Mechanical influence of the extrafusal muscle on the static behaviour of deefferented primary muscle spindle endings in cat

Summary In 16 anesthetized cats 24 afferents of deefferented primary muscle spindle endings from the extensor digitorum longus muscle (EDL) were functionally isolated and their sensitivity to static stretches was tested. Each spindle was carefully located within the EDL using direct focal stimulation. Muscle spindle endings with poor static length sensitivity of stretch were always found in the most peripheral parts of the muscle fibre bundles, near to the aponeurotic and tendineous insertions. Endings having good static sensitivity to stretch were exclusively found in more central portions of the muscle fibre bundles. Using a photographic method, the alterations in the distance between designated points on the muscle surface ware measured during maintained muscle stretch. Only medial portions were markedly extended, whereas little or no increases in length occurred in peripheral parts of the muscle fibre bundles.Quantitatively, a direct relationship was found between the lengthening of those muscle portions, in which the muscle spindles were localized, and the receptors' sensitivity to maintained stretch.Preliminary reports of some of the results were given at the 1. Wissenschaftliche Tagung der Deutschen Gesellschaft für medizinische Physik (Rieboldet al., 1970; Robrechtet al., 1970) and at the Muscle-Spindle Symposium of the Anatomical Society of Great Britain and Ireland, April 4–6, 1974, at the University of Durham (Henatschet al., 1974). The results were presented in more detail in Meyer-Lohmann's Habilitationsschrift (1972).Supported by a grant from the Deutsche Forschungsgemeinschaft (Schwer-punktprogramm Rezeptorphysiologie).     

Assessing debt-to-health swaps: a case study on the Global Fund Debt2Health Conversion Scheme

The Debt2Health Conversion Scheme of the Global Fund to Fight AIDS, Tuberculosis and Malaria is used to reassess a range of recent initiatives that propose debt relief in exchange for spending in the health sector. The experience with debt swaps in the mid 1990s was far from positive, and recent improved insight in the economics of debt relief suggests extreme caution. We argue that the recent spade of debt swap proposals, even if targeting countries and debt titles that fall outside current major international debt relief mechanisms, share most of the design faults of previous initiatives. Proposals such as Debt2Health do not constitute efficient vehicles to increase net transfers to poor countries, to reduce the economic disadvantages of indebtedness, or to strengthen public health systems of partner countries. For debt relief to constitute a valuable mechanism to provide aid, it should be designed as a large-scale and comprehensive operation, with spending earmarked to broad country-established priorities, and reinforce rather than undermine national implementation systems.     

Phase behaviour and solvent diffusion in the system poly(methyl methacrylate)/methanol

The diffusion of methanol into atactic poly(methyl methacrylate) is controlled by the interference of the demixing curve with the concentration dependence of the glass transition. Below the temperature of intersection of the two curves, the sample is always in the glassy state and diffusion is of case II. Above this temperature, absorption of methanol brings the sample through the glassy state into the solution state. With increasing temperature, diffusion changes from case II into Fickian. The maximum degree of absorption is determined by the position of the demixing curve in the temperature‐concentration plane.     

Continuous local intrahippocampal delivery of adenosine reduces seizure frequency in rats with spontaneous seizures

Purpose: Despite different treatment options for patients with refractory epilepsy such as epilepsy surgery and neurostimulation, many patients still have seizures and/or drug‐related cerebral and systemic side effects. Local intracerebral delivery of antiepileptic compounds may represent a novel strategy with specific advantages such as the option of higher local doses and reduced side effects. In this study we evaluate the antiepileptic effect of local delivery of adenosine in the kainic acid rat model, a validated model for temporal lobe epilepsy. Methods: Fifteen rats, in which intraperitoneal kainic acid injection had induced spontaneous seizures, were implanted with a combination of depth electrodes and a cannula in both hippocampi. Cannulas were connected to osmotic minipumps to allow continuous hippocampal delivery. Rats were freely moving and permanently monitored by video‐EEG (electroencephalography). Seizures were scored during 2 weeks of local hippocampal delivery of saline (baseline), followed by 2 weeks of local adenosine (6 mg/ml) (n = 10) or saline (n = 5) delivery (0.23 μl/h) (treatment). In 7 of 10 adenosine‐treated rats, saline was also delivered during a washout period. Results: During the treatment period a mean daily seizure frequency reduction of 33% compared to the baseline rate was found in adenosine‐treated rats (p < 0.01). Four rats had a seizure frequency reduction of at least 50%. Both nonconvulsive and convulsive seizures significantly decreased during the treatment period. In the saline‐control group, mean daily seizure frequency increased with 35% during the treatment period. Conclusions: This study demonstrates the antiseizure effect of continuous adenosine delivery in the hippocampi in rats with spontaneous seizures.     

Suppression of hippocampal epileptic seizures in the kainate rat by Poisson distributed stimulation

Purpose: Hippocampal deep brain stimulation (DBS) is an experimental therapy for patients with pharmacoresistant temporal lobe epilepsy (TLE). Despite the successful clinical application of DBS, the optimal stimulation parameters are undetermined. We evaluate the efficacy of a new form of DBS, using continuous stimuli with Poisson distributed intervals (Poisson distributed stimulation, PDS) in the kainate (KA) rat model, a validated model for human TLE. Methods: Status epilepticus was elicited by injection of KA (i.p.). After development of spontaneous seizures, rats were implanted with hippocampal DBS‐ and depth electroencephalography (EEG) electrodes. After baseline EEG monitoring, one group of rats (n = 13) was treated with PDS and a second (n = 11) received regular high frequency stimulation (HFS) at 130 Hz. Stimulation intensity was 100 μA below the threshold for induction of epileptiform EEG activity. Results: Stimulation intensity was significantly lower for PDS (156 ± 20 μA) than HFS (207 ± 23 μA; p < 0.02). Seven (54%) of 13 rats treated with PDS and 5 (45%) of 11 rats treated with HFS experienced a significant reduction in seizure frequency. In PDS‐improved rats, seizure frequency was reduced to 33% (p < 0.01) of baseline value and in HFS‐improved rats to 50% (p < 0.01). After termination of PDS, seizure rate returned to baseline value. Discussion: Continuous hippocampal PDS significantly reduces the number of spontaneous seizures. Compared to regular HFS, there is a slightly larger number of improved rats and a larger efficacy at a considerably lower stimulus intensity. The first two observations leave room for optimization, whereas a lower intensity is beneficial for battery life.     

Differences in the stimulating capacity of immobilized anti-CD3 monoclonal antibodies: variable dependence on interleukin-1 as a helper signal for T-cell activation.

Monoclonal antibodies to the CD3 antigen on human T lymphocytes have been shown to induce accessory cell-dependent T-cell activation. One function of the accessory cells is cross-linking of CD3 by Fc receptor-binding of the anti-CD3 antibodies. Whether additional accessory signals are still required when anti-CD3 is presented in immobilized form is controversial. In the present study we stimulated purified human T cells with several anti-CD3 monoclonal antibodies, which were immobilized by coating the culture wells with goat anti-mouse IgG. A first group of immobilized anti-CD3 antibodies (anti-Leu-4, UCHT1, anti-T3, WT32 and 64.1) induced vigorous T-cell proliferation in the complete absence of monocytes, even when anti-interleukin-1 beta antiserum was added to the cultures. Other immobilized anti-CD3 antibodies (OKT3, WT31) required interleukin-1 beta in order to induce T-cell proliferation. However, when OKT3 was immobilized by direct coating of the culture wells with OKT3, it was also able to induce accessory cell-independent production of interleukin-2 and T-cell proliferation. Interleukin-1 beta further enhanced the interleukin-2-dependent proliferative response and it could provide help to induce proliferation at doses of immobilized OKT3 which, by themselves, were insufficient for full T-cell activation. We conclude that the requirement for interleukin-1 beta to induce interleukin-2-dependent proliferation of T cells when stimulated with anti-CD3 antibodies is not absolute, but depends on the CD3 epitope recognized, on the way of antibody presentation, on the antibody concentration and on other, still undefined, characteristics of the monoclonal antibodies used.     

The spleen and haemolysis: evaluation of the intrasplenic transit time

The mean intrasplenic red cell transit time (STT) and the slow mixing splenic red cell volume (SSV) have been measured in patients with hereditary spherocytosis (HS), autoimmune haemolytic anaemia (AIHA) and lymphoproliferative disease (LD). There was an inverse relationship between the mean red cell life span (MRCLS) and the STT in HS (r = -0.96, P less than 0.001) and in AIHA (r = -0.90, P less than 0.001). No such relationship existed in LD. The size of the spleen and the SSV were not related to the severity of haemolysis. Our data offer strong evidence for the conditioning effect of the spleen on HS- and AIHA red cells and suggest that the STT is an index of the adverse effect of the spleen on red cells in patients with HS or AIHA.     

Comparison of the Efficacies of Three Fluoroquinolone Antimicrobial Agents, Given as Continuous or Pulsed-Water Medication, against Escherichia coli Infection in Chickens

This study compared the efficacy of continuous or pulsed-water medication with enrofloxacin, danofloxacin, and sarafloxacin in eight groups of 90 chicks each by using an infectious bronchitis virus-Escherichia coli model of colisepticemia. The model produced lesions of typical those occurring in birds with severe colisepticemia; for the infected, nonmedicated birds the mortality was 43.5% and the morbidity was 89%, 17.8% of birds had severe lesions, and the birds had a mean air sac lesion score of 2.58. This experiment showed that continuous dosing and pulsed dosing are clinically equivalent. However, for all fluoroquinolones studied, there was a trend for the continuously mediated birds to have lower mortality and less severe disease than birds receiving pulsed doses. Compared with infected, nonmedicated controls, only birds continuously medicated with enrofloxacin had a significantly lower morbidity (32%), and only birds medicated with enrofloxacin and danofloxacin (continuous and pulsed treatments) had significantly lower mortality (6.7 and 11.0% and 16.8 and 19.2% for continuous and pulsed treatments with enrofloxacin and danofloxacin, respectively). A significantly lower proportion of birds only in the groups medicated with enrofloxacin had severe lesions (for birds receiving continuous and pulsed treatments, 2.2 and 6.7%, respectively). Birds medicated with any of the three fluoroquinolones (continuous and pulsed treatments) except pulsed-water treatment with sarafloxacin had significantly reduced mean air sac lesion scores compared with the scores for nonmedicated birds (air sac lesion scores, 0.60 and 0.83, 1.38 and 1.63, and 1.80 and 2.05 for birds receiving continuous and pulsed treatments with enrofloxacin, danofloxacin, and sarafloxacin, respectively). The performance of the birds that survived the challenge or that recovered after receiving medication was not compromised compared to the performance of noninfected birds. Enrofloxacin was more efficacious than either danofloxacin or sarafloxacin for the treatment of colisepticemia in chickens by medication in drinking water. Similarly, danofloxacin appeared to be more effective than sarafloxacin in treating colisepticemia.