Efficacy of parenteral albuterol in the treatment of asthma. Comparison of its metabolic side effects with subcutaneous epinephrine

Three parenteral routes of albuterol sulfate were compared with placebo in their effects on serum potassium and glucose levels, heart rate, and pulmonary function in adult asthmatic subjects. In addition, the metabolic effects of subcutaneous epinephrine were compared directly with subcutaneous albuterol. Intravenous (IV) albuterol (250 micrograms) caused similar decreases in serum potassium (mean 0.6 +/- 0.3 mEq/L) as 500 micrograms albuterol by intramuscular (IM) or subcutaneous routes. With the combined data from all three albuterol routes, glucose increases (mean 25 +/- 15 mg/dl) and heart rate increases (mean 11 +/- 6 beats/min) were clinically less important than potassium decreases. Subcutaneous epinephrine (0.3 ml, 1:1,000) gave changes in serum potassium, serum glucose, and heart rate statistically similar to those of subcutaneous albuterol (500 micrograms). Peak FEV1 improvement (mean 61 percent) was similar with IV albuterol (250 micrograms), IM albuterol (500 micrograms) or subcutaneous albuterol (500 micrograms). Although the efficacy of albuterol in the doses studied was similar, the decrement in serum K+ produced was also similar and comparable to that produced by a standard dose of epinephrine. The potassium decrease may have important clinical implications.     

Amyloid deposits in aortic and mitral valves

Summary The material from 100 consecutive aortic and mitral valve operations has been studied histologically with particular reference to the presence of amyloid deposits. Sixty seven per cent were positive (aortic 88%, mitral 45%).The simultaneous occurrence of calcification of the valves and amyloid degeneration as well as of calcification and hyalinization was significant. Similarly there was significantly more amyloid in the older age groups, as well as a significant correlation between the degree of hyalinization of the valve and amyloid.]Thirty-two patients had previously suffered from rheumatic fever. The heart valves of these patients did not differ histologically from the others, whereas significantly more amyloid was observed in the stenotic mitral valves than in the mitral valves which were insufficient.     

Parathyroid carcinoma: a case with recurrence treated with extensive vascular surgery to the neck

Parathyroid carcinoma is a slow growing tumor, and the patients most often die from complications to the hypercalcemia. Therefore, any attempt should be made to remove local recurrence and metastasis surgically, as medical treatment is disappointing. A case treated with extensive vascular surgery to the neck is reported.     

Unilateral testicular disease: effect on the contralateral testis (morphometric study)

Unilateral testicular disease has been reported to damage the contralateral testis. In order to find out whether this detrimental influence is permanent in nature or can be avoided by therapeutic measures, and furthermore to quantify the damage, the following experiments were performed. Seventy-five rats were classified into the following five groups: I) testicular torsion persisting for eight hours; II) ipsilateral semicastration after torsion persisting for eight hours; III) semicastration; IV) sham operation as control; V) immunosuppression with azathioprine after torsion persisting for eight hours. The contralateral testes were removed two months later and perfused with fixative via the testicular artery. Stereologic techniques were employed to obtain quantitative morphologic data. Serum hormone levels were determined. The volume density of the contralateral germinal epithelium was not decreased two months after torsion for eight hours, torsion following by semicastration or torsion followed by immunosuppression. The same was true of the total volume of germinal epithelium per rat testis. The hormone levels remained essentially unchanged.     

Respiratory comfort and breathing pattern during volume proportional assist ventilation and pressure support ventilation: a study on volunteers with artificially reduced compliance

OBJECTIVE: To assess respiratory comfort and associated breathing pattern during volume assist (VA) as a component of proportional assist ventilation and during pressure support ventilation (PSV). DESIGN: Prospective, double-blind, interventional study. SETTING: Laboratory. SUBJECTS: A total of 15 healthy volunteers (11 females, 4 males) aged 21-31 yrs. INTERVENTIONS: Decreased respiratory system compliance was simulated by banding of the thorax and abdomen. Volunteers breathed via a mouthpiece with VA and PSV each applied at two levels (VA, 8 cm H2O/L and 12 cm H2O/L; PSV, 10 cm H2O and 15 cm H2O) using a positive end-expiratory pressure of 5 cm H2O throughout. The study was subdivided into two parts. In Part 1, volunteers breathed three times with each of the four settings for 2 mins in random order. In Part 2, the first breath effects of multiple, randomly applied mode, and level shifts were studied. MEASUREMENTS AND MAIN RESULTS: In Part 1, the volunteers were asked to estimate respiratory comfort in comparison with normal breathing using a visual analog scale. In Part 2, they were asked to estimate the change of respiratory comfort as increased, decreased, or unchanged immediately after a mode shift. Concomitantly, the respiratory pattern (change) was characterized with continuously measured tidal volume, respiratory rate, pressure, and gas flow. Respiratory comfort during VA was higher than during PSV. The higher support level was less important during VA but had a major negative influence on comfort during PSV. Both modes differed with respect to the associated breathing pattern. Variability of breathing was higher during VA than during PSV (Part 1). Changes in respiratory variables were associated with changes in respiratory comfort (Part 2). CONCLUSIONS: For volunteers breathing with artificially reduced respiratory system compliance, respiratory comfort is higher with VA than with PSV. This is probably caused by a better adaptation of the ventilatory support to the volunteer's need with VA.     

Assessment of an electronic goniometer designed to measure equinus contracture

To achieve more objective and repeatable measurements of equinus contracture, we developed the equinometer, a device that allows the measurement of ankle range of motion under controlled torque conditions. This study assessed its accuracy across different subjects and examiners. Two examiners used the equinometer to measure the angle of ankle dorsiflexion at 15 N x m torque on five subjects. Accounting for variation in measurements because of subjects, examiners, and placement of device, we used linear mixed-effects models. Accounting for the variation because of subject, different placements of the equinometer within each subject and the adjustment for the effects of examiner and trial sequence, the standard deviation was 0.94 degrees, 95% confidence interval (0.79 degrees, 1.13 degrees). An upper standard deviation of 1.36 degrees is felt to be acceptable for clinical investigation.     

A three-dimensional,anatomically detailed foot model: a foundation for a finite element simulation and means of quantifying foot-bone position

We generated an anatomically detailed, three-dimensional (3-D) reconstruction of a human foot from 286 computerized topographic (CT) images. For each bone, 2-D cross-sectional data were obtained and aligned to form a stacked image model. We calculated the inertial matrix of each bone from the stacked image model and used it to determine the principal axes. Relative angles between the principal axes of the bones were employed to describe the shape of the foot, i.e., the relationships between the bones of the foot. A 3-D surface model was generated from the stacked image models and a detailed 3-D mesh for each bone was created. Additionally, the representative geometry of the plantar soft tissue was obtained from the CT scans, while the geometries of the cartilage between bones were obtained from the 3-D surface bone models. This model served dual purposes: it formed the anatomical foundation for a future finite element model of the human foot and we used it to objectively quantify foot shape using the relationships between the principal axes of the foot bones.     

Atypical familial hemophagocytic lymphohistiocytosis due to mutations in UNC13D and STXBP2 overlaps with primary immunodeficiency diseases

Background

Familial hemophagocytic lymphohistiocytosis is a genetic disorder of lymphocyte cytotoxicity that usually presents in the first two years of life and has a poor prognosis unless treated by hematopoietic stem cell transplantation. Atypical courses with later onset and prolonged survival have been described, but no detailed analysis of immunological parameters associated with typical versus atypical forms of familial hemophagocytic lymphohistiocytosis has been performed.

Design and Methods

We analyzed disease manifestations, NK-cell and T-cell cytotoxicity and degranulation, markers of T-cell activation and B-cell differentiation as well as Natural Killer T cells in 8 patients with atypical familial hemophagocytic lymphohistiocytosis due to mutations in UNC13D and STXBP2.

Results

All but one patient with atypical familial hemophagocytic lymphohistiocytosis carried at least one splice-site mutation in UNC13D or STXBP2. In most patients episodes of hemophagocytic lymphohistiocytosis were preceded or followed by clinical features typically associated with immunodeficiency, such as chronic active Epstein Barr virus infection, increased susceptibility to bacterial infections, granulomatous lung or liver disease, encephalitis or lymphoma. Five of 8 patients had hypogammaglobulinemia and reduced memory B cells. Most patients had a predominance of activated CD8⁺ T cells and low numbers of Natural Killer T cells. When compared to patients with typical familial hemophagocytic lymphohistiocytosis, NK-cell cytotoxicity and NK-cell and CTL degranulation were impaired to a similar extent. However, in patients with an atypical course NK-cell degranulation could be partially reconstituted by interleukin-2 and cytotoxic T-cell cytotoxicity in vitro was normal.

Conclusions

Clinical and immunological features of atypical familial hemophagocytic lymphohistiocytosis show an important overlap to primary immunodeficiency diseases (particularly common variable immunodeficiency and X-linked lymphoproliferative syndrome) and must, therefore, be considered in a variety of clinical presentations. We show that degranulation assays are helpful screening tests for the identification of such patients.     

PM2.5-induced changes in cardiac function of hypertensive rats depend on wind direction and specific sources in Steubenville, Ohio

BACKGROUND: Increases in particulate matter less than 2.5 μm (PM(2.5)) in ambient air is linked to acute cardiovascular morbidity and mortality. Specific components and potential emission sources of PM(2.5) responsible for adverse health effects of cardiovascular function are unclear. Methods: Spontaneously hypertensive rats were implemented with radiotelemeters to record ECG responses during inhalation exposure to concentrated ambient particles (CAPs) for 13 consecutive days in Steubenville, OH. Changes in heart rate (HR) and its variability (HRV) were compared to PM(2.5) trace elements in 30-min time frames to capture acute physiological responses with real-time fluctuations in PM(2.5) composition. Using positive matrix factorization, six major source factors were identified: (i) coal/secondary, (ii) mobile sources, (iii) metal coating/processing, (iv) iron/steel manufacturing, (v) lead and (vi) incineration. Results: Exposure-related changes in HR and HRV were dependant on winds predominately from either the northeast (NE) or southwest (SW). During SW winds, the metal processing factor was associated with increased HR, whereas factors of incineration, lead and iron/steel with NE winds were associated with decreased HR. Decreased SDNN was dominated during NE winds by the incinerator factor, and with SW winds by the metal factor. Metals and mobile source factors also had minor impacts on decreased SDNN with NE winds. Individual elemental components loaded onto these factors generally showed significant associations, although there were some discrepancies. Conclusions: Acute cardiovascular changes in response to ambient PM(2.5) exposure can be attributed to specific PM constituents and sources linked with incineration, metal processing, and iron/steel production.