Self-esteem and racial preference in black children.
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Biomedical subjects
Publications and source records attributed to J Braun.
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In 29 patients with community-acquired pneumonia, 24 patients with hospital-acquired pneumonia and 35 patients with pneumonia in the immunocompromised host the diagnostic value of bronchoalveolar lavage (BAL) with quantitative bacterial and fungal cultures was studied; 32 patients with noninfectious pulmonary diseases and 14 healthy volunteers served as controls. An infectious etiology could be established in 81% of the pneumonia patients without differences between the three groups; significant infection was associated with colony counts of > or = 10(4) cfu/ml. Prior antibiotic therapy lowered the yield of BAL culture only in community-acquired pneumonia (94% vs 55% positive cultures in untreated vs pretreated patients, p < 0.02). Furthermore the culture results were related to the radiographic extension of pulmonary infiltrates (92% positive cultures in multilobar vs 54% in lobar or segmental infiltrates, p < 0.001). Therapeutic consequences of BAL were shown by resistance of the isolated organisms to predefined empiric treatment regimens in 41% community-acquired pneumonia, 43% pneumonia in the immunocompromised host and 67% hospital-acquired pneumonia patients.
In pneumonia local phagocyte activation is crucial for clearing of pathogenic microorganisms. In this context alveolar macrophage interleukin-8 secretion, phagocyte oxidative response and concentrations of lavage proteins were quantified, including interleukin-8, in 31 patients with pneumonia, 13 age matched patients with peripheral lung consolidation and six healthy volunteers; these findings were related to the impairment of gas exchange and the bacterial load in the alveolar space. Increased interleukin-8 levels were found in bronchoalveolar lavage fluid (BALF) and in alveolar macrophage supernatants from patients with pneumonia (214 ng/10(5) AM +/- 121 vs 71 ng/10(5) AM +/- 35 and 66 ng/10(5) AM +/- 30, p < 0.05). Interleukin-8 release from alveolar macrophages correlated with the upregulated spontaneous luminol enhanced oxidative response of pulmonary phagocytes but not with the neutrophil count in BALF. In pneumonia patients a significant difference was found between patients with 10(4) or more colony forming units (CFU)/ml BALF of one pathogen and patients with less CFU or nonspecific microbiological results (261 ng/10(5) AM +/- 89 vs 179 ng/10(5) AM +/- 81 and 7.5 ng/ml BALF +/- 17 vs 0.44 ng/ml BALF +/- 1, p < 0.05). Further, a negative correlation between interleukin-8 release of alveolar macrophages and the arterial pO2 at the time of BALF could be demonstrated (r = -0.47, p < 0.05). The results demonstrate local cellular activation in community-acquired pneumonia, which is related to the bacterial load in the alveolar space and to impairment of gas exchange. This is consistent with the hypothesis that pulmonary phagocytes play a central role in the pathogenesis of bacterial pneumonia, contributing not only to bacterial clearing but also to local tissue damage.
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In gap junctions, identical membrane proteins are linked up in pairs (dyads) that bridge the extracellular space between two apposed cell membranes. Typically, several thousand of these dyads are aggregated in the plane of the membranes and form a junctional plaque with a distinct boundary. The question thus arises as to what maintains the dyads in an aggregated state. From a statistical mechanical analysis of the positions of dyads in a freeze-fracture electron micrograph, we report here that the aggregates are not maintained by an attractive force between pairs of dyads, but probably by the minimization of the repulsive force between apposed membranes. On the basis of this analysis we present a model for the structure of mature gap junctions as well as certain aspects of the formation and disassembly of gap junctions.
The transgenic mouse line M54 was generated by introducing a functionally-rearranged immunoglobulin mu heavy-chain gene into the germ line of a C57B1/6 inbred mouse. Previous examination of the antibodies produced by B-cell hybridomas derived from transgenic M54 mice showed that the presence of the mu transgene grossly altered the immunoglobulin repertoire of unimmunized animals, suggesting that these mice suffer from a serious immunoregulatory perturbation. Studies presented here introduce a new perspective on this functional defect. We show that the lymphoid tissues from these transgenic mice lack virtually all conventional bone-marrow-derived B cells, which constitute the predominant B-cell population in normal mice and which typically produce primary and secondary antibody responses to T-cell-dependent antigens. Moreover, the bone marrow from transgenic M54 mice is depleted of pre-B lymphocytes, indicating a serious defect in early B-cell lymphopoiesis. In contrast, CD5 (Ly-1) B cells, a second B-cell population displaying a characteristic set of cell surface markers which are derived from distinct precursors in the peritoneum, are represented at normal frequencies in these transgenic mice. Thus, the presence of the rearranged immunoglobulin heavy-chain transgene in M54 mice results in an unexpected selective developmental defect that impairs the development of bone-marrow-derived pre-B and B cells without affecting Ly-1 B cells.
BACKGROUND AND OBJECTIVES: Mexiletine is a sodium channel blocker that has been used for the treatment of a variety of neuropathic pain syndromes. A recent double-blinded placebo-controlled study concluded that it was ineffective in the treatment of allodynia associated with neuropathic pain. However, this study failed to achieve adequate plasma levels of mexiletine. This was a study in healthy volunteers that sought to push the drug to dose-limiting side effects and then evaluate the effects on human experimental pain. METHODS: Twelve healthy volunteers were studied using a randomized, double-blind, placebo-controlled crossover study. The subjects were titrated to a maximum dose of 1,350 mg/d or dose-limiting side effects, whichever occurred first. At baseline and day 10 and 17, neurosensory testing, train-of-three thermal pulses, and side-effect measurements were performed and on day 17, intradermal capsaicin was injected on the volar aspect of the forearm and the pain and secondary hyperalgesia to von Frey hair, stroking, and thermal stimuli were measured. RESULTS: Peak plasma levels occurred on day 10 and were 0.36 +/- 0.21 microg/mL. All subjects experienced dose-limiting side effects. The mean maximum tolerable daily dose achieved was 859 mg (range, 300 to 1,350 mg). The side effects reported by the subjects included nausea, lightheadedness, muscle twitching and weakness, blurred vision, headache, tremors, difficulty concentrating, dysphoria, sedation, pruritus, and rash. These side effects occurred at an average daily dose of 993 mg (range, 600 to 1,350 mg). Compared with placebo, mexiletine had no significant effects on any of the neurosensory thresholds and pain scores after intradermal capsaicin. There was a significant reduction in the area of secondary hyperalgesia to von Frey hair stimulation only. There was a significant correlation between plasma mexiletine level and flare response. CONCLUSIONS: Mexiletine has minimal effects on human experimental pain. It is severely limited by side effects and tolerable doses seem to be void of effects on normal neurosensation and facilitated pain induced by capsaicin and thermal heat pulses.
The main outcome parameters in AS and other SpA are pain, disease activity, function, spinal mobility, and structural progression. There are several treatment options, which differ, depending on the localization and severity of the manifestation and the degree of structural changes already present. There is a basic role for physiotherapy to improve and maintain spinal mobility and function and prevent handicap. The basis for drug therapy in AS is NSAIDs, which may also have an influence on structural progression. DMARDs are mainly used in cases with peripheral arthritis. Corticosteroids have a clear role for intra-articular therapy, while the role for systemic use is, in contrast to RA, mainly reserved for subgroups. It is largely unclear whether long-term spinal progression can be prevented by conventional drug therapy. Treatment with biologics such as anti-TNF-alpha therapy is discussed in Part 2 of this review. To be published in the next issue of the Scandinavian Journal of Rheumatology. Surgical treatment of the spine is indicated in cases of severe instability pain, in cases of deformity endangering the patient in daily life by the limited range of vision, and in patients with neurological deficiency. AS-specific problems are spinal fractures and atlantoaxial instability, which need careful management including surgery. Joint replacement therapy is established and beneficial for AS-disturbed joints of the hip and knee.
Therapeutic options for patients with active and severe spondylarthritis (SpA) have been fairly limited in the past decades. There is now accumulating evidence that biological therapy with agents directed against tumour necrosis factor-alpha (TNF-alpha) is highly efficacious in the spondyloarthritides, especially in ankylosing spondylitis (AS) and psoriatic arthritis (PsA). The TNF blocking agents currently available, infliximab (Remicade), etanercept (Enbrel), and adalimumab (Humira), are approved for the treatment of rheumatoid arthritis (RA) in Europe and the USA. In contrast to rheumatoid arthritis (RA) disease-modifying anti-rheumatic drugs (DMARDs) have limited efficacy in SpA. No DMARDs are available for AS patients with active spinal disease. Thus, for AS patients whose condition is not sufficiently controlled with non-steroidal anti-inflammatory drugs (NSAIDs), therapy with TNF blockers may be considered as a first-line treatment. For infliximab, a dose of 3-5 mg/kg seems to be required, and intervals between 6 and 12 weeks are necessary to suppress disease activity continually. The standard dosage of etanercept is 2 x 25 mg subcutaneously (s.c.) per week. There are very few studies with adalimumab (standard dose in RA 20-40 mg s.c. every 1-2 weeks) in SpA. Infliximab and etanercept are now both approved for AS in Europe. There is some evidence that both agents also work in other SpA, especially in PsA. Withdrawal of long-term therapy in AS patients led to relapses of disease after several months. Less radiographic progression after 2 years of continuous treatment with infliximab compared to conventional therapy has been suggested in a small study. Serious adverse events on anti-TNF therapy have remained rare. However, severe infections, including tuberculosis, have been reported. These can be largely prevented by appropriate screening. The benefits of anti-TNF therapy in AS seem to outweigh these shortcomings.
Transorbital penetration of the cranial cavity by a small wooden object can pass unnoticed, while producing severe, life-threatening consequences. The occurrence of a traumatic intracranial aneurysm secondary to a wooden foreign body has not been reported previously in the English literature, to our knowledge. Familiarity with the CT features of this complication is crucial since the CT findings may be the first to suggest penetration of the cavernous sinus by wood, as well as the possibility of a traumatic carotid aneurysm. The CT features of this rare complication are discussed and the pertinent literature is reviewed.
A case of aneurysmal bone cyst arising from the lower occipital squama with intracranial extension is presented. The case is unique in that the cyst showed fluid levels on CT. Another peculiarity of this case was postoperative recurrence.