Characterization of the mechanism of action of tachykinins in rat striatal cholinergic interneurons

Plasma membranes of neutrophil cells contain the redox component of the O2(-)-generating NADPH oxidase complex, namely a heterodimeric flavocytochrome b consisting of an alpha subunit of 22 kDa and a beta subunit of 85-105 kDa of a glycoprotein nature. The NADPH oxidase is dormant in resting neutrophils. When neutrophils are exposed to a variety of particulate or soluble stimuli, the oxidase becomes activated, due to the assembly on the membrane-bound flavocytochrome b of three cytosolic factors, p47phox, p67phox and Rac 2 (or Rac 1). The effect of phenylarsine oxide (PAO), which reacts specifically with vicinal and neighbouring thiol groups in proteins, was assayed on the NADPH oxidase activity of bovine neutrophils, elicited after activation of the oxidase in a cell-free system consisting of plasma membranes and cytosol from resting neutrophils, GTP[S], ATP and arachidonic acid; the effect of PAO on the oxidase activation itself was measured independently. PAO preferentially inhibited oxidase activation rather than the elicited oxidase activity, and inhibition resulted from binding of PAO to the membrane component of the cell-free system. To determine the PAO-binding protein responsible for the loss of oxidase activation, we used photoaffinity labeling with a tritiated azido derivative of PAO, 4-[N-(4-azido-2-nitrophenyl)amino-[3H]acetamido]phenylarsine oxide, ([3H]azido-PAO). Photoirradiation of plasma membranes from resting neutrophils in the presence of [3H]azido-PAO resulted in the prominent labeling of a protein of 85-105 kDa whose migration on SDS/PAGE coincided with that of the beta subunit of flavocytochrome b as identified by immunoreaction. Upon deglycosylation, the photolabeled band at 85-105 kDa was shifted to 50-60 kDa as was the immunodetected beta subunit. Similar results were obtained with isolated flavocytochrome b in liposomes. Photoaffinity labeling of the beta subunit of the membrane-bound flavocytochrome b or the isolated flavocytochrome b in liposomes resulted in abolition of oxidase activation in the reconstituted cell-free system. Incorporation of [3H]azido-PAO into flavocytochrome b was negligible when photoaffinity labeling was performed on neutrophil membranes that had been previously activated. The results suggest that the beta subunit of flavocytochrome contains two target sites for PAO which are accessible in resting neutrophils, but not in activated neutrophils.     

A teratoid Wilms' tumor with raised serum alpha-fetoprotein level

Tumor markers are used to diagnose certain cancers and can be useful in monitoring the response to treatment. We describe a renal tumor with the features of a teratoid nephroblastoma associated with a raised serum level of alpha-fetoprotein (AFP). The serum AFP remained high during chemotherapy but returned to normal after nephrectomy. AFP was demonstrated by immunohistochemistry in cysts lined by enteric-type epithelium within the tumor. Cytogenetic examination of the tumor showed a clone of cells with trisomy 8. Raised serum AFP has not previously been described in teratoid Wilms' tumor.     

Who suffers most from leg ulceration?

This study examines health-related quality of life (HRQoL) in patients with leg ulceration and determines which patient groups are affected most by this condition. A cross-sectional study using the Nottingham Health Profile (NHP) and age/sex-matched normal scores in patients entering six clinical audit cycles was carried out. The 758 patients included in the study (mean age 74.6 years, 64% women) had been affected by leg ulceration for a median of 10.5 months (range 0.5 to 708). Patients produced significantly higher scores than age/sex-matched normal values for all domains of the NHP, indicating poorer HRQoL (all p < 0.001). Increasing age led to greater deficits in energy (p < 0.001) and mobility (p < 0.001) with greater social isolation (p = 0.044). Women experienced poorer energy, sleep patterns, mobility and emotional reactions (all p < 0.001), and increased physical pain and social isolation (p < 0.05) compared to men. However, higher scores may be expected for older women based on age/sex-matched normal values. After adjustment for age/sex-matched normal values, it was the younger patients who experienced a greater deficit in HRQoL over all domains of the NHP, with men scoring higher than women in the domains of bodily pain, sleep and social isolation (p < 0.001) and energy (p = 0.015). Leg ulceration has a major impact on patients' HRQoL as detected by the NHP. The excess in scores compared with age/sex-matched normal values indicate that it is younger male patients in whom ulceration makes a greater impact on HRQoL.     

Bracing of patients after fusion for degenerative problems of the lumbar spine--yes or no?

The majority of spine fusions currently performed are for degenerative conditions. Controversy exists regarding whether to routinely brace patients during the postoperative period. The benefits of a rigid orthosis have yet to be documented in a scientific study, and the cost of a custom-molded orthosis can be quite high. An extensive literature search reveals few articles dealing with the subject, and none with an adequate study design to convincingly support or refute the use of external braces. In addition to the questions of whether an external brace is effective, the mechanism of action also remains unclear. It has been difficult to document mechanical effectiveness, so perhaps the effect is psychologic. In addition, it is possible that some, not all, fusion patients may benefit from a brace--yet our ability to select such a patient is poor. As a result, we have solicited the views of two experienced surgeons on the topic. Dr. Connolly argues that an external orthosis is advisable in many cases; Dr. Grob feels that the rigidity of internal fixation should be adequate to obviate the need for external bracing.     

The phylogeny of the wrist

BACKGROUND: Long-term results on LASIK are not available to date. We therefore evaluated the predictability, stability and complication rate after LASIK in moderate--to-high myopia. PATIENTS AND METHODS: We treated 70 eyes (41 patients) using the Automatic Corneal Shaper and the Keracor 116 excimer laser. Patients were followed for 1, 6, 12 and 24 months. Spectacle refraction, visual acuity, rate of retreatment, and patient satisfaction were evaluated. RESULTS: At 24 months the results were as follows: Myopia -5 to -9.9 D (n = 18): 94% within 1 D; regression between 1 and 12 (12 and 24) months > 1 D in 6% (6%); uncorrected acuity 20/40 or better in 83%; no loss of 2 ore more lines of visual acuity; 89% highly satisfied. Myopia -10 to -14.9 D (n = 12): 88% within 1 D; regression between 1 and 12 (12 and 24) months > 1 D in 20% (0%); uncorrected acuity 20/40 or better in 72%; 4% lost 2 or more lines of visual acuity; 96% highly satisfied. Myopia -15 to -29 D (n = 22): 33% within 1 D; regression between 1 and 12 (12 and 24) months > 1 D in 41% (18%); uncorrected acuity 20/40 or better in 7%; no loss of 2 or more lines of visual acuity; 67% highly satisfied. CONCLUSION: LASIK is an accurate, effective and stable procedure for correcting myopia of -5 to -10 D. Results are less precise in myopia up to -15 D, and some visual loss occurs in a number of patients. In myopia > -15 D, results are not satisfactory because of poor accuracy and low stability.