Consequences of exposure to peri-articular injections of micro- and nano-particulate cobalt–chromium alloy

Metal hip replacements generate both metal particles and ions. The biological effects of peri-articular exposure to nanometre and micron sized cobalt chrome (CoCr) wear particles were investigated in a mouse model. Mice received injections of two clinically relevant doses of nanoparticles (32 nm), one of micron sized (2.9 μm) CoCr particles or vehicle alone into the right knee joint at 0, 6, 12 and 18 weeks. Mice were analysed for genotoxic and immunological effects 1, 4 and 40 weeks post exposure. Nanoparticles but not micron particles progressively corroded at the injection site. Micron sized particles were physically removed. No increase of Co or Cr was seen in peripheral blood between 1 and 40 weeks post exposure to particles. No significant inflammatory changes were observed in the knee tissues including ALVAL or necrosis. DNA damage was increased in bone marrow at one and forty weeks and in cells isolated from frontal cortex at 40 weeks after injection with nanoparticles. Mice exposed to the micron sized, but not nanoparticles became immunologically sensitized to Cr(III), Cr (VI) and Ni(II) over the 40 week period as determined by lymphocyte transformation and ELISpot (IFN-γ and IL-2) assays. The data indicated that the response to the micron sized particles was Th1 driven, indicative of type IV hypersensitivity. This study adds to understanding of the potential adverse biological reactions to metal wear products.     

Stromal osseous metaplasia in a low-grade ovarian adenocarcinoma

BACKGROUND: Stromal osseous metaplasia is a rare and curious finding in tumors of the ovary. CASE REPORT: The patient, a 66-year-old P3 G3 white female, had a past history of stage 1c left ovarian, well-differentiated endometrioid adenocarcinoma removed in 1981. She was treated with radiotherapy. The tumor recurred 21 years later with prominent stromal osseous metaplasia that had not been present in the primary. DISCUSSION: The pathogenesis of osseous metaplasia in epithelial tumors of the ovary is unclear; however, it is probable that a metaplastic process involving multipotential stromal stem cells results in bone formation. CONCLUSION: Benign osseous metaplasia in ovarian tumors is rare and its histogenesis remains unclear. As far as we know, this process does not appear to have any prognostic or pathological significance.     

Age effects on antidepressant-induced manic conversion

BACKGROUND: Antidepressant drug therapy can precipitate mania in vulnerable individuals, but little is known about the effects of age on this phenomenon. OBJECTIVE: To pharmacoepidemiologically evaluate the risk of conversion to mania by antidepressant class and patient age. DESIGN, SETTING, AND PATIENTS: Using an administrative national database of more than 7 million privately insured individuals, linked outpatient and pharmacy claims were analyzed for mental health users aged 5 to 29 years (N = 87,920). MAIN OUTCOME MEASURES: The proportion and cumulative hazard of manic conversion were analyzed by antidepressant class and subject age among children, adolescents, and young adults with an anxiety or nonbipolar mood disorder in the United States between January 1, 1997, and December 31, 2001. Manic conversion was defined as a new diagnosis of bipolar illness. RESULTS: During median follow-up of 41 weeks (range, 8-251 weeks), manic conversion occurred in 4786 patients (5.4%). Multivariate analyses using time-dependent Cox proportional hazards models indicated that an increased risk of manic conversion was associated with antidepressant category vs no antidepressant exposure (hazard ratios: 2.1 for selective serotonin reuptake inhibitors, P<.001; 3.8 for "other" antidepressants, P<.001; and 3.9 for tricyclic antidepressants, P =.002). Antidepressant x age interactions revealed inverse age effects for selective serotonin reuptake inhibitors and other antidepressants (beta = -.05; P<.001 for both) but not for tricyclic antidepressants (beta = -.02; P =.25). Peripubertal children exposed to antidepressants were at highest risk of conversion (number needed to harm: 10 [95% confidence interval, 9-12] among 10- to 14-year-olds vs 23 [95% confidence interval, 21-25] among 15- to 29-year-olds). CONCLUSIONS: Patient age is an effect modifier on the risk of antidepressant-associated manic conversion. Treatment with antidepressants is associated with highest conversion hazards among children aged 10 to 14 years.     

Neurofibromatosis type 1: the role of neuroradiology.

Neurofibromatosis type 1 is the commonest of the phakomatoses with a prevalence of 1 in 3-4000. In common with most of the other phakomatoses it is a genetic disorder with typical dermatological manifestations. Many organ systems can be affected but brain, spine, cranial nerve and peripheral nerve involvement is frequent. In this review we will describe the central nervous system manifestations of neurofibromatosis type 1 and discuss some of the controversies raised by investigating children with this disorder.     

CT angiography of intracranial aneurysms related to arteriovenous malformations: a cautionary tale

Computed tomographic angiography (CTA) has a high sensitivity and specificity for the detection of intracranial aneurysms and is increasingly used as the primary imaging modality in the investigation and pretreatment planning of patients presenting with acute subarachnoid haemorrhage. We present two cases in which CTA failed to demonstrate arteriovenous malformations associated with intracranial aneurysms.