Twin study of genetic and environmental effects on lipid levels

A study of 106 pairs of monozygotic (MZ) and 94 pairs of dizygotic (DZ) twins tested the hypothesis that part of the previously described genetic influence on blood lipid levels can be ascribed to closer similarities among MZ than among DZ twin pairs in environmental factors that affect lipid levels. Participants were adult twin volunteers (age 17-66; 64 male and 136 female pairs) who were selected from the NH & MRC Twin Registry or were respondents to advertisements. They completed a 4-day weighed food diary from which mean nutrient intake was derived. Information on lifestyle and demographic variables was obtained by questionnaire and a nonfasting blood sample was taken for measures of total, low-density lipoprotein (LDL) cholesterol, and high-density lipoprotein (HDL) cholesterol and the HDL2 and HDL3 subfractions. Height and weight were measured, and body mass index (BMI) was calculated (kg/m2). Estimates of the heritability of sex-adjusted lipid levels were 0.72 for total cholesterol, 0.79 for HDL cholesterol, 0.69 for HDL2, 0.20 for HDL3, 1.06 for LDL cholesterol, and 0.44 for sex-adjusted BMI. In all cases except for HDL3, genetic variance was statistically significant. After adjusting for the effects of environmental variables in three different ways, the estimates of heritability were somewhat lower for total cholesterol, HDL2, and BMI, and those for HDL cholesterol (borderline) and LDL cholesterol (definitely) remained statistically significant but were decreased. A genetic influence on HDL3 was not found. Adjusted heritability estimates obtained from one method of analysis were 0.35 for total cholesterol, 0.49 for HDL, 0.04 for HDL2, -0.34 for HDL3, 0.66 for LDL, and 0.32 for BMI. These results suggest that the assumptions made in the classical twin study approach are not appropriate when examining genetic effects on lipid levels or BMI, or indeed on any biological variable that may be affected by environmental factors that tend to be more similar in MZ twins than in DZ twins. In these circumstances, more complex models may be needed to differentiate between genetic and environmental influences.     

ROLE OF NITRIC OXIDE IN THE CONTROL OF THE RENAL MEDULLARY CIRCULATION

1. Nitric oxide (NO) has been implicated as an important controller in the short- and long-term regulation of arterial pressure. Studies performed in our laboratory have demonstrated that chronic intravenous administration of the NO synthase inhibitor N^G-nitro-L-arginine methyl ester (L-NAME) selectively decreases renal medullary blood flow, causes sodium and water retention and leads to hypertension. 2. To determine the importance of the renal medullary effects in this model of hypertension, further studies were conducted to examine the influence of selective stimulation or inhibition of renal medullary NO on whole kidney function and cardiovascular homeostasis. With the use of a unique catheter to directly infuse into the renal medullary interstitial space, stimulation (bradykinin or acetylcholine) or inhibition (L-NAME) of renal medullary NO selectively increased or decreased renal medullary blood flow. 3. The changes in medullary flow in these experiments were associated with parallel changes in sodium and water excretion independent of alterations in renal cortical blood flow or glomerular filtration rate. 4. Studies were then undertaken to examine the long-term effects of selective NO inhibition in the renal medulla on cardiovascular homeostasis. Chronic infusion of L-NAME directly into the renal medullary interstitial space of uninephrectomized Sprague-Dawley rats led to a selective decrease in renal medullary blood flow that was sustained throughout the 5 day L-NAME infusion period. The decrease in medullary blood flow was associated with retention of sodium and the development of hypertension and the effects were reversible. 5. The data reviewed indicate that NO in the renal medulla has a powerful influence on fluid and electrolyte homeostasis and the control of blood pressure.     

Anaesthetic hazards of the 'passion gap'. A case report

Dental abnormalities cause problems for both dentist and anaesthetist. The anaesthetic hazards associated with the 'passion gap'--a term used in the western Cape Province for removal of the top four incisor teeth, a practice widespread among members of the Cape Coloured community--are discussed. Recommendations are made to assist the anaesthetist when dealing with such a patient.     

Inpatient management of asthma in the Chicago suburbs: the Suburban Asthma Management Initiative (SAMI).

BACKGROUND: Assessment of inpatient asthma management has generally been limited to urban settings, including Chicago, which is known for its high asthma morbidity and mortality. Previously published data have been based on survey methodology. The Suburban Asthma Consortium (SAC) sought to obtain patient-based data unique to the Chicago suburbs to improve asthma care in those areas. OBJECTIVE: To evaluate current inpatient asthma management based on the 1997 National Asthma Education and Prevention Program (NAEPP). DESIGN: Retrospective chart review of all hospitalized patients 3-65 years bearing asthma-related ICD-9 codes for fiscal year 2002 in community, nonteaching hospitals in Chicago suburbs. RESULTS: Nine hundred two cases were submitted from seven hospitals. The majority ( > or = 75%) received inhaled bronchodilators, systemic steroids, oxygen and pulse oximetry. Antibiotic use (67%), chest radiography (85%), complete blood count (77%), and electrolytes (59%) appeared excessive in view of NAEPP recommendations. Peak flow monitoring (PFM) was recorded on admission in 45% of patients 5 years old and older; 52% had PFM during hospitalization. Thirty-eight percent of patients were taking ICS prior to admission; of those not on ICS, only 12% were newly diagnosed asthmatics. Overall, 51% of patients were discharged with ICS. Patients were more likely to receive ICS at discharge if they had required intensive care (ICU), had been on ICS prior to admission, were referred to an asthma specialist while hospitalized, or were insured. Patients with Medicare/Medicaid (MC/MA) had more repeat emergency visits and hospitalizations, longer lengths of stay, and received less ICS at discharge. Depending on the parameter, 41% or less patients received discharge planning education and were not more likely to have received education if in the ICU. Results ranged significantly between hospitals for most parameters (p < 0.05 or less). CONCLUSION: Study subjects received appropriate acute therapy and oxygen monitoring, but there was a divergence from NAEPP recommendations regarding PFM, ICS use, antibiotics, and laboratory evaluation. Patients receiving MC/MA experienced higher morbidity and received less ICS. Discharge asthma education was suboptimal for most hospitals. Most parameters demonstrated significantly wide practice variations between hospitals. Peak flow monitoring and patient education findings differed significantly from those in survey-conducted studies.     

Implementing a simpler approach to mission-based planning in a medical school.

Changes in the education, research, and health care environments have had a major impact on the way in which medical schools fulfill their missions, and mission-based management approaches have been suggested to link the financial information of mission costs and revenues with measures of mission activity and productivity. The authors describe a simpler system, termed Mission-Aligned Planning (MAP), and its development and implementation, during fiscal years 2002 and 2003, at the School of Medicine at the University of Texas Health Science Center at San Antonio, Texas. The MAP system merges financial measures and activity measures to allow a broad understanding of the mission activities, to facilitate strategic planning at the school and departmental levels. During the two fiscal years mentioned above, faculty of the school of medicine reported their annual hours spent in the four missions of teaching, research, clinical care, and administration and service in a survey designed by the faculty. A financial profit or loss in each mission was determined for each department by allocation of all departmental expenses and revenues to each mission. Faculty expenses (and related expenses) were allocated to the missions based on the percentage of faculty effort in each mission. This information was correlated with objective measures of mission activities. The assessment of activity allowed a better understanding of the real costs of mission activities by linking salary costs, assumed to be related to faculty time, to the missions. This was a basis for strategic planning and for allocation of institutional resources.     

Direct excitatory effects of neuropeptide Y (NPY) on rat hippocampal neurones in vitro

Intracellular recordings from granule cells of the rat dentate gyrus show neuropeptide Y (NPY) applied by pressure ejection from pipettes containing 1.2-12 microM by pressures of less than 200 kPa for 1-5 s in duration to consistently evoke membrane depolarisations accompanied by a reduction in membrane resistance. The depolarisations were accompanied by an increase in excitability. Since the depolarisations evoked by NPY were not attenuated by either tetrodotoxin or kynurenic acid a direct excitatory action of NPY is postulated.     

Cognitive evoked potentials and disorders of recent memory

P3 potentials evoked by spoken words were recorded from seven patients with disorders of recent memory and seven age-matched controls. Inclusion criteria included a clearly identifiable P3 to pure tone stimuli. Absence or marked decrement of P3 to word stimuli was seen in the patients even though they could perform the word task. The results are consistent with an encoding disorder and failure in elaboration of information processing.     

Albumin Adsorption and Retention on C18-Alkyl-Derivatized Polyurethane Vascular Grafts

The short-term albumin affinity and thrombo-resistance of a polyether polyurethane vascular graft have been improved. The method is based on the C18 alkylation of the polymer. Thrombus formation by a planimetric technique and albumin retention on wire-reinforced polyurethane tubes, both C18 alkylated and untreated, were measured in short-term (4-h) exposure at femoral arterial sites in the dog. 125I-Albumin was preabsorbed on tubes and then exposed to blood for successive 2-h periods. Albumin uptake on alkylated tubes prior to blood exposure and retention following 2 h of blood exposure were significantly greater than on controls. Following a fast desorption phase in blood, the remaining albumin was more slowly desorbed from alkylated than from control tubes. Reincubation with albumin and blood reexposure produced a similar tendency, suggesting blood conditioning does not reduce the albumin affinity-enhancing property of C18 alkylation in the short term. Blood-preconditioning experiments suggested endogenous albumin has a high affinity for the C18-alkylated surface. Scanning electron microscopic examination showed thrombus and platelet densities were higher on control than on alkylated surfaces. These results suggest in vivo albumin affinity is increased for C18-alkylated polyurethane, which may be linked to decreased thrombus formation on these surfaces.