Glass yttrium-90 microspheres for patients with colorectal liver metastases.

Total calculated uniform liver doses of up to 150 Gy were achieved using glass yttrium-90 microspheres administered via the hepatic artery and targeted to tumour using angiotensin II in seven patients with colorectal liver metastases. No toxicity was observed. Hepatic metastatic progression was delayed in six patients. Median survival was 11 months (range 5-25 + months).

The effect of angiotensin II on tumor blood flow and the delivery of microparticulate cytotoxic drugs.

Colorectal hepatic metastases have a notoriously poor response to conventional systemic chemotherapy. We have synthesised cytotoxic drug (doxorubicin and mitomycin C) containing spheres 40 microns in diameter, using human albumin and ethyl cellulose as matrices. Introduction of these cytotoxic microspheres into the hepatic artery should embolise to the tumor and provide a controlled release depot for the anticancer agent. The vasoconstrictor, angiotensin II (AII) has been shown to increase tumor blood flow relative to normal tissue when administered via the hepatic artery, therefore we have investigated the effect of AII on targeting of cytotoxic microspheres to hepatic metastases. Patients with hepatic metastatic colorectal carcinoma had hepatic arterial catheters inserted at laparotomy and connected to subcutaneous injection ports. Peroperatively, 99mTc-labelled albumin microspheres were administered via the arterial catheter. Fifteen minutes later, AII was infused (10 micrograms per minuter for 4 min) via the catheter and 131I-labelled albumin microspheres were administered as a bolus at the midpoint of the AII infusion. Multiple biopsies were taken of normal liver and tumor metastasis and the tissue radioactivity counted for 99mTc and 131I. Further studies were performed postoperatively in which 99mTc-labelled microspheres were administered via the hepatic artery catheter and their distribution was followed using tomographic SPECT scanning. Combined results of this study suggested that AII can increase tumor SPECT scanning. Combined results of this study suggested that AII can increase tumor blood flow rates relative to normal hepatic tissue by approximately 3-fold.

Pheochromocytoma of the heart.

A patient with a pheochromocytoma involving the posterior wall of the left ventricle and the coronary sinus is reported. Complete surgical removal of the tumor was possible, although it caused a perioperative myocardial infarction. The literature regarding cardiac pheochromocytoma is reviewed.

A comparison of regional and systemic chemotherapy for hepatic metastases.

A 48-year-old man with colorectal liver metastases underwent insertion of an hepatic arterial infusion catheter for regional chemotherapy. Postoperative hepatic arterial perfusion scintigraphy showed that only part of the liver was being perfused by this route. Chemotherapy was administered weekly via the catheter. In effect, part of the liver received regional chemotherapy, whereas the remainder of the organ was exposed to systemic chemotherapy. Ultrasonography demonstrated shrinkage of the metastases in the area of liver receiving regional therapy, whereas disease progression occurred in the region of liver receiving 'systemic' treatment. This patient demonstrates that tumour may respond to regional chemotherapy despite disease progression on systemic therapy and suggests that a controlled trial would yield valuable data.

Saphenous vein grafts for anatomical variations encountered at surgical insertion of a hepatic artery catheter.

Fifty-five consecutive patients, with colorectal metastases confined to the liver, underwent surgical placement of a hepatic artery catheter. At angiography, abnormal hepatic arterial anatomy was present in 33% of patients. In the majority of patients, the hepatic artery catheter was inserted in the conventional manner. In eleven patients with unusual arterial anatomy, a saphenous vein graft was used to create a conduit for the catheter. Satisfactory perfusion was obtained in all patients.

Psychological morbidity in the first year after breast surgery.

In this prospective study, the psychological morbidity associated with the treatment of breast cancer was assessed. The study population comprised all patients referred to one centre with a recently diagnosed breast lump, who were to undergo surgery. Psychological morbidity was assessed preoperatively and at 6 and 12 months postoperatively by modified Rotterdam Symptom Checklist. Three hundred and twenty patients completed all three questionnaires: 93 women undergoing mastectomy, 73 women having conservation therapy for breast cancer and 156 women having biopsy for benign breast disease. Patients with a breast malignancy smaller than 4 cm in diameter were treated by lumpectomy and radiotherapy, anti-oestrogen therapy or chemotherapy alone or in combination. Psychological morbidity among patients with malignant disease was significantly greater than that seen in the group with benign disease. Among cancer patients, a significant decrease in anxiety and depression occurred during the year following surgery. The study failed to demonstrate any psychological advantage associated with breast conservation.

Biomechanical performance of Bankart repairs in a human cadaveric shoulder model.

The objective of this study was to develop a method to evaluate the biomechanical performance of Bankart repairs in a human cadaveric shoulder in a clinically relevant orientation. Twenty fresh-frozen human cadaveric shoulder girdles were used to compare the biomechanical performance of intact anteroinferior capsulolabral complexes with the biomechanical performance of three Bankart lesion reconstruction techniques. Repairs were performed on surgically created Bankart lesions. Evaluations were performed with the shoulders in glenohumeral abduction and external rotation. The repair techniques employed interosseous sutures, Mitek GII suture anchors, or Acufex T-Fix devices. The suture material used in all repairs was No. 2 Ti-Cron. The biomechanical performance of the three reconstruction techniques did not differ, but each was significantly inferior compared with that of the intact shoulder samples. The interosseous repairs failed by suture pullout through soft tissue. Repairs in the Mitek GII group failed by pullout of the suture anchors, suture breakage, or pullout of the suture through soft tissue. Repairs in the T-Fix group failed by pullout of the suture through soft tissue or failure of the polymer portion of the T-Fix suture.

Structural properties of the intact and the reconstructed coracoclavicular ligament complex.

Numerous procedures have been described for the operative management of acromioclavicular joint injuries, but surprisingly little information is available on the ultimate mechanical behavior of the native coracoclavicular ligament complex or on the various methods of reconstruction. We tested 19 fresh-frozen cadaveric bone-ligament-bone preparations of the coracoclavicular ligament in uniaxial tension at 25 mm/min until failure. Seven specimens were left intact, six had the trapezoid ligament sectioned, and six had the conoid ligament sectioned. Reconstruction of the coracoclavicular ligament was achieved using coracoacromial ligament transfers, woven polyester slings, suture anchors, and Bosworth screws; all reconstructions were also tested to failure. The intact coracoclavicular ligament failed by avulsion or midsubstance tear at 500 (+/-134) N, with a stiffness of 103 (+/-30) N/mm and elongation to failure of 7.7 (+/-1.9) mm. There was no significant difference between the contributions of the conoid or trapezoid ligaments in this loading configuration. Coracoclavicular slings and suture anchors provided strength similar to that of the coracoclavicular ligament, but with significantly greater deformations (14 to 26 mm). Screw fixation resulted in comparable stiffness and superior strength to the coracoclavicular ligament, but only if bicortical purchase was obtained. Coracoacromial ligament transfers were the weakest and least stiff, and augmentation with another form of coracoclavicular fixation is recommended. These results provide a useful baseline for comparison of the initial performance of reconstructive techniques with the performance of the native coracoclavicular ligament.

Single photon emission computed tomographic studies (SPECT) of hepatic arterial perfusion scintigraphy (HAPS) in patients with colorectal liver metastases: improved tumour targetting by microspheres with angiotensin II.

As intra-arterial chemotherapy for liver metastases of colorectal origin becomes accepted, methods of further improving drug delivery to the tumour have been devised. Degradable microspheres have been shown to reduce regional blood flow by transient arteriolar capillary block, thereby improving uptake of a co-administered drug, when injected into the hepatic artery. In our study of five patients, we combined hepatic arterial perfusion scintigraphy (HAPS) and SPECT to assess the localization of approximately 1 X 10(5) labelled microspheres of human serum albumin (99Tcm MSA) in tumour. In addition, in three patients, we assessed the effect of an intra-arterial infusion of the vasoactive agent angiotension II during HAPS. Results were interpreted by comparing transaxial slices with corresponding slices of a tin colloid liver-spleen scan. Two of five patients showed good localization of 99Tcm MSA in tumour without an angiotensin II infusion. Of the three patients receiving angiotensin II, all showed good tumour targetting with the vasoconstrictor compared with only one of these three before its use. Thus, hepatic arterial infusion of angiotensin II greatly improves microsphere localization in tumour in some patients with colorectal liver metastases. This technique may be useful in the assessment of tumour targetting before and during locoregional therapy.

Clinical evaluation of angiotensin II enhanced perfusion scintigraphy in metastatic liver disease.

The hepatic perfusion index (HPI) may be of value in the diagnosis of liver micro-metastases. However, raised values of HPI also occur in some benign liver conditions (e.g. cirrhosis), thereby weakening the diagnostic power of this test. It has been suggested that infusion of the vaso-active agent angiotensin II might improve the predictive value of dynamic scintigraphy because it has been shown to alter liver perfusion in patients with metastatic liver disease. Basal HPI values were not significantly different in a group of patients with metastases (n = 10) and a group with cirrhosis (n = 9). A significant rise in HPI occurred in the metastatic group using angiotensin II enhancement (p less than 0.01, Wilcoxon test). In the cirrhotic group there was no significant increase in the HPI with angiotensin II enhancement. Within the groups, there was considerable variation in response, with eight of ten metastatic and five of nine cirrhotic patients showing a rise in HPI during an angiotensin II infusion. As a result, there was complete overlap in the angiotensin II enhanced HPI for the two groups. Angiotensin II enhancement of HPI is therefore unlikely to improve the diagnostic power of dynamic scintigraphy in individual patients with established hepatic disease.

The biodegradation of albumin microspheres used for regional chemotherapy in patients with colorectal liver metastases.

The poor results of systemic chemotherapy for colorectal liver metastases have focussed attention on the use of regional chemotherapy. Embolizing, biodegradable particles can be coadministered with anticancer drugs to slow temporarily the arterial blood flow and increase drug uptake within the tumour-bearing liver. Alternatively, such microspheres can be loaded with cytotoxic agents and act as slow-release mechanisms following embolization. In both instances, size and rate of degradation are important. The aim of this study was to evaluate the biological degradation of albumin microspheres in the liver of patients with colorectal liver metastases. Seven patients with advanced liver metastases had a 200-250 mg bolus dose of customized albumin microspheres (diameter range: 20-40 microns), labelled throughout with covalently bound 131I, injected into the hepatic artery. The abdomen was imaged immediately before injection to give an estimation of background count rate, and daily after injection for five days. Activity-time curves were constructed for the liver region. The median biological half-time of the particles within the whole liver was 2.4 days (range: 1.5-11.7 days), but was longer in tumours than in normal liver in some patients. The rate of microsphere degradation within tumours may be an important factor in the efficacy of microsphere-based regional therapy, and can be studied accurately by the technique we have employed.

Arteriovenous shunting of microspheres in patients with colorectal liver metastases: errors in assessment due to free pertechnetate, and the effect of angiotensin II.

In patients receiving locoregional therapy for liver metastases degradable microspheres are being increasingly used in an attempt to improve cytotoxic delivery to the tumour. However, counterproductive arteriovenous shunting through the liver following intrahepatic arterial injection can occur, leading to deposition in the lung. Measurement of the degree of shunting is important in the monitoring of this kind of therapy. In this study we describe the use of technetium-labelled microspheres of serum albumin (99Tcm MSA) to measure baseline shunting during hepatic arterial perfusion scintigraphy in five patients with liver metastases of colorectal origin, and assess the significance of the values obtained for relative lung uptake (RLU) which we define as: RLU = Activity in lung field/Activity in liver + lung fields X 100%. We found that shunting was less than 5% in all cases, zero shunting occurring in 14 of the 16 patients studied. The sources of error in this technique have been assessed, the most important being the presence of free pertechnetate in the injectate. The use of Boots 10 ml vials and glass syringes respectively to dispense and administer this radiopharmaceutical reduces this error to a small predictable level. In our small group of patients, we found no evidence to suggest that use of the vasoactive agent angiotensin II significantly increases baseline shunting in patients with colorectal liver tumour.

Microvascular reconstruction of the lower extremity in the elderly.

The natural changes of aging increase perioperative medical risk factors in the elderly population. Aggressive preoperative patient evaluation and perioperative monitoring can effectively decrease morbidity and mortality rates to equal those of younger patients. The surgical strategy must take into account the increased incidence of atherosclerosis in the inflow and free-tissue transfer recipient vessels. Lower extremity microvascular reconstruction can be performed safely and successfully in the elderly patient.

Microvascular reconstruction of the foot: weight-bearing patterns, gait analysis, and long-term follow-up.

Between 1980 and 1989, 46 free-tissue transfers (32 skin flaps, 14 muscle flaps) were performed in 44 patients for foot reconstruction. Patient age averaged 25.8 years (range 2 to 74 years). Length of follow-up averaged 43 months. Flap survival rate was 96 percent. Debulking was done in 16 skin and 8 muscle flaps. The ulceration rate in 25 patients with weight-bearing flaps was 32 versus 11 percent in 19 patients with non-weight-bearing flaps. Time before ambulation averaged 6.4 months following weight-bearing reconstruction and 4.5 months following non-weight-bearing reconstruction. All patients with either abnormal foot-mat diagrams or major gait abnormalities had significant underlying radiologic foot abnormalities or nerve injuries. We conclude that both skin and muscle free flaps frequently need secondary debulking procedures to improve function. The ulceration rate tends to be higher in weight-bearing flaps than in non-weight-bearing flaps. Underlying bony architecture and nerve function affected weight-bearing patterns and gait more than type of wound coverage.

Between passion and policy: litigating the Guckenberger case.

This article describes the Guckenberger lawsuit from the perspective of the attorneys who litigated the case on behalf of Boston University. It first discusses the events leading to the lawsuit, including then-Provost Jon Westling's speeches, his articulation of new policies regarding documentation for accommodations requests, and the university's refusal to allow course substitutions for required foreign language courses. The article then describes the main events in the lawsuit that resulted from those policy changes, focusing first on pretrial matters, such as the university's search for experts, the various motions filed prior to trial, and tactical issues. Moving to the trial itself, the article discusses the nature of the witness and expert testimony presented to the court and touches on the differences of opinion expressed at trial by experts in the field of learning disabilities. Finally, the article sets forth the court's ruling on the major issues in the case and reflects on the case's impact on institutions of higher education.

Reinforcement-driven dimensionality reduction--a model for information processing in the basal ganglia.

Although anatomical studies of the basal ganglia show the existence of extensive convergence and lateral inhibitory connections, physiological studies failed to show correlated neural activity or lateral interaction in these nuclei. These seemingly contradictory results could be explained with a model in which the basal ganglia reduce the dimensionality of cortical information using optimal extraction methods. Simulations of this model predict a transient change in the efficacy of the feed-forward and lateral synapses following changes in reinforcement signal, causing an increase in correlated firing rates. This process ultimately restores the steady-state situation with diminished efficacy of lateral inhibition and no correlation of firing. Our experimental results confirm the model's predictions: rate correlations show a drastic decrease between the input stage (cortex) and output stage (pallidum). Moreover, preliminary analysis revealed that pallidal correlations show a transient increase following discrepancies between the animal's predictions and reality. We therefore propose that by using a reinforcement-driven dimensionality reduction process the basal ganglia achieve efficient extraction of cortical salient information that may then be used by the frontal cortex for execution and planning of forthcoming actions.

Salvaging unstable or recurrent dislocating total hip arthroplasty with the constrained acetabular component.

PURPOSE: To review cases of implantation of constraining acetabular components for unstable or recurrent dislocating total hip arthroplasty at the Department of Orthopaedics, Concord Hospital, Sydney. METHODS: A retrospective analysis was performed on prospectively collected data of 13 consecutively enrolled patients. RESULTS: From 1989 to 2000, 13 constraining acetabular components were implanted into 13 patients as a revision procedure. The surgical approach for the implantation of the constrained liner was posterolateral in 11 cases; a modified Hardinge approach was applied in 2 cases. The mean clinical follow-up duration was 43 months (range, 14-121 months) and the mean age at the time of surgery was 73 years (range, 52-84 years). No patients were lost to follow-up. Indications for using the constrained acetabular component were recurrent dislocation in revision hip replacements (n=8), and intra-operative instability (n=5). There were no episodes of dislocation of the constrained arthroplasty. In 7 cases, the constrained component was implanted into a previously well-fixed shell. CONCLUSION: We recommend the judicious use of the constrained component in cases of hip instability during or after total hip arthroplasty when other methods are not successful.

Total hip arthroplasty for arthrodesed hips.

The benefits of converting an ankylosed or arthrodesed hip to total hip arthroplasty have been reported in the literature as have the technical difficulties associated with this procedure. This review, however, outlines the experience of a single surgeon (WJMB) at a single institution using uncemented prostheses. Between November 1991 and June 1996, 5 arthrodesed hips underwent uncemented total hip arthroplasty in 4 males and 1 female. Clinical and radiological follow-up review was for at least three years in all patients. In general, patients were satisfied with the outcome of their surgery with Harris Hip scores improving from an average of 62 preoperatively to an average of 72 postoperatively. The surgical outcome in these difficult cases was not as satisfactory as for routine total hip arthroplasty. Meticulous preoperative planning is required to aim toward leg length restoration and restoration of the abductor moment arm. A modular prosthesis allows versatility at surgery.

Remote Control Systems' Radiotelemetry Receiver 7060: its use in clinical colonic motility measurement.

A new radiotelemetry receiver type 7060 for use with radiopills is described. Its performance under laboratory conditions was assessed and its use for clinical colonic pressure measurements evaluated. The receiver, which resembles a small microcomputer, was easy to set up and worked reasonably well under ward conditions. Difficulties were experienced with the belt aerial supplied with the receiver, which did not reliably pick up signals from a freely moving radiopill. The receiver is not suitable for ambulatory applications. Its main clinical use is in situations where frequent sampling of the radiopill's signal over a long period of time is essential (e.g. colonic pressures). The large quantity of data generated can be fed from the receiver's analogue or digital output on line to a recorder.

A novel approach for assessing the quality and effectiveness of IACUC oversight in investigator compliance.

In research facilities that are registered with the U.S. Department of Agriculture (USDA), funded by the Public Health Service, or accredited by the Association for the Assessment and Accreditation of Laboratory Animal Care (AAALAC) International, the Institutional Animal Care and Use Committee (IACUC) is charged with oversight and evaluation of animal care and use under the terms of the Animal Welfare Act and the Guide for the Care and Use of Laboratory Animals. Although the committee's oversight of investigator compliance may be evaluated annually during USDA inspections and triennially during AAALAC International site visits, routinely assessing the quality and effectiveness of the IACUC's performance is difficult. To measure the successfulness of IACUC oversight, our committee retained a management consultant to objectively design and conduct a confidential survey that could be used to determine how the IACUC could improve the process of facilitating researcher compliance with federal regulations and accreditation standards. The consultant based the content of the survey on confidential interviews with all IACUC members, the IACUC administrator, and a cross sectional representation of the key animal-user population at the facility. The survey was then distributed to the entire animal-user population. Vice-presidents, directors, principal investigators, and technicians were included in the distribution. With a response rate of 34%, the survey results indicated that the facilitation process warranted refinements. The consultant provided the IACUC with its recommendations, which were based on the discernible trending information indicated in the survey responses. The IACUC developed a specific plan of action to address the consultant's recommendations and intends to re-survey the animal-user population once the action plan has been fully implemented. In summary, the survey is an excellent way to assess the quality and effectiveness of IACUC oversight in investigator compliance by determining the level of researcher satisfaction. The evaluation, review, and follow-up process using a confidential interview and questionnaire technique can enhance the performance and effectiveness of IACUC oversight.