Molecular diagnosis of skin-associated infectious agents.

Molecular pathology is a relatively new division of laboratory medicine that detects, characterizes, and/or quantifies nucleic acids to assist in the diagnosis of human disease. Molecular assays augment classic areas of laboratory medicine by providing additional diagnostic data more quickly or by providing results that are not obtainable using standard methods. For these reasons, molecular pathology is the most rapidly growing area in laboratory medicine.

Tobacco use and skin disease.

BACKGROUND: The primary objective of this review is to evaluate the mucocutaneous manifestations of tobacco use. METHODS: Computerized literature searches were conducted for English language articles related to skin/mucous membrane disease and use of tobacco. The primary criterion for assessing data quality and validity was the demonstration of a causal relationship between tobacco use and skin/mucous membrane disease. RESULTS: This review of the literature shows that a number of disorders and diseases of the skin and mucous membranes are related to tobacco use. CONCLUSIONS: Since millions of persons use tobacco despite its well publicized relationship to increased mortality, knowledge of the mucocutaneous morbidity associated with tobacco use may help physicians in counseling their patients.

Antiviral agents.

The potential severity of many viral infections and the lack of appropriate treatment for these diseases have been a source of endless frustration and helplessness for clinicians. The newly developed field of antiviral therapy is expanding at an astounding rate, with new discoveries each day. Although physicians are not yet able to cure many of the viral infections, such as HSV, HIV, and CMV, a means of controlling them is available. It is hoped that the research and investigations currently under way will lead to a future era of antiviral drugs that will be able to eradicate these diseases.

Reduction of postherpetic neuralgia in herpes zoster.

BACKGROUND: Persons 50 years of age and older are not only at increased risk of developing herpes zoster, they are also more likely to suffer the long-term morbidity of postherpetic neuralgia (PHN). PHN is pain persisting after the rash of herpes zoster has healed. PHN affects at least 40% of all herpes zoster patients over age 50 and over 75% of herpes zoster patients over age 75; PHN is the single most common neurologic condition in elderly patients. OBJECTIVE: The objective of this review is to evaluate interventions that may reduce or even eliminate PHN. No single therapy has been consistently effective for PHN. The most effective approach appears to be with the use of antiviral therapy early in the course of herpes zoster. The goals of ongoing studies in herpes zoster are to develop interventions that will further reduce the symptoms of PHN and/or to eliminate PHN by prophylaxis using the varicella vaccine. CONCLUSIONS: Reduction of PHN can best be achieved with the use of antiviral medication early in the course of herpes zoster; other classes of drugs are minimally effective in treating established PHN. Widespread use of the varicella vaccine may lead to secondary reductions in PHN in the distant future.

Human papillomavirus, smoking, and cancer.

BACKGROUND: The effect of smoking on human papillomavirus (HPV) activity and subsequent dysplasia and neoplasia remains controversial. OBJECTIVE: To determine any reported effects of smoking on either HPV activity or HPV-related dysplasia/cancer using retrospective analysis of the literature from 1966 through 1998 via Toxline and PubMed to search for "smoking," "papillomavirus," and "cancer." CONCLUSION: Several recent large studies demonstrated that smoking was associated with a greater incidence of cervical, vulvar, penile, anal, oral, and head and neck cancer in a dose-dependent fashion, while other studies did not show any correlation between smoking and cervical dysplasia after multivariate adjustment. Recent studies have also indicated that smoking may be more closely related to high-grade lesions of the cervix and vulva. These data provide evidence of an association between HPV, smoking, and cancer. Progression of dysplasia likewise seems to be associated with smoking. Several groups have attempted to discern whether the connection between smoking and cervical cancer is from local immunosuppression and/or from direct carcinogenic effects.

Thoracic duct function in fetal, newborn, and adult sheep.

We measured thoracic duct lymph flow rate versus outflow pressure in 7 chronically catheterized adult sheep and in 6 newborn lambs and compared our results to data previously obtained from 10 fetal sheep. In fetal sheep the thoracic duct lymph flow rate was 34.5 +/- 17.2 ml/hr or 11.7 +/- 6.0 ml/kg/hr. Fetal thoracic duct lymph flow deviated from baseline between 8 and 12 torr outflow pressure and lymph stopped at 18 +/- 2.5 torr. In newborn lambs the thoracic duct lymph flow rate was 49.5 +/- 22.0 ml/hr or 7.4 +/- 2.5 ml/kg/hr. The range of outflow pressures over which newborn lymph flow deviated from baseline was between 15 and 18 torr and lymph flow stopped at 26.2 +/- 6.4 torr. Adult sheep thoracic duct lymph flow rate was 130 +/- 74 ml/hr or 2.3 +/- 1.3 ml/kg/hr. Adult lymph flow deviated from baseline between 25 and 35 torr and stopped at an outflow pressure of 41.7 +/- 6.7 torr. The ability of the thoracic duct to return lymph against an outflow pressure improves with maturation. However, lymph flow rate corrected for body weight is greatest in immature animals. The higher corrected lymph flow rate in conjunction with the decreased ability to pump against an outflow pressure may help account for immature animals predisposition for edema.

Hydrops in fetal sheep from rapid induction of anemia.

We operated on 14 singleton fetal sheep at 126 +/- 3 d gestation and produced nonimmune anemia in 12 of them to study the mechanisms responsible for hydrops. Two fetuses served as controls. Partial exchange transfusions were performed daily to lower the hematocrit while we measured arterial blood gas tensions; Hb concentration; oxygen saturation; arterial oxygen content; aortic, central venous, and umbilical venous pressures; heart rate; plasma protein concentration; and colloid osmotic pressure. Hydrops developed in six of the fetuses and did not develop in six others, although both groups were anemic to the same degree, had similar total amounts of blood withdrawn based on kilograms of dry weight, and had similar dry weights. The fetuses who had hydrops became anemic more rapidly than the nonhydropic fetus (5.2 +/- 1.9 versus 8.3 +/- 2.7 d; p < 0.05) and had more blood exchanged each day (197 +/- 56 versus 113 +/- 28 mL/kg dry body wt/d; p = 0.008). Umbilical venous pressures increased in both hydropic and nonhydropic fetuses, but the central venous pressure became elevated only in the hydropic fetuses. Changes in heart rate, arterial pH and blood gas tensions, arterial oxygen content, plasma protein concentration, colloid osmotic pressure, and aortic pressure were similar in both groups. At autopsy the hydropic fetuses had 78 +/- 47 mL of ascites and 20 +/- 26 mL of pleural fluid. The water content of the hydropic fetuses and of the hydropic fetuses' placentas was greater than that of the nonhydropic fetuses. We conclude that a more rapid development of anemia is associated with hydrops in fetal sheep.(ABSTRACT TRUNCATED AT 250 WORDS)

Feasibility of hepatocellular transplantation via the umbilical vein in prenatal and perinatal lambs.

Hepatocellular transplantation has previously been performed in experimental animals by infusion of hepatocyte suspensions into the spleen or portal venous system. Cells injected into these sites flow to the liver and engraft within the hepatic parenchyma. We designed this study to evaluate the feasibility of hepatocellular transplantation through the umbilical vein in the prenatal or perinatal periods. Allogeneic sheep hepatocytes were harvested, stained with the vital fluorescent dye DiI, and injected into the umbilical vein of fetal lambs at 85% gestation and term. Hemodynamic studies performed to assess the physiological impact of transplantation on the recipient animal demonstrated that the procedure was well tolerated. No significant short-term complications were encountered and no lesions were found by conventional histological examination at necropsy 1-17 days after transplantation. Engrafted cells were identified within the liver by fluorescent microscopy and flow cytometry in 4/7 animals constituting 1.2-5% of the hepatocyte population. Fluorescent cellular material with the morphology of hepatocytes, noncellular material, and fluorescent phagocytic cells were seen occasionally in other organs including lung, brain, adrenal, and placenta. These studies demonstrate the feasibility of performing hepatocellular transplantation in the fetus via the umbilical vein in experimental animals.

Thoracic duct lymph flow in fetal sheep with increased venous pressure from electrically induced tachycardia.

The intent of this study was to investigate thoracic duct lymph flow, as it is related to the development of hydrops fetalis during rapid atrial pacing. We studied 6 fetal sheep at 128 +/- 6 days of gestation who had chronically placed thoracic duct catheters, aortic and superior vena cava catheters, and atrial pacing electrodes. Atrial pacing at 317 beats/min caused an elevation in central venous pressure from a baseline value of 3 Torr to 7 Torr without affecting pH, arterial blood gas tensions, aortic blood pressure, total protein concentration, or colloid osmotic pressure, although there was a small rise in hematocrit. The thoracic duct lymph flow rate at baseline was 41 +/- 6 ml/h. After atrial pacing for 6 h, the lymph flow rate as measured over at least three consecutive 10-min intervals, and presumably the transvascular fluid filtration rate, increased to 67 +/- 7 ml/h if it was collected at an outflow pressure of 3 Torr, equal to the venous pressure prior to the onset of atrial pacing. However, if the lymph was collected instead at an outflow pressure of 7 Torr, equal to the actual venous pressure measured with rapid atrial pacing, then the lymph flow rate diminished to 48 +/- 5 ml/h. This difference in lymph flow secondary to the increase in venous pressure could account for a maximum of 19 ml/h of edema that accumulates in fetal interstitium and body cavities with atrial pacing.(ABSTRACT TRUNCATED AT 250 WORDS)

The effect of outflow pressure upon thoracic duct lymph flow rate in fetal sheep.

Edema develops when lymph does not return to the venous circulation at a rate equal to the rate of capillary filtration. Fetal sheep develop edema as well as an increased central venous pressure while undergoing atrial pacing at 320 beats per min. We hypothesized that the increased central venous pressure augmented the appearance of fetal edema by impairing the return of thoracic duct lymph to the venous circulation. To investigate this hypothesis, we studied the effect of outflow pressure upon thoracic duct lymph flow in 10 unanesthetized fetal sheep who had low resistance lymph catheters placed in the cervical thoracic duct near its junction with the left jugular vein. After the ewe and fetus recovered for 5 d, we altered the outflow pressure of the lymph catheter by adjusting its height with respect to amniotic fluid pressure and measured the resultant change in thoracic duct lymph flow rate. We found that lymph flow rate was constant over the range of outflow pressures (central venous pressures) normally encountered but decreased in a linear fashion at pressures greater than 0.68 kPa (5.1 torr). Lymph flow stopped at an outflow pressure of 2.40 kPa (18 torr). The data points are best fit by two lines obtained by a piecewise linear regression rather than a single line obtained from a linear regression. We conclude that fetal thoracic duct lymph flow is sensitive to elevations in outflow pressure. Lymph flow begins to diminish at outflow pressures corresponding to central venous pressures commonly encountered in pathologic conditions and may augment the appearance of fetal edema.