Clinical reactivation after liver transplantation with an unusual minor strain of hepatitis B virus in an occult carrier.

Hepatitis B virus (HBV) DNA is detectable in a number of liver transplant candidates who are negative for hepatitis B surface antigen (HBsAg). After liver transplantation (LT), such patients may have molecular and/or serologic evidence of HBV replication. However, clinical disease from reactivation of occult HBV infection after LT has not been described. We report a patient who underwent LT for cryptogenic cirrhosis and had to be retransplanted twice for hepatic artery thrombosis. The patient was negative for HBsAg and positive for anti-hepatitis B core (HBc) and anti-HBs before all LT procedures and developed acute hepatitis B shortly after receiving the third graft. The HBV strain isolated at that time exhibited an unusual in frame insertion of a CAG motif within the HBV polymerase (HBV(INS+)). HBV(INS+) was detected retrospectively as a minor species in pretransplantation sera and the explanted native liver by insertion-specific polymerase chain reaction. This case in an occult HBV carrier shows that clinically apparent, endogenous reinfection of the graft may occur with minor HBV variants that are not detectable in pretransplantation samples by standard diagnostic procedures. This has implications for the analysis of sources of acute hepatitis B in patients after LT and possibly for consideration of antiviral prophylaxis in anti-HBc/anti-HBs/HBV DNA-positive patients.     

Movement disorders after intervertebral disc surgery: Coincidence or causal relationship?

It is well known that brain injury or central traumatic lesions may result in the subsequent appearance of movement disorders such as dystonia or tremor. The concept that peripheral lesions to neural structures may be involved in the pathogenesis of movement disorders has been discussed controversely but has gained more widespread acceptance only recently. Here, we report on 6 patients who developed movement disorders after spinal disc surgery. The movement disorders became manifest with a delay of 1 day to 12 months after surgery. Of the six patients, 4 underwent cervical disc surgery, and 2 patients were operated on for lumbar disc herniation; 2 patients presented with paroxysmal kinesigenic segmental dystonia, 1 patient with focal dystonia, 2 with unilateral tremor, and 1 with bilateral tremor. The appearance of the movement disorder was associated with persistent dermatomal or segmental pain. In all patients, the anatomic distribution of the movement disorder was related to the nerve root or spinal segment of the corresponding disc level and the manifestation was in close temporal relation to the surgery. We conclude that spinal disc surgery may be another, thus far neglected, cause for movement disorders. The postoperative pain syndrome in all patients should be considered as an important factor of pathogenesis. Overall, movement disorders associated with disc surgery appear to be rare, yet they may cause significant discomfort to the affected individual.     

Effects of graft pooling of foetal rat and mouse tissue and immunosuppression in the 6-hydroxydopamine rat model of Parkinson’s disease

 We employed intracerebral co-transplantation of foetal xenogeneic striatal mouse tissue and allogeneic rat substantia nigra into the adult rat brain to elucidate the effects of xenogeneic mouse graft on the function and survival of an allogeneic rat graft in 6-hydroxydopamine lesioned Sprague-Dawley rats. Foetal mouse striatum (STR) and rat substantia nigra (VM) were transplanted as non-pooled separate deposits or a pooled cell suspension with or without cyclosporin A (Cy A). Immunosuppressed recipients of pooled rat and mouse co-grafts showed a significantly better compensation of amphetamine-induced rotational behaviour compared with non-immunosuppressed animals with pooled rat and mouse co-grafts 3 and 6 weeks post-grafting.Tyrosine hydroxylase (TH) immunohistochemistry revealed a non-significant reduction in survival in pooled (1806.3±367.5 cells) rat and mouse co-transplants without immunosuppression compared with immunosuppressed pooled (3383.3±732.7 cells) animals with allo- and xenogeneic tissue and controls (3506.4±839.3 cells). Graft volumes were significantly reduced in pooled transplants without immunosuppression (0.1±0.026 mm³; ANOVA post-hoc SchefféF-test, P<0.0001) compared with immunosuppressed recipients (0.7±0.1 mm³) and controls (0.6±0.1 mm³). In non-pooled allo- and xenogeneic grafts without immunosuppression the survival rate of the TH-immunoreactive cells and graft volumes were reduced (2359.3±479.5 cells; 0.2±0.043 mm³) compared with immunosuppressed animals (2927.3±946.6 cells; 0.6±0.2 mm³) and controls (2701.1±693.8 cells; 0.3±0.1 mm³) without reaching a level of significance. Rejection of mouse tissue was observed in all non-immunosuppressed recipients. In summary: (i) continued immunosuppression yielded significant beneficial effects on function and beneficial effects on survival of pooled grafts with an immunogenetic disparity; (ii) the rejection of a xenogeneic graft component may compromise survival and function of other, allogeneic graft components; and (iii) transplantation of non-pooled allo- and xenogeneic tissues may result in a better survival of the graft compared with pooled cell suspensions. Received: 25 March 1996 / Accepted: 1 December 1996     

Prediction of the average skin temperature in warm and hot environments

The prediction of the mean skin temperature used for the Required Sweat Rate index was criticised for not being valid in conditions with high radiation and high humidity. Based on a large database provided by 9 institutes, 1999 data points obtained using steady-state conditions, from 1399 experiments and involving 377 male subjects, were used for the development of a new prediction model. The observed mean skin temperatures ranged from 30.7 °C to 38.6 °C. Experimental conditions included air temperatures (T _a) between 20 and 55 °C, mean radiant temperatures (T _r) up to 145 °C, partial vapour pressures (P _a) from 0.2 to 5.3 kPa, air velocities (v _a) between 0.1 and 2 m/s, and metabolic rates (M) from 102 to 620 W. Rectal temperature (T _re) was included in the models to increase the accuracy of prediction. Separate models were derived for nude (clothing insulation, I_cl, ≤0.2 clo, where 1 clo=0.155 m² · °C · W⁻¹, which is equivalent to the thermal insulation of clothing necessary to maintain a resting subject in comfort in a normally ventilated room, air movement=10 cm/s, at a temperature of 21 °C and a humidity of less than 50%) and clothed (0.6 ≤ I_cl ≤ 1.0 clo) subjects using a multiple linear regression technique with re-sampling (non-parametric bootstrap). The following expressions were obtained for nude and clothed subjects, respectively: T _sk=7.19 + 0.064T _a + 0.061T _r + 0.198P _a− 0.348v _a + 0.616T _re and T _sk=12.17 + 0.020T _a + 0.044T _r + 0.194P _a − 0.253v _a + 0.0029M + 0.513T _re. For the nude and clothed subjects, 83.3% and 81.8%, respectively, of the predicted skin temperatures were within the range of ±1 °C of the observed skin temperatures. It is concluded that the proposed models for the prediction of the mean skin temperature are valid for a wide range of warm and hot ambient conditions in steady-state conditions, including those of high radiation and high humidity. Accepted: 7 February 2000     

Experimental rat model for therapeutic retinal pigment epithelium transplantation—unequivocal microscopic identification of human donor cells by in situ hybridisation of human-specific Alu sequences

Transplantation of retinal pigment epithelial (RPE) cells is discussed as a possible therapeutic approach for retinal degeneration. Xenogeneic transplantation of human RPE cells in animal models has been studied extensively. Various methods have been used to identify the graft cells, but these methods interfere with cell behaviour so that the monitored physiological post-transplantation course may be influenced. In the present study, we applied a method for an unequivocal identification of the graft cells without interfering cell metabolism or behaviour using in situ hybridisation (ISH) of human specific Alu sequences. Visualisation of the strong extended nuclear signal of Alu sequences was much easier than that of the small nuclear signals of donor-specific sex chromosome probes. With Alu probe, even single graft cells can be identified and their development can be observed in short-term and long-term studies. With this procedure, we could prove that donor cells were injected correctly into the subretinal space by a special injection technique that we developed previously. In combination with immunohistochemistry, donor cells could be clearly discriminated from macrophages, which contained phagocytosed donor cell fragments. Application of these ISH methods for species-specific identification was valuable for follow-up-studies of RPE transplantation.     

Opioid activities of human β-casomorphins

Summary Opioid activities of human -casomorphin-4,-5,-7 and -8 and, for comparison, of the corresponding bovine -casomorphins were studied in the guinea-pig ileum preparation. Binding parameters, i.e. K _d -values and binding site concentrations, for the interaction of human and bovine -casomorphins with opioid receptors in rat brain homogenates were determined in inhibition experiments, using [³H]-(d-Ala², MePhe⁴, Gly-ol⁵)enkephalin, [³H]-(d-Ala², d-Leu⁵)enkephalin and [³H]ethylketazocin as -, - and -opioid receptor ligands. Analysis of binding data was performed using a non-linear curve fitting program. All -casomorphins examined displayed opioid activity. The affinity was highest for -receptors, less so for -receptors and lowest for -receptors. It is suggested that human -casomorphins might play a role as food hormones.     

Knochenheilung und dynamischer Interferenzstrom (DIC). —Erste vergleichende tierexperimentelle Studie an Schafen Teil II: Physikalische und chemische Ergebnisse

Zusammenfassung Zusätzlich wurden physikalische und chemische Untersuchungen über den Einfluß von dynamischem Interferenzstrom (DIC) auf die Knochenheilung durchgeführt, nachdem bei 24 Schwarzkopfschafen eine Querosteotomie des Radius vorgenommen worden war. Nach instabiler Osteosynthese wurde die Osteotomiezone wiederholt mit DIC verschiedener mA—Stärken behandelt. (Methodische Einzelheiten sind in Teil I beschrieben). Die Behandlung mit dynamischem Interferenzstrom führte im behandelten Gewebe zu steigenden Temperaturen, die von den mA—Stärken abhängig waren. Weiterhin wurden Zusammenhänge zwischen DIC—mA—Intensität und dem Vorkommen von Hydroxyprolin, einer kollagenspezifischen Aminosäure, nachgewiesen, welches eine erhöhte Calcifizierungsaktivität zur Folge hatte. Messungen des Calcium— und Phosphorgehaltes im neugebildeten Knochengewebe wiesen bei den mit DIC behandelten Tieren vollständige Mineralisation zu einem viel früheren Zeitpunkt als bei den unbehandelten, nach gleichem Verfahren operierten Kontrolltieren auf. Ob DIC einen spezifischen Reiz auf die Knochenneubildung heilender Knochen ausübt, ist noch nicht vollständig geklärt.

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Bone healing and Dynamic Interferential Current (DIC)

Summary In the course of supplementary physical and chemical investigations of the influence ofDynamicInterferential Current (DIC) on bone healing 24 black-head sheep were subjected to transversal osteotomy of the radius. After an instable osteosynthesis the site was exposed to repeated therapy with DIC of varying mA intensity. (Methodological details are described in part 1.) DIC therapy resulted in altering the temperatures in the treated tissue, dependent on the mA intensity. Further associations were verified between DIC intensity and the occurrence of hydroxyprolin, an amino acid specific collagen, which also reflected increased calcifying activity. Measurements of the calcium and phosphorus levels in the regenerated (newly forming) bone tissue documented full mineralization in the DIC-treated animals at a much earlier date than in the untreated controls that had undergone similar operations. Whether DIC specifically stimulates osteogenesis within healing bones is still unclear.

     

Cardiac structural and functional changes during long-term antihypertensive treatment with lacidipine and atenolol in the European Lacidipine Study on Atherosclerosis (ELSA)

OBJECTIVES: To evaluate and correlate the effects of long-term antihypertensive treatment on left ventricular (LV) mass and carotid structural changes in a large group of essential hypertensive patients, participating in the European Lacidipine Study on Atherosclerosis (ELSA). DESIGN: In four (Brescia, Glasgow, Naples and Pisa) of 23 centres participating in the ELSA study, an echocardiographic examination was performed at baseline and repeated, until the end of the 4-year study, in essential hypertensive patients, followed-up for carotid quantitative ultrasound examination of intima-media thickness (IMT), after random allocation to treatment with either lacidipine or atenolol (and added hydrochlorothiazide, as required for control of blood pressure). METHODS: M-mode, two-dimensional guided echocardiography was used to measure left ventricular (LV) wall thickness and dimensions, from which LV mass was calculated, using an anatomically validated formula (Penn Convention) and indexed to body surface area (left ventricular mass index, LVMI). The echocardiographic tracings were blindly evaluated in a single reading centre (Brescia). Bilateral IMT was measured at the site of common carotid and bifurcation far walls (CBMmax). RESULTS: At baseline, cardiac and carotid ultrasound scans were available in 278 patients (mean age 54 +/- 7 years, 57% males, 22% obese). A significant correlation was observed between baseline LVMI and CBMmax (r = 0.22, P < 0.001), independent of age. In multivariate analysis, CBMmax and mean 24-h pulse pressure were most strongly associated with baseline LVMI. A significant reduction in LVMI was observed both during lacidipine (n = 96) (-12.5% reduction) and atenolol (n = 78) (-13.9% reduction) treatments (up to 4 years) (P < 0.001 for both, without significant differences between treatments). Changes in LVMI were not related to changes in carotid wall thickness. In multivariate analysis, baseline LV mass and mean 24-h systolic blood pressure changes were significantly associated with changes in LV mass. CONCLUSIONS: In this large, long-term controlled study, antihypertensive treatment with atenolol or lacidipine was accompanied by a similar and significant decrease in LV mass. Treatment-induced changes in LV mass were related to baseline LV mass and changes in 24-h mean systolic blood pressure, without any correlation with changes in carotid structure. In the whole ELSA population, carotid IMT changes have been shown to be unrelated to blood pressure reduction, but significantly influenced by the type of antihypertensive treatment.     

Regulation of the tolerogenic function of steady‐state DCs

Dendritic cells (DCs) are master regulators of T‐cell responses. After sensing pathogen‐derived molecular patterns (PAMPs), or signals of inflammation and cellular stress, DCs differentiate into potent activators of naïve CD4⁺ and CD8⁺ T cells through a process that is termed DC maturation. By contrast, DCs induce and maintain peripheral T‐cell tolerance in the steady state, that is in the absence of overt infection or inflammation. However, the immunological steady state is not devoid of DC‐activating stimuli, such as commensal microorganisms, subclinical infections, or basal levels of proinflammatory mediators. In the presence of these activating stimuli, DC maturation must be calibrated to ensure self‐tolerance yet allow for adequate T‐cell responses to infections. Here, we review the factors that are known to control DC maturation in the steady state and discuss their effect on the tolerogenic function of steady‐state DCs.