Gene-targeted inhibition of transactivation of human immunodeficiency virus type-1 (HIV-1)-LTR by antisense oligonucleotides

We have used an in vitro approach to study the efficiency of antisense oligonucleotides in inhibiting LTR-(HIV-1)-directed CAT expression catalyzed by tat protein, the functional protein of the transactivator gene. We selected the target sequence localized near the 5 end of the tat mRNA. The following conclusions can be drawn from the data presented here: a) Antisense oligonucleotides modified by conjugation of cholesterol at the 3 end have a severalfold higher inhibitory response, b) inhibitory response is dependent on the mode of introducing oligonucleotides, and c) the inhibition by antisense oligonucleotides is sequence specific and directed towards the targeted region. This approach could be useful for targeting functional regions of regulatory gene products and designing gene-targeted inhibitors of virus replication.Dedicated to Professor Klaus Ring on his 60th birthday.     

Nutrition and immunology: from the clinic to cellular biology and back again

Diet and immunity have been known to be linked to each other for centuries. In the last 30 years systematic studies have confirmed that nutrient deficiencies impair immune response and lead to frequent severe infections resulting in increased mortality, especially in children. Protein-energy malnutrition results in reduced number and functions of T-cells, phagocytic cells and secretory immunoglobulin A antibody response. In addition, levels of many complement components are reduced. Similar findings have been reported for moderate deficiencies of individual nutrients such as trace minerals and vitamins, particularly Zn, Fe, Se, vitamins A, B6, C and E. For example, Zn deficiency is associated with profound impairment of cell-mediated immunity such as lymphocyte stimulation response, decreased CD4+:CD8+ cells, and decreased chemotaxis of phagocytes. In addition, the level of thymulin, which is a Zn-dependent hormone, is markedly decreased. The use of nutrient supplements, singly or in combination, stimulates immune response and may result in fewer infections, particularly in the elderly, low-birth-weight infants and malnourished critically-ill patients in hospitals. The interactions between nutrition and the immune system are of clinical, practical and public health importance.     

Unemployment, depression, and health: a look at the African-American community

OBJECTIVES: While the unemployment rate of African-American people is more than twice that of the white population, the research on the impact of unemployment on the health of this population is scarce. This study analysed the impact of unemployment on depression and well being among African-American people, and the factors associated with well being. METHODS: Logistic and multiple regression models were used to analyse panel data collected in the National Survey of Families and Households 1987-1992. African-American (1369) and white (6660) respondents were analysed separately. Outcome variables included an index of depression and self reported health status. MAIN FINDINGS: Differences between employment and unemployment groups were less significant for African-Americans than for the white population in predicting depression and well being. Health enhancing factors such as education and wealth were significantly associated with better health and lower depression indices among the white population but not consistently so among African-Americans. Satisfaction with personal relationships was the strongest predictor of well being for both groups. CONCLUSION: Research should focus on the special needs and circumstances of African-Americans, because protective factors may not have the same impact in different groups of the population.     

Laparoscopic management of benign solid and cystic lesions of the liver

OBJECTIVE: The authors present their experience in the laparoscopic management of benign liver disease. The aim of the study is to analyze technical feasibility and evaluate immediate and long-term outcome. SUMMARY BACKGROUND DATA: Indications for the laparoscopic management of varied abdominal conditions have evolved. Although the minimally invasive treatment of liver cysts has been reported, the laparoscopic approach to other liver lesions remains undefined. METHODS: Between September 1990 and October 1997, 43 patients underwent laparoscopic liver surgery. There were two groups of benign lesions: cysts (n = 31) and solid tumors (n = 12). Indications were solitary giant liver cysts (n = 16), polycystic liver disease (n = 9), hydatid cyst (n = 6), focal nodular hyperplasia (n = 3), and adenoma (n = 9). Only solid tumors, hydatid cysts, and patients with polycystic disease and large dominant cysts located in anterior liver segments were included. All giant solitary liver cysts were considered for laparoscopy. Patients with cholangitis, cirrhosis, and significant cardiac disease were excluded. Data were collected prospectively. RESULTS: The procedures were completed laparoscopically in 40 patients. Median size was 4 cm for solid nodules and 14 cm for solitary liver cysts. Conversion occurred in three patients (7%), for bleeding (n = 2) and impingement of a solid tumor on the inferior vena cava (n = 1). The median operative time was 179 minutes. All solitary liver cysts were fenestrated in less than 1 hour. There were no deaths. Complications occurred in 6 cases (14.1%). Two hemorrhagic and two infectious complications were noted after management of hydatid cysts. There were no complications after resection of solid tumors. Three patients received transfusions (7%). The median length of stay was 4.7 days. Median follow-up was 30 months. There was no recurrence of solitary liver or hydatid cysts. One patient with polycystic disease had symptomatic recurrent cysts at 6 months requiring laparotomy. CONCLUSION: Laparoscopic liver surgery can be accomplished safely in selected patients with small benign solid tumors located in the anterior liver segments and giant solitary cysts. The laparoscopic management of polycystic liver disease should be reserved for patients with a limited number of large, anteriorly located cysts. Hydatid disease is best treated through an open approach.     

Management of ventricular septal defect: a survey of practice in the United Kingdom.

BACKGROUND: A survey of pediatric cardiac surgeons was performed to establish current opinions in the United Kingdom concerning closure of ventricular septal defect. METHODS: Questionnaires were sent to 14 pediatric cardiac centers in 1995 (16 surgeons, 100% response), and again in 1997 (20 surgeons, 100% response). RESULTS: Results are presented for 1997, with findings from 1995 shown in parentheses. Eleven (6) surgeons used bypass exclusively, 9 (10) sometimes used circulatory arrest. Operative techniques were similar, although the material used for the patch varied. Multiple defects were approached via the transatrial route by 18 (15), right ventriculotomy by 11 (7) and left ventriculotomy by 7 (6). The juxta-arterial defect was approached via the transpulmonary route by 16 (13), a combination by 9 (11), transatrial by 10 (6), and transventricular by 9 (5). The most common indications for pulmonary arterial banding were "Swiss cheese" defect for 13 (13), and functionally single ventricle for 5 (6). Ventricular septal defect associated with coarctation was repaired in two stages by 13 (10), a single stage by 5 (3), or either by 1 (3). CONCLUSIONS: Pediatric cardiac surgeons in the United Kingdom demonstrate a uniform, evidence-based approach to the management of ventricular septal defect.     

Carcinoma of the penis metastasizing to the dorsal spine. A case report

Carcinoma of the penis tends to have a predictable route of spread by direct invasion and by regional lymphatic involvement to the inguinal group of lymph nodes. Blood-borne distant spread is rare, last to occur, and is seen in 1-3% of cases. Metastasis to the spine is even rarer. We encountered one such case who presented with spinal metastasis, as documented by the whole body bone scan, and this was later followed by involvement of the inguinal nodes. This case is unique in its site of metastatic presentation as well as its pattern of presentation.     

The lateral pectoral flap

The lateral pectoral flap is a new pedicled flap based on the superficial thoracic artery which arises from the subscapular artery and courses along the lateral border of pectoralis major. The flap consists of skin, subcutaneous tissue and the underlying pectoral epimysium. It has been used successfully to resurface contralateral soft tissue defects over the fingers, thumb and dorsum of the hand in eight cases. The advantages of this flap are that it provides reliable soft tissue cover to the hand, which can be kept in an elevated position resting comfortably on the contralateral pectoral region with the forearm and arm aligned conveniently in the cross-chest position. It does not interfere with clothing and dressing the lower part of the body in contrast to the groin, hypogastric or lower abdominal flaps, and it allows early ambulation. Primary closure of the donor site in the majority of cases is an added benefit.     

Chronic hypoxia differentially alters the responses of pulmonary arteries and veins to endothelin-1 and other agents.

The effects of chronic hypoxia on the responses of rat large pulmonary arteries and veins to vasoactive agents have been examined. Endothelin-1-induced contractions of pulmonary arteries and pulmonary veins were reduced by chronic hypoxia. In contrast, chronic hypoxia augmented sarafotoxin 6c-induced contractile responses in pulmonary veins but not in pulmonary arteries. Chronic hypoxia augmented the constrictor effect of phenylephrine in pulmonary arteries, but not in pulmonary veins. The thromboxane receptor agonist, U46619 (9,11-dideoxy-9alpha,11alpha-epoxy-methanoprostaglandin++ + f2alpha) contracted pulmonary arteries and pulmonary veins, and although maximal responses were not altered in chronically hypoxic preparations, the EC50 value in pulmonary arteries was increased following chronic hypoxia. The relaxant effects of acetylcholine and isoprenaline on pulmonary arteries were potentiated by chronic hypoxia. In contrast, ionomycin-mediated relaxations of pulmonary arteries and pulmonary veins were reduced, while sodium nitroprusside-induced relaxation of pulmonary arteries and veins were not altered by chronic hypoxia. Previous studied have looked primarily at the effects of chronic hypoxia on pulmonary arteries. This data provides evidence that chronic hypoxia also causes selective changes in the reactivity of large pulmonary veins.     

"False inhibition" of demand pacemaker due to leakage of fluid into the pacemaker lead socket

"False inhibition" of a demand pacemaker usually occurs with a microfracture of the lead system resulting in a galvanic potential at the site of the fracture or with sensing of myopotential with exercise. An increase in the slope of the leading half edge of the pulse contour is generally considered diagnostic of lead fracture. We report the case of a patient in whom "false inhibition" at rest and an increase in the slope of the leading half edge of the pulse contour were caused by leakage of fluid into the pacemaker lead socket.