Abnormal renal vasodilation to an amino acid infusion in congestive heart failure: normalization by enalapril

In congestive heart failure (CHF), the neurohormonal mechanisms that cause renal vasoconstriction, particularly those depending on the renin-angiotensin system, could interfere with renal vasodilating mechanisms. To elucidate this issue, we studied the kidney response to an amino acid infusion (known to cause renal vasodilation in healthy individuals) in eight patients with CHF. We found that the amino acid infusion (0.7 mL/kg/h of a 10% solution) elicited no renal hemodynamic response, in marked contrast to healthy subjects. We next hypothesized that the renin-angiotensin system (known to be activated in heart failure) has a role in the lack of response to the amino acid infusion. To test this hypothesis, we repeated the study after two 5-mg doses of enalapril, an inhibitor of the angiotensin-converting enzyme, administered 12 hours apart. After enalapril treatment, the amino acid infusion caused a 45% increase in mean renal blood flow (RBF) from 383 +/- 55 to 557 +/- 51 mL/min at the fifth hour (P < 0.05). This normalization of the renal response to the amino acid infusion occurred without changes in cardiac output or in systemic vascular resistance. Hence, the renal fraction of the cardiac output increased during the amino acid infusion. The recovery of the renal vascular response was not accompanied by an increase in glomerular filtration rate (GFR; filtration fraction decreased), suggesting a predominant efferent arteriole dilatation. Our study shows that, in heart failure, the kidney loses its ability to increase RBF in response to an amino acid load. This lack of renal vascular response can be restored by inhibiting the renin-angiotensin system and is unrelated to changes in systemic hemodynamics.     

Model of functional restriction in chronic obstructive pulmonary disease, transplantation, and lung reduction surgery.

Mechanical interactions between lung and chest wall are important determinants of respiratory function. When chest wall expansion during maximal inhalation generates insufficiently negative pleural pressures, the lungs remain functionally underinflated; this may be termed functional restriction. To explore mechanisms and effects of functional restriction in patients with emphysema, and to predict effects of single lung transplantation and lung volume reduction surgery (LVRS), we used a computational model based on standard physiology and measurements from individual patients. The model's lungs, separated by a compliant mediastinum, exhibit flow limitation according to the equal pressure point approach of Mead and coworkers. Pulmonary elastic recoil pressure is characterized by an exponential equation modified to reflect airway closure. Simulated respiratory maneuvers can be specified by variations in flow or pressure at the airway opening or in respiratory muscle activation. Model simulations successfully mimic recordings from individual patients. Input parameter values may then be altered to predict effects of surgical interventions in these same patients. The model simulations show the following. Single lung transplantation in emphysema can cause functional restriction of the normal transplanted lungs, and larger transplanted lungs may perform less well than smaller ones. LVRS improves lung and chest wall function in emphysema, but not in normal states. Surgical reduction of the native emphysematous lung after single lung transplantation can reduce functional restriction of the transplant and thereby improve its function.     

Evaluation of Mycology Laboratory Proficiency Testing

Changes over the last decade in overt proficiency testing (OPT) regulations have been ostensibly directed at improving laboratory performance on patient samples. However, the overt (unblinded) format of the tests and regulatory penalties associated with incorrect values allow and encourage laboratorians to take extra precautions with OPT analytes. As a result OPT may measure optimal laboratory performance instead of the intended target of typical performance attained during routine patient testing. This study addresses this issue by evaluating medical mycology OPT and comparing its fungal specimen identification error rates to those obtained in a covert (blinded) proficiency testing (CPT) program. Identifications from 188 laboratories participating in the New York State mycology OPT from 1982 to 1994 were compared with the identifications of the same fungi recovered from patient specimens in 1989 and 1994 as part of the routine procedures of 88 of these laboratories. The consistency in the identification of OPT specimens was sufficient to make accurate predictions of OPT error rates. However, while the error rates in OPT and CPT were similar for Candida albicans, significantly higher error rates were found in CPT for Candida tropicalis, Candida glabrata, and other common pathogenic fungi. These differences may, in part, be due to OPT's use of ideal organism representatives cultured under optimum growth conditions. This difference, as well as the organism-dependent error rate differences, reflects the limitations of OPT as a means of assessing the quality of routine laboratory performance in medical mycology.     

Cow's milk IgE and IgG antibody responses to cow's milk formulas

For comparison of the antigenicity and allergenicity of three cow's milk formulas, serum IgE antibodies to cow's milk, β‐lactoglobulin and casein, and IgG antibodies to β‐lactoglobulin were analyzed in 94 infants with a family history of allergy. They were participating in a randomized trial comparing the allergy prophylactic effect of feeding an extensively hydrolyzed (N), a partially hydrolyzed (PH), and a regular cow's milk formula (RM). Only infants who had been formula‐fed for 3 months or more were included. IgE antibodies to cow's milk proteins were more common in the RM group (22/34) than in the N (2/31) and PH groups (3/29). There was a strong correlation between sensitization to cow's milk and β‐lactoglobulin ( r =0.85, P <0.001). The IgG responses to β‐lactoglobulin were low in the N group, intermediate in the PH group, and high in the RM group. High responses, as well as detection of IgE antibodies, were associated with development of atopic disease. The low antigenicity and allergenicity of the extensively hydrolyzed formula support its use in allergy prophylaxis. The partial hydrolysate seemed to be less suitable for this purpose.