Treatment of systemic and renal-limited vasculitic disorders with pooled human intravenous immune globulin

Idiopathic crescentic glomerulonephritis is characterized by an absence of immunohistological evidence of immune deposits, often with evidence of segmental glomerular necrosis. Such pauciimmune crescentic glomerulonephritis is the most common renal manifestation seen in patients with Wegener's granulomatosis, polyarteritis nodosa, and glomerulonephritis associated with other systemic vasculitic disorders (i.e., Churg-Strauss syndrome). Recently, the idiopathic crescentic glomerulonephritides, either in renal-limited form or in association with other systemic vasculitic disorders, were found to have in common a serologic marker, antineutrophil cytoplasmic autoantibodies. These cytoplasmic and perinuclear antineutrophil cytoplasmic autoantibodies are specific for constituents of neutrophil primary granules and monocyte lysosomes. As serologic markers for vasculitic disorders, they are also felt to be directly involved in the pathogenesis of necrotizing vascular injury.In vitro, both perinuclear and cytoplasmic antineutrophil cytoplasmic autoantibodies are capable of causing cytokineprimed neutrophils to undergo degranulation and respiratory burst, releasing toxic oxygen species and lytic enzymes. Antiidiotype antibodies which inhibit antineutrophil cytoplasmic autoantibodiesin vitro, in a V region-dependent manner, are found in pooled humanγ-globulin preparations. Intravenous immune globulin infusionsin vivo have produced dramatic improvements in the necrotizing vascular injury produced by antineutrophil cytoplasmic autoantibodies, and a rapid reduction in these autoantibody levels is seen post-intravenous immune globulin infusion in most patients. The proposed mechanisms of action of intravenous immune globulin in vasculitic disorders include Fc-dependent mechanisms, and F(ab′)₂-dependent mechanisms are likely important. Intravenous immune globulin infusions appear to have an important place in the management of the necrotizing vascular injury. Blinded, randomized, placebo-controlled trials will be necessary to establish definitively intravenous immune globulin as a therapeutic option in vasculitic disorders.     

Regulation of MAC-1 (CD11b/CD18) expression on circulating granulocytes in endurance runners

PURPOSE: We tested the hypothesis that degranulation of granulocytes and upregulation of the granulocyte integrin MA-1 (CD11b/CD18) are related to exercise duration and/or intensity. We also investigated whether or not the expression of MAC-1 would be influenced by body temperature or dehydration. Moreover, we tested the hypothesis that changes in leukocyte counts and changes in MAC1 expression with endurance exercise are independently regulated. METHODS: In eight amateur runners, MAC-1 (CD11b/CD18) surface expression on granulocytes was determined by fluorescent antibody cell sorting, before and after an incremental maximal treadmill test, a moderate 3-h run, and a competitive marathon race. RESULTS: Expression CD11b on granulocytes was increased by 10+/-9.6% (P < 0.05) after the maximal treadmill test and by 84+/-76% (P < 0.01) after the marathon run. There was no change in CD11b expression after the moderate 3-h run. CD18 expression was not significantly changed after any of the exercise protocols. CONCLUSION: Expression of CD11b on granulocytes is increased with intense endurance exercise, either incremental maximal treadmill testing or competitive marathon running, but not in moderate endurance training. Thus, exhaustive exercise may be one mechanism for the upregulation of integrin adhesive receptors on granulocytes. This phenomenon could be in part responsible for increased adhesion of granulocytes to endothelial cells and could facilitate tissue infiltration after endurance exercise.     

Balancing the equation: The significance of professional and lay perceptions in the promotion of cervical screening amongst minority ethnic women

Studies of minority ethnic women and cancer screening have, in the past, suffered from many theoretical and methodological weaknesses. In addition, no attempts have been made to study the complexity of the issue involved in the intercultural context, or the possible contribution of women's experiences to low uptake rates. In order to further our understanding of the issues, an alternative approach, participatory action research (PAR), was adopted to identify factors that might have contributed to the persistently low participation of minority ethnic women in the cervical screening programme, and address them collaboratively. This paper presents the key findings of the ‘problem identification' phase of the project. Using mainly the focus-group method, it explores both smear takers' and minority ethnic women's perceptions and experiences of cervical screening. Data suggest that there was a divergence in perceptions held by these groups regarding cervical screening, which contributed to negative experiences for both groups. There is also clear evidence of dysfunctional clinical communication arising from these differing perceptions. Opportunistic screening at post-natal examination adopted by many general practices appeared to have perpetuated the perceptions that the majority of minority ethnic women held about the purpose of the smear test. Compounded by language differences, the majority of women who had undergone smear testing understood neither the purpose of screening programme nor the procedure of the test. This has clear implications for promoting regular uptake, and more importantly for informed consent and choice.     

Giant cell angiofibroma of the eyelids: an unusual presentation of tuberous sclerosis

The authors describe a patient with a history of mental retardation and seizures who presented with unusually large edematous, pedunculated eyelid lesions of unknown etiology. The histopathology revealed features consistent with giant cell angiofibroma, a variant of the angiofibromas commonly seen in tuberous sclerosis.     

Discriminative stimulus produced by the imidazoline I2 site ligand, 2 -BFI

2-(2-Benzofuranyl)-2-imidazoline, RX801077 (2-BFI) which has high affinity for imidazoline I(2) binding sites and very low aflinity for α(2)-adrenoceptors, has been investigated for its ability to produce a discriminative stimulus (cue) in drug-discrimination studies in rats since the existence of such a cue could assist in determining the functionality of I(2) sites. All rats subjected to training proved able to discriminate the training dose of 2-BFI (33 μmol/kg i.p) from saline vehicle and lower (5-14 μmol/kg) doses exhibited dose-dependent substitution. The mixed α(2)-adrenoceptor/I( 2) site ligand idazoxan fully substituted at 40μmol/kg. However, ethoxy idazoxan (11 μmol/kg) and fluparoxan (13 μmol/kg), selective α( 2)-adrenoceptor antagonists, also fully substituted for 2- BFI as did the monoamine oxidase (MAO) inhibitors moclobemide (99 μmol/kg) and pargyline (153 μmol/kg). A lower dose of moclobemide (16 μmol/kg) exhibited partial substitution. The α( 2)-adrenoceptor agonists clonidine (0.1 μmol/kg) and guanabenz (1.4 μmol/kg), and the benzodiazepine diazepam (14 μmol/kg), failed to substitute for 2-BFI indicating cue specificity. However, 2-BFI (14-50 μmol/kg) substituted partially but dose-dependently for clonidine (0.1 μmol/kg) in rats trained to distinguish the latter from saline. Changes in rates of response were independent of the degree of substitution. The observed pattern of drug substitution is consistent with the previously reported ability of 2-BFI to decrease MAO activity and thus increase extracellular monoamines.     

The future of general surgery

The origin of the term "general surgery" is uncertain, but it is known that it has been in the lexicon of surgical parlance for more than a century. Although specialization began at least 150 years ago, it became a major trend at the end of World War I. The potential fragmentation of the specialty is the most significant problem currently faced by general surgeons. Other areas affecting the future of general surgery are discussed, including residency requirements, manpower analyses, and physician reimbursement. Because of rapid technologic changes and the aging of the population, surgeons need to incorporate those features that will improve patient care into their practices to meet the needs of the future.     

Dendritic L-type calcium currents in mouse spinal motoneurons: implications for bistability

The intrinsic properties of mammalian spinal motoneurons provide them with the capability to produce high rates of sustained firing in response to transient inputs (bistability). Even though it has been suggested that a persistent dendritic calcium current is responsible for the depolarizing drive underlying this firing property, such a current has not been demonstrated in these cells. In this study, calcium currents are recorded from functionally mature mouse spinal motoneurons using somatic whole-cell patch-clamp techniques. Under these conditions a component of the current demonstrated kinetics consistent with a current originating at a site spatially segregated from the soma. In response to step commands this component was seen as a late-onset, low amplitude persistent current whilst in response to depolarizing-repolarizing ramp commands a low voltage clockwise current hysteresis was recorded. Simulations using a neuromorphic motoneuron model could reproduce these currents only if a noninactivating calcium conductance was placed in the dendritic compartments. Pharmacological studies demonstrated that both the late-onset and hysteretic currents demonstrated sensitivity to both dihydropyridines and the L-channel activator FPL-64176. Furthermore, the alpha1D subunits of L-type calcium channels were immunohistochemically demonstrated on motoneuronal dendrites. It is concluded that there are dendritically located L-type channels in mammalian motoneurons capable of mediating a persistent depolarizing drive to the soma and which probably mediate the bistable behaviour of these cells.