Incidence of hypertension in the Framingham Study.

Incidence and trends in incidence of definite hypertension were analyzed based on 30 years follow-up of 5,209 subjects in the Framingham Heart Study cohort. Based on pooling of 15 two-year periods, hypertension incidence per biennium increased with age in men from 3.3 per cent at ages 30-39 to 6.2 per cent at ages 70-79, and in women from 1.5 per cent at ages 30-39 to 8.6 per cent at ages 70-79. No consistent trend in incidence rates was evident for either sex from the 1950s through the 1970s. The proportion of hypertensive subjects receiving antihypertensive medication has increased since 1954-58 and exceeded 80 per cent for both men and women ages 60-89 years in 1979-81. Incidence data presented in this report may serve as a baseline for assessing the impact of future public health efforts in the primary prevention of hypertension.     

Donor availability as the primary determinant of the future of heart transplantation

Heart transplantation has now achieved a therapeutic status similar to that of cadaveric renal transplantation. Depending on patient selection criteria, it is estimated that as many as 15,000 people per year could conceivably benefit from a heart transplant, but the actual number of persons who will benefit is severely constrained by donor supply. Availability of heart donors was estimated based on data obtained on 1,955 organ donors in the United States. The results show that because of age and other contraindications, only 400 to 1,100 viable donor hearts may be available each year. Donor supply is the most critical determinant of the future of heart transplantation since it will dictate the number of transplants performed, the survival of transplant recipients, the total program expenditures associated with heart transplantation, the nature of the legal and ethical issues involved, the number of cardiac transplant programs required to make optimal use of the available donor hearts, and the future role of mechanical circulatory support systems.     

Operative cholangiography

The value of operative cholangiography in the management of biliary tract disease has been questioned. To better define the role of cholangiography, we reviewed 579 consecutive cholecystectomies done by 1 group of surgeons in a small rural practice over 8 years. Cholangiography demonstrated unsuspected common bile duct disease in 5% of the procedures, while 12% of the patients were spared an unnecessary choledochotomy after a normal cholangiogram was obtained. There was no morbidity, mortality, or prolongation of the hospital stay attributed to the cholangiographic procedure. These findings bolster the argument for routine cholangiography as a safe, effective, and helpful screening examination for patients who are at risk for having common bile duct disease.     

CD4-positive/heat-stable antigen-positive thymocytes cause graft-versus-host disease across non-major histocompatibility complex incompatibilities

Single-positive thymocytes are the immediate precursors of peripheral recent thymic emigrants (RTE) which develop into mature peripheral T cells. The functional ability of RTE is unclear but their state of differentiation may be relevant to the development of tolerance to peripheral “self” antigens. Since RTE are difficult to analyze, precursor CD4⁺/8⁻ thymocytes were assessed in a model in vivo to determine their functional capability and their susceptibility to tolerance induction. The ability of both heat-stable antigen-positive (HSA⁺) (immature) and HSA⁻ (mature) single-positive thymocytes to cause graft-versus-host disease (GVHD) across non-major histocompatibility complex differences was examined. Both HSA⁻ and HSA⁺ CD4⁺/8⁻ thymocytes from C3H mice caused lethal GVHD in AKR recipients as did CD4⁺ peripheral T cells in controls. Further, neonatal C3H thymocytes also caused lethal GVHD in AKR recipients. Since CD4⁺/8⁻ thymocytes are the precursors of RTE, these results suggest that RTE are not susceptible to tolerance induction to “minor” antigens and may have a normal immune function in vivo. This would suggest that peripheral tolerance may be dependent upon the manner of antigen presentation rather than T cell maturity.     

An epidemiologic study of smoking and primary infertility in women.

OBJECTIVE: To determine the relationship between cigarette smoking and primary female infertility. DESIGN: Retrospective, case-control study. SETTING: Population-based and randomly selected from eight geographic areas in the United States. PARTICIPANTS: Women, 20 to 54 years of age, who were randomly selected to serve as the control group of the Cancer and Steroid Hormone Study were used for this study. Within this group, there were 483 women who were classified as having experienced primary infertility and 2,231 women eligible to serve as controls. Primary infertility, defined as 24 consecutive months of unprotected intercourse without conception, was documented from a calendar of each women's reproductive and contraceptive history. RESULTS: Smoking one pack of cigarettes per day (odds ratio = 1.36) and starting to smoke before 18 years of age (odds ratio = 1.30) were significantly associated with increased risk of infertility. Life table and proportional hazards analysis indicated that smoking did not significantly increase the time required to conceive among infertile women. CONCLUSIONS: Number of cigarettes smoked and age when the women began smoking contributed to infertility in this study. It is reasonable, therefore, to recommend that women stop smoking when they are attempting to become pregnant.     

Regulation of autoimmune response

Recent work on such apparently disparate fields as T-cell receptor peptide-induced regulation, superantigens, antigen-induced tolerance, models of peripheral tolerance, apoptosis, and T-cell receptor antagonists demonstrates a similarity in immune response from a regulatory perspective. In many systems, a ‘tolerance’ pathway is observed, characterized broadly as an initial disturbance in the immune system, with a resulting predominance of effector cells, followed by a homeostatic response (often requiring CD8⁺ cells) which leads the effector population into T-cell receptor downregulation, T-cell inactivation, anergy and, often, eventual apoptotic death. In the regulated immune response, mixed populations of anergized and apoptosing T cells can be found. In some cases, anergy appears to lead to death while, in other instances, cells revert to a functional state. This review focuses on recent papers examining each of these topics in an attempt to obtain a preliminary, integrated picture of immune regulation in autoimmune diseases.     

Scale-up of Adhesive Transdermal Drug Delivery Systems

Pharmaceutical Research -     

Febrile-range hyperthermia augments pulmonary neutrophil recruitment and amplifies pulmonary oxygen toxicity

Febrile-range hyperthermia (FRH) improves survival in experimental infections by accelerating pathogen clearance, but may also increase collateral tissue injury. We hypothesized that FRH would worsen the outcome of inflammation stimulated by a non-replicating agonist and tested this hypothesis in a murine model of pulmonary oxygen toxicity. Using a conscious, temperature-controlled mouse model, we showed that maintaining a core temperature at FRH (39 degrees C to 40 degrees C) rather than at euthermic levels (36.5 degrees C to 37 degrees C) during hyperoxia exposure accelerated lethal pulmonary vascular endothelial injury, reduced the inspired oxygen threshold for lethality, induced expression of granulocyte-colony stimulating factor, and expanded the circulating neutrophil pool. In these same mice, FRH augmented pulmonary expression of the ELR(+) CXC chemokines, KC and LPS-induced CXC chemokine, enhanced recruitment of neutrophils, and changed the histological pattern of lung injury to a neutrophilic interstitial pneumonitis. Immunoblockade of CXC receptor-2 abrogated neutrophil recruitment, reduced pulmonary vascular injury, and delayed death. These combined data demonstrate that FRH may enlist distinct mediators and effector cells to profoundly shift the host response to a defined injurious stimulus, in part by augmenting delivery of neutrophils to sites of inflammation, such as may occur in infections. In certain conditions, such as in the hyperoxic lung, this process may be deleterious.