Preventive Treatment Modalities Research Articles

Diabetic nephropathy.

Diabetic nephropathy remains a leading cause of end-stage renal disease (ESRD) in western societies, accounting for over one-third of all patients beginning renal replacement therapy. Patients with Type 2 diabetes comprise the largest and fastest-growing single disease group requiring renal support therapy. In addition to the high risk of progression to ESRD, diabetic nephropathy is associated with a very high risk of cardiovascular morbidity and mortality, which is not abolished by dialysis and renal transplantation. While the prognosis of patients with diabetic nephropathy has considerably improved, a greater focus has recently been placed on treating diabetic patients early in order to prevent future organ failure. Microalbuminuria is an important intermediary end-point that correlates strongly with future advanced renal disease and cardiovascular mortality. Recent evidence indicates that optimum glycaemic control, tight blood pressure control, and the regular screening for and early treatment of microalbuminuria are necessary to prevent the development and progression of diabetic renal disease. By utilizing such strategies, the challenge is to reduce the cumulative incidence of overt nephropathy, with its associated increase in cardiovascular mortality, and the requirement for renal support therapy. Over the next 5-10 years, the patient with Type 2 diabetes will need to be the specific focus of such preventive treatment modalities.

Frequency and Carrier Risk Associated with Common BRCA1 and BRCA2 Mutations in Ashkenazi Jewish Breast Cancer Patients

Based on breast cancer families with multiple and/or early-onset cases, estimates of the lifetime risk of breast cancer in carriers of BRCA1 or BRCA2 mutations may be as high as 85%. The risk for individuals not selected for family history or other risk factors is uncertain. We determined the frequency of the common BRCA1 (185delAG and 5382insC) and BRCA2 (6174delT) mutations in a series of 268 anonymous Ashkenazi Jewish women with breast cancer, regardless of family history or age at onset. DNA was analyzed for the three mutations by allele-specific oligonucleotide hybridization. Eight patients (3.0%, 95% confidence interval [CI] 1.5%-5.8%) were heterozygous for the 185delAG mutation, two (0.75%, 95% CI 0.20-2.7) for the 5382insC mutation, and eight (3.0%, 95% CI 1.5-5.8) for the 6174delT mutation. The lifetime risk for breast cancer in Ashkenazi Jewish carriers of the BRCA1 185delAG or BRCA2 6174delT mutations was calculated to be 36%, approximately three times the overall risk for the general population (relative risk 2.9, 95% CI 1.5-5.8). For the 5382insC mutation, because of the low number of carriers found, further studies are necessary. The results differ markedly from previous estimates based on high-risk breast cancer families and are consistent with lower estimates derived from a recent population-based study in the Baltimore area. Thus, presymptomatic screening and counseling for these common mutations in Ashkenazi Jewish women not selected for family history of breast cancer should be reconsidered until the risk associated with these mutations is firmly established, especially since early diagnostic and preventive-treatment modalities are limited.

Transfusion-associated graft-versus-host disease.

Transfusion-associated graft-versus-host disease (TA-GVHD) is a devastating immunologic complication of blood transfusion. Patients at highest risk include premature infants and other patients who are immunosuppressed as a result of either congenital or acquired disease or because of the administration of immunosuppressive therapy. An additional high-risk group is immunocompetent patients who are heterozygous at a particular HLA locus and who receive blood from a donor who is homozygous at the same locus. The clinical syndrome consists of fever, skin rash, diarrhea, hepatic dysfunction, and bone marrow aplasia. The outcome is nearly always fatal, despite attempted treatments that have included the use of immunosuppressive agents. Hemorrhage and infection are the most common causes of death. Both humoral and cytotoxic mechanisms have been implicated in the pathophysiology of TA-GVHD. The complication of TA-GVHD can be prevented by the use of irradiated blood components. The use of ultraviolet B light-irradiated blood products and leukoreduction filters are also being investigated as potential preventive treatment modalities.

Acute pharmacologic preconditioning as a new concept and alternative approach for prevention of skeletal muscle ischemic necrosis

The phenomenon of ischemic preconditioning for augmentation of ischemic tolerance has been well documented in the myocardium of common laboratory animals and human cardiomyocytes. The cellular mechanism of ischemic preconditioning is unclear, but adenosine is most likely the mediator in the rabbit, dog, pig and human. We have demonstrated recently that the protective effect of ischemic preconditioning and adenosine against ischemic injury can also be induced in pig skeletal muscles [116]. We speculate that adenosine is a potential treatment modality for prevention of skeletal muscle ischemic injury in vascular and musculoskeletal reconstructive surgery and in muscle and limb procurement for transplantation in the future. It is hoped that this review will stimulate workers at other laboratories to join the adventure in exploring the cellular mechanism and clinical application of adenosine for augmentation of skeletal muscle ischemic tolerance.

Biopsy of canine ear tissue for detection ofBorrelia burgdorferifollowingIxodes damminifeeding

A punch biopsy method was developed to detect and cultivate Borrelia burgdorferi from canine ear tissue. The biopsy procedure was sensitive in that spirochetes were detected in 100% of the dogs upon which infected ticks had fed. B. burgdorferi could be cultured as early as 6 days after tick feeding at which time the organisms could not be concurrently recovered from peripheral blood. The ear punch biopsy provides a reliable method for sampling live canines and should prove useful for detecting early B. burgdorferi infection and for monitoring duration of non-disseminated infection. Additionally, the procedure will aid in the development of an animal model for evaluation of preventive and therapeutic treatment modalities.

Biopsy of canine ear tissue for detection of Borrelia burgdorferi following Ixodes dammini feeding.

A punch biopsy method was developed to detect and cultivate Borrelia burgdorferi from canine ear tissue. The biopsy procedure was sensitive in that spirochetes were detected in 100% of the dogs upon which infected ticks had fed. B. burgdorferi could be cultured as early as 6 days after tick feeding at which time the organisms could not be concurrently recovered from peripheral blood. The ear punch biopsy provides a reliable method for sampling live canines and should prove useful for detecting early B. burgdorferi infection and for monitoring duration of non-disseminated infection. Additionally, the procedure will aid in the development of an animal model for evaluation of preventive and therapeutic treatment modalities.

Meeting the oral health needs of institutionalized elderly.

Numerous impairments cause suffering to the institutionalized elderly person. The medically compromised or severely demented patient, especially one with swallowing difficulties, presents a challenge to the dental practitioner. This paper summarizes typical geriatric dental problems that caregivers in a long-term care (LTC) facility should find recognizable. It also describes palliative and preventive treatment modalities that help improve the quality of life for such institutionalized patients.

Efficacy of intravenous infusion of prostacyclin (PGI 2) or prostaglandin E 1 (PGE 1) in augmentation of skin flap blood flow and viability in the pig

The dose-response effects of 6-h intravenous infusion of PGI 2 (0, 5, 10, 25 or 75 ng/kg/min) or PGE 1 (0, 25, 50, 100 or 300 ng/kg/min) on skin hemodynamics and viability were studied in 4 × 10 cm random pattern skin flaps (n=24) raised on both flanks of the pig. Infusion of PGI 2 or PGE 1 was started immediately after intravenous injection of a loading dose 30 min before skin flap surgery. PGI 2 infusion significantly (P<0.05) increased the total skin flap capillary blood flow at the dose of 10 ng/kg/min, compared with the control. However, the distance of blood flow along the skin flap from the pedicle to the distal end, i.e. perfusion distance, was not increased. Consequently, the length and area of skin flap viability was also not significantly increased. The effect of PGI 2 infusion on skin blood flow was biphasic. Specifically, higher doses (≥ 25 ng/kg/min) of intravenous PGI 2 infusion produced no beneficial effect on the skin flap capillary blood flow. PGI 2 infusion at the dose of 10 or 75 ng/kg/min did not significantly increased plasma renin activities or plasma levels of norepinephrine compared with the control, therefore the biphasic effect of PGI 2 on skin flap blood flow was not related to circulating levels of norepinephrine or angiotensen. Intravenous infusion of PGE 1 did not produce any therapeutic effect on the skin capillary blood flow in the random pattern skin flaps at all doses tested. At the dose of 300 ng/kg/min, the mean arterial blood pressure was 17% lower (P<0.05) than the control, but the skin capillary flow still remained similar to the control. It was concluded that intravenous infusion of PGI 2 or PGE 1 was not effective in augmentation of distal perfusion or length of skin viability in the porcine random pattern skin flaps. Drug treatment modalities for prevention or treatment of skin flap ischemia is discussed.

Nosocomial pneumonia in children

Nosocomial pneumonia continues to be a leading cause of fatal nosocomial infection in the United States. Although there are differences in pathogens by age, the importance of nosocomial pneumonia is apparent in the adult population as well as in the pediatric patient groups. The ability to diagnose these infections utilizing clinical suspicion and microbiologic/rapid diagnostic tests will allow the clinician to effectively treat nosocomial pneumonia in the critically ill patient. Unfortunately, these treatment modalities and preventive measures have not kept pace with our understanding of the pathogenesis of this infection. The pediatric patient population presents several unique and specific infection control, diagnostic and treatment problems for the practicing clinician. The appropriate infection control and isolation policies for specific viral and multiple antibiotic resistant bacterial isolates remains a cornerstone in the prevention of nosocomial pneumonia. The judicious use of empiric antibacterial chemotherapy remains important in the treatment of patients with nosocomial pneumonia. However, in the pediatric patient population the recognition that viral and fungal etiologies are important causes of nosocomial pneumonia challenge the clinician to apply the appropriate diagnostic and effective treatment regimens in pediatric nosocomial pneumonias. The epidemiologic data for the clinician's own institution in regards to etiologic causes of nosocomial pneumonia, drug susceptibility patterns as well as the seasonal and patient distribution of these infections are critical. Nosocomial pneumonia will continue to remain a significant cause of morbidity, mortality, and hospital cost in the United States in the upcoming decades. The advent of new rapid diagnostic testing and improved treatment modalities for effective therapy and prevention will be aided by the advent of immunologic therapy for these disease states.(ABSTRACT TRUNCATED AT 250 WORDS)

Trends in Oral Health in the Aging Population

Increased survival of the natural dentition, persistence of periodontal disease, deterioration of prior dental restorations, root surface caries, and continued incidence of oral cancer represent a complex of emerging oral health problems of the aged in the United States. Additional data on the epidemiology of oral mucous membrane syndromes will help to characterize the prevalence of these diseases in the aging population as well. Improvement in the utilization and accessibility of dental services by the aging cohorts will contribute to the prevention of oral disease in the future. Combined with the substantial growth in the size of this cohort of the population and alterations in the prevalence of these oral health status indicators, changes in the need for and projected utilization of professional oral health services can continue to be anticipated. Clinical research directed toward assessment of efficacy of treatment modalities for prevention of dental disease and maintenance of dental health are essential for the projection of dental health manpower needs for the future. This should also lead to the development of appropriate academic and training programs to meet the changing needs of the elderly.