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.     

Blood flow acceleration in the carotid and brachial arteries of healthy volunteers: respective contributions of cardiac performance and local resistance

Summary— The influence of local resistance and cardiac performance on peripheral blood acceleration was investigated in 14 healthy male volunteers. Steady and pulsatile flow was studied in the brachial and in the common carotid arteries, ie, two territories that exhibit marked differences in resistive characteristics. Instantaneous blood velocity (V), mean blood velocity (V_m) and artery diameter (D) were evaluated at rest by an ultrasonic range-gated pulsed Doppler flowmeter using a double transducer probe, thus allowing the calculation of mean blood flow (Q). Mean local resistance (R) was obtained by dividing the mean arterial pressure by Q. The peak value of the local acceleration of the blood was obtained by computer-assisted calculation of the first derivative of instantaneous blood velocity (G_max = +dV/dt_max). Peak aortic blood acceleration (GAo) was simultaneously measured from the suprasternal notch using a pulsed Doppler velocity meter. In the brachial and the common carotid arteries, G_max was of a similar magnitude (551 ±30 and 555 ± 44 cm/s², respectively) despite major differences in the respective D, V_m, Q and R values. In neither artery was there a relationship between G_max and either resting Q or R. At the brachial artery level, G_max was positively related to GAo ( r = 0.79, P = 0.0008). At the common carotid artery level, there was a weak, although non significant relationship between G_max and GAo ( P = 0.08). Our results indicate that the local acceleration of peripheral blood flow in the brachial artery is related rather to upstream central impulse than to downstream hemodynamics, and suggest some regional differences in the hemodynamic determinants of the local acceleration of peripheral blood flow.     

Atlantoaxial instability in Down's syndrome: clinical and radiological screening

One hundred and thirty children with Down's syndrome were screened for the presence of atlantoaxial instability, using both clinical examination and radiographs of the cervical spine taken in flexion and hyperextension views. Seven children were found to have radiological evidence of atlantoaxial instability, with an atlanto-dens interval greater than 5.0 mm in one or all positions. Although a full clinical history was obtained from the attending parent and each child underwent a complete neurological examination, there were no factors detected which differentiated between those with radiological evidence of atlantoaxial instability and those with a normal atlantodens distance. It is recommended that children with Down's syndrome be screened twice, at the ages of 5-10 years and at 15 years.     

Patterns of burn adjustment.

For many years, burn professionals have attempted to assess the outcomes of different types of burn injury and the factors that are related to good patterns of coping with the aftermath of thermal injury. Most writers have attempted to use objective criteria such as return to work or preexisting psychologic problems (e.g., alcoholism) in determining the success of rehabilitation, but much controversy over the forms of assessment persists. It is agreed that antisocial personality, organic brain syndromes, and lack of social support all undermine good recovery for patients with burns. The authors have attempted to look at the subjective side of the patient's adjustment by providing representative examples of several types of burn adjustment in terms of personality features, all of which would tend to complement other approaches. The use of denial, the ways in which hostility is managed by the patient, and how he or she uses key persons in the environment are examined. The cognitive, emotional (affective), and behavioral styles of patients are examined as part of this pilot study of cluster patterns or types of adjustment.     

Adjuvant therapy for adenocarcinoma of the rectum

Surgical resection continues to be the primary curative modality for patients with adenocarcinoma of the rectum. However, local tumor recurrence in the pelvis and/or distant metastasis may occur in spite of complete excision of grossly visible malignant disease. Surgical and pathologic staging can identify a subset of surgically treated rectal cancer patients at high risk for tumor relapse and death. Irradiation and chemotherapy have been used as adjuvant therapy in conjunction with surgery as single modalities and in combination for patients with high risk rectal cancer. Evidence from controlled clinical trials indicates a significant decrease in local tumor recurrence, and a significant improvement in disease-free and overall survival with the use of combined postoperative irradiation and chemotherapy in this setting. A current national clinical trial in the United States of America is studying whether irradiation can be combined with new chemotherapy regimens which have shown significant therapeutic benefit as surgical adjuvant therapy for patients with high risk colon cancer (5FU + levamisole) and for patients with metastatic colorectal cancer (5FU + leucovorin) to further improve the efficacy of surgical adjuvant therapy for adenocarcinoma of the rectum.

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Resumen La resección quirúrgica continúa siendo la modalidad curativa primaria en pacientes con adenocarcinoma del recto. Sin embargo, la recurrencia local del tumor en la pelvis y/o las metástasis distantes puede ocurrir a pesar de la resección completa de la enfermedad maligna macroscópicamente visible. La estadificación operatoria y patológica puede indentificar un subgrupo de pacientes tratados quirúrgicamente con alto riesgo de relapso tumoral y meserte. La irradiación y la quimioterapia han sido utlizados como terapia adyuvante en unión con la cirugía como modalidades únicas y en combinación para pacientes con cáncer rectal de alto riesgo. La evidencia surgida de ensayos clínicos controlados señala una disminución significativa en las tasas de recurrencia tumoral local, y una superación significativa en las tasas globales de sobrevida y de sobrevida libre de enfermedad con el uso de la combinación postoperatoria de irradiación y quimioterapia. Un ensayo clínico nacional que se ejecute en el momento actual en los Estados Unidos investiga si la irradiación puede ser combinada con los nuevos regímenes quimioterapéuticos que han demostrado beneficio significantivo como terapia quirúrgica adyuvante en pacientes con cáncer de colon de alto riesgo (5 FU + levamisol) y en pacientes con cáncer colorrectal metastásico (5 FU + leucovorin) con el propósito de mejorar aún más la eficicacia de la terapia quirúrgica adyuvante en el adenocarcinoma del recto.

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Résumé La chirurgie est le principal moyen thérapeutique de l'adénocarcinome du rectum. La récidive tumorale pelvienne et/ou à distance peut cependant se produire malgré une résection apparemment complète. Un bilan d'extension chirurgical et anatomopathologique peut identifier un sous-groupe de patients susceptible de présenter une récidive ou d'en mourir. La radio-et chimiothérapie ont été préconisées comme traitement adjuvant après l'exérèse chirurgicale, soit seule, soit combinée, chez cez patients à risque. Les résultats de plusieurs essais thérapeutiques semblent indiquer que la radio-et la chimiothérapie combinée à la chirurgie diminuent significativement le taux de récidives locales et améliorent significativement la survie globale et la survie sans maladie. Un essai actuellement en cours aux Etats-Unis étudie si la radiothérapie peut être utilement combinée avec les nouveaux régimes chimiothérapeutiques ayant fait preuve de leur efficacité chez les patients à risque (5FU + lévamisole) ou chez les patients ayant des métastases (5FU + leucovin).