Kernicteric findings at autopsy in two sick near term infants.
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Biomedical subjects
Publications and source records attributed to D Burns.
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With the growing use of endovascular therapy for intracranial aneurysms, it is important that we understand at a cellular level the processes that lead to lesion obliteration. We present autopsy findings, including electron and light microscopic studies, of a basilar artery aneurysm that was successfully embolized with the Guglielmi detachable coil system 4 weeks before the patient died.
Litigation and regulatory assaults on the tobacco companies may create a willingness among tobacco manufacturers to bargain resources and acceptance of public policy changes for limitations of liability, as has been seen by the recent settlement with the Liggett Group. Two elements absolutely critical to any plan are the elimination of tobacco advertising and promotion and the removal of addiction as a reason for tobacco use. Minimal components of any settlement should include: (a) acceptance by the tobacco manufacturers of the causal relationship between tobacco use and disease, and the addictive nature of nicotine; (b) a total ban on tobacco advertising and promotion; (c) FDA jurisdiction over tobacco products and their nicotine content, with the intent of removing nicotine as soon as acceptable nicotine substitution products are available; (d) reimbursement to the states for Medicaid and other state expenditures attributable to smoking, to the maximum extent feasible; (e) funding for local, state, and federal programmes and research in tobacco control; (f) acceptance of legislation and regulations protecting the right of non-smokers to breathe air free of tobacco smoke; (g) funding for a large, national, media-led, anti-tobacco campaign; and (h) cessation assistance for addicted smokers. If negotiations toward a settlement proceed, it is essential that the public health community participate in defining the elements of any agreement to ensure that whatever agreement develops is focused on reducing tobacco-related disease rather than continuing the profitability of American tobacco companies. That participation requires articulation of the core elements essential to an acceptable agreement. If resolution of the public health issues surrounding continued sale of tobacco products can be reached in the United States, it may provide a model for similar resolution in other countries.
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BACKGROUND: Earlier studies indicate that nurses and physicians have a knowledge deficit regarding pulmonary artery catheters. OBJECTIVE: To evaluate critical care nurses' knowledge of pulmonary artery catheters. METHODS: A 31-item, multiple-choice questionnaire was administered to 168 critical care nurses from institutions in a southern California metropolitan area. Fourteen demographic questions were included to determine variables such as critical care nursing experience, educational background, work area, and frequency of pulmonary artery catheter use that may have affected participants' scores. The investigators traveled to the institutions to explain and conduct the study. RESULTS: The mean knowledge score was 16.4 of 29 questions (56.8% items correct), with a standard deviation of 3.74. The range of correct scores was 8 to 25. Two questions were not factored into the statistical analysis because they were specific to the physician's role in pulmonary artery catheter insertion. The variables that correlated with higher scores were CCRN certification, attendance at a pulmonary artery catheter class, years of critical care experience, and frequent use of the pulmonary artery catheter. Of the respondents, 39% were unable to identify a pulmonary artery wedge measurement value from a waveform recording. CONCLUSIONS: Critical care nurses' knowledge of pulmonary artery catheters is related directly to the frequency of their exposure to it, critical care nursing experience, attendance at a pulmonary artery catheter class, and CCRN certification. Additional research is needed on a larger scale to validate these findings and determine if critical care nurses' knowledge of pulmonary artery catheters is sufficient to maintain quality standards of safety and optimal patient care.
Interleukin 2 (IL-2) and granulocytes-macrophage colony-stimulating factor (GM-CSF) are activators of the lymphocyte and granulocyte/macrophage series, respectively. We conducted a phase IB trial to identify the maximally tolerated dose and to assess immunological effects of the combination. Thirty-four patients with incurable cancers received 2.5, 5, or 10 microgram/kg GM-CSF s.c. either before or concurrently with 1.5 or 3.0 million units/m2/day IL-2. The most common laboratory and clinical side effects included an elevation of the total WBC or eosinophil count due to GM-CSF, and constitutional symptoms due to IL-2. Grade 3 or 4 toxicities included hypotension, thrombocytopenia, elevations in aspartate aminotransferase or bilirubin, renal toxicity, gastrointestinal hemorrhage, arrhythmia, and constitutional symptoms. Two patients receiving 5.0 microgram/kg GM-CSF plus concurrent 3.0 million units IL-2 experienced dose-limiting grade 3 or 4 neurological toxicity, which reversed almost completely. An increase in the serum-soluble IL-2 alpha chain receptor was observed with administration of GM-CSF, IL-2, or the combination. IL-2 therapy enhanced lymphokine-activated killer activity, antibody-dependent cellular cytotoxicity, and lymphocyte activation, with increased CD16 and CD56 expression. GM-CSF increased expression of human leukocyte antigen DR on peripheral blood monocytes and decreased surface expression of CD16 on circulating monocytes and polymorphonuclear cells. Lymphokine-activated killer activity and CD16 expression on monocytes and lymphocytes and CD56 expression on lymphocytes were significantly lower in patients receiving GM-CSF simultaneously with IL-2 than in patients receiving the sequential treatment. Antitumor activity was observed in the lungs of four of eight renal cell carcinoma patients with pulmonary metastases treated with concurrent GM-CSF and IL-2. Although no or minimal shrinkage was observed in the patients' large primary tumors, these results warrant further study. The recommended initial Phase II dose and schedule is 1.25 microgram/kg/day GM-CSF, given concurrently with 1.5 million Roche units/m2/day (4.5 x 10(6) international units/m2/day) IL-2, with subsequent escalation of GM-CSF to 2.5 microgram/kg/day after careful observation for toxicities.
BACKGROUND AND PURPOSE: A 2.9 degrees C reduction in the intraischemic rectal temperature of neonatal piglets is associated with less brain damage compared with animals with normothermic rectal temperatures. This investigation studied one potential mechanism for this observation: better maintenance of energy stores and less brain acidosis secondary to reduced metabolic activity associated with modest hypothermia. METHODS: 31P MR spectroscopy was used to study piglets before, during, and after 15 minutes of partial brain ischemia with intraischemic rectal temperatures of either 38.3 +/- 0.4 degrees C (n = 10, normothermic) or 35.4 +/- 0.5 degrees C (n = 10, hypothermic). Animals were followed up for up to 72 hours after ischemia and were evaluated clinically and by brain histology. RESULTS: Values for pHi remained 0.15 to 0.20 pH units greater in modestly hypothermic than in normothermic piglets during ischemia and the initial 30 minutes after ischemia (P = .049, group effect). Phosphocreatine, beta-ATP, and inorganic phosphorus were similar between groups. The relationship between the intraischemic energy state and subsequent clinical evidence of brain damage (irrespective of group assignment) revealed lower pHi over the last 7 minutes of ischemia for abnormal compared with normal piglets (5.98 +/- 0.22 versus 6.39 +/- 0.24, respectively; P = .002). In contrast, intraischemic beta-ATP (41 +/- 19% versus 57 +/- 21% of control) and inorganic phosphorus (273 +/- 31% versus 224 +/- 92% of control) for abnormal and normal piglets, respectively, did not differ between groups. CONCLUSIONS: Intraischemic modest hypothermia attenuates the severity of brain acidosis during and 30 minutes after ischemia compared with normothermic animals and supports the concept that attenuated brain acidosis is a potential mechanism by which hypothermia may reduce ischemic brain damage.
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The progression zone of a progressive addition spectacle lens cannot provide a sharp retinal image as it presents the pupil with a range of powers through which to view an object. The resulting blur is explored mathematically. The nature of this blur is extraordinary but its visual significance is very slight and is less than previously believed. Peripheral astigmatism, found in all such lenses, may lower their visual performance.
Surveys to determine learning and behavioral changes that result from education about human immunodeficiency virus (HIV) and acquired immune deficiency syndrome (AIDS) should be constructed to account for high levels of background knowledge and knowledge of safer sex practices among college students. This article evaluates the learning and behavioral changes of students enrolled in an HIV/AIDS education course offered by the Department of Biological Sciences at Rutgers University as part of a university-wide HIV/AIDS education program. Responses of students in the HIV/AIDS class were compared with those of students enrolled in other biology classes, using paired and unpaired t tests and multivariate discriminant analysis. Participants revealed they had significant knowledge about HIV/AIDS as a result of the HIV/AIDS class, but students campus-wide had a far higher level of general knowledge about HIV/AIDS than the authors expected. In addition, many students already were practicing behaviors that would reduce their risk of HIV infection. Because students were so knowledgeable about HIV and claimed they practiced safer sex, it was difficult to demonstrate significant changes in behavior as a result of the classroom experience.
Abnormalities in corticotropin-releasing hormone (CRH) secretion, noradrenergic neurotransmission, and serotonergic activity in the central nervous system (CNS) have all been hypothesized to exist in alcoholic patients, as have abnormalities in hypothalamic-pituitary adrenal function. To test these hypotheses, we continuously sampled cerebrospinal fluid (CSF) from alcoholic patients after 38-124 days of abstinence and from normal volunteers via a flexible, indwelling lumbar subarachnoid catheter and measured CRH, norepinephrine (NE), 3-methoxy-4-hydroxyphenylglycol (MHPG), tryptophan, and 5-hydroxyindoleacetic acid (5-HIAA) concentrations at 10-min intervals, from 11:00 through 17:00 h. The spinal canal catheter was inserted at approximately 08:00 h. Serial plasma ACTH, cortisol, and NE concentrations were also measured. A mixed liquid meal was consumed at 13:00 h. CSF CRH concentrations were lower in alcoholic patients than in normal volunteers (26 +/- 15 vs. 60 +/- 30 pg/ml, respectively, p < 0.05 by ANOVA), as were CSF NE levels (0.33 +/- 0.09 vs. 1.15 +/- 0.51 pmol/ml, respectively, p < 0.01). Plasma NE and CSF MHPG levels were normal in the alcoholic patients. CSF tryptophan and 5-HIAA and plasma ACTH and cortisol concentrations did not differ between the groups. These studies extend our finding of reduced spinal canal CSF CRH concentrations in depressed patients to abstinent chronic alcoholics.(ABSTRACT TRUNCATED AT 250 WORDS)
BACKGROUND: Gene transfer can potentially alter vessel wall biology and intervene in the pathogenesis of human disease. Although several methods for vector delivery have been described, systematic comparisons of these methods are unavailable. Therefore, this study compared three catheter-based strategies and a surgical technique to assess efficient and selective gene transfer to the vascular wall. METHODS AND RESULTS: The common carotid arteries and internal jugular veins of New Zealand White rabbits were infected with recombinant adenovirus encoding either firefly luciferase or a nuclear-localizing variant of beta-galactosidase. Delivery of recombinant virus was achieved by one of four methods: (1) instillation within a surgically isolated vessel segment (dwell), (2) a double-balloon catheter, (3) a perforated balloon catheter (Wolinsky), or (4) an angioplasty balloon catheter coated with a hydrophilic adsorbent polymer (Hydrogel). Vessel segments were analyzed 4 days after infection for luciferase and beta-galactosidase activity and for the extent of injury to the vessel wall. Luciferase activity in vessels infected using the double-balloon method was substantially greater than that achieved by catheter-based methods (P < .05). The dwell and double-balloon methods yielded selective expression in intimal cells, whereas arteries infected using perforated or Hydrogel-coated balloon catheters demonstrated expression primarily in medial cells. Tissue injury was most pronounced with the perforated balloon catheter. CONCLUSIONS: Prototype catheters permit relatively efficient direct gene transfer to vascular endothelium; however, delivery methods for targeting the medial cells are inefficient. Modifications are needed to optimize direct gene transfer and minimize tissue injury.
Paraffin (known in some Western countries as kerosene) ingestion is the most common form of acute childhood poisoning in most developing countries. South African black communities reflect a similar pattern, yet the true size and cost of the problem are not known. Without such baseline data the effect of interventions cannot be evaluated. The aim of the study was to determine the incidence and treatment cost of paraffin poisoning in the Cape Peninsula, to identify high-risk areas and to discuss which measures offered the most economical and best preventive potential for this paediatric hazard. A 12-month retrospective study was undertaken in 1990. Relevant patient data were extracted from the files of 6 major Cape Peninsula hospitals. Treatment costs were calculated based on differential hospital costs per inpatient per day, with outpatient costs at one-third of the costs per day. Age-specific rates for affected residential areas were calculated to identify high-risk areas. A total of 436 children (62,5% male), mostly between the ages of 12 and 36 months, were treated at an estimated cost of R111 673. This amount would have been sufficient to provide 95% of households in the 8 identified high-risk areas with child-resistant paraffin containers. In these areas age-specific paraffin poisoning rates ranged from 1,8/1,000 to 7,7/1,000. Strategically planned interventions can be cost-effective when weighed against the treatment cost of cases of paraffin poisoning.
The evaluation of adipose tissue distribution has become an essential component of investigations on the complications of obesity. However, a major limitation is lack of methodology for accurate estimation of adipose tissue mass in the different regions of the body. Therefore, we have tested the accuracy and precision of magnetic resonance imaging (MRI) as a method to measure adipose tissue mass in regions of the body not accessible with standard anthropometric methods. The mass of subcutaneous and intraabdominal adipose tissue estimated by MRI was compared with that obtained by direct weighing of the same adipose tissue compartments after dissection in human cadavers. MRI was performed on three unembalmed cadavers (two males, one female) who were subsequently dissected to isolate intraperitoneal, retroperitoneal, and subcutaneous adipose tissues. These same components were delineated by MRI. The results of the two methods were highly congruent. For the various compartments, the mean of the difference between the two methods was only 0.076 kg (95% confidence interval + 0.005 kg and + 0.147 kg). The "limits of agreement" between the two techniques were -0.066 kg and +0.218 kg. Multiple repeated estimates of mass of adipose tissue compartments were made to determine reproducibility of the MRI measurement; the coefficient of variation for repeated measures was below 14%. The results of this study show that MRI is an accurate and precise technique to evaluate adipose tissue mass in subcutaneous and intraabdominal compartments. Furthermore, MRI was found to be a valid method to separately evaluate the mass of intraabdominal subcompartments of intraperitoneal and retroperitoneal adipose tissue.
Cis-unsaturated fatty acids activate soluble protein kinase C (PKC) in vitro and in intact platelets. The following studies were conducted to determine the effects of oleate on individual isoenzymes of PKC in human platelets. Human platelets were found to contain predominantly PKC alpha, beta I, beta II, and delta with minor immunoreactivity for PKC epsilon, zeta, and eta. In intact platelets, sodium oleate caused a time-dependent redistribution of PKC alpha, beta II, and delta from cytosol to membrane fractions with little effects on PKC beta I. On the other hand, PMA and thrombin induced translocation of all four isoenzymes of PKC. In vitro, oleate partially activated (50% of Vmax) purified calcium-dependent PKC (alpha, beta I, and beta II) with an EC50 of 50 microM whereas it fully activated (100% of Vmax) purified calcium-independent PKC (predominantly delta) with an EC50 of 5 microM. The selective effects of oleate on PKC isoenzymes were investigated in platelet cytosol which contains endogenous PKC and its physiologic substrates. Under these conditions, oleate potently activated calcium-independent PKC causing the phosphorylation of the 40-kDa substrate. Activation of calcium-dependent isoforms occurred only at higher concentrations of oleate. Thus, oleate activates multiple isoenzymes of PKC with predominant effects on calcium-independent PKC.
A group of 80 menstruating rhesus (Macaca mulatta) monkeys, with an average estimated age of 11.1 +/- 4.1 yr SD, were first randomly allocated to four similar test rooms (20 monkeys/room) and then randomly allocated to one of the five dose groups (four females/dose group/room). Each day, the females self-ingested capsules containing doses of 0, 5, 20, 40 or 80 micrograms Aroclor 1254/kg body weight. After 25 months of daily dosing, approximately 90% of the treated females attained a qualitative pharmacokinetic steady state with respect to the concentration of polychlorinated biphenyl in their adipose tissue. The test monkeys were monitored daily for health and menstrual status, as well as feed and water consumption. On a weekly basis, each female's body weight was determined and a detailed clinical examination was conducted. Minor treatment effects included a slight, but not statistically significant, decrease in feed and water consumption as well as a decreased feed conversion ratio and a slight increase in the duration of menses. Statistically significant, dose-related treatment effects included inflammation and/or prominence of the tarsal (Meibomian) glands, eye exudate, and various finger and toe nail changes. These results were found at doses lower than those previously reported for non-human primates.
A group of 80 menstruating rhesus (Macaca mulatta) monkeys, with an average estimated age of 11.1 +/- 4.1 yr SD were first randomly allocated to four similar test rooms (20 monkeys/room), and then randomly allocated to one of five dose groups (four females/dose group/room). Each day, the monkeys self-ingested capsules containing doses of 0, 5, 20, 40 or 80 micrograms Aroclor 1254/kg body weight. After 25 months of daily dosing, approximately 90% of the treated females attained a qualitative pharmacokinetic steady state with respect to the concentration of polychlorinated biphenyl (PCB) in their adipose tissue. Subsequently, oestrogen and progesterone concentrations in serum were determined for one complete oestrous cycle and various immunological tests were conducted, while the monkeys continued to receive their daily dose of PCB. During the prebreeding phase of the study, blood for clinical and analytical monitoring including haematology, serum biochemistry, serum hydrocortisone, serum proteins (alpha 1, alpha 2, beta and gamma-globulins), serum immunoglobulins (A, G and M) and thyroid variables (thyroxine/triiodothyronine (T3) uptake ratio, percentage T3 uptake and free thyroxine index), were obtained monthly, as were specimens to ascertain the concentration of PCB in the blood, adipose tissue and faeces. Major findings among treated monkeys included the following: changes in haematology (decreased erythrocyte count, haematocrit, reticulocyte count, and mean platelet volume), serum biochemistry (decreased cholesterol and total bilirubin), immunotoxicity (decreased antibody production to sheep red blood cells and alterations in the percentage of T helper and T suppressor cells) and pathology (the number of regions of sebaceous gland lobules per unit of histological length was significantly reduced). These effects were observed at PCB doses lower than those previously reported for non-human primates.