Weak androgen levels, glucocorticoid therapy, and bone mineral density in postmenopausal women with rheumatoid arthritis

OBJECTIVE: To study dehydroepiandrosterone sulfate (DHEAS) and androstenedione (AND) status in postmenopausal women with rheumatoid arthritis (RA), the effects of glucocorticoid therapy on DHEAS and AND levels, and their relationship with bone mineral density (BMD). METHODS: Forty-six postmenopausal women with RA were separated into two groups based on whether they had a negative history for glucocorticoid therapy (n = 24) or were currently on glucocorticoid therapy (n = 22). The control group was composed of 39 postmenopausal women who had never received hormone replacement therapy. Serum DHEAS and AND levels were measured using a radioimmunoassay. BMD was determined at the lumbar spine (L2-L4) and femoral neck using a DEXA Hologic QDR-1000 densitometer. Results. RA patients and controls were similar in age, weight, body mass index, and years since menopause. DHEAS and AND levels were lower in the glucocorticoid-treated RA group than in the other two groups. The glucocorticoid-treated RA group also had a significantly lower femoral BMD value than the nonglucocorticoid-treated RA group. Lumbar BMD was similar in the two RA groups and in the controls. CONCLUSION: Decreases in DHEAS and AND levels in postmenopausal women with RA are probably related to glucocorticoid therapy rather than to the disease itself.     

Familial communicating syringomyelia

Calssical cervical syringomyelia was found in 3 members of one family. All 3 underwent air myelogram, and a Chiari malformation type I and postural collapse of the spinal cord was found in each case. An affected 7-year-old boy was discovered after a clinical and radiological survey of 8 first-degree relatives on the basis of mild scoliosis, pyramidal tract signs in the lower limbs and enlarged sagittal diameter of the cervical canal. One other member had basilar impression of the skull but no neurological abnormalities. No positive correlation was found between either the size of the cystic cord enlargement or descent of the ectopic tonsils with the duration or severity of the neurological findings. Suboccipital decompressive craniotomy and upper cervical laminectomy in one case was followed by improvement in strength and sensation 1 year later. Progression in familial syringomyelia appears to occur through a mechanism identical to that in the sporadic form and surgery is therefore also indicated. In affected families, routine survey of close relatives for abnormal neurological signs, and radiological evidence of scoliotic deformity of the spine, enlarged cervical canal and bone abnormalities at the craniovertebral junction may prove valuable for early detection. A dominantly inherited, genetically determined malformation seems to be the probable mechanism of inheritance in this family.     

Transfusion free surgery: single institution experience of 27 consecutive liver transplants in Jehovah's Witnesses

BACKGROUND: Despite the risks associated with transfusion, the medical community continues to view blood as a safe and abundant product. In this article, we provide an effective strategy to accomplish orthotopic liver transplantation without transfusion. STUDY DESIGN: From June 1999 through July 2004, 27 liver transplantations were performed in Jehovah's Witness patients at the USC-University Hospital (24 adults, 3 children). Nineteen of these were living donor (LD) and eight were deceased donor (DD) liver transplants. Preoperative blood augmentation with erythropoietin and iron was achieved. At induction, all LD and six of eight DD recipients underwent acute normovolemic hemodilution (ANH), and the operation was conducted under conditions of moderate anemia. Cell scavenging techniques were used. Acute normovolemic hemodilution and salvaged blood were returned as needed during bleeding or on completion of transplantation. RESULTS: The preoperative liver disease severity score was higher in the deceased donor group. We had 100% graft and patient survivals in the LD group, and 75% in the DD recipients. Two DD recipients died. The remaining are all alive and well, with a mean followup of 965 days (range 266 to 1,979 days) in the LD group and 624 days (range 119 to 1,132 days) in the DD group. CONCLUSIONS: Preoperative blood augmentation and acute normovolemic hemodilution provide a safe cushion against operative blood loss. Elective living donor liver transplantation allows full implementation of a transfusion-free strategy in the setting of early hepatic failure, portal hypertension, and anemia. This feat is an important step toward global standardization of transfusion-free surgical practice and an important response to widespread blood shortages and transfusion risks.     

Multifunctional role of Erk5 in multiple myeloma

Multiple myeloma is characterized by the accumulation of terminally differentiated B cells in the bone marrow, due to increased proliferation and restricted apoptosis of the myelomatous clone. Here we have studied the participation of a novel mitogen-activated protein kinase (MAPK) route, the extracellular signal-regulated kinase 5 (Erk5) pathway, in the regulation of myeloma cell proliferation and apoptosis. Erk5 was expressed in cells isolated from patients and in myeloma cell lines. The myeloma growth factor interleukin 6 (IL-6) activated Erk5, and this activation was independent of Ras and Src. Expression of a dominant-negative form of Erk5 restricted the proliferation of myeloma cells and inhibited IL-6-dependent cell duplication. This dominant-negative form also sensitized myeloma cells to the proapoptotic action of dexamethasone and PS341. The latter compound caused a profound decrease in the amount of endogenous Erk5 and was less effective in inducing apoptosis when the level of Erk5 was increased by transfection of Erk5. These results place the Erk5 route as a new regulatory signaling pathway that affects multiple myeloma proliferation and apoptosis.     

Cerebrovascular events associated with infusion through arterially malpositioned triple-lumen catheter: report of three cases and review of literature

Analysis of 10 adult patients treated from January 1998 to November 2004 for arterial misplacement of triple-lumen catheter (TLC) during internal jugular vein cannulation was performed. Three cases that developed neurologic symptoms occurring in the context of infusion through a TLC that was arterially malpositioned are presented, along with the review of literature. In 7 patients, the diagnosis of arterial misplacement was suspected by the color or flow characteristics of blood and confirmed by a combination of blood gas analysis, connecting catheter to transducer, and/or chest film. In the remaining 3 patients, intraarterial misplacement was not suspected. In these patients, the initial review of chest films by qualified physicians prior to starting infusion failed to detect malposition of the catheter. Retrospectively, subtle clues suggestive of arterially placed TLCs were found. All 3 patients developed neurologic symptoms. Initiation of neurologic workup delayed a correct diagnosis by 6 to >48 hours. A volumetric pump was used for infusion in all patients. Of the 3 patients with neurologic symptoms, 1 recovered completely, 1 became comatose, and 1 partially improved.Based on our observations and review of literature, we conclude that cursory examination of chest films to verify proper positioning of central venous catheter attempted through the internal jugular vein may fail to detect arterial malposition. Infusion by volumetric pump precludes backflow of blood in the intravenous tubing as an indicator. Neurologic symptoms concurrent with the infusion of fluids and medication should raise suspicion of accidental arterial infusion.