Effect of photodynamic therapy on blood flow in normal and tumor vessels

The aim of this series of experiments was to determine the dynamic blood flow changes that occur in normal and neoplastic tissues during photodynamic therapy. Mice bearing SMT-F tumors and rats with transplanted chondrosarcomas were injected with graded doses of dihematoporphyrin ether. Studies of changes in single-vessel and whole-tumor blood flow were carried out with 630 nm light activation. A helium neon laser Doppler velocimeter was used to stimulate dihematoporphyrin ether, as well as to measure changes in flow velocity in both single-vessel and whole-tumor models. There was a reduction of flow velocity in all vessels and tumors in animals injected with 1 to 40 mg/kg dihematoporphyrin ether intraperitoneally. The extent of flow reduction was related to drug dose administered. Decreases in blood flow began within 10 seconds of light stimulation and were maximal within 5 minutes. Both normal and tumor vessels responded similarly. We conclude that photodynamic therapy leads to significant microcirculatory changes that may be pertinent to the mechanism of tumor necrosis.     

Nicotine applied by transdermal patch induced HSV-1 reactivation and ocular shedding in latently infected rabbits.

The identification of factors involved in herpes virus latency and reactivation is critical to a better understanding of the mechanisms essential to viral neuroinvasiveness and neurovirulence. Recurrent episodes of ocular herpes infections cause irreversible corneal scarring and are the primary cause of loss of vision due to an infectious agent in industrialized countries. In this study, we examined the ability of nicotine, a compound known to be involved in stress-associated immunomodulation and recognized as one of the most frequently used addictive agents, to induce ocular shedding in rabbits latently infected with herpes simplex virus type 1 (HSV-1) strain McKrae. New Zealand white rabbits latently infected with HSV-1 at 3-4 weeks post-inoculation were randomly divided into two groups. The corneas of all rabbits were free of lesions as verified by slit lamp biomicroscopy. One group received nicotine by transdermal patch (21 mg/day) for 20 days and the other group served as the control. Reactivation data were obtained by detection of virus in tear film collected by ocular swabbing performed concurrently with the administration of nicotine. Compilation of data from three separate experiments demonstrated that 16.5% (258/1560) of the swabs taken from rabbits treated with nicotine were positive for virus, compared with 8.3% (53/639) of swabs taken from controls. Rabbits receiving nicotine exhibited a significantly (P < 0.0001) higher rate of ocular shedding than controls. The concentration of nicotine in the serum was determined at various times (0-24 hrs) after new patch replacement. Peak (average) serum level of nicotine was obtained 8 hours after patch replacement and exhibited a broad range of values (0.233 microg/mL-6.21 microg/mL). These results suggest that an initial systemic exposure to nicotine significantly increases HSV-1 reactivation. Further studies are needed to reveal any effects of nicotine dependency and nicotine withdrawal on herpesvirus reactivation.     

Subclavian vein thrombosis: a continuing challenge

Subclavian vein thrombosis is a relatively uncommon but potentially morbid disease entity. To determine the frequency, cause, and best mode of treatment of this problem, we performed a chart review of all patients with a diagnosis of subclavian vein thrombosis at two major metropolitan hospitals during a 6-year period. A total of 40 patients were identified with subclavian vein thrombosis, which represented 3.5% of all venous thromboses detected during the 6-year period. No side or sex predilection was noted and the majority of patients were outpatients. The cause was fairly evenly divided among intravenous catheters (32%), anatomic abnormalities (45%), and carcinoma with postoperative radiation (22.5%). Despite the increasing use of the subclavian veins for pacemaker leads, hyperalimentation, and permanent intravenous access for chemotherapy, there has not been an increase in diagnosed subclavian vein thrombosis. Anatomic abnormalities with compression of the vein respond well to either heparinization or lytic therapy but require surgery if the venous abnormality persists. Treatment consisted of lytic therapy in 20%, heparinization in 55%, and elevation with removal of the central line in 25% of patients. All patients responded well to treatment, with a decrease in swelling and symptoms; no patient progressed to venous gangrene and only one (2.5%) had a documented pulmonary embolus. Medical treatment provides excellent long-term benefit in most cases unless complicated by an anatomic abnormality.     

Very low versus undetectable maternal serum alpha-fetoprotein values and fetal death

Very low maternal serum alpha-fetoprotein (MSAFP) levels (less than 10 ng/mL) are known to be associated with non-viable pregnancies, including conditions such as fetal death, molar pregnancies, and non-pregnancies. There has not been agreement, however, as to whether very low MSAFP levels indicate already existing fetal deaths or are actually predictive. We analysed 230 pregnancies with MSAFP levels less than 10 ng/mL from among 15,807 women (1.5 per cent) screened consecutively during a three-year period and identified 26 non-viable pregnancies, 22 of which were diagnosed sonographically as part of the screening process (17 missed abortions, 3 blighted ova, 2 non-pregnancies). Furthermore, 20 of these 22 pregnancies were associated with essentially undetectable MSAFP levels (less than 5 ng/mL). Our data indicate that pregnancies with MSAFP values less than 5 ng/mL are the group most strongly associated with fetal non-viability and that very low MSAFP values are not strongly predictive for fetal death.     

Gender difference in anaerobic capacity: role of aerobic contribution.

The purpose of this study was to evaluate effects of gender on anaerobic and aerobic contributions to high-intensity exercise. A group of 38 subjects (22 women, 16 men) performed modified Wingate tests against resistances of 0.086 kg kg-1 body mass (0.844 N kg-1) for women and 0.095 kg kg-1 body mass (0.932 N kg-1) for men. The aerobic contribution to total work performed was determined from breath-by-breath analyses of expired gases during each test. Total work in 30 s was 30% lower (Student's t test; P < 0.01) in women than men (211 +/- 5 J kg-1 versus 299 +/- 14 J kg-1). Aerobic contribution was only 7% lower (P = 0.12) in women than men (53 +/- 1 J kg-1 versus 57 +/- 2 J kg-1). The anaerobic component of the work performed, determined by subtraction of the aerobic component from total work in 30 s, was 35% lower (P < 0.01) in women than men (158 +/- 5 J kg-1 versus 242 +/- 15 J kg-1). It is concluded that, because women provide a relatively higher (P < 0.01) portion of the energy for a 30-s test aerobically than men (25% versus 20%), total work during a Wingate test actually underestimates the gender difference in anaerobic capacity between women and men.     

Cigarette smoking increases white blood cell aggregation in whole blood.

We studied the effect of chronic cigarette smoking on white blood cell aggregation, increased aggregation predisposes to microvascular occlusion and damage. Current smokers had significantly increased white blood cell aggregation when compared with non smokers. The presence of chronically activated white blood cells in current smokers may be relevant in the pathogenesis of ischaemic vascular disease.     

Central nervous system site of action for the hypotensive effect of clonidine in the cat

The purpose of our study was to determine whether clonidine exerts its centrally mediated hypotensive action at three sites that influence arterial pressure located in the medulla, specifically associated with the intermediate area of the ventrolateral medulla. The "intermediate area" lies approximately 1.5 mm caudal to the border of the trapezoid body (caudal border) and 4 mm lateral to the midline. One of the sites that influence arterial pressure lies in the nucleus reticularis rostroventrolateralis. The second site lies in close proximity to the rostral part of the nucleus reticularis lateralis (rLRN) and also near the A1 area. The third site lies in the most rostral area and medial to the nucleus reticularis rostroventrolateralis, that is in the nucleus paragigantocellularis lateralis. Unilateral microinjections of 0.22 and 0.43 nmol of clonidine into the rLRN produced dose-dependent decreases in arterial pressure. The 0.43 nmol dose of clonidine had no effect when unilaterally or bilaterally microinjected into either the nucleus reticularis rostroventrolateralis or into the nucleus paragigantocellularis lateralis. Microinjection of the alpha-2 adrenoceptor antagonist, idazoxan (16.6 nmol), unilaterally into rLRN had no effect per se, but prevented the hypotensive effect of a subsequent microinjection of clonidine. Similarly, bilateral microinjection of idazoxan into rLRN counteracted the hypotensive effect of i.v. administered clonidine. These data indicate that clonidine acts at alpha-2 adrenoceptors in the rLRN to produce hypotension.     

Seniors' assessment of their health and life satisfaction: the case for contextual evaluation.

Health care professionals have been puzzled by the highly positive statements on health and life satisfaction made by seniors, particularly when compared to professionally collected data. In 1987-1988, a stratified, random sample of 520 seniors living independently in the community (70-99 years) were interviewed in their own homes. The above response pattern again held. However, it was apparent that opinions on life satisfaction vary with type of health problem. Content analysis of the spontaneous remarks made by the participants indicates that the overall, current, and anticipated levels of satisfaction expressed were associated significantly with the historical perspective or lifeview of the participants, and with their state of health. Utilizing the theoretical concept "sense of coherence" gives direction to understanding these phenomena.     

Neuropsychological and biomedical assessment of depression-dementia syndromes

Evaluating the clinical significance of cognitive dysfunction in patients who exhibit signs of both depression and dementia is one of the more formidable challenges in psychiatry. This article reviews cognitive dysfunction associated with depression, the concept of "pseudodementia," and the syndromal phenomenology of coexisting depression and Alzheimer's-type dementia. The state of the art in neuropsychologic, electroencephalographic, metabolic, and neuroradiographic techniques for evaluating dementia and depression syndromes will be discussed, as will implications for the treatment of such patients.     

Immunosuppression with cis-Platinum (II) Diammino-dichloride: Effect on Antibody Plaque-Forming Spleen Cells

A new antitumor compound, cis-platinum (II) diamminodichloride, suppressed antibody plaque-forming cells in C(3)H mice when given in a single dose of 10 mg per kg of body weight within 2 days before or after sensitization.