Autologous chondrocyte implantation. Culture in a TGF-beta-containing medium enhances the re-expression of a chondrocytic phenotype in passaged human chondrocytes in pellet culture

An increasing number of patients are treated by autologous chondrocyte implantation (ACI). This study tests the hypothesis that culture within a defined chondrogenic medium containing TGF-beta enhances the re-expression of a chondrocytic phenotype and the subsequent production of cartilaginous extracellular matrix by human chondrocytes used in ACI. Chondrocytes surplus to clinical requirements for ACI from 24 patients were pelleted and cultured in either DMEM (Dulbecco's modified eagles medium)/ITS+Premix/TGF-beta1 or DMEM/10%FCS (fetal calf serum) and were subsequently analysed biochemically and morphologically. Pellets cultured in DMEM/ITS+/TGF-beta1 stained positively for type-II collagen, while those maintained in DMEM/10%FCS expressed type-I collagen. The pellets cultured in DMEM/ITS+/TGF-beta1 were larger and contained significantly greater amounts of DNA and glycosaminoglycans. This study suggests that the use of a defined medium containing TGF-beta is necessary to induce the re-expression of a differentiated chondrocytic phenotype and the subsequent stimulation of glycosaminoglycan and type-II collagen production by human monolayer expanded chondrocytes.     

Cost and health status analysis after autologous chondrocyte implantation and mosaicplasty: a retrospective comparison

OBJECTIVES: Chondral defects of the knee cartilage are prevalent. Autologous chondrocyte implantation (ACI) and mosaicplasty are increasingly used to treat symptomatic knee defects. This study assessed the costs and health status outcomes after ACI and mosaicplasty. METHODS: Patients were eligible to participate in this cross-sectional study if they received ACI or mosaicplasty at the Royal National Orthopaedic Hospital between 1997 and 2001 or were on a waiting list for ACI. Secondary-care resource use was collected to 2 years postoperatively using a resource collection proforma. Participants responded to postal questions about sociodemographic characteristics and knee-related (Modified Cincinnati Knee Rating System) and general health status (EQ-5D). RESULTS: Fifty-three ACI, twenty mosaicplasty, and twenty-two patients waiting for ACI participated. The average cost per patient was higher for ACI (10,600 pounds sterling: 95 percent confidence interval [CI], 10,036 pounds sterling-11,214 pounds sterling) than mosaicplasty (7,948 pounds sterling: 95 percent CI, 6,957 pounds sterling-9,243 pounds sterling). Postoperatively, ACI and mosaicplasty patients (combined) experienced better health status than those waiting for ACI. ACI patients tended to have better health status outcomes than mosaicplasty patients (not statistically significant). Estimated average EQ-5D social tariff improvements for quality-adjusted life year (QALY) calculations were 0.23 (ACI) and 0.06 (mosaicplasty). Average costs per QALY were 23,043 pounds sterling (ACI) and 66,233 pounds sterling (mosaicplasty). The incremental cost effectiveness ratio (ICER) for providing ACI over mosaicplasty was 16,349 pounds sterling. CONCLUSIONS: Average costs were higher for ACI than mosaicplasty. However, both the estimated cost per QALY and ICER for providing ACI over mosaicplasty fell beneath an implicit English funding threshold of 30,000 pounds sterling per QALY. Prospective studies should include measures of utility to confirm the estimated cost utility ratios of ACI and mosaicplasty.     

Effects of preincisional ketamine treatment on natural killer cell activity and postoperative pain management after oral maxillofacial surgery

Poorly controlled pain may lead to increased risk of cancer metastasis by suppressing natural killer (NK) cell activity. Ketamine may be beneficial by potentiating opioid-induced analgesia. We enrolled 59 participants in a randomized double-blind, placebo-controlled clinical trial and assigned them to receive propofol plus (1) saline, 2 mL; (2) ketamine, 0.5 mg/kg; or (3) ketamine, 1.2 mg/kg, followed by a standardized anesthesia protocol. The visual analogue scale (VAS) and 24-hour opioid consumption measured postoperative pain perception. NK cell activity was measured before and 24 hours after ketamine administration using the chromium 51 release assay. Nonparametric analysis of VAS data revealed that women receiving 0.5 mg/kg of ketamine reported less pain (P <.05) compared with the saline 1.2 mg/kg-ketamine groups. This finding was not evident in men. Comparing opioid consumption among the 3 groups (using analysis of variance) revealed a drug-gender interaction (P < .05): 0.5 mg/kg of ketamine decreased postoperative opioid consumption for women more than for men. Although not statistically significant, women receiving 0.5 mg/kg of ketamine had the least NK cell suppression compared with preoperative values (repeated analysis of variance). These findings suggest that for women, low-dose ketamine may be beneficial.     

The role of the cholinergic system in the development of increased naloxone potency in mice

Pretreatment of mice with the anticholinesterase (anti ChE) drugs tacrine or physostigmine augmented the antinociceptive potency of morphine given 3 h later, but had no effect on the antagonist potency of naloxone. Pretreatment with either of these anti ChE drugs together with morphine not only augmented the potency of a subsequent dose of morphine, but also enhanced the antagonist potency of naloxone to a greater extent than after pretreating with morphine only. Neostigmine did not affect the potency of either morphine or naloxone, suggesting that this phenomenon involved central cholinergic mechanisms. Atropine prevented the increase in naloxone potency caused by morphine pretreatment, and greatly reduced the effect of morphine plus the anti ChE drugs. The effects of these various pretreatments on the development of “acute dependence” to morphine was also studied. None of the three anti ChE drugs caused any change in this phenomenon, as tested by naloxone-precipitated jumping, although this was significantly increased by pretreatment with either atropine sulphate or atropine methyl nitrate. It is concluded that the increase in naloxone potency following morphine pretreatment involves both a cholinergic mechanism plus narcotic analgesic action. This phenomenon does not seem to be related to the development of either acute tolerance or acute dependence.     

THE EFFECTS OF INTRACISTERNAL ADMINISTRATION OF α-ADRENORECEPTOR AGONISTS ON THE SYSTEMIC BLOOD PRESSURE AND ITS RESPONSE TO HEAD-UP TILTING IN ANAESTHETIZED CATS

1. The effects of intracisternal injections of the α-adrenoreceptor agonists clonidine (0.2, 0.63 and 2.0μg/kg), xylazine (0.5, 8.0 and 50μg/kg), oxymetazoline (2.0 and 8.0μg/kg), noradrenaline (12.5, 50 and 100μg/kg) and α-methylnoradrenaline (5.0 and 25;μ/kg) on mean arterial pressure and the reflex pressure responses to bilateral carotid occlusion and 45° vertical head-up tilting have been investigated in chloralose-urethane-anaesthetized cats. 2. All the a-adrenoreceptor agonists tested caused dose-dependent reductions in mean arterial pressure (P<0.05, Anova, d.f. = 1,58) and the reflex pressor response to bilateral carotid occlusion (P < 0.05, Anova, d.f. = 1,58). 3. Only xylazine (50μg/kg) and noradrenaline (100μg/kg) produced a significant depression of the magnitude of the pressure compensatory response to tilting (P<0.05, Anova, d.f. = 1, 58) whilst all the agonists tested caused an increase in the period required for pressure compensation to occur (P<0.05, Anova, d.f. = 1,58). The action of the a-adrenoreceptor agonists to depress mean arterial pressure and the reflex responses to bilateral carotid occlusion and tilting could be reversed by the subsequent intracisternal injection of the a-adrenoreceptor antagonist piperoxane (50 or 100μg/kg). 5.Clonidine (0.63 μg/kg) decreased the perfusion pressure of the vascularly isolated autoperfused hindquarters (P<0.05, Anova, d.f. = 1,19), but had no significant effect on the reflex rises in perfusion pressure evoked by bilateral carotid occlusion or tilting. Noradrenaline (50 jug/kg) significantly reduced the reflex response to tilting (P<0.05, Anova, d.f. = 1,19), but had no effect on the other hindquarter parameters. Oxymetazoline (8.0 μg/kg) caused no significant change in any of these parameters. 6. It is concluded that intracisternally administered a-adrenoreceptor agonists may cause some depression of orthostatic cardiovascular reflexes via a central interaction with adrenergic mechanisms.     

Portable gas analyser Cosmed K4b2 compared to a laboratory based mass spectrometer system

AIM: The purpose of this study was to systematically test the accuracy of an automated, portable, gas analysis system, the Cosmed K4b2 with a laboratory based mass spectrometer system, the Morgan EX670 across a number of gas and ventilation parameters. METHODS: Eight subjects (mean+/-SE) age, 23.7+/-1.1 y, height, 1.78+/-0.01 m, mass, 74.4+/-2.1 kg performed a V.O2max test and a submaximal exercise test at 150, 200, 250 and 300 Watts (W), on an SRM cycle ergometer. The Morgan EX670 system and the K4b2 were randomly connected in series, using the same breath for the calculation of gas and ventilatory parameters. RESULTS: The K4b2 system reads significantly higher than the Morgan EX 670 for both VO2 and V.CO2 at 250 (VO2/V.CO2: p<0.05, p<0.002), and 300 W (VO2/V.CO2: p<0.002, p<0.005). Unsystematic bias between the 2 analysers varies between 1% and 16% and systematic bias between 3% and 8%. CONCLUSION: There are some significant unsystematic and systematic differences between these 2 systems and laboratories should endeavour to utilise either one or the other piece of equipment to test their subjects.     

Optimal management for surgically Stage 1 serous cancer of the uterus

OBJECTIVE: To describe the outcomes of patients who have undergone well-conducted surgery and found to have Stage 1 serous uterine cancer. METHODS: This retrospective cohort study includes women who have been treated for Stage 1 serous cancer of the uterus from 1985 to 2001. Cases were included from the regional cancer centers in Hamilton, London, Sunnybrook Toronto and Cancer Care Manitoba. RESULTS: Forty-three women met the inclusion criteria: Complete surgical staging (n = 27), surgery followed by pelvic radiation therapy (n = 4), surgery followed by whole abdominal radiation therapy (n = 6), surgery followed by adjuvant chemotherapy (n = 6). Patient age or depth of invasion did not influence survival. Progression free interval was 22 months (SD = 14.29). Recurrence rate was highest for adjuvant chemotherapy (66%). Survival was assessed by treatment modality and a statistically significant poorer survival was seen in the adjuvant chemotherapy group (OR 17.5; 95% CI 1.3-227.6). No comment can be made on a superior treatment regimen given the small numbers in each treatment strata. CONCLUSION: This study supports the findings of others in the literature. In a group of patients where surgical staging shows limited disease (i.e., surgically Stage 1 disease), then surgery alone appears to be adequate treatment.