Treating hyperlipidemia in African Americans.

The purpose of this paper is to provide information concerning the treatment of hyperlipidemia in African Americans. There is a similar prevalence of hypercholesterolemia in Blacks and Whites, but Blacks have been neglected in most pharmacological studies of hyperlipidemia. Intimal atherosclerotic involvement of the aorta and coronary artery occurs in young Black and White males. Epidemiological studies suggest there is a higher mortality rate due to coronary disease in Blacks vs Whites in the United States. Thirty-four percent of Blacks require a fasting lipid profile and 9% of Black adults aged 20 years or older would require lipid-lowering therapy. However, fewer Blacks (26%) than Whites (47%) are aware of their hypercholesterolemia. Studies with lovastatin and pravastatin show efficacy in the treatment of hypercholesterolemia. The Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) is designed to determine all-cause mortality for subjects receiving pravastatin vs a control group receiving "usual care." Randomized, blinded, prospective trials are needed to assess the impact of hyperlipidemia as a risk factor, and the impact of its reduction in African Americans.

Endotoxemia alters splanchnic capacitance.

The splanchnic circulation constitutes a major portion of the total capacitance vasculature and may affect venous return and subsequently cardiac output during low output states. This study assessed the effects of rapid (10 microg/kg over 5 min) and slow (10 microg/kg over 60 min) induction of endotoxin (Escherichia coli) shock on splanchnic blood volume in 8 farm swine. Blood volume was measured by using Tc99m-labeled erythrocytes and radionuclide imaging. Baseline arterial pressure (MAP), central venous pressure (CVP), and liver, splenic, mesenteric and total splanchnic volumes were stable during the 30-min baseline. Approximately 30 min after the rapid endotoxin infusion, splenic volume decreased by 45%, whereas liver volume increased by 40% and MAP decreased by 60% (P < 0.01). The reduction in splenic volume occurred within 10 min of the endotoxin infusion, whereas liver volume changes occurred after MAP reduction. The slow endotoxin infusion also reduced splenic volume by approximately 50% (P = 0.05), whereas MAP declined by 30% (P < 0.05). However, the slow endotoxin infusion lowered liver volume (P < 0.05). Mesenteric volume was unaffected by the fast or slow endotoxin infusion. Total splanchnic volume was unaffected by the fast infusion but decreased by 37% in the slow infusion group (P < 0.05). In summary, E. coli endotoxin reduces splenic blood volume and increases liver blood volume after acute hypotension ensues. Endotoxin does not increase total splanchnic blood volume and may actually decrease total splanchnic volume in the absence of circulatory collapse. This endotoxin shock model is not associated with blood volume pooling in the splanchnic capacitance circulation.

Functional assessment of internal mammary artery bypass grafts: case reports and review of the literature.

The utility of intra-arterial Doppler flow in assessing internal mammary artery (IMA) bypass grafts has infrequently been reported. Two patients are described in which Doppler evaluation of the IMA graft provided valuable diagnostic information prior to intervention. Also provided is a review of the available literature concerning evaluation of pathology in IMA grafts.

A longitudinal study of type-specific antibody responses to Plasmodium falciparum merozoite surface protein-1 in an area of unstable malaria in Sudan.

Merozoite surface protein-1 (MSP-1) of Plasmodium falciparum is a malaria vaccine candidate Ag. Immunity to MSP-1 has been implicated in protection against infection in animal models. However, MSP-1 is a polymorphic protein and its immune recognition by humans following infection is not well understood. We have compared the immunogenicity of conserved and polymorphic regions of MSP-1, the specificity of Ab responses to a polymorphic region of the Ag, and the duration of these responses in Sudanese villagers intermittently exposed to P. falciparum infections. Recombinant Ags representing the conserved N terminus (Block 1), the conserved C terminus, and the three main types of the major polymorphic region (Block 2) of MSP-1 were used to determine the specificity and longitudinal patterns of IgG Ab responses to MSP-1 in individuals. Abs from 52 donors were assessed before, during, and after malaria transmission seasons for 4 yr. Ags from the Block 1 region were rarely recognized by any donor. Responses to the C-terminal Ag occurred in the majority of acutely infected individuals and thus were a reliable indicator of recent clinical infection. Ags from the polymorphic Block 2 region of MSP-1 were recognized by many, although not all individuals after clinical malaria infections. Responses to Block 2 were type specific and correlated with PCR typing of parasites present at the time of infection. Responses to all of these Ags declined within a few months of drug treatment and parasite clearance, indicating that naturally induced human Ab responses to MSP-1 are short lived.

Human antibody response to Plasmodium falciparum merozoite surface protein 2 is serogroup specific and predominantly of the immunoglobulin G3 subclass.

MSP2 is a merozoite surface protein of Plasmodium falciparum and, as such, is a potential component of a malaria vaccine. In this study, we have used a panel of recombinant MSP2 antigens in enzyme-linked immunosorbent assays to investigate the recognition of MSP2 by antibodies from malaria-immune human serum. These recombinant antigens include full-length proteins of serogroups A and B and fragments representing the conserved, group-specific, or repeat regions of each serogroup. Ninety-five percent of the serum samples tested contained MSP2-specific antibodies: 81% of serum samples tested responded to serogroup A, and 86% responded to serogroup B. The antibody response is directed almost exclusively towards dimorphic and polymorphic regions of MSP2; the conserved regions are rarely recognized, and antibodies to serogroups A and B do not cross-react. Interestingly, the antibody response is predominately of the cytophilic and complement-fixing subclass immunoglobulin G3.

Measurement of intestinal vascular capacitance in dogs: an application of blood pool scintigraphy.

To define relative changes in intestinal vascular capacitance, we developed a model that allowed us to construct intestinal vascular pressure-volume relationships (PVR). Thirteen alpha-chloralose-anesthetized and splenectomized dogs were studied using a pneumatic constrictor and a small catheter to change and measure portal venous pressure. A small lead sheet was placed beneath the abdominal wall. Relative changes in intestinal blood volume (IBV) were determined by in vivo blood pool scintigraphy with 99mTc-labeled erythrocytes and were expressed as percentages corrected for specific activity and abdominal wall radioactivity. PVRs were constructed using data recorded during graded inflations of the portal venous constrictor. The abdominal wall contributed 32.4 +/- 7.7% (SD) of the total counts. During a 4-h control period, PVRs varied by no more than 6% (of IBV). In the isolated intestinal circulation, the change in IBV was precisely proportional to the volume of blood added, indicating that this method can detect very small changes in volume (< or = 5 ml). Nitroglycerin (25 micrograms.kg-1.min-1) increased capacitance by 20%. Although it measures only relative changes, the model is stable and sensitive, provides reproducible measurement of intestinal PVRs, and, with adaptation, may prove useful in patient studies.

Is real-time quality assessment of health care an achievable goal?

Hospital-wide and real-time clinical outcome evaluation systems promote optimal quality of care with contained costs. These measurements of achieved health care benefits are critical for the ongoing process of national health care improvement. A practical hospital-wide quality improvement method, developed in the Veterans Administration Medical Center-Salt Lake City (VAMC-SLC), that evaluates positive, neutral, and negative outcome in relation to the mutual interactions between the health care provider, equipment, methodology, and patient is discussed. Real time or retrospective application of this analytical template to high risk procedures generates patient, practitioner, equipment, and methodology specific data to coordinate hospital-wide continuous quality improvement and cost containment efforts. It also allows system-wide comparative assessments of progress in the achievement of benefits within the national health care plan.

Nature of papain products resulting from inactivation by a peptidyl O-acyl hydroxamate.

Mass spectrometry has been used to provide insights into the mechanism of inhibition of cysteine proteases by a hydroxylamine derivative, CBZ-Phe-Gly-NH-O-CO-(2,4,6-Me3)Ph. An oxidized form of papain resulting from the incubation of the enzyme with the peptidyl hydroxamate in the absence of a reducing agent has been identified as a sulfinic acid. The presence of a covalent enzyme-inhibitor complex of molecular mass consistent with a sulfenamide adduct of papain could also be detected by this method. Implications on the mechanism of inactivation of cysteine proteases by peptidyl hydroxamates are discussed.

Assessment of the splanchnic vascular capacity and capacitance using quantitative equilibrium blood-pool scintigraphy.

A series of human and animal experiments were carried out to assess the usefulness of equilibrium blood pool scintigraphy (EBPS) to study acute changes of the splanchnic vascular capacity and the splanchnic vascular pressure-volume (P-V) relationship. Corrected regional abdominal count rate changes, before and after various pharmacologic interventions, were used to assess regional splanchnic vascular volume changes. Animals were instrumented to manipulate and record splanchnic venous pressures. In patients, splanchnic vascular capacity increased by 5.2 +/- 6.9% (p less than 0.001) after 0.6 mg sublingual nitroglycerin while no significant change was noted after sugar pills (0.9 +/- 5.2%, p greater than 0.3). In dogs, splanchnic vascular capacity decreased by a mean of 16% during infusion of angiotensin (p less than 0.001) and increased by a mean of 32% during infusion of nitroprusside (p less than 0.001). The splanchnic vascular P-V curve was shifted rightwards during nitroglycerin administration. Thus, using the radionuclide technique we detected the expected qualitative and quantitative shifts in splanchnic capacity and capacitance. We conclude that EBPS is a useful method to assess acute changes of 1) the splanchnic vascular P-V relationship, in invasive animal studies, and 2) the splanchnic vascular capacity in noninvasive human and animal studies.

Volume-pressure analysis of reflex changes in forearm venous function. A method by mental arithmetic stress and radionuclide plethysmography.

Mental arithmetic stress is known to cause forearm arterial dilation, but the venous responses, including possible changes in the volume-pressure relation, have not been defined. Hence, 10 apparently normal subjects, eight men and two women, mean age 46 +/- 9 years, were studied before and during mental arithmetic stress. Changes in forearm venous volume were estimated with 99mTc blood pool scintigraphy. Group variability of this measurement technique was 1.8 +/- 2.3%. A brachial blood pressure cuff was used to obtain venous occluding pressures of 0, 10, 20, and 30 mm Hg. Mental arithmetic stress increased group systolic and diastolic blood pressure from 126 +/- 12 to 152 +/- 20 mm Hg and from 83 +/- 8 to 93 +/- 15 mm Hg, respectively (p less than 0.001). Heart rate increased from a mean of 75 +/- 15 to 85 +/- 17 beats/min (p less than 0.01). There was no evidence of interaction between or nonlinearity of the volume-pressure plots. Linear regression then yielded the equations V = 99.8 + 0.96P before and V = 86.3 + 0.96P during mental arithmetic stress, which represents a 13.5 +/- 1.6% decrease in forearm vascular volume (p less than 0.001). We conclude that 1) a linear relation exists between forearm venous volume and pressure at physiologic pressures before and during mental arithmetic stress; 2) mental arithmetic stress causes forearm venoconstriction; and 3) such venoconstriction takes place by a parallel shift in the volume-pressure relation (i.e., a shift in unstressed venous volume).

Is the residual translesional pressure gradient useful to predict regional myocardial perfusion after percutaneous transluminal coronary angioplasty?

Routine assessment of the severity of a coronary artery lesion with coronary cineangiography is limited by its variability and poor correlation with blood flow and postmortem findings. In this investigation, we compared the usefulness of the final coronary artery translesional pressure gradient and the final angiographic coronary percent stenosis to assess immediate percutaneous transluminal coronary angioplasty (PTCA) success. To accomplish this, pressure gradients and percent stenoses were compared to stress thallium-201 regional myocardial perfusion before and after 56 uncomplicated PTCAs in 51 patients with single-vessel coronary artery disease. There were 39 men and 12 women; their mean age was 59 +/- 12 years. No patient had evidence of myocardial infarction. A new quantitative method to assess regional myocardial perfusion was used. Patients exercised for 433 +/- 130 seconds before PTCA and for 545 +/- 126 seconds after PTCA (p less than 0.001). Group coronary stenosis and translesional pressure gradient decreased from 77 +/- 11% and 48 +/- 5 mm Hg, respectively, before PTCA, to 25 +/- 11% and 9 +/- 5 mm Hg, respectively, after PTCA (p less than 0.001). Regional myocardial perfusion in the segment of the diseased (dilated) coronary artery increased after PTCA from 77 +/- 17% to 94 +/- 9% (p less than 0.001). Although a significant relationship was noted between regional myocardial perfusion and percent stenosis and translesional pressure gradient, a large individual scatter was present (r values lower than 0.55). We conclude that the final translesional pressure gradient during PTCA is not a better measure of immediate PTCA success than the angiographic percent stenosis.

The development and evaluation of a mu-capture ELISA detecting Chlamydia-specific IgM.

A mu-capture enzyme-linked immunosorbent assay (ELISA) for detecting chlamydia-specific IgM was developed by use of the heat stable, lipopolysaccharide group-specific antigen and an alkaline phosphatase-labelled anti-chlamydia group-specific monoclonal antibody conjugate. The test was used to study the serological response in chlamydial respiratory tract infection among patients with acute respiratory tract symptoms in Cambridgeshire during the past 7 years. Results were compared with those of the complement fixation test (CFT) in routine use as well as those of a whole inclusion indirect immunofluorescence (WIF) test for IgM. Correlation between results of the mu-capture ELISA and those of the WIF test was 87.5%. The percentage of patients in whom specific IgM was found fell with increasing age. This may be due to lack of recall of IgM as a response to reinfection. Chlamydia-specific IgM was more likely to be detected when the CFT titre was greater than or equal to 64 and was rarely detected more than 6 months after the onset of symptoms. However, several patients less than 20 years of age were found to have specific IgM with CF antibody titres less than 64. We have found the mu-capture ELISA a useful test for the diagnosis of respiratory tract chlamydial infections, particularly in younger patients.

A complete proton and carbon-13 NMR analysis of fluocinonide, a fluorinated corticosteroid.

This paper presents a complete analysis of the proton and carbon-13 NMR spectra of 21-acetoxy-6 alpha,9-difluoro-11 beta-hydroxy-16 alpha,17-(1-methylethylidene) bis-(oxy) pregna-1,4-diene-3,20-dione, a potent anti-inflammatory fluorosteroid. The 300 MHz proton spectrum was analyzed using a combination of the two-dimensional homonuclear chemical shift correlation (COSY) technique and one-dimensional NOE difference spectra. Exact coupling constants and chemical shifts were obtained by spectral simulation and iteration. The carbon-13 spectrum was assigned from the proton spectrum via a two-dimensional heteronuclear chemical shift experiment, and long-range fluorine-proton couplings were confirmed by a fully coupled heteronuclear COSY-type experiment.