Visual system dysfunction in migraine: a review of clinical and psychophysical findings

This paper reviews both clinical and experimental literature relating to visual dysfunction in migraine, starting with the eye and progressing via the retina and visual pathways to the visual cortex. Migraine is associated with (i) a pupillary sympathetic hypofunction, and (ii) a cortical hypersensitivity to visual stimuli (perhaps only in migraine with aura), the pathogenesis of which remains to be determined. Various hypotheses are discussed, and it is proposed that the methods of visual psychophysics may represent a useful approach in the future study of cortical hyperexcitability in migraine. Paradoxically, little research has been directed towards understanding (i) the photophobia of migraine attacks, and (ii) how migraine may be triggered by visual stimuli. Research aimed at elucidating the mechanisms of these phenomena may enhance understanding of the pathogenes is of migraine.     

Cognitive processing in migraine: a failure to find facilitation in patients with aura

Recent interest in cognitive processing in migraine has been based on the assumption that cortical hyperexcitability in migraine with aura may manifest itself in the form of response time advantages in migraine as compared to controls. The study reported here attempted to replicate and extend the findings of Wray and colleagues (Brain 1995;118:25–35). Using identical cognitive tasks, three experiments failed to find differences between migraine with aura patients and controls: furthermore, an additional group of patients without aura were also statistically indistinguishable from controls with respect to response times. Error rates were consistently high across experiments, indicating that subjects were responding at or near chance levels. These findings cast doubt on the utility of straightforward cognitive psychological methods for the study of cortical hyperexcitability in migraine. Some theoretical difficulties concerning the interpretation of response times in the context of migraine pathophysiology are discussed.     

Isolation of plasma membrane from human neutrophils and determination of cytochrome b and quinone content

Analyses of plasma membrane and other subcellular fractions indicate that the primary location of cytochrome b in human neutrophils is not the plasma membrane. The procedure developed for the purification of plasma membrane from fresh human neutrophils yielded a 14-fold enrichment in the marker enzyme 5’-nucleotidase and a 10-fold enrichment in ouabain-sensitive ATPase. On sucrose density gradients, the peak density of 5’-nucleotidase activity was 1.12 g/ml, and was shifted after digitonin addition to 1.15 g/ml. Protein in the plasma membrane equalled approximately 8 percent of the whole cell protein. A b-type cytochrome was found to be present in the plasma membrane fraction at a concentration of 205 pmol/mg of protein, which is three times greater than that in the neutrophil overall. Although this cytochrome has been reported previously in the neutrophil, this is the first determination for purified plasma membrane and may indicate that b-type cytochrome has a dual localization in the human neutrophil. Differential centrifugation results suggest that the primary location is in the granules, probably specific granules. Quinone content in the plasma membrane was found to be 740 pmol/mg of protein, a concentration two times greater than in the whole cell. Such a small enhancement of quinone indicates that quinone also is not primarily located in the plasma membrane.     

Low-dose immune tolerance induction in hemophilia A patients with inhibitors

In patients with hemophilia A and inhibitory alloantibodies against factor VIII, various dosage schedules are used to obtain immune tolerance. In this study, we have evaluated the results of 13 years of low-dose immune tolerance induction and factors that are predictive of a positive result. The effect of immune tolerance induction in relation to age at inhibitor development, number of exposure days, age at start of therapy, maximum inhibitor titer, factor VIII products involved, and virologic status were determined. We evaluated 24 patients with severe hemophilia A and inhibitors who were treated with regular infusions with low-dose (25 U/kg every other day) factor VIII to obtain immune tolerance. In 21 of 24 patients (87%), immune tolerance induction was successful. The response time was determined by two factors: the highest inhibitor level and the age at inhibitor development. In patients with maximum inhibitor levels of less than 40 Bethesda units (BU)/mL, immune tolerance was obtained sooner than in patients with inhibitor levels exceeding 40 BU/mL (P = .005). Patients in whom an inhibitor developed before the age of 2.5 years also tended to have a quick immune response (P = .014). Immune tolerance with low-dose factor VIII is often successful in hemophilia A patients with inhibitors. Young children and patients with maximum inhibitors of less than 40 BU/mL show a relatively rapid response.     

Bone marrow ablation followed by allogeneic marrow grafting during first complete remission of acute nonlymphocytic leukemia

Of 33 patients who had undergone allogeneic bone marrow transplantation during first complete remission of acute nonlymphocytic leukemia, 21 patients have now been followed in continued complete remission for 6- 64 mo (median greater than 18 mo) without maintenance chemotherapy. The median age of the surviving patients is 27 yr. Transplant-related complications occurring throughout the first year after marrow grafting were fatal in 7 patients, and leukemic recurrence led to the death of 5 patients. The actuarial long-term disease-free survival is 60% and the actuarial remission rate is 79%.     

Co-morbidity, not age predicts adverse outcome in clostridium difficile colitis

AIM To examine whether age alone or comorbidity is a risk factor for death in older adults who developed Clostridium difficile (Cd)colitis during hospitalization.METHODS A retrospective, observational study design was performed in our Lady of Mercy Medical Center, a 650-bed, urban,community-based, university-affiliated teaching hospital. 121 patients with a positive diagnosis of Cd colitis (aged 23- 97 years) were studied, and data pertinent to demographic variables,medical history, co-morbidity, physical examination, and laboratory results were collected. Age was examined as a continuous variable and stratified into Age1 (＜80 vs 80 + );Age2 ( ＜ 60, 60 - 69, 70 - 79 and 80 + ); or Age3 (＜ 60, 60 - 69, 70 - 79, 80 - 89, 90 + ).RESULTS Cd colitis occurs more frequently with advancing age (55% of cases ＞80 years).However, age, per se, had no effect on mortality. A history of cardiac disease (P= 0.036), recurrent or refractory infection ＞4 weeks (P--0.007), Iow serum total protein (P=0.034), Iow serum albumin (P=0.001),antibiotic use ＞4 weeks (P＜0.010), use of over 4 antibiotics (P=0.026), and use of certain classes of antibiotics (P = 0.035 - 0.004) were predictive of death. Death was strongly predicted by the use of penicillin-like antibiotics plus clindamycin, in the presence of hypoalbuminemia, refractory sepsis, and cardiac disease ( P = 0.00005). CONCLUSION Cd colitis is common in the very old. However, unlike co-morbidity, age alone does not affect the clinical outcome (survival vs death).     

Filtration versus gravity leukapheresis in febrile granulocytopenic patients: a randomized prospective trial

Forty-eight patients with fever greater than 38.3 degrees C for at least 24 hr despite broad spectrum antibiotics and an absolute granulocyte count less than 1000/microliter were randomly allocated to 4 days of granulocyte transfusions obtained by leukapheresis using filtration (n = 27) or gravity (n = 21) techniques, the latter permitting simultaneous nonmechanical collection of granulocytes and platelets utilizing hydroxyethyl starch as a sedimenting agent. Patient characteristics and dose of granulocytes obtained from both techniques were similar. Complete response to granulocyte transfusions was established by a reduction in temperature to less than 37.2 degrees C sustained for at least 48 hr after the fourth transfusion with sterilization of cultures where previously positive and diminution of measurable infection when present. This occurred in 6/21 (29%) for gravity leukapheresis and 9/27 (33%) for filtration leukapheresis. An additional group had diminution in temperature and clinical improvement during transfusions (6/21 gravity leukapheresis versus 10/27 filtration leukapheresis). Eighty-six percent of patients transfused with gravity leukapheresis cells were alive at day 20 compared with 81% for filtration leukapheresis cells. Transfusion reactions were comparable. Thus, gravity leukapheresis appears to be as efficacious as filtration leukapheresis for treating granulocytopenic febrile patients, with the added advantages of availability to any blood bank without new equipment, of having platelets as by-products, and of not requiring donor heparinization.     

Persistence of myeloid progenitor cells expressing BCR-ABL mRNA after allogeneic bone marrow transplantation for chronic myelogenous leukemia

Previous studies have shown that tumor-specific bcr-abl mRNA can often be detected by polymerase chain reaction. (PCR) for months to years after allogeneic bone marrow transplantation (BMT) for chronic myelocytic leukemia (CML). Nevertheless, the presence of bcr-abl mRNA by itself does not invariably predict for clinical relapse post-BMT. This has led to the hypothesis that bcr-abl mRNA might be expressed in cells that have lost either proliferative or myeloid differentiation potential. To directly characterize the cells detected by PCR in patients with CML after allogeneic BMT, we first identified five individuals in whom PCR-positive cells could be detected at multiple times post-BMT. Bone marrow samples from these individuals were cultured in vitro and single erythroid, granulocytic, and macrophage colonies, each containing 50 to 100 cells, were examined for the presence of bcr-abl mRNA by PCR. PCR-positive myeloid colonies could be detected in four of five individuals in marrow samples obtained 5 to 56 months post-BMT. Overall, 7 of 135 progenitor cell colonies (5.2%) were found to be PCR-positive. The expression of bcr-abl mRNA appeared to be equally distributed among committed erythroid, macrophage, and granulocyte progenitors. These patients have now been followed-up for an additional 20 to 33 months from the time of progenitor cell PCR analysis but only one of these individuals has been found to have cytogenetic evidence of recurrent Ph+ cells. These results show that long-term persistence of PCR-detectable bcr-abl mRNA after allogeneic BMT can be caused by the persistence of CML-derived clonogenic myeloid precursors that have survived the BMT preparative regimen. These cells continue to have both proliferative and myeloid differentiation capacity in vitro. Nevertheless, these PCR-positive cells do not appear to either expand or differentiate in vivo for prolonged periods, suggesting the presence of mechanisms for suppression of residual clonogenic leukemia cells in vivo.