M. Stewart West

Effects of fluvastatin on coronary atherosclerosis in patients with mild to moderate cholesterol elevations (Lipoprotein and Coronary Atherosclerosis Study [LCAS]).

Despite the potential for reduced morbidity and mortality, aggressive intervention against mild to moderate hypercholesterolemia in patients with coronary heart disease (CHD) remains controversial and infrequently practiced. Eligible patients in the 2.5-year Lipoprotein and Coronary Atherosclerosis Study were men and women aged 35 to 75 years with angiographic CHD and mean low-density lipoprotein (LDL) cholesterol of 115 to 190 mg/dl despite diet. Patients (n = 429; 19% women) were randomized to fluvastatin 20 mg twice daily or placebo. One fourth of patients were also assigned open-label adjunctive cholestyramine up to 12 g/day because prerandomization LDL cholesterol remained > or = 160 mg/dl. The primary end point, assessed by quantitative coronary angiography, was within-patient per-lesion change in minimum lumen diameter (MLD) of qualifying lesions. Across 2.5 years, mean LDL cholesterol was reduced by 23.9% in all fluvastatin patients (+/- cholestyramine) (146 to 111 mg/dl) and by 22.5% in the fluvastatin only subgroup (137 to 106 mg/dl). Primary end point analysis (340 patients) showed significantly less lesion progression in all fluvastatin versus all placebo patients, deltaMLD -0.028 versus -0.100 mm (p <0.01), and for fluvastatin alone versus placebo alone, deltaMLD -0.024 versus -0.094 mm (p <0.02). A consistent angiographic benefit with treatment was seen whether baseline LDL cholesterol was above or below 160 or 130 mg/dl. Beneficial trends with treatment were also consistently seen in clinical event rates but were not statistically significant. Thus, lipid lowering by fluvastatin in patients with mildly to moderately elevated LDL cholesterol significantly slowed CHD progression.

Protection of breast-fed infants against Campylobacter diarrhea by antibodies in human milk

To investigate the role of breast-feeding in preventing diarrhea caused by Campylobacter jejuni , we followed 98 Mexican children prospectively for 2 years beginning at their birth. Attack rates of diarrhea in children less than 6 months of age who were not fed human milk were 2.3 times greater than those in children of the same age who were fed human milk. Breast-fed children remained free of diarrhea for a longer time than non-breast-fed children ( p C. jejuni for non-breast-fed infants was significantly greater ( p C. jejuni were high in colostrum, decreased during the first month of breast-feeding, and generally persisted throughout lactation. Human milk consumed by children in whom Campylobacter diarrhea developed did not contain secretory IgA antibodies to the glycine acid-extractable common antigen of Campylobacter . This study shows an association between Campylobacter antibodies in human milk and prevention of diarrhea caused by Campylobacter .

Laboratory profile of sickle cell disease: A cross-sectional analysis

We have collected steady-state laboratory data for over 2600 patients, age 2 years and over, with sickle cell anemia (HbSS), HbSC disease, and HbS-beta(+)-thalassemia. The packed cell volume (PCV) is lower in males than in females until 17 or 18 years of age in HbSS and ages 13 to 15 in HbSC, but then becomes consistently higher in males. After age 40, the PCV falls in HbSS. The steady-state leukocyte count in HbSS is higher than that in normals, blunting the utility of this measurement in the assessment of infection. In HbSC and HbS-beta(+)-thalassemia, the leukocyte counts are more often within the range of normal. Platelet counts in HbSS are often found to be above normal and show a downward trend with age. There is a progressive rise in creatinine with age. In HbSS, this rise begins at age 14 and may be accounted for by the increased muscle mass that occurs with puberty. The further deterioration of renal function in patients over 20 may be a result of the known adverse effects of sickle cell disease upon the kidney. Our data provide a basis to compare perturbations caused by intercurrent complications and new therapies, as well as to contrast with similar information from other populations of patients with sickle cell disease.

Protection against infection with Giardia lamblia by breast-feeding in a cohort of Mexican infants

To determine whether breast-feeding protects infants against symptomatic and asymptomatic infection by Giardia lamblia, we followed 197 infants in a poor area of Mexico City from birth to 18 months of age; symptoms and feeding status were recorded weekly. Stool specimens were collected every 1 to 2 weeks and tested for Giardia by enzyme-linked immunosorbent assay. A mean of 1.0 Giardia infection per child-year was detected; 94 infants had a total of 139 infections; 17% of infections were symptomatic. Ninety-one percent of infants were breast fed from birth and 38% were breast fed at 1 year of age. Lack of breast-feeding was a significant risk factor for first Giardia infection at all ages. The adjusted incidence rate ratio for first Giardia infection for none versus complete breast-feeding was 5.0 (confidence interval (CI) 1.5 to 16.9; p = 0.009), and for none versus any breast-feeding, 1.8 (CI 1.1 to 2.8; p = 0.013). Symptomatic Giardia infection was also associated with lack of breast-feeding (none vs any: incidence rate ratio = 2.5; CI 0.9 to 6.8; p = 0.077), but breast-feeding did not protect against chronic carriage of Giardia. Other significant risk factors for Giardia infection were presence of animals in the household (p = 0.005) and the use of water or nonmilk liquid for infant feedings (p = 0.035). We conclude that breast-feeding protects infants against Giardia by mechanisms that include preventing the establishment of infection.

The lipoprotein and coronary atherosclerosis study (LCAS): Design, methods, and baseline data of a trial of fluvastatin in patients without severe hypercholesterolemia

Few direct clinical data are available regarding whether cholesterol-lowering therapy should be extended to patients with coronary heart disease (CHD) and normal or only slightly elevated plasma cholesterol concentrations. The one published angiographic trial designed to examine this question found no benefit. Additional prospective data will be provided by the Lipoprotein and Coronary Atherosclerosis Study (LCAS), a randomized, double-blind, placebo-controlled trial of fluvastatin therapy (20 mg twice daily) monitored by both quantitative coronary angiography (QCA) and, in a subset of patients, positron-emission tomography (PET). Eligible subjects in LCAS were men and women 35-75 years of age with low-density lipoprotein (LDL) cholesterol of 115-190 mg/dL on stable dietary therapy and with angiographic evidence by caliper measurement of at least one coronary atherosclerotic lesion causing 30-75% diameter stenosis. Among the 429 patients randomized (mean age 58.8, 81% male), mean baseline LDL cholesterol was only 145.6 mg/dL. Any patient with mean prerandomization LDL cholesterol of 160 mg/dL or higher also received open-label adjunctive cholestyramine. The primary endpoint is within-patient per-lesion change in minimum lumen diameter (MLD) as measured by QCA at baseline and 2.5-year follow-up. All evaluable lesions had MLD at least 0.8mm less than the reference lumen diameter at either baseline or follow-up and MLD at least 25% of the reference lumen diameter at baseline. Data obtained on myocardial perfusion changes (99 patients underwent initial PET), special lipid particles, and coagulation factors may help define which patients with CHD and relatively low LDL cholesterol will benefit from lipid-lowering treatment.

Defects in interleukin-2 stimulation of neonatal natural killer cytotoxicity to herpes simplex virus-infected cells

Natural killer cytotoxicity (NKC) is an important early defense mechanism in viral infections. We determined the ability of interleukin-2 (IL-2), an NKC stimulator, to enhance defective neonatal NKC to virus-infected cells. Human recombinant IL-2-stimulated adult and cord blood NKC to herpes simplex virus-infected cells in a time-dependent and dose-dependent fashion. The highest level of neonatal IL-2-stimulated cytotoxicity approached the level of unstimulated cytotoxicity when adult cells are used. Single-cell experiments suggested that the cord blood defect was due not to decreased adherence but to lysis or recycling defects. IL-2 stimulated adhesion in the presence of antibody but had no stimulatory effect on antibody-dependent cellular cytotoxicity. The relative defects in IL-2 stimulation of neonatal NKC suggest that its lone use as a therapeutic or protective agent against herpes simplex virus infections is unlikely to be successful, and may require concomitant adult cells if NKC is a critical mechanism.

Sexual function of women taking antihypertensive agents : a comparative study

Objective:To develop a method to evaluate the effects of clonidine and prazosin on sexual function in hypertensive women.Design:Crossover, active-drug controlled pilot study.Setting:Community recruitment to a university-based teaching hospital.Patients:Ten premenopausal and eight postmenopausal women with mild hypertension and unimpaired sexual function.Intervention:Periodic, self-administered daily diaries assessed the sexual arousal and desire and orgasmic function of women receiving placebo, clonidine, and prazosin.Measurements and main results:Using analysis of variance for orgasmic characteristics and comparison of the percentages of yes responses to the sexual function questions, no significant difference in the levels of sexual function of women receiving placebo, clonidine, and prazosin was found. However, there was a suggestion that clonidine and prazosin affected some aspects of sexual function. Of the women who received clonidine first, fewer were receptive to partner approach during medication therapy (49%) than during placebo (61%). Fewer women wished for their partners to approach them (WISH) during therapy (41% and 53% for clonidine and prazosin, respectively) than during placebo (60%). In the group that received prazosin first, WISH was affected (32% for prazosin, 31% for clonidine, 45% for placebo). Orgasmic strength increased from 2.1 on placebo to 2.7 on clonidine (second medication), measured on a four-point Likert scale.Conclusions:This pilot study developed a method using self-administered daily diaries for evaluating the effects of antihypertensive agents on sexual function in hypertensive women. These potential effects need to be evaluated in larger studies.

Human milk secretory immunoglobulin A to Shigella virulence plasmid-coded antigens

Although antibodies to the lipopolysaccharide antigens of Shigella have been demonstrated in human milk, such antibodies do not explain the putative protective effect of breast-feeding against symptomatic Shigella infection. Shigella species do not share related lipopolysaccharides, but they do possess closely related virulence plasmids that code for the proteins essential for cell invasion. We therefore sought to determine the frequency, amount, and duration of excretion of human milk antibodies to these shared virulence plasmid-associated antigens in populations of different rates of Shigella infection frequency (Mexico City, high; Houston, low). Such antibodies were present in the milk of virtually all the Mexican women but also were present in a large proportion of milk samples from the women living in Houston. The amounts of these antibodies were highest in colostrum but after 2 weeks of lactation fell to stable levels. The frequency and persistence of these antibodies in the milk of the women from Houston suggest that the memory and drive for secretion of these antibodies is extremely long lived.

Baseline characteristics of subjects in the lipoprotein and coronary atherosclerosis study (LCAS) with fluvastatin

A total of 429 subjects (79 women and 350 men), aged 35-75 years, have been enrolled in a randomized clinical trial of fluvastatin therapy for hypercholesterolemia. The progression and regression of atherosclerotic lesions will be assessed by quantitative angiography and positron emission tomography (PET) after 2.5 years of treatment. Patients were included in the trial if they had angiographically documented lesions that occluded 30-75% of the diameter of a major coronary vessel. Of the 429 subjects, 99 were also studied by PET at rest and during static exercise of sustained handgrip combined with administration of dipyridamole. All subjects were instructed in an American Heart Association/National Cholesterol Education Program (AHA/NCEP) Step I or Step II diet. Of the total, 107 subjects (25%) had low density lipoprotein cholesterol (LDL-C) > or = 160 mg/dL and were given cholestyramine, 8 g/day. All subjects were randomized to placebo or fluvastatin, the newest 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor to be introduced into the U.S. market. Fluvastatin is entirely synthetic and is similar in efficacy to the other available HMG-CoA reductase inhibitors. Its pharmaceutical profile (i.e., low systemic exposure) makes fluvastatin a good candidate for use in combination lipid-lowering therapy. The majority of subjects were recruited through a community campaign and the remainder through cardiac catheterization laboratories and the medical records of hospitals in the Texas Medical Center. Approximately 8,500 prospects from the community campaign were screened and 272 were randomized, a conversion rate of approximately 3%.(ABSTRACT TRUNCATED AT 250 WORDS)

Motility of the small intestine in preterm infants who later have necrotizing enterocolitis

Frank H. Morriss, Jr., MD, Mary lynn Moore , RN, Tina Gibson, BSN, a n d M. S tewa r t West, PhD From the Department of Pediatrics, University of Iowa College O f Medicine, Iowa City, the Department of Pediatrics, Medical School of the University of Texas Health Science Center at Houston, the Department of Internal Medicine, Baylor College of Medicine, Houston, and the University Childrens Hospital at Hermann, Houston, Texas