On the Theory of Ion Transport Across the Nerve Membrane, III. Potassium Ion Kinetics and Cooperativity (with x = 4, 6, 9)

The calculations of Part II of this series have been extended to square (x = 4) and octahedral (x = 6) arrangements of subunits in a potassium channel (or gate). The conclusion is the same as before: experimental induction and superposition properties of gK(t), on depolarization, seem to rule out any significant degree of interaction or cooperativity between the (protein?) subunits of K⁺ channel. Calculations for x = 4, 6, and 9 have also been made for a square lattice of interacting channels (periodic boundary conditions). Because of apparent rapid convergence with x, it seems fairly safe to conclude that this model is unsatisfactory. There is some difficulty with superposition but the principal shortcoming is a failure to produce induction behavior. Aggregation models for the K⁺ channel are also discussed briefly here. They, too, appear rather unpromising (for the same reasons as seem to exclude conformational cooperativity within a channel).     

Some characteristics of an exceptionally potent inhaled anesthetic: thiomethoxyflurane

The authors sought to test whether a deviation existed for the correlation between anesthetic potency and the oil/gas partition coefficient at an extreme of lipid solubility. For thiomethoxyflurane, the sulfur analog of methoxyflurane, the oil/gas partition coefficient was 7230 +/- 50 SEM, and MAC (minimum alveolar concentration of thiomethoxyflurane required for anesthesia) in 4 dogs was 0.035 +/- 0.008 percent of 1 atm. This agrees with the potency predicted by the lipid solubility, although thiomethoxyflurane is 7 1/2 times more potent than methoxyflurane, to date the most potent available anesthetic. Thiomethoxyflurane water/gas and blood/gas partition coefficients were 5.4 +/- 0.3 and 68.1 +/- 1.5, respectively. The latter coefficient accords with the prolonged recovery associated with this agent. Renal and hepatic blood chemistries measured on the 1st and 7th days following anesthesia showed only small changes from preanesthetic values.     

Biology and pharmacology of recombinant human interleukin-1β-induced rat ear inflammation

A single, 10 ng intradermal injection of human recombinant interleukin-1 (rIL-1) into rat ears produced acute inflammation. Tissue wet weight (edema) and total myeloperoxidase activity (PMN accumulation), peaked at 3 hours and returned to base line at 3 days. Given orally, 1 hour prior to rIL-1 injection, cyproheptadine, dexamethasone, conventional NSAID's, or mixed cyclooxygenase/lipoxygenase inhibitors were potent antagonists of edema and moderate antagonists of PMN accumulation. In addition, the putative DMARD's, auranofin, dapsone, and levamisole were effective inhibitors of rIL-1 induced inflammation.     

Colon perforation following percutaneous nephrostomy and renal calculus removal

Two patients had colonic perforation as a result of percutaneous nephrostomy placement followed by track dilatation and renal calculus removal. We present the technical aspects of nephrostomy placement and stone removal, as well as the clinical diagnosis and management of these cases. Both patients recovered well with conservative therapy and required no surgical intervention. This report reviews the anatomic considerations for percutaneous nephrostomy in patients undergoing renal stone removal.     

Disability in patients with head and neck cancer

BACKGROUND: Patients with head and neck cancer often experience debilitating speech, eating, and respiratory problems as well as the psychological effects of loss of function and change in body image. These patients often become unemployed as a result of their disease process, which adds financial burden to their already stressful lives. Yet the specific factors associated with unemployment have not been systematically studied. METHODS: This multisite study used survey and chart data to determine the predictors of work-related disability. RESULTS: Of the 384 patients who were working prior to their diagnosis of head and neck cancer, 52% (n = 201) were disabled by their cancer treatment. Multivariate analysis demonstrated significant links between disability and chemotherapy (odds ratio [OR], 3.4; P <.001), neck dissection status (OR, 2.3; P =.01), pain scores (OR, 1.2; P =.01), and time since diagnosis (OR, 0.9; P =.04). CONCLUSIONS: More than half of the patients in this study were disabled by their head and neck cancer or treatment. Patients with head and neck cancer who have undergone chemotherapy or neck dissection or have high pain scores are at increased risk for disability from their cancer or their treatment. Efforts to prevent (if possible), better assess, and treat pain and other adverse effects of head and neck cancer treatments may also have the potential to reduce patient disability.     

The trigeminal trophic syndrome: an unusual cause of nasal ulceration

Trigeminal trophic syndrome (TTS) is an unusual complication after peripheral or central damage to the trigeminal nerve, characterized by anesthesia, paresthesias, and ala nasi ulceration. We describe a patient with classic TTS after trigeminal rhizotomy who underwent several extensive evaluations for nasal ulceration and received prolonged immunosuppressive therapy for a presumed autoimmune disorder before the correct diagnosis was made. An understanding of the predisposing factors and clinical presentation of TTS is important to ensure a timely diagnosis of this difficult-to-treat illness. Differentiation of TTS from malignancy, infection, or vasculitis is possible on the basis of clinical history, tissue biopsy, and serologic evaluation.     

Exposures of elderly volunteers with and without chronic obstructive pulmonary disease (COPD) to concentrated ambient fine particulate pollution

The elderly and individuals who have chronic obstructive pulmonary disease (COPD) may be sensitive to particulate matter (PM) air pollution. We evaluated short-term health responses of 13 elderly volunteers with COPD and 6 age-matched healthy adults to controlled exposures of ambient PM pollution in suburban Los Angeles. Using a Harvard particle concentrator and a whole-body chamber, we exposed each person on separate occasions to approximately 200 microg/m(3) concentrated ambient particles (CAP) less than 2.5 mum in diameter and to filtered air (FA). Each exposure lasted 2 h with intermittent mild exercise. We found no significant effects of CAP on symptoms, spirometry, or induced sputum. A significant negative effect of CAP on arterial oxygenation (measured by pulse oximetry) immediately postexposure was more pronounced in healthy subjects. Peripheral blood basophils increased after CAP in healthy but not in COPD subjects. In both groups, red cell counts increased slightly 1 day after exposure to FA but not to CAP. Preexposure ectopic heartbeats were infrequent in healthy subjects, but increased modestly during/after CAP exposure relative to FA. Ectopic beats were more frequent in COPD subjects, but decreased modestly during/after CAP relative to FA. Heart-rate variability over multi-hour intervals was lower after CAP than after FA in healthy elderly subjects but not in COPD subjects. Thus, in this initial small-scale study of older volunteers experimentally exposed to ambient PM, some acute cardiopulmonary responses were consistent with effects reported from epidemiologic studies. Unexpectedly, individuals with COPD appeared less susceptible than healthy elderly individuals. Further investigation of older adults is warranted to understand the pathophysiology and public health significance of these findings.     

Differentiated thyroid carcinoma that express sodium-iodide symporter have a lower risk of recurrence for children and adolescents

The sodium-iodide symporter (NIS) is expressed by papillary (PTC) and follicular (FTC) thyroid carcinoma, and is essential for iodine uptake. We hypothesized that PTC and FTC with detectable NIS immunostaining would be more amenable to radioactive iodine ((131)I) treatment and follow a more benevolent course. To test this, we determined NIS expression by immunohistochemistry in 23 PTC, 9 FTC, and 12 benign thyroid lesions from children and adolescents. NIS expression was determined by two blinded examiners and graded as absent = 0, minimal = 1, moderate = 2, intense = 3, and very intense = 4. NIS was detected in 35% (eight of 23) of PTC, 44% (four of 9) of FTC, 25% (two of eight) of benign tumors, and 100% (four of four) of autoimmune lesions. The intensity of NIS expression was similar in PTC (0.61 +/- 0.24), FTC (0.56 +/- 0.24), and benign tumors (0.50 +/- 0.33) but was more intense in autoimmune lesions (3.0 +/- 0.7, p < 0.005). Distant metastases were found only among PTC with undetectable NIS (two of 15, 13%), and recurrence developed exclusively from PTC and FTC with undetectable NIS (four of 20, 20% versus zero of 12, p = 0.043). The dose of iodine 131 required to achieve remission in the five patients with PTC who had undetectable NIS (213.3 +/- 53 mCi) was greater than that required by patients with similar age and extent of disease for whom NIS expression is unknown (109 +/- 22 mCi, p = 0.06). We conclude that NIS expression is associated with a lower risk of recurrence for PTC and FTC of children and adolescents.