Recovery of slow skeletal muscle after injury in the senescent rat

We studied the contractile, histological and biochemical characteristics of regenerating slow (soleus) muscles of aged rats and the effect of IGF-1 treatment on these parameters. Regenerating soleus muscles were studied 21 days after myotoxic injury. In senescent rats (24 month old), the in situ isometric maximal tetanic force (P0), resistance to fatigue (T20%P0) and shortening speed with an afterload of 20%P0 (SS20%P0) were lower (p<0.05) in regenerating soleus muscles as compared to uninjured controlateral soleus muscles. Moreover, the expression of type 1 myosin heavy chain (MHC-1) was decreased by injury in the soleus muscles of senescent rats (p<0.05). Furthermore, a single injection of IGF-1 (3 microg) into the soleus of senescent rats only slightly increased the level of sarcoplasmic reticulum type 2 Ca(2+)-ATPase in regenerating soleus muscles (p<0.01). Contrary to senescent animals, regenerating soleus of adult rats (10 month old) did not present significantly lower P0 and MHC-1 expression than uninjured controlateral muscles (p>0.05). In conclusion, the regeneration of a slow muscle is more uncompleted 3 weeks after myotoxic injury in senescent rats than in adult rats. It cannot be made more effective by a single injection of IGF-1 into the senescent slow muscle.     

Evolution of the Old World Arenaviridae and their rodent hosts: generalized host-transfer or association by descent?

Ten scenarios optimizing the number of cospeciation events between the phylogenies of the Old World Arenaviridae (OWA) and their murine hosts are tested while attempting to answer the following questions. Does the coevolutionary model explain their respective distribution? What kind of evolutionary events could have most frequently contributed to the horizontal and/or vertical transmission of the OWA? How to define secondary hosts and to interpret their existence in the evolutionary process? Where are the geographical origins of the OWA? All scenarios support the "diffuse coevolution" hypothesis previously proposed for the OWA, in which parallel phylogeny and/or host switches on closely related hosts can be considered as the most common mechanisms of transmission. The scenarios allow defining more precisely the concepts of principal and secondary hosts. Such scenarios also suggest that the diversity of the viruses and their rodent hosts could be higher than currently expected and that cophylogeny could have been underestimated. The "diffuse coevolution" hypothesis permits to interpret the transfer of the viruses to distant hosts as a result of a disturbance in their regular mode of dispersion, which could match with the periods of emergence as human parasites. The comparison of the viral phylogeny with the host cladogram also suggests that the viruses parasitized the Murinae before several lineages became distinct and spread in Africa. This supposes that the origin of the arenaviruses has to be found out of Africa.     

Inadequate pharmacotherapy in patients with obsessive-compulsive disorder

OBJECTIVE: To determine the adequacy of drug treatment for patients with obsessive compulsive disorder (OCD). DESIGN: Retrospective. METHOD: One hundred and fifty outpatients with OCD, admitted at the University Medical Centre in Utrecht, the Netherlands, were evaluated for severity as measured with the 'Yale-Brown obsessive compulsive scale' (Y-BOCS). RESULTS: At the intake, 35% of the patients used no medication, 58% used an antidepressant, less than 1% an antipsychotic and 6% a benzodiazepine. The average active dose was taken by 12% of the patients, 5% took the maximum dosage and 41% too low a dosage. Consequently, 6 out of the 10 patients used the correct medication (antidepressant) and less than 20% used a sufficiently high dosage. Of the patients, 38% had never previously taken antidepressants, 31% had previously used one antidepressant, 17% two different antidepressants and 12% at least three different antidepressants; 13% had taken the antidepressant at the highest dosage, 18% at the average active dosage and 31% at too low (thus ineffective) a dosage. This means that from a pharmacotherapeutic viewpoint not more than 1 in 8 patients had had an adequate treatment history. CONCLUSION: The results of this study show that only 1 in 8 OCD patients were treated appropriately.     

Plasma levels of total and free tissue factor pathway inhibitor (TFPI) as individual pharmacological parameters of various heparins

The release of circulating tissue factor pathway inhibitor (TFPI) into plasma by heparins is thought to contribute to their overall antithrombotic activity. In the presented study in healthy volunteers, we measured the heparin-induced increase of circulating total and free TFPI antigen and the aXa- and aIIa activity after subcutaneous (s.c.) injection of 9000 aXa-U of four different heparins: unfractionated heparin (UFH) (13.0 kDa), a medium molecular weight (MW) heparin with a narrow MW range (HF) (10.5 kDa), certoparin (6.0 kDa) and enoxaparin (4.5 kDa). Based on the administration of equi-active aXa doses, certoparin induced the highest increase in total TFPI determined as AUC (p <0.01). The lowest effect was observed for UFH (p <0.0001). However, the AUC of released free TFPI significantly increased in the order: enoxaparin < UFH < certoparin < HF, showing MW dependency with the exception of UFH. Comparing the effects of equi-gravimetric heparin doses, the MW dependency becomes even more pronounced. The mismatch of UFH may be due to its poor bioavailability, which becomes obvious from its low ex vivo aXa activity. In contrast to the TFPI releasing potency, the ex vivo aXa activity continuously decreased with increasing MW. Although the ex vivo aIIa activity of the heparins increased in the same order like the release of free TFPI, there was no clear correlation. This is attributed to the fact that the aIIa activity of heparin is not only dependent on the MW, but, in contrast to its TFPI releasing effect, also on the percentage of material with high affinity to AT. In conclusion, besides the aXa- and aIIa activity, the TFPI releasing effect of heparins is an additional parameter of their individual pharmacological profile.     

MRI of unusual lesions in the internal auditory canal

We report the MRI findings of six unusual lesions of the internal auditory canal: three haemangiomas, one lipoma, one metastasis and one traumatic neuroma. We compare the findings to those of 20 intracanalicular schwannomas. We noted the site and size of the tumour, its signal intensity, borders and the homogeneity of enhancement were studied on T1-weighted images before and after intravenous contrast medium and T2-weighted images. Most schwannomas were homogeneous lesions, isointense on T1- and T2-weighted images, and strongly enhancing. Spontaneous high signal on T1-weighted images, heterogeneous contrast enhancement and extranodular enhancement were helpful for recognising lesions other then schwannomas; site, size and signal on T2-weighted images were not. All the haemangiomas had a specific pattern of contrast enhancement, with an anterior core intensely enhancing portion and a posterior portion which enhanced moderately or not at all. Received: 4 November 1999/Accepted: 19 July 2000     

Effect of intravenous tropisetron on modulation of pain and central hypersensitivity in chronic low back pain patients

The activation of 5-hydroxytryptamine-3 (5-HT-3) receptors in spinal cord can enhance intrinsic spinal mechanisms of central hypersensitivity, possibly leading to exaggerated pain responses. Clinical studies suggest that 5-HT-3 receptor antagonists may have an analgesic effect. This randomized, double-blind, placebo-controlled crossover study tested the hypothesis that the 5-HT-3 receptor antagonist tropisetron attenuates pain and central hypersensitivity in patients with chronic low back pain. Thirty patients with chronic low back pain, 15 of whom were women (aged 53 ± 14 years) and 15 men (aged 48 ± 14 years), were studied. A single intravenous injection of 0.9% saline solution, tropisetron 2 mg, and tropisetron 5 mg was administrated in 3 different sessions, in a double-blind crossover manner. The main outcome was the visual analogue scale (VAS) score of spontaneous low back pain before, and 15, 30, 60, and 90 minutes after drug administration. Secondary outcomes were nociceptive withdrawal reflexes to single and repeated electrical stimulation, area of reflex receptive fields, pressure pain detection and tolerance thresholds, conditioned pain modulation, and area of clinical pain. The data were analyzed by analysis of variance and panel multiple regressions. All 3 treatments reduced VAS scores. However, there was no statistically significant difference between tropisetron and placebo in VAS scores. Compared to placebo, tropisetron produced a statistically significant increase in pain threshold after single electrical stimulation, but no difference in all other secondary outcomes was found. A single-dose intravenous administration of tropisetron in patients with chronic low back pain had no significant specific effect on intensity of pain and most parameters of central hypersensitivity.     

The impact of critical point drying with liquid carbon dioxide on collagen-hydroxyapatite composite scaffolds

Collagen-hydroxyapatite composites for bone tissue engineering are usually made by freezing an aqueous dispersion of these components and then freeze-drying. This method creates a foamed matrix which may not be optimum for growing cell colonies larger than a few hundred micrometres due to the limited diffusion of nutrients and oxygen, and the limited removal of waste metabolites. Incorporating a network of microchannels in the interior of the scaffold which may permit the flow of nutrient-rich media has been proposed as a method to overcome these diffusion constraints. A novel three-dimensional printing and critical point drying technique previously used to make collagen scaffolds has been modified to create collagen-hydroxyapatite scaffolds. This study investigates the properties of collagen and collagen-hydroxyapatite scaffolds and whether subjecting collagen and hydroxyapatite to critical point drying with liquid carbon dioxide results in any changes to the individual components. Specifically, the hydroxyapatite component was characterized before and after processing using wavelength-dispersive X-ray spectroscopy, X-ray diffraction and infrared spectroscopy. Critical point drying did not induce elemental, crystallographic or molecular changes in the hydroxyapatite. The quaternary structure of collagen was characterized using transmission electron microscopy and the quarter-staggered array characteristic of native collagen remained after processing. Microstructural characterization of the composites using scanning electron microscopy showed the hydroxyapatite particles were mechanically interlocked in the collagen matrix. The in vitro biological response of MG63 osteogenic cells to the composite scaffolds were characterized using the Alamar Bluetrade mark, PicoGreentrade mark, alkaline phosphate and Live/Deadtrade mark assays, and revealed that the critical point dried scaffolds were non-cytotoxic.     

The influence of polymorphonuclear leukocytes and macrophages on the growth of lymphocytes and fibroblasts in vitro.

The influence of polymorphonuclear leukocytes (PMNL) and macrophage plasma, nuclei and lysosome extracts have been tested on lymphocytes and fibroblasts growth in vitro. The stimulatory activity of PMNL lysosomes has been shown on lymphocyte and fibroblast growth. The macrophage lysosomes have shown a similar but lower activity. The role of lysosomes has been suggested in reparation and wound healing processes, presumably in inflammatory cell infiltrated regions.     

Prognostic factors in patients with endocrine tumours of the duodenopancreatic area

Background—Thedevelopment of endocrine tumours of the duodenopancreatic area (ETDP)is thought to be slow, but their natural history is not well known. Theaim of this study was to determine the factors that influence survivalof patients with ETDP.
Patients/Methods—Eightytwo patients with ETDP (44 non-functioning tumours, 23 gastrinomas,seven calcitonin-secreting tumours, four glucagonomas, threeinsulinomas, one somatostatinoma) followed from October 1991 to June1997 were included in the study. The following factors wereinvestigated: primary tumour size, hormonal clinical syndrome, livermetastases, lymph node metastases, extranodular/extrahepatic metastases, progression of liver metastases, local invasion, complete resection of the primary tumour, and degree of tumoral differentiation. The prognostic significance of these factors was investigated by uni-and multi-variate analysis.
Results—Twenty eightpatients (34%) died within a median of 17 months (range 1-110) fromdiagnosis. Liver metastases (p =0.001), lymph node metastases (p = 0.001), progression of liver metastases (p<0.00001), lack of completeresection of the primary tumour (p = 0.001), extranodular/extrahepaticmetastases (p =0.001), local invasion (p = 0.001), primary tumour size3 cm (p = 0.001), non-functioning tumours (p = 0.02), and poortumoral differentiation (p = 0.006) were associated with anunfavourable outcome by univariate analysis. Multivariate analysisidentified only liver metastases (risk ratio (RR) = 8.3; p<0.0001),poor tumoral cell differentiation (RR = 8.1; p = 0.0001), and lack ofcomplete resection of the primary tumour (RR = 4.8; p = 0.0007) asindependent risk factors. Five year survival rates were 40and 100% inpatients with and without liver metastases, 85 and 42% in patientswith and without complete resection of primary tumour, and 17 and 71%in patients with poor and good tumour cell differentiation respectively.
Conclusion—Livermetastases are a major prognostic factor in patients with ETDP.Progression of liver metastases is also an important factor which mustbe taken into account when deciding on the therapeutic approach. Theonly other independent prognostic factors are tumoral celldifferentiation and complete resection of the primary tumour.

Keywords:prognostic factors; survival; endocrine tumours; gastrinoma; cell differentiation; liver metastases