Selective monoalkylation of p-tert-butylcalix-[4]-arene in a methyl carbonate ionic liquid.

Methyl carbonate ionic liquids are shown to readily mono-deprotonate p-tert-butylcalix-[4]-arenes initiating the formation of an organic mono-anionic p-tert-butylcalix-[4]-arate salt, methanol and carbon dioxide. These calix-[4]-arate salts have been successfully used in alkylation reactions with dialkyl sulfates and alkyl halides to form a mono-alkylated single product with high yield. This method avoids the common use of alkali metal bases such as caesium fluoride hence providing a safer and more selective synthetic route.

Comparison of cartilage histopathology assessment systems on human knee joints at all stages of osteoarthritis development.

OBJECTIVE: To compare the MANKIN and OARSI cartilage histopathology assessment systems using human articular cartilage from a large number of donors across the adult age spectrum representing all levels of cartilage degradation. DESIGN: Human knees (n=125 from 65 donors; age range 23-92) were obtained from tissue banks. All cartilage surfaces were macroscopically graded. Osteochondral slabs representing the entire central regions of both femoral condyles, tibial plateaus, and the patella were processed for histology and Safranin O - Fast Green staining. Slides representing normal, aged, and osteoarthritis (OA) tissue were scanned and electronic images were scored online by five observers. Statistical analysis was performed for inter- and intra-observer variability, reproducibility and reliability. RESULTS: The inter-observer variability among five observers for the MANKIN system showed a similar good Intra-class correlation coefficient (ICC>0.81) as for the OARSI system (ICC>0.78). Repeat scoring by three of the five readers showed very good agreement (ICC>0.94). Both systems showed a high reproducibility among four of the five readers as indicated by the Spearman's rho value. For the MANKIN system, the surface represented by lesion depth was the parameter where all readers showed an excellent agreement. Other parameters such as cellularity, Safranin O staining intensity and tidemark had greater inter-reader disagreement. CONCLUSION: Both scoring systems were reliable but appeared too complex and time consuming for assessment of lesion severity, the major parameter determined in standardized scoring systems. To rapidly and reproducibly assess severity of cartilage degradation, we propose to develop a simplified system for lesion volume.

Impact loading of articular cartilage during transplantation of osteochondral autograft.

Surgical reconstruction of articular surfaces by transplantation of osteochondral autografts has shown considerable promise in the treatment of focal articular lesions. During mosaicplasty, each cylindrical osteochondral graft is centred over the recipient hole and delivered by impacting the articular surface. Impact loading of articular cartilage has been associated with structural damage, loss of the viability of chondrocytes and subsequent degeneration of the articular cartilage. We have examined the relationship between single-impact loading and chondrocyte death for the specific confined-compression boundary conditions of mosaicplasty and the effect of repetitive impact loading which occurs during implantation of the graft on the resulting viability of the chondrocytes. Fresh bovine and porcine femoral condyles were used in this experiment. The percentage of chondrocyte death was found to vary logarithmically with single-impact energy and was predicted more strongly by the mean force of the impact rather than by the number of impacts required during placement of the graft. The significance of these results in regard to the surgical technique and design features of instruments for osteochondral transplantation is discussed.

Artefacts in the mechanical characterization of porcine articular cartilage due to freezing.

Many experimental protocols for investigating articular cartilage mechanics have involved the use of a freeze-thaw cycle for storage or tissue manipulation. It was hypothesized that mechanical properties are altered due to freeze-thaw cycling. The aim of this study, therefore, was to examine the possibility of protocol-induced artefacts in the mechanical properties of porcine articular cartilage specimens related specifically to freeze-thaw events. Twenty-eight osteochondral specimens [14 from the femoral condyles (FCs) and 14 from the patella-femoral (PF) groove] were tested in confined compression before and after being frozen at -20 degrees C for 7 days. The fluid-independent and fluid-dependent mechanical properties (aggregate modulus of the solid phase and the half-life of stress relaxation respectively) were determined and compared. The aggregate modulus decreased by 13.5 per cent and 20.1 per cent for the PF and FC regions respectively (p = 0.002) and the half-life of the stress relaxation at 10 per cent strain decreased by 6.4 per cent and 12.6 per cent for the PF and FC specimens respectively (p = 0.0341). In conclusion, it has been shown that the protocol used, which involved freezing to -20 degrees C and thawing after 7 days, caused artefacts in the mechanical properties of porcine osteochondral specimens. It is suggested that protocols requiring freezing must be critically reviewed to eliminate such artefacts.

Biomechanical assessment of lateral stiffness elements in the suspension system of a backpack.

The purpose of this study was to examine the change in load distribution characteristics associated with adding lateral stiffness elements (rods) to a rucksack (backpack). A load distribution mannequin was instrumented with two 3D load cells to allow determination of the load applied to the shoulders and upper torso independent of the load applied to the hips and lower trunk. Position and mass of the payload (25 kg) were fixed at the centre of the volume of the rucksack and held constant during all testing. It was hypothesized that lateral rods would provide a force bridge that transfers part of the vertical load of the pack from the upper back and shoulders to the hip belt thereby reducing the vertical load on the torso, and possibly reducing the horizontal reaction force that produces a shear load on the spine. Results showed that these active stiffness elements shifted 14% of the vertical load from the upper torso to the pelvic region with lumbar shear load remaining relatively unchanged for all combinations of shoulder strap and waist belt tension. The lateral rods also provided a mean increase of 12% in the extensor moment at the L3-L4 level, thus reducing some demand on the erector spinae muscles.

Short-term load bearing capacity of osteochondral autografts implanted by the mosaicplasty technique: an in vitro porcine model.

Articular surface congruency and graft stability are considered essential factors in the success of osteochondral grafting; however, quantitative measures of short-term load bearing capacity of grafts implanted by the mosaicplasty technique have not been reported. The purpose of this study was to develop a live tissue in vitro model to examine short-term fixation strength of mosaicplasty autografts immediately after and 1 week following graft implantation. Cylindrical osteochondral autografts were implanted in vitro by the mosaicplasty technique on five pairs of porcine femoral condyles within one and a half hours of animal sacrifice. Immediately following the surgical procedure, graft push-in and pull-out strength tests as well as indentation tests to determine modulus of the surrounding cancellous bone were performed on half of the specimens from the distal femurs of each animal. The remaining specimens, matched for location in the contralateral leg, were incubated in culture medium for 7 days prior to performing the same set of mechanical tests. Averaged push-in and pull-out graft fixation strength decreased 44% from 135.7 to 75.5N over the 7-day period, while no change in modulus was detected in the surrounding cancellous bone. These in vitro results demonstrate a substantial deterioration of short-term fixation strength of mosaicplasty grafts from the immediate post-operative state. Such a reduction in short-term graft load bearing capacity may pose a threat to the surgically established articular surface congruency and blood vessels formed during the early stages of the healing response.

Pseudo-renal failure following the delayed diagnosis of bladder perforation after diagnostic laparoscopy.

We present a case of bladder injury as a complication of gynaecological laparoscopic surgery. A young female presented with peritonitis, an acute systemic inflammatory response and biochemical features of acute renal failure secondary to urinary peritonitis. Laparotomy with drainage of urine from the peritoneal cavity and repair of the bladder perforation resulted in rapid resolution of the biochemical abnormalities.

The effect of a disposable probe cover on pulse oximetry.

The re-use of pulse oximeter probes presents the possibility of between-patient contamination. Use of a disposable polyethylene cover may reduce this risk. In a controlled, prospective study we examined the effect of such a cover on the accuracy of pulse oximetry. Each of ten volunteer subjects was monitored simultaneously by two identical Nellcor pulse oximeters, one with a plastic cover and the other, without a cover, used as a control. The pulse oximetry (SpO2) reading for each probe was recorded while subjects breathed 21% O2 and again while they breathed 10% O2. The probe cover was then swapped onto the other probe and the recordings were repeated. Ninety-five per cent limits of agreement in SpO2 (mean difference in SpO2 (1.95 x standard deviation of difference) between covered and non-covered probes were -0.6% to 0.6% while breathing 21% oxygen and -2.0% to 2.9% while breathing 10% oxygen. We conclude that a protective plastic sheath may induce a small error in pulse oximetry reading that is most marked during hypoxaemia. This error is unlikely to be of clinical significance.

Industrial scale-up of countercurrent chromatography: predictive scale-up.

This study describes how scale-up in countercurrent chromatography (CCC) can be simply predicted on a process scale CCC device by running a preliminary analytical-sized sample and having knowledge of the stationary-phase retention at scale-up conditions. Results have shown that simple experimentation can lead within a day to a process with the capability of several kilograms per day (tons per year) compound yield, and that this is feasible with benchtop CCC units.

Epidural ropivacaine with fentanyl following major gynaecological surgery: the effect of volume and concentration on pain relief and motor impairment.

In a prospective, randomized, double-blind study, 40 patients undergoing gynaecological oncology surgery received either 0.1% ropivacaine with fentanyl 1 microgram ml-1 or 0.2% ropivacaine with fentanyl 2 micrograms ml-1. A PCEA pump was set to deliver ropivacaine 8 mg with fentanyl 8 micrograms with each successful demand and a lockout period of 15 min without background infusion. Patients were observed for rest and activity pain VAS, side effect incidence, peak expiratory flow rate (PEFR), leg strength, sensory block to cold and pinprick, and PCEA usage into the second postoperative day. Passive and active pain scores for both groups were both satisfactory and comparable for the duration of the study. There were no differences between groups with regard to side effects. There was a 24% increase in total drug used in the high-concentration/low-volume group (P < 0.05). The study demonstrated that PCEA ropivacaine with fentanyl is an effective means of postoperative analgesia for this patient population. Reduced drug consumption with high-volume/low-concentration solution confirms similar findings by other investigators using alternate local anaesthetic agents, and suggests that the therapeutic ratio of ropivacaine is widened if a low-concentration/high-volume solution is used.

Economic value of gemcitabine compared to cisplatin and etoposide in non-small cell lung cancer.

Although chemotherapy costs have not been highlighted traditionally, there is increasing pressure to demonstrate the value of new treatments within the health care budget. Pharmaceutical companies are assessing the economic value of their products before launch. Gemcitabine is a nucleoside analogue developed for use in solid tumours. The purpose of this model was to investigate the clinical outcomes and potential cost savings for gemcitabine used as monotherapy compared to cisplatin and etoposide combination therapy in late stage non-small cell lung cancer (NSCLC), in a palliative (as opposed to aggressive) chemotherapy setting. Gemcitabine treatment data were taken from a large NSCLC study and data from retrospective chart reviews identified through the National Oncology Data Base. The model population and effectiveness of the two regimens were judged to be similar, except for baseline performance status. If drug costs were not included, the probability distribution resulting from the simulation showed median cost savings per cycle ranging from $US 1504 to $US 7425, with a medium value of $US 2154. The model suggested that gemcitabine would result in cost savings per cycle more than 90% of the time. Outpatient versus inpatient drug administrations accounted for the majority of potential cost savings. Most of the remaining cost savings were attributable to the difference in febrile neutropenia and antiemetic use. This economic model showed susbstantial savings if gemcitabine was used instead of cisplatin and etoposide combination therapy in the United States' community care setting. Some savings would be realized even if the location of treatment for both regimens was mostly outpatient. Assessment of the product's economic value before launch has assisted in our understanding of the potential areas of cost savings for gemcitabine and has guided us in the design of prospective randomized studies which included pharmacoeconomic endpoints.

Structured role assignment and other techniques for facilitating process in adolescent psychotherapy groups.

The application of various types of techniques for structuring the interchange and feedback process in adolescent psychotherapy groups is described. Techniques include random assignment of "roles" for each member during sessions, "parent hot seat" exercises, group goal booklets, and negotiation exercises. These have proved helpful in ensuring effective group participation, providing practice in social skills and verbalization of feelings, and in the development of other specific mastery skills.

Biofeedback, cognitive training and relaxation techniques as multimodal adjunct therapy for hospitalized adolescents: a pilot study.

Modifications and adjuncts to traditional therapy techniques appear to be necessary for successfully treating hospitalized adolescents with impaired social and verbal skills, and a history of acting-out behavior. Modified therapy groups were combined with a structured biofeedback and cognitive training program to help these adolescents control anger and modify their behavior. Used in conjunction with training and practice in relaxation techniques, this multimodal treatment approach appeared to be helpful in both reducing incidents of acting out on residential units, and in reaching individualized therapeutic goals. The present paper describes use of this multimodal approach within selected residential settings, and outlines the structured materials developed by the authors.

Legal issues affecting residential child care workers.

Most respondents felt that child care workers' legal concerns should be addressed by requiring (1) thorough, legally approved written procedures and guidelines for all day-to-day procedures and responsibilities; (2) legally approved comprehensive record-keeping systems; and (3) access to legal support and counsel. When child care workers follow legal guidelines and a facility's procedure manuals carefully, documenting their activities in an approved record-keeping system, they can expect to be in a positive situation in any legal contest and to have behavior measured from a legal standpoint by a standard described as what a "reasonable person" would be expected to do in a similar situation and circumstance.

An experimental study of the effect of structured videotape feedback on adolescent group psychotherapy process.

Group psychotherapy with disturbed undersocialized adolescents requires modification of traditional group psychotherapy methods. The effectiveness of a structured, brief video-tape feedback and discussion on group psychotherapy process with this population was studied by an analysis of detailed ratings of each "statement", or process unit; in randomly selected videotapes from a control and experimental group during a nine-month period. Significant differences in level of intimacy of verbal content and in frequency of feedback about behavior in content indicate that this technique is effective in facilitating group psychotherapy goals.

Pre-therapy training for adolescents in group psychotherapy: contracts, guidelines, and pre-therapy preparation.

Although adolescents in psychotherapy groups have been described as requiring more structure and preparation than adults, and as generally showing more critical deficits in verbal feedback and other interpersonal skills necessary for successful group functioning, no specific, detailed programs for preparation and pretraining of adolescents for group therapy are described in the literature. The present paper outlines a specific program developed for outpatient adolescent psychotherapy groups which has successfully speeded development of group cohesion, increased expression of positive expectancies for treatment reduced time spent in "pass-time" discussion, decreased verbalized concerns over confidentiality issues, and facilitated growth of patient skills in giving and receiving verbal feedback.

Development of a closed-loop artificial pancreas.

A closed-loop glucose controlled insulin infusion system was developed, consisting of elements for continuous blood glucose analysis, a computer control system, and infusion systems. Improvements include decreased size, cost reduction and better performance. The algorithm used was a piecewise linear representation of the sigmoidal curve commonly employed. The apparatus has been applied to simulation of the healthy beta cell and glucose clamp studies.