Chondrocyte-seeded hydroxyapatite for repair of large articular cartilage defects. A pilot study in the goat

The aim of this study was to evaluate the potential for restoration of a large cartilage defect in the goat knee with hydroxyapatite (HA) loaded with chondrocytes. Isolated chondrocytes were suspended in fibrin glue, seeded on top of the HA, and then the composite graft was implanted in the defect. After transplantation, cell behaviour, newly synthesised matrix and the HA-glue interface were assessed histologically after 2, 4, 12, 26 and 52 weeks. Special attention was paid to the incorporation process of HA in the subchondral bone and interactions between this biomaterial and the fibrin-glue-chondrocyte suspension. Chondrocytes in the glue proved to survive the transplantation procedure and produced new metachromatically stained matrix two weeks after implantation. The glue-cell suspension had penetrated the superficial porous structure of the HA. Four weeks after surgery, islands of hyaline-like cartilage were observed at the HA-glue interface. A layer of fibrous tissue was formed surrounding the HA graft, resulting in a relatively instable fixation of the HA in the defect. This instability of the graft in the defect, possibly together with early weight bearing, resulted in a gradual loss of the newly formed hyaline cartilage-like repair tissue. Progressive resorption of the HA occurred without any sign of active bone remodelling from the host site. One year after surgery part of the defect which extended down to the cancellous bone had been predominantly restored with newly formed lamellar bone. Only small HA remnants were still present at the bottom of the original defect. Resurfacing of the joint had occurred with fibrocartilaginous repair tissue. The absence of adequate fixation capacity of the HA near the joint space resulted in a relative instability of the graft with progressive resorption. Therefore, HA is not a suitable biomaterial to facilitate the repair of large articular cartilage defects.     

The molecular biology of polycystic kidney disease

In recent years there have been a number of developments in polycystic kidney disease (PKD) research. The genes associated with the predominant forms of autosomal dominant PKD have been cloned, and the gene associated with a mouse model for autosomal recessive PKD has been identified and characterized. Other studies have yielded new information regarding the role of the epidermal growth factor receptor gene in promoting renal cyst formation. In this review article we summarize recent published data on the molecular genetics of autosomal dominant and autosomal recessive PKD and provide a working model of how multiple genes participate in the PKD disease pathway.     

Antiviral properties of 3-quinolinecarboxamides: a series of novel non-nucleoside antiherpetic agents

Despite the long history in medicine, the pathophysiological mechanism(s) of seasonal affective disorder (SAD) remain largely unknown. By employing a meta-analytic methodology, the authors of this study attempted to verify the validity of different pathophysiological mechanism(s) proposed for SAD. The findings showed that for phototherapy of medium light intensity, a combination of morning-evening therapy regime yielded the best therapeutic effect, and the antidepressant effect of the morning-evening light regime was superior to a single pulse of light administered at other times of day. Furthermore, the data showed that the antidepressant effect of a single pulse of light was similar for morning, midday, and evening light. These findings supported the photon-count hypothesis and refuted the proposed photoperiod, melatonin, and phase-shifting models of SAD.     

Amyotrophic lateral sclerosis and viruses

Amyotrophic lateral sclerosis (ALS) is a disease of unknown etiology. A number of theories have been pursued to explain the cause of ALS, including viral infection. This review examines the evidence implicating viruses in the pathogenesis of ALS, as well as current studies of naturally occurring and experimental models of virus-induced motor neuron disease (MND). The association of viruses and ALS remains to be established. The study of animal models of virus-induced MND may shed light on processes relevant to the etiology of ALS.     

Improvement in the laboratory methods of assessing the safety of the of the pertussis component of DPT vaccine adsorbed]

The mouse paw edema test and the tests for the determination of leukocytosis-stimulating and histamine-sensitizing activity are reproducible if standard samples are used and the properties under test are evaluated with reference to the characteristics of standard samples. The standard character of the weight gain test on mice is also enhanced if all conditions of the test are standardized. The most accurate information on the toxicity of the pertussis component of adsorbed DPT vaccine can be obtained if a single human dose (0.5 ml) is injected to mice and the toxicity of the vaccine is estimated from the weight gain registered in the test mice and the control animals. The use of standard samples in each test makes it possible to observe the conditions for controlling the toxicity of the tested preparations.     

Impaired dynamic cerebral autoregulation in carotid artery stenosis

BACKGROUND AND PURPOSE: If it could be determined whether cerebral blood flow can be maintained (autoregulated) during transient falls in arterial blood pressure, we might be able to identify patients with carotid stenosis who are at risk of stroke. However, conventional methods of determining autoregulation in such patients are invasive and/or expensive. METHODS: We used a new noninvasive method to estimate dynamic cerebral autoregulation in 27 patients with carotid stenosis and 21 age-matched normal controls. After a stepwise fall in arterial blood pressure, we determined the rate of rise of middle cerebral artery blood flow velocity compared with that of arterial blood pressure. We compared the method with a conventional method of determining cerebral hemodynamics, CO2 reactivity. RESULTS: Autoregulatory index (ARI) was significantly reduced in middle cerebral arteries ipsilateral to a stenosed/ occluded carotid artery: mean +/- SD 3.3 +/- 2.2 compared with normal controls (6.3 +/- 1.1; P < .0001) and nonstenosed carotid arteries in patients (5.9 +/- 2.1; P < .002). A subgroup of patients with severe impairment was identified. ARI returned to normal after carotid endarterectomy was performed. In a number of cases, ARI was impaired in the presence of CO2 reactivity. CONCLUSIONS: This simple technique allows identification of impaired autoregulation in patients with carotid artery disease. It may allow identification of patients at risk from transient falls of blood pressure as may occur at the onset of antihypertensive therapy and during surgery. It may allow a subgroup of patients with asymptomatic carotid stenosis who are at risk of hemodynamic stroke to be identified.