T-cell subsets in autologous and allogeneic peripheral blood stem cell concentrates.

BACKGROUND AND OBJECTIVES: Regulatory T cells (Tregs) and other T-cell subsets are of importance in the setting of autologous and allogeneic stem cell transplantations. We conducted a study to assess the content of peripheral blood stem cell concentrates and related apheresis parameters in the autologous and allogeneic setting. MATERIAL AND METHODS: We characterized 53 donors, patients and peripheral blood stem cell concentrates (PBSC) regarding the content of CD45(+) cells, lymphocytes, CD3(+) cells, CD3(+) CD4(+) T cells, CD3(+) CD4(+) CD25(+) T cells, CD3(+) CD4(+) CD25(+) CD127(low/negative) Tregs and CD34(+) cells and calculated cell yields, recruitment factors and collection efficiency for all cell types. We compared allogeneic data with autologous data. RESULTS: Autologous PBSC show significantly lower concentrations of T-cell subsets compared to allogeneic PBSC (17,112/µl CD4(+), 14,858/µl CD4(+) CD25(+) and 1579/µl CD3(+) CD4(+) CD25(+) CD127(low/negative) Tregs in autologous compared to 65,539/µl CD4(+), 44,208(+) /µl CD4(+) CD25(+) and 5040/µl CD3(+) CD4(+) CD25(+) CD127(low/negative) Tregs in allogeneic PBSC, respectively), in contrast to CD34(+) concentrations (5342/µl CD34(+) in autologous compared to 2367/µl CD34(+) in allogeneic PBSC, respectively). Accordantly, all T-cell yields are lower in the autologous setting compared to allogeneic PBSC. However, recruitment factor and collection efficiency of all cell types are higher in autologous compared to allogeneic PBSC, but not all parameters differ significantly when groups are compared. CONCLUSION: T-cell subsets and especially Tregs are a substantial part of PBSC transplantation, as considerable recruitment during apheresis occurs. In large volume apheresis, the collection efficiency of Treg is comparable to that of CD34(+) cells, while recruitment factors are even higher.

Coagulation activation and fluid retention associated with the use of black cohosh: a case study.

Black cohosh is one of the most popular herbal therapies for premenstrual discomfort, hot flushes and other climacteric and menopausal symptoms. Most often, it is tolerated well. However, there are some recent reports on serious adverse events, probably associated with this complementary and alternative herbal medicine. We report a case of coagulation activation, fluid retention and transient autoimmune hepatitis most likely triggered by the use of black cohosh. Diagnostic procedures aimed to explain lower leg edema are not uncommon in the age group of women suffering from climacteric and menopausal symptoms. Therefore, black cohosh-induced fluid retention and coagulation activation should be considered in differential diagnosis, especially if thrombosis has been excluded.

Selenium and zinc in patients with acute and chronic uveitis.

Patients with chronic inflammation often show decreased serum levels of trace elements. This study aimed to investigate serum levels of selenium and zinc in patients with uveitis. Twenty-four patients (13 female, 11 male) with a mean age of 40.6 +/- 15.5 yr were included in this study. According to their underlying disease, they were divided into acute (n = 13) or chronic (n = 11) uveitis. Selenium and zinc determination was performed by atomic absorption spectroscopy in EDTA blood samples. Patients with acute or first-time uveitis showed selenium and zinc concentrations within the normal range. In contrast to this, patients with chronic recurrent uveitis tend to result in decreased selenium and zinc levels. Especially selenium showed a remarkable reduction in serum concentration below the normal range. Furthermore, there was a tendency to decreased trace element concentrations with increasing age. A sex dependency could not been found. Especially patients with chronic, recurring uveitis show remarkable decreased selenium concentration in the EDTA-blood. Further studies should investigate possible positive effects of therapeutic selenium and zinc supplementation in patients with chronic, recurrent uveitis.

[Selenium and cataract--risk factor or useful dietary supplement?]. / Selen und Katarakt--Risikofaktor oder sinnvolle Nahrungsergänzung?

BACKGROUND: The exact role of selenium in cataract development is still unclear. Both protective and toxic effects and mechanisms have been postulated in the past. Accordingly, the selenium contents in human lenses and blood sera in different forms of cataract were investigated. METHODS: 123 patients (76 female and 37 male) with a mean age of 69.8 years (range: 17 to 91 years) were enrolled in this study. Overall, 84 lenses (after ECCE) and 110 blood serum samples were investigated by atomic absorption spectroscopy. Interpretation of data was accompanied by exact preoperative investigations including Scheimpflug techniques. RESULTS: A significant increase of selenium content of the lenses was found with increasing lens opacification and colouration. Lenses with a mature cataract showed the highest selenium contents in the lens compared to other cataract forms. Opposite results were detected in blood serum. Lenses of diabetics showed already at a younger age changes in selenium content. Smokers showed both decreased selenium contents in the lens and decreased selenium concentration in blood serum. CONCLUSIONS: An obvious correlation between the type of cataract and selenium content of the lens seems to exist. The question by which mechanism selenium acts directly or by selenium-dependent enzymes acts lens opacification remains speculative up to now.

Closed-loop stimulation using intracardiac impedance as a sensor principle: correlation of right ventricular dP/dtmax and intracardiac impedance during dobutamine stress test.

Changes of the unipolar right ventricular impedance during the cardiac cycle are related to the changing content of blood (low impedance) and tissue (high impedance) around the tip of the pacing electrode. During myocardial contraction, the impedance continuously increases reaching its maximum in late systole. This impedance increase is thought to correlate with right ventricular contractility, and thus, with the inotropic state of the heart. In the new Inos2 DDDR pacemaker, integrated information from the changing ventricular impedance (VIMP) is used for closed-loop regulation of the rate response. The aim of this study was to analyze the effect of increasing dobutamine challenge on RV contractility and the measured impedance signals. In 12 patients (10 men, 68 +/- 12 years) undergoing implantation of an Inos2 DDDR pacemaker (Biotronik), a right ventricular pigtail catheter was inserted for continuous measurements of RV-dP/dtmax and simultaneous VIMP signals during intrinsic and ventricular paced rhythm. Then, a stress test with a stepwise increase of intravenous dobutamine (5-20 micrograms/kg per min) was performed. To assess the relationship between RV contractility and measured sensor signals, normalized values of dP/dtmax and VIMP were compared by linear regression. There was a strong and highly significant correlation between dP/dtmax and VIMP for ventricular paced (r2 = 0.93) and intrinsic rhythm (r2 = 0.92), although the morphologies of the original impedance curves differed quite substantially between paced and intrinsic rhythm in the same patient. Furthermore, VIMP correlated well with sinus rate (r2 = 0.82), although there were at least four patients with documented chronotropic incompetence. We conclude, that for intrinsic and ventricular paced rhythms sensor signals derived from right ventricular unipolar impedance curves closely correlate with dP/dtmax, and thus, with a surrogate of right ventricular contractility during dobutamine stress testing. Our results suggest that "inotropy-sensing" via measurement of intracardiac impedance is highly accurate and seems to be a promising sensor principle for physiological rate adaptation in a closed-loop pacing system.

[Local anesthetics in the aqueous humor in local anesthesia of the eye]. / Lokalanaesthetika im Kammerwasser bei örtlicher Betäubung am Auge.

Local anesthetics injected retrobulbarly are detectable in the aqueous humor. From 40 patients who received a total dose of 140 mg lidocaine, 15 mg bupivacaine, and 30 mg etidocaine, samples of aqueous humor were taken between 30 and 90 minutes after administration (average 57 minutes). The mean lidocaine concentration was 1.02 micrograms/ml, that of bupivacaine 0.075 micrograms/ml. Etidocaine, used only for facial nerve block in front of the ear, could not be detected in the aqueous humor. All three substances were found in the central venous blood. It therefore appears unlikely that any of them are transported via the blood-aqueous barrier, whether actively or passively. Local anesthetics can inhibit corneal cell proliferation and result in lens opacification when administered into the conjunctival sac. It may be that local anesthetics detected in the aqueous humor have similar effects resulting from contact with the cornea and lens.

Feline leukemia virus-induced immunodeficiency syndrome in cats as a model for evaluation of antiretroviral therapy.

Severe progressive immunodeficiency syndrome can be induced experimentally with a molecularly cloned isolate of feline leukemia virus (FeLV-FAIDS). The resultant disease syndrome is characterized by persistent viremia, lymphopenia, progressive weight loss, persistent diarrhea, enteropathy, and opportunistic infections. The onset of clinical immunodeficiency disease is prefigured by the replication of the FeLV-FAIDS variant virus in bone marrow and other tissues. The FeLV-FAIDS system can be used to evaluate antiviral agents which act on steps in the replication cycle which are conserved among retroviruses (e.g. reverse transcriptase, protease, assembly). The persistence and magnitude of viremia serves as a useful parameter in antiviral studies because it can be easily measured, presages the eventual development of immunodeficiency, and provides a convenient indicator of therapeutic efficacy either in preventing de novo FeLV infection or in reversing or ameliorating established infection. We describe here the evaluation of 2',3'-dideoxycytidine (ddC) against FeLV-FAIDS infection - both in vitro in cell culture assay systems and in vivo in cats administered ddC either via intravenous bolus dosage or via controlled release subcutaneous implants. We found that, although controlled release delivery of ddC inhibited de novo FeLV-FAIDS replication and delayed onset of viremia when therapy was discontinued (after 3 weeks), an equivalent incidence and level of viremia were established rapidly in both ddC-treated and control cats. The FeLV model, therefore, can be used to assess rapidly experimental single agent or combined antiviral therapies for persistent retrovirus infection and disease.

Laser raman spectroscopy of a complementary base pair in the Hoogsteen configuration.

Cocrystallization of m9Ade and m1Thy from water yielded crystals of te Hoogsteen base pair, m9Ade x m1Thy, as demonstrated by X-ray diffraction data. The Raman spectrum of the Hoogsteen base pair in the crystalline state was obtained and compared to the crystals of the individual monomers. Frequency changes between the heterobase dimer and both m9Ade and m1Thy are indicative of the base pairing interaction. Utilizing previously reported vibrational analyses for m9Ade, the frequency changes are clearly associated with modes involving the internal coordinates most sensitive to a Hoogsteen hydrogen bonding interaction. The spectrum of an equimolar mixture of e9Ade and ch1Ura in CHCl3 was also compared to the spectrum of the separate monomers in solution. The numerous frequency shifts and band intensity changes observed in the mixture from that of the individual monomers suggest a cyclic dimer is formed although the nature of the base pairing interaction is not clear.