Cerebrospinal fluid rhinorrhea: depiction with MR cisternography in dogs

Canine cerebrospinal fluid rhinorrhea, which occurs frequently in purebred beagles, was demonstrated in two dogs on magnetic resonance images after cisternal introduction of gadolinium-DTPA dimeglumine.     

An electronic stethoscope is judged better than conventional stethoscopes for anesthesia monitoring

A prototype electronic monitoring stethoscope was constructed from readily available, high-quality components. It consisted of a conventional precordial or esophageal probe connected to a microphone by a rubber adapter. The microphone was connected by lightweight wire to an amplifier and headphones. Twenty-one anesthesia clinicians evaluated the stethoscope and responded to a multiple-choice preference questionnaire. The electronic stethoscope was judged to perform better than the conventional stethoscope in most categories evaluated. The electronic device was perceived to be louder, clearer in sound reproduction, more efficacious for monitoring, and easier to use continuously, and its head-phones were considered more comfortable than the conventional carpiece. Based on our results, we conclude that amplified stethoscopes have the potential to improve monitoring. Further development of electronic stethoscope monitoring seems warranted and is continuing.     

Failure of Dietary Protein and Phosphate Restriction to Retard the Rate of Progression of Chronic Renal Failure: A Prospective, Randomized, Controlled Trial

SUMMARY Ninety-five patients (63 male, 32 female), age 45±2 years(mean±SEM) with chronic renal failure of varied aetiologywere randomized to receive either a conventional low proteindiet (0.6 g/kg/day protein, 800 mg phosphate; n=33), a low phosphatediet (providing approximately 1000 mg phosphate plus an orallyadministered phosphate binder, minimum protein intake 0.8 g/kg/day;n=30) or to control (minimum protein intake 0.8 g/kg/day, nophosphate restriction; n=32). Patients were reviewed for a minimumof 6 months before randomization and were withdrawn from thestudy if plasma creatinine exceeded 900 µmol/1, plasmaphosphate was > 2.0 mmol/1 or at the onset of uraemic symptoms. Following randomization patients were studied for an averageof 19±3 months. Mean plasma creatinine rose from 398±33to 600±50 µmol/1. Dietary protein intake was estimatedat 0.69±0.02 g/kg/day in the low protein group, 1.02±0.05in the low phosphate and 1.14±0.05 in the controls, phosphateintake was 815±43, 1000± 47, and 1315±57mg/day, respectively. Urinary urea excretion and protein catabolicrates were significantly reduced (p<0.01) only in those onprotein restriction, at 213±9 mmol/24 hours and 0.71g/kg/day, respectively. Phosphate excretion was significantlylower (p<0.05) in both the low protein group (17.9±0.8mmol/24 hours) and the low phosphate group (18.6±1.0mmol/24 hours) compared to controls. Changes in body weight,muscle mass and serum transferrin, albumin and immunoglobulinswere comparable between the groups. Mean blood pressure followingrandomization was 150/89±3/1 (low protein), 148/87±3/1(low phosphate) and 146/87±3/1 (controls). Progression of renal failure was analysed by rate of fall ofcreatinine clearance (ml/min/ 1.73 m²/month), by rate of deteriorationderived from reciprocal plasma creatinine against time plots(1/mmol/year) and to assess individual patient's response totreatment by two phase linear regression (‘breakpoint’)analysis of reciprocal plasma creatinine/time plots. Progressionwas analysed only in patients seen for at least 3 months followingrandomization. The rate of fall of creatinine clearance was not significantlydifferent between the groups (ANOVA): 0.56±0.08 ml/min/1.73m2/month (low protein, n=28), 0.44±0.07 (low phosphate,n=23) and 0.69±0.11 (control, n=27). In 50 patients (18low protein, 16 low phosphate and 16 control) whose rate ofprogression could be calculated before and after randomization,there was a fall in rate of progression averaging 0.18 ml/min/1.73m2/month in those on low protein diet and those on low phosphatediet, but a rise of 0.08 in the controls. These differenceswere, however, not statistically significant. Similar resultswere obtained when the rates of deterioration were calculatedfrom plasma creatinine. Significant individual improvements(p<0.01) in rates of progression by ‘breakpoint’analysis occurred in 17 patients: six on low protein, sevenon low phosphate and in four controls. Sixty-one (72 per cent)of the patients examined by this method showed no significantchange in the rate of progression while seven patients had acceleratedprogression. There was no difference in the requirement formaintenance dialysis facilities between groups. No significant benefit of protein and phosphate restrictionwas therefore demonstrated.     

Post-traumatic headache: from classification challenges to biological underpinnings

The ICHD-II criteria for post-traumatic headache (PTH) are strictly outlined. PTH can be subdivided into an acute and a chronic forms, the former likely nociceptive in nature, the latter likely neuropathic. The time of transition between the acute and the chronic forms is artificial and in the future should be better based on clear clinical or rather biological data. Chronic PTH often presents as one of the primary headache syndromes, e.g. migraine or tension-type headache. Its biology is poorly understood and whether it merely represents the expression of the primary headache or it has a distinct pathogenesis remains unclear. The frontal lobe is often affected in traumatic head injury. Its dysfunction can cause an array of clinical consequences that have an impact on the patient's symptomatology and therapeutic outcome. Its recognition is likely to improve patient management quality.     

Histamine levels in stored platelet concentrates. Relationship to white cell content

The histamine levels in samples from platelet concentrates (PC) were measured at various storage times by a radioenzymatic assay. Elevated histamine levels were detected in 5 of 14 PC after 3 days of storage (range, less than 1 to 13.3 ng/ml) and in 9 of 14 PC after 5 days (range, less than 1 to 22.2 ng/ml). A very good linear correlation (r = 0.913) was found between the initial white cell content of the PC and the histamine level at 5 days of storage. The rise in histamine content was not influenced by the type of plastic container. The results indicate a process of histamine release by the white cells during storage. Although histamine is metabolized rapidly in vivo, a critical histamine threshold could be reached in man by the rapid infusion of stored PC containing high levels of histamine. This could explain some unexpected transfusion reactions in patients receiving PC.     

Model for the physics and physiology of fluid administration

This article describes a model designed to provide an understanding of fluid flow in intravenous systems and human subjects. Experiments were developed which demonstrate that the model can represent common clinical situations. The model depicts physical devices as ideal resistors, pressure sources, and flow sources. The patient's venous system is depicted as a combination of ordinary and Starling resistors. For flows between 0 and 300 ml/hr, both physical devices and patients are adequately represented by a straight line representing the pressure-flow relationship (PFR): pressure = opening pressure + flow × resistance, where the slope is the resistance to fluid flow and the intercept is the opening pressure. The PFR for a normal vein is characterized by a flat slope (vein resistance =22±20 mm Hg/L/hr, mean ± SD) and a low intercept (opening pressure =15±8 mm Hg). The PFR for a partially obstructed vein has a resistance equal to that of an unobstructed vein and an opening pressure elevated approximately equal to the pressure obstructing the vein. For perivascular tissue, the PFR has a steep slope (tissue resistance =1,125±1,376 mm Hg/L/hr), while tissue opening pressure depends on the amount of fluid infused. At the onset of fluid extravasation (infiltration), tissue pressure usually is lower than venous pressure (8±8 versus 15±8 mm Hg), until fluid fills the distensible tissue compartment. In clinical practice, when infiltration or obstruction occurs, flow decreases and the clinician adjusts the roller clamp until correct flow resumes; no problem is obvious. The combined model for the intravenous tubing and venous systems explains the behavior of current clinical infusion devices.Presented in part at the Sixth Medical Monitoring Technology Conference, Vail, CO, March 1986; at the Annual Meeting of the American Society of Anesthesiologists, Las Vegas, NV, October 1986; at the Seventh Medical Monitoring Technology Conference, Vail, CO, March 1987; at a meeting on Computers in Critical Care and Pulmonary Medicine, San Diego, CA, June 1987; at the Annual Meeting of the American Society of Anesthesiologists, Atlanta, GA, October 1987; at the Regional Meeting of the Association for the Advancement of Medical Instrumentation, Cincinnati, OH, October 1987; at the Institute of Electrical and Electronics Engineers Ninth Annual Conference of the Engineering in Medicine and Biology Society, Boston, MA, November 1987; and at a meeting of the American Society of Hospital Pharmacists, Atlanta, GA, December 1987.Supported in part by grants from IVAC Corp.The author thanks the following individuals for important intellectual and/or technical assistance: Peter Basser, PhD, Avital Cnaan, PhD, Adriane Concus, MD, John Fox, MD, David Gissen, MD, David Joseph, MD, Anne Kamara, David Leith, MD, Leonard Lind, MD, Richard Morris, MB, BS, Barbara Orlowitz, MEE, Mary Anne Palleiko, RN, Beverly Philip, MD, Daniel Raemer, PhD, David Scott, MB, BS, John Stelling, MPH, and Marie vanRensberg, MB. At IVAC Corp: Walter Bochenko, BSEE, MBA, Robert Butterfield, BSEE, Douglas Christian, RPh, MBA, Alan Davison, BS, David Doan, PhD, Alan Somerville, BSEE, MS, Robin Wernick, BSEE, MS.     

Autoantibodies against bactericidal/permeability-increasing protein in patients with cystic fibrosis

Cystic fibrosis (CF), a genetic disorder, is characterized by chronic pulmonary infection/inflammation which leads to respiratory failure. The presence of anti-neutrophil cytoplasmic autoantibodies (ANCA) has previously been observed in the sera of patients with CF. In view of the known relationship of ANCA with primary vasculitis and of their putative pathogenetic role in these disorders, we studied the presence, specificity and isotype of ANCA and their clinical associations in 66 adult CF patients. None of the 66 CF samples had autoantibodies to the major ANCA antigens, proteinase 3 or myeloperoxidase. However, 60/66 (91%) CF samples contained IgG and 55/66 (83%) IgA, autoantibodies to bactericidal/permeability increasing protein (BPI), a recently characterized ANCA specificity. All the IgA anti-BPI-positive samples were also IgG anti-BPI-positive. The autoantibody specificity was confirmed by inhibition assay and immunoblotting of CF sera against a neutrophil granule preparation. Furthermore, in this cross-sectional study, anti-BPI levels were inversely correlated with the observed reductions in FEV1 and FVC (IgA anti-BPI and FEV1: r = 0.508, <it>p</it> &lt; 0.0001), and both IgG and IgA anti-BPI levels were higher in CF patients with secondary vasculitis (<it>n</it> = 6) than in those without (<it>p</it> &lt; 0.05). ANCA with specificity for BPI were present in the majority of CF sera in this study and autoimmune processes may be associated with the development of pulmonary injury in CF.      

Anti-inflammatory effects of a cyclosporine receptor-binding compound, D-43787

By virtue of its binding to cyclophilin, the cellular receptor for cyclosporine (CsA), we could identify a new compound D-43787 [N-[(1-tert-butyloxycarbonyl)-indolin-2-(S)-carbonyl]-indolin-2-(S)-carbonacid-[N-epsilon-benzyloxycarbonyl)-2-(S)-lysin methylester]-amide] exhibiting immunomodulating properties. It inhibited cell proliferation induced by 12-O-tetradecanoylphorbol-13-acetate (TPA)/ionomycin and anti-CD3/CD28 with an IC(50) of 0.3 microM. The protein phosphatase calcineurin, which is the target of the CsA-cyclophilin complex, is not inhibited by D-43787. It inhibited T helper cell (Th) 2 cytokines interleukin (IL)-4, -5, and -13 more effectively than the Th1 cytokine interferon (IFN)-gamma in human primary T cells. The IC(50) for IL-5 and IL-13 in TPA/ionomycin-stimulated peripheral blood mononuclear cells (PBMC) is 0.7 +/- 0.1 and 0.5 +/- 0.1 microM, respectively, whereas the IC(50) for IFN-gamma is 2.0 +/- 0.4 microM. When PBMC were stimulated with anti-CD3/CD28, the IC(50) for IL-4, -5, and -13 were 1.5 +/- 0.2, 1.8 +/- 0.2, and 1.9 +/- 0.4 microM, respectively. IFN-gamma was only partially inhibited under these conditions. This effect was even more pronounced in pure CD4(+) T cells. Pretreatment of human monocytes with D-43787 inhibited lipopolysaccharide-induced proinflammatory cytokines IL-6 and TNFalpha with an IC(50) of 1.2 +/- 0.1 and 4.7 +/- 0.9 microM, respectively. In vivo, D-43787 potently inhibited late-phase eosinophilia in actively sensitized and challenged guinea pigs (10 mg/kg, i.p.: 51%) and Brown-Norway rats (1 mg/kg, intrapulmonary: 66% 30 mg/kg, i.p.: 50%). In adjuvant-induced arthritis, D-43787 (10-40 mg/kg, b.i.d., i.p.) dose dependently reduced edema development on both hind paws. The potency of D-43787 was comparable with that of indomethacin and dexamethasone. In conclusion, we characterized a novel Th2 selective immunosuppressive drug with possible anti-asthmatic/anti-inflammatory effects. Its mode of action is distinct from that of CsA.     

In vivo efficacy in airway disease models of N-(3,5-dichloropyrid-4-yl)-[1-(4-fluorobenzyl)-5-hydroxy-indole-3-yl]-glyoxylic acid amide (AWD 12-281), a selective phosphodiesterase 4 inhibitor for inhaled administration

N-(3,5-Dichloro-pyrid-4-yl)-[1-(4-fluorobenzyl)-5-hydroxy-indole-3-yl]-glyoxylic acid amide (AWD 12-281) is a highly potent and selective phosphodiesterase 4 (PDE4) inhibitor that was designed to have a metabolic profile that was optimized for topical administration. The aim of the current study was to explore the pharmacological profile of intratracheally administered AWD 12-281 in different models of asthma and chronic obstructive pulmonary disease (COPD) in comparison with steroids. To assess the anti-inflammatory potential of AWD 12-281, the antigen-induced cell infiltration in bronchoalveolar lavage fluid (BALF) of Brown Norway rats was determined. AWD 12-281 (ID50 of 7 microg/kg i.t.) as well as beclomethasone (0.1microg/kg i.t.) suppresses late-phase eosinophilia when administered intrapulmonary. Furthermore, AWD 12-281 has also strong anti-inflammatory properties when tested in lipopolysaccharide-induced acute lung neutrophilia in Lewis rats (ID50 of 0.02 microg/kg i.t.), ferrets (ID50 of 10 microg/kg i.t.), and domestic pigs (2-4 mg/pig i.t. or 1 mg/kg i.v.). In pigs, AWD 12-281 was as effective as beclomethasone (0.4 mg/pig i.t.) and dexamethasone (0.28 mg/kg i.v.), although at 3 to 10 times the dosage. The bronchodilatory activity of AWD 12-281 was assessed in sensitized guinea pigs. AWD 12-281 (1.5 mg/kg i.t., 1-h pretreatment) inhibited allergen-induced bronchoconstriction by 68% (parameter airway resistance). In sensitized BP-2 mice AWD 12-281 abolished the allergen-induced bronchial hyperresponsiveness and eosinophilia in BALF, showing dose dependence. When given orally, i.v. or i.t., AWD 12-281 has a considerably lower emetic potential than cilomilast in ferrets and roflumilast in pigs. When given topically by inhalation, no emesis could be induced in dogs up to the highest feasible dose (15 mg/kg in 50% lactose blend). These results indicate that AWD 12-281 is a unique potential new drug for the topical treatment of asthma and COPD.     

The effect of cuff pressure deflation rate on accuracy in indirect measurement of blood pressure with the auscultatory method

The importance of cuff deflation rate in the auscultatory method of measuring blood pressure was investigated using a computer-based model. To determine the relationship between the cuff deflation rate and the measurement error, two cuff deflation protocols were used, one based on heart rate (mm Hg per heartbeat), the other on a constant rate (mm Hg per second). The different deflation protocols and rates were tested using a constant blood pressure of 120/80 mm Hg and heart rates ranging from 40 to 120 beats/min. It was confirmed that a cuff deflation rate that is time based will introduce larger errors at low heart rates. Using heart rate as a basis for cuff deflation rate yields a constant error that is independent of heart rate. The currently used standard of 3 mm Hg/s could result in a maximum error of 2.5 mm Hg in both systolic and diastolic pressures at a heart rate of 72 beats/min. The maximum systolic and diastolic errors increase to more than 4 mm Hg at 40 beats/min. A deflation rate of 2 mm Hg/beat, however, yields a maximum error of 2 mm Hg for both systolic and diastolic pressures, independent of heart rate. A cuff deflation rate based on heart rate is recommended to help minimize changes in measurement error when measuring blood pressure if a wide range of heart rates will be encountered.Supported by grants from IVAC, San Diego, CA, and Physio Control, Redmond, WA.