) indicated that use of the journalistic format for abridged articles would very likely stop them from submitting papers to BMJ, and 13% (95% CI 11%–16%) said the use of the enhanced-abstract version would stop them from submitting to BMJ. Publishers of general medical journals who publish shortened articles should consider that authors and readers prefer a more conventional style of abridged papers.     

Effect of Bupivacaine and Levobupivacaine on Exocytotic Norepinephrine Release from Rat Atria

Background: The cardiotoxic mechanism of local anesthetics may include interruption of cardiac sympathetic reflexes. The authors undertook this investigation to determine if clinically relevant concentrations of bupivacaine and levobupivacaine interfere with exocytotic norepinephrine release from cardiac sympathetic nerve endings.

Methods: Rat atria were prepared for measurements of twitch contractile force and 3[H]-norepinephrine release. After nerve endings were loaded with 3[H]-norepinephrine, the tissue was electrically stimulated in 5-min episodes during 10 10-min sampling periods. After each period, a sample of bath fluid was analyzed for radioactivity and 3[H]-norepinephrine release was expressed as a fraction of tissue counts. Atria were exposed to buffer alone during sampling periods 1 and 2 (S1 and S2). Control atria received saline (100 [mu]l each, n = 6 atria) in S3-S10. Experimental groups (n = 6 per group) received either bupivacaine or levobupivacaine at concentrations (in [mu]M) of 5 (S3-S4), 10 (S5-S6), 30 (S7-S8), and 100 (S9-S10).

Results: Bupivacaine and levobupivacaine decreased stimulation-evoked fractional 3[H]-norepinephrine release with inhibitory concentration 50% values of 5.1 +/- 0.5 and 6.1 +/- 1.3 [mu]m. The inhibitory effect of both local anesthetics (~70%) approached that of tetrodotoxin. Local anesthetics abolished the twitch contractions of atria with inhibitory concentration 50% values of 12.6 +/- 5.0 [mu]m (bupivacaine) and 15.7 +/- 3.9 [mu]m (levobupivacaine). In separate experiments, tetrodotoxin inhibited twitch contractile force by only 30%.     

Inflammatory central nervous system disease in lupus-prone MRL/lpr mice: comparative histologic and immunohistochemical findings

The brains of pathogen-free autoimmune MRL/lpr, NZBWF1 and NZB mice were examined for central nervous system (CNS) inflammation in premoribund 8-week-old animals and at ages when active systemic lupus erythematosus (SLE) was present. CNS inflammation was observed only in MRL/lpr mice. Immunohistochemical studies of brains from young MRL/lpr mice found that infiltrates were composed primarily of CD4+ cells. Older MRL/lpr mice (22 and 26 weeks of age) had CD4+ cells predominantly, but CD8+ and B220+ cells were also present. Perivascular leakage of IgG was a prominent and unexpected finding in the MRL/lpr model. Congenic MRL/+ mice with late-onset autoimmunity had no inflammatory cells in brain tissue, and there was no perivascular staining with IgG or albumin. Our findings suggest that MRL/lpr mice are a useful model for studies of lupus-associated CNS inflammatory disease, and perivascular leakage may be a primary mechanism for entry of IgG into the brain.     

Influence of urbanization of the western coast of the United Arab Emirates on trace metal content in muscle and liver of wild Red-spot emperor (Lethrinus lentjan).

We hypothesized that increased ambient concentrations of metals, as a consequence of escalating urbanization and industrialization of the Gulf region will respond in increased contamination of edible fish species. In this study, we report concentrations of chromium, manganese, cobalt, copper, zinc, arsenic, cadmium, mercury and lead in meat and liver of wild Red-spot emperor (Lethrinus lentjan) from three sampling points at the UAE coast. Analysis was performed by the ICP-MS/microwave digestion. Our study has shown that meat and liver metal content was significantly higher in areas with higher industrial activity, although metal values did not exceed permitted levels of fish for human consumption.