Effect of 2-chloroadenosine on cerebrovascular reactivity to hypercapnia in newborn pig.

The effect of local administration of vasodilative concentrations of the adenosine receptor agonist 2-chloroadenosine (2-CADO) on the hyperemic responses of the pial and parenchymal microcirculations to graded hypercapnia was determined. The cranial window and brain microdialysis-hydrogen clearance techniques were utilized in two groups of isoflurane-anesthetized newborn pigs to measure changes in pial diameters and local CBF, respectively, in response to graded hypercapnia in the absence and presence of 2-CADO. Progressive size-dependent dilations of pial arterioles [small = 41 +/- 7 microns (mean +/- SD), intermediate = 78 +/- 13 microns, and large = 176 +/- 57 microns in diameter] occurred in response to graded hypercapnia alone (PaCO2 = 58 and 98 mm Hg) and to superfusions of 2-CADO (10(-5) M) during normocapnia; the magnitude of the dilative response to each of these stimuli was inversely proportional to vessel size. When hypercapnia was induced concomitantly with 2-CADO superfusion, the dilative effects of each stimulus were directly additive. Similarly, local microdialysis infusion of 10(-5) M 2-CADO, which doubled CBF during normocapnia, did not affect the hyperemic response of the parenchymal circulation to graded hypercapnia (PaCO2 = 69 and 101 mm Hg). Our findings are consistent with the participation of adenosine in the mediation of cerebral hypercapnic hyperemia. If, however, adenosine is not involved in this dilative response, our results indicate that concomitant vascular and neuromodulatory actions induced by adenosine receptor stimulation do not affect the mechanism responsible for the hypercapnic hyperemic response.     

Analysis of Implantation in Assisted Reproduction Through the Use of Serial Human Chorionic Gonadotropin Measurements

Purpose: Our purpose was to examine implantation of singleton pregnancies achieved following various assisted reproductive technologies (ARTs) through the appearance and rising titers of serum human chorionic gonadotropin (hCG) levels. Methods: A total of 114 singleton pregnancies resulting from in vitro fertilization and intrauterine insemination was analyzed. Patients were divided into five groups according to the type of ovarian stimulation protocol [gonadotropin stimulation with/without the use of gonadotropin-releasing hormone agonist (GnRHa), long protocol, or flare-up technique] and to the day of embryo transfer (day 2 or day 3 after oocyte retrieval). Serial serum hCG levels were measured between 10 and 25 days after fertilization and log-transformed. Linear regression analyses were performed and extrapolated to hCG = 10 mIU/ml (hCG ₁₀ ), which was used as an estimate of detectable implantation. The slopes of the regression lines were used to estimate the rising speed of hCG. Results: There were no significant differences in the days of hCG in maternal serum to reach 10 mIU/ml (implantation) or in the slopes of the regression lines for all five studied groups. Conclusions: The appearance of hCG in maternal serum was used to assess the time of clinically detectable implantation. Furthermore, because hCG production is a marker of trophoblastic activity, its serum doubling time was used as an indicator of embryo quality. Results showed that in various ART protocols with and without GnRHa, there were no significant differences in implantation time or embryo quality. Embryo development in early pregnancy follows a preprogrammed-timing schedule and depends mainly on the embryonic age of the health, successfully implanted conceptus.     

Effect of temperature in focal ischemia of rat brain studied by 31P and 1H spectroscopic imaging

³¹P, ¹H and lactate spectroscopic imaging was used to evaluate the effects of hypothermia on focal cerebral ischemia produced by middle cerebral artery occlusion. The effects on high energy phosphate metabolism, pH, lactate and NAA were investigated in 24 spontaneously hypertensive rats subjected to either permanent or transient ischemia. Under either normothermic (37.5°C) or hypothermic (32°C) conditions, with permanent 6-h occlusion, there was little difference between groups in either the NMR measurements or the volume of infarction. In animals that underwent 3 h of ischemia followed by 12 h of reperfusion, the ischemic changes in lactate, pH, NAA, and high-energy phosphate returned toward control values, and there was a protective effect of hypothermia (infarct volume of 211 ± 26 and 40 ± 14 mm³ in normothermic and hypothermic groups, respectively). Thus, hypothermia did not ameliorate the changes in lactate, pH, NAA, or high energy phosphate levels occurring during ischemia, however, during reperfusion there was an improvement in both the recovery of these metabolites and pathological outcome in hypothermic compared with normothermic animals.     

Indwelling epidural catheters for pain control in gynecologic cancer patients

Seven patients with severe pain caused by an advanced, incurable gynecologic malignancy were treated with an indwelling epidural catheter connected to an implantable subcutaneous port through which morphine was infused. There were few major complications associated with insertion or maintenance of the system. The average usage was 60 days, although the system functioned continuously for 6 months in one patient. Pain distribution in these women ranged from the upper abdomen to the lower extremities. All patients, including one with liver metastases, reported good to excellent pain control with the epidural narcotics. Two subjects with upper abdominal pain occasionally required supplemental oral oxycodone, but the other five patients had adequate pain relief with the epidural system alone. The indwelling epidural system provides excellent analgesia for patients with advanced, incurable gynecologic cancer.     

Selective inactivation of viruses in the presence of human platelets: UV sensitization with psoralen derivatives.

Inactivation of viruses in blood products requires that the method employed display selectivity in its action for viral elements while not affecting the biological entity of interest. Several methods have been developed for the treatment of human plasma or products derived from human plasma. An effective technique for the treatment of the cellular components of blood has been lacking, in part due to the inability to develop agents capable of selectively targeting viral agents in the milieu of cellular material. In this paper, we examine the behavior of a group of viral sensitizers designed to be added to cellular samples and be activated upon exposure to UVA light. Upon activation, these agents are capable of disrupting nucleic acids of the virus in a manner that renders them inactive for proliferation. The selectivity observed in this inactivation is determined by the chemical structure of the sensitizer, which can be varied to increase viral killing capacity while diminishing collateral damage to cellular and protein constituents.     

Efficacy of short‐term oral cobalamin therapy for the treatment of cobalamin deficiencies related to food‐cobalamin malabsorption: A study of 30 patients

Background: It has been suggested that oral cobalamin (vitamin B₁₂) therapy may be an effective therapy for treating cobalamin deficiencies related to food‐cobalamin malabsorption. However, the duration of this treatment was not determined. Patients and method: In an open‐label, nonplacebo study, we studied 30 patients with established cobalamin deficiency related to food‐cobalamin malabsorption, who received between 250 and 1000 μg of oral crystalline cyanocobalamin per day for at least 1 month. Endpoints: Blood counts, serum cobalamin and homocysteine levels were determined at baseline and during the first month of treatment. Results: During the first month of treatment, 87% of the patients normalized their serum cobalamin levels; 100% increased their serum cobalamin levels (mean increase, +167 pg/dl; P < 0.001 compared with baseline); 100% had evidence of medullary regeneration; 100% corrected their initial macrocytosis; and 54% corrected their anemia. All patients had increased hemoglobin levels (mean increase, +0.6 g/dl) and reticulocyte counts (mean increase, +35 × 10⁶/l) and decreased erythrocyte cell volume (mean decrease, 3 fl; all P < 0.05). Conclusion: Our findings suggest that crystalline cyanocobalamin, 250–1000 μg /day, given orally for 1 month, may be an effective treatment for cobalamin deficiencies not related to pernicious anemia.     

Effects of inotropes on human leucocyte numbers, neutrophil function and lymphocyte subtypes

We have investigated the effects of inotropes with different adrenergic receptor specificity on differential white cell count, lymphocyte subtypes and neutrophil function in healthy volunteers. Six healthy, male volunteers were enrolled into this randomized, placebo-controlled pilot study. Each volunteer was studied on four separate occasions during a 2-h infusion of various agents, and for 2 h after stopping the infusion. The agents investigated were adrenaline 0.1 microgram kg-1 min-1, dobutamine 5 micrograms kg-1 min-1, dopexamine 2 micrograms kg-1 min-1 and 5% glucose 0.5 ml kg-1 h-1. Venous blood was sampled at 0, 30, 120 and 240 min. Haemodynamic monitoring was continued throughout the study. Full blood count, white cell differential count and enumeration of lymphocyte subtypes were performed. Neutrophil function tests included chemoluminescence, and assessment of neutrophil chemotaxis, phagocytosis and adhesion. The Wilcoxon signed rank test was used to compare differences between placebo and active drugs at each time compared with baseline. There was a significant increase in white cell count, lymphocyte count and neutrophil count with adrenaline, and a small but significant decrease in these variables with dobutamine and dopexamine. These changes were also apparent for absolute CD3+, CD4+ and CD8+ lymphocyte counts. Neutrophil respiratory burst in response to f-methionyl-leucyl-phenylalanine increased significantly only with adrenaline at 30 min (P = 0.046). There were no other significant changes in tests of neutrophil function. Infusion of inotropes was associated with changes in white cell numbers, lymphocyte subtypes and neutrophil respiratory burst. In healthy volunteers, adrenaline had effects different from those of dobutamine and dopexamine. The clinical relevance of such effects requires further investigation in critically ill patients.      

Molluscum contagiosum occurring in an epidermal cyst--report of 3 cases.

We present three unusual cases of molluscum contagiosum occurring in epidermal cysts. All of them are asymptomatic, elevated, oval nodules diagnosed clinically as epidermal inclusion cyst or prurigo nodularis. Histology showed true epidermal cysts containing molluscum bodies throughout the cyst wall and some type of laminated material within the cyst itself. The lesion, in all three cases developed in the pubic area of young adult men.