High prevalence of methicillin-resistant Staphylococcus aureus (MRSA) on doctors' neckties.

We set out to investigate whether neckties worn by doctors are more likely to be contaminated with Methicillin resistant Staphylococcus aureus (MRSA) compared to neckties worn by preclinical medical undergraduates who have never been exposed to a hospital environment. We discovered that more than half (52%) of neckties worn by doctors were contaminated with Staphylococcus and out of these, 62% of them were identified as MRSA. In contrast, none of the student's ties were contaminated with MRSA. Due to the high prevalence of staphylococcus detected on doctors' neckties, we recommend that health care workers do not wear neckties.

Patients who talk and deteriorate: a new look at an old problem.

BACKGROUND AND METHODS: We sought to review established prognostic indicators applied to Asian population, and to identify new risk factors for deterioration in patients who talked and deteriorated after traumatic brain injury (TBI). This retrospective study used our prospectively maintained TBI database. From August 1999 to July 2001, 324 patients were admitted to the neurosurgical intensive care unit (ICU). Thirty-eight patients (11.8%) talked between injury and subsequent deterioration into coma. Independent outcome predictors were studied. RESULTS AND CONCLUSION: Fourteen patients had subdural haematomas, 9 extradural haematomas, 19 contusions/haematomas and 3 subarachnoid haemorrhages. 81.5% of the patients had mass lesions potentially requiring surgery. Twenty patients had good functional recovery at 6 months (Glasgow Outcome Score 4 and 5); 18 were dead or vegetative. Age, gender, type of intracranial lesion and presence of coagulopathy were significantly correlated with outcome. Intracranial haematomas continue to be most significant in patients who talk and deteriorate. Coagulopathy was the strongest prognostic predictor of poor outcome with fibrinolytic parameters being reliable prognostic markers of head injury. Early identification, continued monitoring and treatment of coagulopathy should be our new look at improving outcome of these patients.

The adaptor protein BLNK is required for b cell antigen receptor-induced activation of nuclear factor-kappa B and cell cycle entry and survival of B lymphocytes.

B lymphocytes lacking the adaptor protein B cell linker (BLNK) do not proliferate in response to B cell antigen receptor (BCR) engagement. We demonstrate here that BCR-activated BLNK(-)/- B cells fail to enter the cell cycle, and this is due to their inability to induce the expression of the cell cycle regulatory proteins such as cyclin D2 and cyclin-dependent kinase 4. BCR-stimulated BLNK(-)/- B cells also do not up-regulate the cell survival protein Bcl-x(L), which may be necessary for the cells to complete the cell cycle. In addition, BLNK(-)/- B cells exhibit a high rate of spontaneous apoptosis in culture. Examination of the various BCR-activated signaling pathways in mouse BLNK(-)/- B cells reveals the intact activation of Akt and mitogen-activated protein kinases but the impaired activation of nuclear factor (NF)-kappaB that is known to regulate genes involved in cell proliferation and survival. The inability to activate NF-kappaB in BCR-stimulated BLNK(-)/- B cells is due to a failure to induce the degradation of the inhibitory kappaB protein. In all these aspects, BLNK(-)/- B cells resemble xid B cells that have a mutation in Bruton's tyrosine kinase (Btk). Recently, phospholipase C (PLC)-gamma2 has also been demonstrated to be essential for NF-kappaB activation. Since BLNK has been shown separately to interact with both Btk and PLC-gamma2, our finding of normal Btk but impaired PLC-gamma2 activation in BCR-stimulated BLNK(-)/- B cells strongly suggests that BLNK orchestrates the formation of a Btk-PLC-gamma2 signaling axis that regulates NF-kappaB activation. Taken together, the NF-kappaB activation defect may be sufficient to explain the similar defects in BCR-induced B cell proliferation and T cell-independent immune responses in BLNK(-)/-, Btk(-)/-, and PLC-gamma2(-)/- mice.

B cell development and activation defects resulting in xid-like immunodeficiency in BLNK/SLP-65-deficient mice.

Engagement of the B cell receptor (BCR) leads to the activation of tyrosine kinases and other signaling molecules that ultimately determine the type and magnitude of the B lymphocyte's cellular response. The adaptor protein BLNK/SLP-65 plays a pivotal role in BCR signal transduction by coupling Syk activation to downstream elements such as Grb2, phospholipase C-gamma, Vav and Nck. We have generated BLNK(-/-) mice to determine the physiological role of this protein in B cell development and activation. BLNK(-/-) mice exhibit an incomplete block in B cell development with a severe inhibition of pro-B to pre-B cell differentiation. BLNK(-/-) sIgM(+) cells can develop, seed the peripheral lymphoid tissues and accumulate in numbers overtime. However, these mutant B cells failed to mature and are non-responsive to BCR cross-linking in terms of proliferation and up-regulation of activation markers such as CD69 and CD86 (B7-2). In addition, the CD5(+) subset of B cells is absent. The immune response to T cell-independent antigen but not T cell-dependent antigen is also impaired. Overall, the phenotype of BLNK(-/-) mice bears a striking resemblance to that of xid mice which is the murine model of human XLA that has a mutation in Bruton's tyrosine kinase. This raises the interesting possibility that mutation in BLNK/SLP-65 may be responsible for certain human immunodeficiencies.

Ultraviolet B-induced suppression of immune responses in interleukin-4-/- mice: relationship to dermal mast cells.

Ultraviolet B radiation is immunosuppressive by multiple mechanisms. In interleukin-4-/- mice, ultraviolet B radiation was not able to suppress delayed-type hypersensitivity or contact hypersensitivity responses when the sensitizing antigen was applied to nonirradiated sites. In contrast, ultraviolet B significantly suppressed contact hypersensitivity responses to haptens applied to irradiated sites in interleukin-4-/- mice. In mast cell depleted Wf/Wf mice, ultraviolet B radiation also significantly suppressed contact hypersensitivity responses to sensitizing antigens applied to irradiated but not to unirradiated sites. In both interleukin-4-/- mice and Wf/Wf mice, the mast cell product, histamine, was immunosuppressive implicating mast cells as the dysfunctional cell in interleukin-4-/- mice. The prevalence of dermal mast cells was similar in wild-type and interleukin-4-/- mice. Dermal mast cells of interleukin-4-/- mice, however, express very low levels of c-kit and did not significantly degranulate in response to ultraviolet B. Ultraviolet radiation induced significant and similar levels of serum interleukin-10 in wild-type and interleukin-4-/- mice. We conclude that interleukin-4 indirectly affects ultraviolet B suppression of contact hypersensitivity and delayed-type hypersensitivity responses to sensitizing antigens applied at sites other than those irradiated by providing a critical differentiative signal for dermal mast cells. This study further emphasizes the central role of mast cells in the initial processes by which ultraviolet B radiation is immunomodulatory for immune responses to sensitizing antigens applied to nonirradiated sites.

Role of magnetic resonance imaging and magnetic resonance imaging--guided surgery in the evaluation of patients with early-stage breast cancer for breast conservation treatment.

Magnetic resonance imaging (MRI) may be more sensitive than mammography for detecting breast cancer and may have an adjunctive role in assessing patients with early-stage disease for breast conservation treatment. This study was performed to analyze the impact of breast MRI on the clinical management of 83 patients being considered for breast conservation treatment. Eighty-three consecutive cases of patients undergoing breast MRI during standard workup and evaluation for breast conservation treatment from 1993 to 1996 were retrospectively reviewed. Records were reviewed for patient and tumor characteristics, mammographic findings, MRI findings, timing of MRI study, findings from MRI-guided surgery (when done), and whether the patient underwent breast conservation treatment. MRI definitely altered management in 15 patients (18%), may have affected management in 4 patients (5%), and did not change management in 64 patients (77%). Thirteen patients underwent additional surgery because of MRI findings; the positive predictive value for MRI-guided surgery was 38% (5 of 13). Ultimately, 82% of the patients received breast conservation treatment. No predictive factor was identified to characterize the patients most likely to have management affected by MRI findings. These findings suggest that breast MRI may be useful in the evaluation of patients with early-stage breast cancer for breast conservation treatment. A larger study population and outcome data will be required to confirm these findings and to define those patients most likely to benefit from breast MRI.