Post-cancer fatigue is not associated with immune activation or altered cytokine production.

BACKGROUND: Prolonged fatigue after cancer treatment is common. The pathophysiology of such post-cancer fatigue (PCF) is unknown, although cross-sectional studies suggest increased pro-inflammatory cytokine production. This study investigated the association between cytokine levels and fatigue from the time of treatment to 12 months later. PATIENTS AND METHODS: A representative nested case-control series was derived from a prospective cohort of women treated for early-stage breast cancer, including 13 PCF cases and 15 matched control subjects who recovered uneventfully. Serum levels and in vitro production of the cytokines interleukin (IL)-1α, IL-2, interferon (IFN)-γ, IL-4, IL-6, IL-10, IL-12, and tumour necrosis factor (TNF)-ß were measured by multiplex immunoassay in longitudinally collected samples. In addition, serum levels of neopterin and the anti-inflammatory regulators, IL-1 receptor antagonist, sIL-6R, and sTNF-rII, were assayed by enzyme-linked immunosorbent assay. Flow cytometric analysis of activated leukocyte subsets was performed. RESULTS: No significant differences in any of these parameters were found between cases and control subjects. Cytokine levels and symptoms showed no clear correlation pattern. CONCLUSION: The findings in this well-characterised subject group argue against the notion that PCF is mediated by peripheral inflammation.

Spotted dermopathy in a diabetic patient due to insulin allergy.

A rare case of diabetic patient who developed multiple cutaneous hyperpigmented spots following bovine isophane (NPH) insulin injection is described here.

Blood volume determination by the carbon monoxide method using a new delivery system: accuracy in critically ill humans and precision in an animal model.

OBJECTIVE: To evaluate accuracy and repeatability of blood volume determinations made by the carbon monoxide method, using a ventilator-driven administration system. DESIGN: Prospective within-patient comparison, using simultaneous measurements by two methods to determine accuracy. Prospective laboratory investigation in animals to estimate repeatability. SUBJECTS: For accuracy: Nineteen ventilated critically ill patients in a university hospital intensive care unit. For repeatability: Six anesthetized, mechanically ventilated normovolemic pigs because this is impossible to perform in humans. INTERVENTIONS: In the accuracy study, a small mass of carbon monoxide was administered via a closed breathing system and arterial blood samples were taken from existing cannulas. In the repeatability study, an intramuscular sedative was given, followed by an inhalational anesthetic induction and mechanical ventilation via a tracheal tube. Left axillary artery and external jugular vein cannulas were sited. Anesthesia was maintained using an intravenous infusion. Five sequential circulating hemoglobin and blood volume estimations were made using the carbon monoxide method. MEASUREMENTS AND MAIN RESULTS: The small carboxyhemoglobin increase produced by uptake of a small, known mass of carbon monoxide was used to estimate the circulating blood volume. Simultaneous measurement, using 51Cr-labeled red blood cells, was performed. Twenty measurements were made in 19 patients. The bias (mean difference between blood volume measurements by the two methods) was 397 mL (5.53 mL x kg(-1)) +/-415 mL (+/-5.95 mL x kg(-1)); the limits of agreement (mean difference +/-2 SD) were -433 mL and 1227 mL (-6.36 mL x kg(-1) and 17.42 mL x kg(-1)). Therefore, 95% of expected differences will lie between these limits. The mean blood volume was 75.8 mL x kg(-1) in the animals. The coefficient of variation of repeated estimates was 9.49%. Mean circulating hemoglobin mass was 7.31 mmol with a coefficient of variation of 10.18%. The mean hemoglobin concentration, by co-oximetry, was 5.014 mmol x L(-1), coefficient of variation, 2.99%. CONCLUSION: This arrangement is a potential bedside method of estimating blood volume and circulating hemoglobin mass. We have rendered the technique more acceptable clinically by creating a ventilator-driven administration system.

Preparation and testing of cyclosporine microsphere and solution formulations in the treatment of polyarthritis in rats.

We prepared a microencapsulated sustained-release formulation of cyclosporine A (CsA) and compared its efficacy to the solution formulation of cyclosporine A (Sandimmune, Sandoz) in an attempt to improve the treatment of rheumatoid arthritis. Microspheres containing cyclosporine were prepared with poly(lactic co-glycolic acid) (PLGA), a polymer in the submicron particle range of 0.22-0.8 micron. Studies were carried out to determine uptake rates and mechanisms of lymphocyte inhibition mediated by macrophages containing CsA microspheres in vitro. The results of these studies were used to establish whether lower doses of the microencapsulated cyclosporine could be used in in vivo studies in the polyarthritic rat model for rheumatoid arthritis. In vitro dissolution testing revealed that CsA was released extremely slowly from microspheres for up to 48 hr (0.002%). Radiolabeled 3H CsA was incorporated into some PLGA microspheres or the microspheres were labeled using a 99mTc radioligand when needed, and radiolabeling efficiency was consistently above 50%. Uptake studies at various microsphere-to-macrophage ratios (1:1, 1:5, 1:10) were carried out using 99mTc radiolabeled microspheres and macrophages obtained from normal and polyarthritic rats. Normal macrophages behaved significantly differently from arthritic macrophages throughout the study. Arthritic macrophages cause increased amounts of CsA to be released (68% of the dose) into the culture medium past 24 hr compared to normal macrophages (48% of the dose). This factor may account for the significantly increased inhibition (68.2%) of mixed lymphocyte culture proliferation in the presence of arthritic macrophages containing CsA-loaded PLGA microspheres over normal macrophages (48.2%) that were pre-exposed to the same microsphere dose. The equivalent quantity of CsA as that contained in the microspheres when placed in solution or the same quantity of blank PLGA microspheres caused decreased levels of lymphocyte inhibition when compared to the effects of CsA microspheres in macrophages of normal cells, but significantly decreased levels of inhibition in arthritic cells. From the in vivo studies, it is evident that CsA microspheres, even at low dose levels, were highly effective in inhibiting polyarthritis in rats.

Morphological and histochemical effects of 2,3,7,8-tetrachlorodibenzo-p dioxin (TCDD) on marmoset (Callithrix jacchus) testes.

The testes of marmosets (Callithrix jacchus), which had been treated with a single dose of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) (0.3 microgram to 10 micrograms/l kg body weight (BW)) were studied after 7 days using morphological and histochemical techniques. Light microscopic and electron microscopic examination revealed decreased intercellular contact in the germinal epithelium, as indicated first by enlarged intercellular spaces between the Sertoli's cells and between the Sertoli's cells and neighboring germ cells (i.e., spermatogonia and preleptotene spermatocytes), particularly in the basic compartment of the germinal epithelium. Second, decreased intercellular contact was indicated by the accumulation of premature spermatids and spermatocytes in the tubular lumen after TCDD treatment. The Sertoli's cells exhibited an increased amount of lipids, phagolysosomes, and vacuoles in their cytoplasm. Spermatids were frequently affected by TCDD, particularly during early spermiogenesis. These alterations included vacuolization of the cytoplasm and the development of additional germinal vesicles. This special effect on spermiogenesis became even more evident quantitatively by determination and counting of tubular stages in semithin sections. Tubular determination on the basis of the appearance of spermatids revealed that the ratio of tubular stages I to III became lower and that of stages V to VII became higher, dose dependently, indicating a maturation stop at the beginning of spermiogenesis caused by TCDD treatment. After TCDD treatment, Leydig's cells were morphologically unaffected, but histochemical investigations revealed decreased activity of 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD). The sensitivity of the applied methods was different in view of the level of unaffection. The effect of Leydig's cells, as indicated by the decreased activity of 3 beta-HSD, had already been found at a dose of 1 microgram/kg BW TCDD, whereas clear-cut morphological and morphometrical effects were seen at 3 micrograms/kg BW for the first time. Moreover, with the special effect on spermiogenesis in marmoset monkeys, the findings demonstrate that the toxicity of TCDD on testicular morphology is species specific.

Electric field detection with a piezoelectric polymer-jacketed single-mode optical fiber.

The detection of electric fields with a piezoelectric polymer-jacketed single-mode optical fiber is proposed. The polymer-jacketed fiber is incorporated as the sensing arm of a Mach-Zehnder fiber-optic interferometer. Calculations are presented for the fractional phase change/unit electric field strength of monochromatic light propagating in a poly(vinylidene fluoride)-jacketed fiber as a function of jacket radius. A minimum detectable field strength of 6.0 microV/m is estimated for a 1-km length of jacketed fiber.