[Will heart catheters besides hospitalization also become superfluous?. Interview by Dr. med. Ulrike Wepner].
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Biomedical subjects
Publications and source records attributed to D Waters.
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Weight loss late in the course of human immunodeficiency virus (HIV) disease is common and often multifactorial. Increased energy expenditure in response to opportunistic disease, as well as to HIV infection itself, can lead to protein-calorie malnutrition similar to that observed in starvation. Weight loss of as little as 5 percent in patients with HIV infection is associated with an increased risk of disease progression. Loss of body cell mass carries a particularly poor prognosis, and aggressive measures should be taken to stop such depletion. Patients exhibiting unexpected weight loss should be carefully examined to exclude decreased food intake, malabsorption, occult infection or neoplasm as the etiology of the weight loss. Early aggressive treatment of HIV disease and underlying opportunistic pathology, along with adequate pharmacologic, hormonal, nutritional and physical therapy, can often restore normal weight and body composition.
BACKGROUND: Percutaneous coronary revascularization is widely used in improving symptoms and exercise performance in patients with ischemic heart disease and stable angina pectoris. In this study, we compared percutaneous coronary revascularization with lipid-lowering treatment for reducing the incidence of ischemic events. METHODS: We studied 341 patients with stable coronary artery disease, relatively normal left ventricular function, asymptomatic or mild-to-moderate angina, and a serum level of low-density lipoprotein (LDL) cholesterol of at least 115 mg per deciliter (3.0 mmol per liter) who were referred for percutaneous revascularization. We randomly assigned the patients either to receive medical treatment with atorvastatin, at 80 mg per day (164 patients), or to undergo the recommended percutaneous revascularization procedure (angioplasty) followed by usual care, which could include lipid-lowering treatment (177 patients). The follow-up period was 18 months. RESULTS: Twenty-two (13 percent) of the patients who received aggressive lipid-lowering treatment with atorvastatin (resulting in a 46 percent reduction in the mean serum LDL cholesterol level, to 77 mg per deciliter [2.0 mmol per liter]) had ischemic events, as compared with 37 (21 percent) of the patients who underwent angioplasty (who had an 18 percent reduction in the mean serum LDL cholesterol level, to 119 mg per deciliter [3.0 mmol per liter]). The incidence of ischemic events was thus 36 percent lower in the atorvastatin group over an 18-month period (P=0.048, which was not statistically significant after adjustment for interim analyses). This reduction in events was due to a smaller number of angioplasty procedures, coronary-artery bypass operations, and hospitalizations for worsening angina. As compared with the patients who were treated with angioplasty and usual care, the patients who received atorvastatin had a significantly longer time to the first ischemic event (P=0.03). CONCLUSIONS: In low-risk patients with stable coronary artery disease, aggressive lipid-lowering therapy is at least as effective as angioplasty and usual care in reducing the incidence of ischemic events.
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Human papillomavirus (HPV) is widely accepted as the primary etiologic agent in the development of cervical cancer. DNA of a particular HPV type, HPV 16, is found in about half of tumors tested. Inconsistent with this causal relationship, however, population-based studies of HPV DNA prevalence have often failed to find high rates of anogenital HPV infection in countries with high cervical cancer rates. To examine this issue, we used serology to compare HPV 16 exposure in healthy volunteer blood donors in the United States (n = 278) and similar subjects from a country with 3-fold higher cervical cancer rates, Jamaica (n = 257). Jamaican sexually transmitted disease (STD) patients (n = 831) were also studied to examine in detail the relation of HPV 16 antibodies with sexual history. Serology was conducted using an ELISA employing HPV 16 virus-like particles (VLPs). Age-adjusted seroprevalence rates were greatest among male (29%) and female (42%) STD patients, intermediate in male (19%) and female (24%) Jamaican blood donors and lowest among male (3%) and female (12%) U.S. blood donors. The higher seroprevalence in women was significant, and prevalence tended to increase with age. In multivariate logistic regression, controlling for age and gender, Jamaican blood donors were 4.2-fold (95% CI 2.4-7.2) and STD patients 8.1-fold (95% CI 5.0-13.2) more likely to have HPV 16 VLP antibodies than U.S. blood donors. Among STD patients, HPV 16 antibodies were associated with lifetime number of sex partners and years of sexual activity, as well as other factors. Our data suggest that HPV 16 VLP antibodies are strongly associated with sexual behavior. Moreover, exposure to HPV 16 appears to be much greater in Jamaica than in the United States, consistent with the high rate of cervical cancer in Jamaica.
This study evaluates the use of electrocardiographic (ECG) gated single-photon emission computed tomographic (SPECT) myocardial perfusion imaging for the prediction of viability in patients undergoing revascularization, who have coronary disease and left ventricular dysfunction. Fifty patients underwent technectium-99m (Tc-99m) sestamibi ECG gated SPECT imaging preoperatively at rest and 1 week after revascularization, whereas 36 (72%) also underwent imaging 6 weeks after revascularization. Images were interpreted by the consensus of 3 experienced readers without knowledge of patient identity or time of imaging (pre- or postrevascularization) for perfusion and wall motion using a 17-segment model. Results of perfusion alone were compared with perfusion and wall motion combined. One hundred five coronary artery territories were revascularized, 96 of which were viable and 9 nonviable. Perfusion alone predicted 87 to be viable and 18 nonviable (sensitivity 86%, specificity 55%, positive predictive value 95%, negative predictive value 28%, and overall accuracy 85%). Perfusion and wall motion combined identified 95 territories to be viable (sensitivity 95%; p <0.025; specificity 55%, positive predictive value 96%, negative predictive value 50%, and overall accuracy 91%; p <0.05). Thus, Tc-99m sestamibi ECG gated SPECT myocardial perfusion imaging at rest allows assessment of both perfusion and wall motion, which significantly improves the sensitivity and overall accuracy for determination of viability in comparison with perfusion alone.
Mother-to-child transmission of human T-cell lymphotropic virus type I (HTLV-I) is primarily due to prolonged breast-feeding (>6 months) in the postnatal period. Most infant infections are not identifiable until 12 to 18 months of age by available whole virus Western blot serologic tests because of their inability to distinguish passively transferred maternal antibody from infant antibody. We investigated two methods to assess more accurately the time of infant infection. In prospectively collected serial biospecimens, HTLV-I-specific immunoglobulin (Ig) isotypes of IgM and IgA were determined by Western blot and HTLV-I proviral DNA was detected by polymerase chain reaction (PCR). IgA and IgG reactivity was assessed in periodic serum samples from 16 HTLV-I-seropositive children while IgM reactivity was assessed in 9 of the 16 children. Approximately three to five samples were tested for each child. IgG reactivity was observed in 100% of children at 24 months of age and 73% of children at 6-12 months of age; however, this could represent maternal and not infant antibody. Both IgA and IgM reactivity were insensitive indicators of infection, with only 50% of children showing reactivity at 24 months of age. PCR testing was performed in biospecimens obtained from 11 of these children. An estimated median time of infection of 11.9 months was determined by PCR, which was similar to the median time to infection determined by whole virus Western blot (12.4 months; P = 0.72). PCR tests support a median time to infection that is similar to that estimated by whole virus Western blot.
The pathogenesis of human T-cell lymphotropic virus type I (HTLV-I) in adult T-cell leukemia/lymphoma (ATL) and HTLV-I associated myelopathy/tropical spastic paraparesis (HAM/TSP) is poorly understood. We prospectively followed up and evaluated the virologic correlates of infection in transfusion recipients after seroconversion, in asymptomatic carriers, and in ATL and HAM/TSP patients. Proviral DNA levels (copies/105 lymphocytes) were determined by real-time automated polymerase chain reaction and antibody titers by end-point dilution by use of an HTLV-I enzyme-linked immunoassay. In early infection, proviral load was initially elevated (median, 212 copies/105 lymphocytes at time 1) and later decreased (median, 99 copies at time 2, and 27 copies at time 3). Corresponding antibody titers were low at time 1 (1:2154), had significantly increased by time 2 (1:12312), and were stable by time 3 (1:4694). These viral markers were significantly lower in asymptomatic carriers than in HAM/TSP or ATL patients. Therefore, proviral load and antibody titers may be useful as predictive markers of disease among carriers.
We show that an applied electric field in which the polarity is reversed every 15 minutes can improve the outcome from severe, acute spinal cord injury in dogs. This study utilized naturally injured, neurologically complete paraplegic dogs as a model for human spinal cord injury. The recovery of paraplegic dogs treated with oscillating electric field stimulation (OFS) (approximately 500 to 600 microV/mm; n = 20) was compared with that of sham-treated animals (n = 14). Active and sham stimulators were fabricated in West Lafayette, Indiana. They were coded, randomized, sterilized, and packaged in Warsaw, Indiana, and returned to Purdue University for blinded surgical implantation. The stimulators were of a previously unpublished design and meet the requirements for phase I human clinical testing. All dogs were treated within 18 days of the onset of paraplegia. During the experimental applications, all received the highest standard of conventional management, including surgical decompression, spinal stabilization (if required), and acute administration of methylprednisolone sodium succinate. A radiologic and neurologic examination was performed on every dog entering the study, the latter consisting of standard reflex testing, urologic tests, urodynamic testing, tests for deep and superficial pain appreciation, proprioceptive placing of the hind limbs, ambulation, and evoked potential testing. Dogs were evaluated before and after surgery and at 6 weeks and 6 months after surgery. A greater proportion of experimentally treated dogs than of sham-treated animals showed improvement in every category of functional evaluation at both the 6-week and 6-month recheck, with no reverse trend. Statistical significance was not reached in comparisons of some individual categories of functional evaluation between sham-treated and OFS-treated dogs (ambulation, proprioceptive placing); an early trend towards significance was shown in others (deep pain), and significance was reached in evaluations of superficial pain appreciation. An average of all individual scores for all categories of blinded behavioral evaluation (combined neurologic score) was used to compare group outcomes. At the 6-month recheck period, the combined neurologic score of OFS-treated dogs was significantly better than that of control dogs (p = 0.047; Mann-Whitney, two-tailed).
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A store-and-forward teledermatology service was established between two general practices and the department of plastic surgery at Derriford Hospital in Plymouth. An academic lawyer and an expert in risk management made an assessment of the service. They looked at the following issues: medicolegal problems; security; confidentiality; and risk. None of them was considered insoluble and there is no reason why such issues should prevent the National Health Service from developing telemedicine services. All organizations considering telemedicine need to ensure that the proposed telemedicine service satisfies the issues raised in this study.
In 66 patients unable to exercise referred for pharmacologic stress single-photon emission computed tomographic myocardial perfusion imaging, a moderate dose of dobutamine was combined with intravenous dipyridamole and the results were compared with standard intravenous dipyridamole stress. The combined stress protocol resulted in increased defect size and reversibility with technetium-99m sestamibi single-photon emission computed tomographic myocardial perfusion imaging.
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Controversy exists as to the clinical roles and relative specificities of cardiac troponin T or I in patients with unstable angina pectoris (UAP). We measured troponin T and I levels on admission in 123 patients with UAP. Of the 107 patients with normal creatine kinase during the first 24 hours, troponin T and I were elevated in 14 and 13 patients, respectively. At 30 days, 5 of 14 patients (36%) with elevated troponin T and 3 of 93 patients (3.2%) with normal troponin T had acute myocardial infarction (odds ratio [OR], 16.7; 95% confidence interval [CI] 3.4 to 81.5; p <0.001). Of 13 patients with elevated troponin I, 5 patients (39%) and 3 of 94 patients (3.2%) with normal troponin I had acute myocardial infarction (odds ratio, 21.7; 95% CI 4.3 to 110; p <0.001). No deaths occurred within 30 days. Both markers demonstrated equivalent sensitivity (63%) and specificities (troponin T: 91%; troponin I: 92%) for myocardial infarction. Meta-analysis of 12 published troponin T and 9 troponin I studies in patients with UAP produced risk ratios of 4.2 (95% CI 2.7 to 6.4, p <0.001) for troponin I compared with 2.7 (95% CI 2.1 to 3.4, p <0.001) for troponin T. Comparison of the sensitivities and specificities of both markers using summary receiver operating characteristic curves showed no significant difference in their abilities to predict acute myocardial infarction and cardiac death. Troponin T and I show similar prognostic significance for acute myocardial infarction or death in the same patients with UAP. The 2 markers are equally sensitive and specific, as confirmed by meta-analysis, and this supports a role in risk stratification.
The goal of the Myocardial Ischemia Reduction with Aggressive Cholesterol Lowering (MIRACL) study is to determine whether early, rapid, and profound cholesterol lowering therapy with atorvastatin can reduce early recurrent ischemic events in patients with unstable angina or non-Q-wave acute myocardial infarction. Within 1 to 4 days of hospitalization for one of these conditions, 2,100 patients will be randomly assigned to receive atorvastatin, 80 mg/day, or placebo in a double-blind design. Both groups receive dietary counseling. Over a 16-week follow-up period, the primary outcome measure is the time to occurrence of an ischemic event, defined as death, nonfatal acute myocardial infarction, cardiac arrest with resuscitation, or recurrent symptomatic myocardial ischemia requiring emergency rehospitalization. Secondary outcome measures are the time to occurrence and incidence of each of the primary outcome components, as well as nonfatal stroke, worsening angina, congestive heart failure requiring hospitalization, and need for coronary revascularization not anticipated before randomization. The sample size of 1,050 patients in each group is expected to provide 95% power to detect a 30% reduction in the primary outcome measure with a 5% level of significance. The results of the MIRACL study will determine the utility of profound cholesterol lowering as an early intervention in acute coronary syndromes.
OBJECTIVE: Our objective was to examine the influence of pregnancy on human immunodeficiency virus type 1 viral load by measuring human immunodeficiency virus type 1 ribonucleic acid levels during pregnancy and post partum. STUDY DESIGN: One or more plasma or serum specimens obtained before and during the third trimester, and at 2, 12, and 24 months post partum were available for 160 human immunodeficiency virus type 1-seropositive women enrolled in the Mothers and Infants Cohort Study between January 1986 and January 1991. All specimens were frozen and stored at -70 degrees C until analyzed in batch for human immunodeficiency virus type 1 ribonucleic acid by polymerase chain reaction. A multivariate longitudinal random effects model was developed to examine changes in human immunodeficiency virus type 1 ribonucleic acid levels over time. RESULTS: Overall, human immunodeficiency virus type 1 ribonucleic acid levels rose significantly during the study period, particularly during the second year post partum (mean, 0.09 log per year; 95% confidence interval, 0.03 to 0.15 logs per year; p = 0.005). However, the mean slope during pregnancy was not significantly different from zero (p = 0.65). CONCLUSION: Pregnancy had little immediate effect on human immunodeficiency virus type 1 viral load in most human immunodeficiency virus type 1-seropositive women.
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