Biomedical subjects
Publications and source records attributed to D O'Farrell.
Diastasis of the pubic symphysis is a well documented injury typically associated with high energy trauma. Three cases in horse riders are here described, emphasising the appropriate modern investigation, including computed tomography, and orthopaedic and urological management.
PURPOSE: When irradiating a tumor that abuts or displaces any normal structures, the dose constraints to those structures (if lower than the prescribed dose) may cause dose inhomogeneity in the tumor volume at the tumor-critical structure interface. The low-dose region in the tumor volume may be one of the reasons for local failure. The aim of this study is to quantitate the effect of tumor dose inhomogeneity on local control and recurrence-free survival in patients with skull base chordoma. METHODS AND MATERIALS: 132 patients with skull base chordoma were treated with combined photon and proton irradiation between 1978 and 1993. This study reviews 115 patients whose dose-volume data and follow-up data are available. The prescribed doses ranged from 66.6 Cobalt-Gray-Equivalent (CGE) to 79.2 CGE (median of 68.9 CGE). The dose to the optic structures (optic nerves and chiasm), the brain stem surface, and the brain stem center was limited to 60, 64, and 53 CGE, respectively. We used the dose-volume histogram data derived with the three-dimensional treatment planning system to evaluate several dose-volume parameters including the Equivalent Uniform Dose (EUD). We also analyzed several other patient and treatment factors in relation to local control and recurrence-free survival. RESULTS: Local failure developed in 42 of 115 patients, with the actuarial local control rates at 5 and 10 years being 59% and 44%. Gender was a significant predictor for local control with the prognosis in males being significantly better than that in females (P = 0.004, hazard ratio = 2.3). In a Cox univariate analysis, with stratification by gender, the significant predictors for local control (at the probability level of 0.05) were EUD, the target volume, the minimum dose, and the D5cc dose. The prescribed dose, histology, age, the maximum dose, the mean dose, the median dose, the D90% dose, and the overall treatment time were not significant factors. In a Cox multivariate analysis, the models including gender and EUD, or gender and the target volume, or gender and the minimum target dose were significant. The more biologically meaningful of these models is that of gender and EUD. CONCLUSION: This study suggests that the probability of recurrence of skull base chordomas depends on gender, target volume, and the level of target dose inhomogeneity. EUD was shown to be a useful parameter to evaluate dose distribution for the target volume.
PURPOSE: To determine the temporal lobe (TL) damage rate in 96 patients treated with high-dose proton and photon irradiation for chordomas and chondrosarcomas of the base of the skull. METHODS AND MATERIALS: The records of 96 consecutive patients treated at Massachusetts General Hospital (MGH) and Harvard Cyclotron Laboratory (HCL) between June 1984 and 1993, for chordomas and chondrosarcomas of the base of the skull were reviewed. All the patients had undergone some degree of resection of the tumor prior to radiation therapy. Seventy-five patients were classified as "primary tumors" and 21 as recurrent or regrowing tumors after one or more surgical procedures. All the patients were randomized to receive 66.6 or 72 cobalt Gray equivalent (CGE) on a prospective dose-searching study by proton and photon irradiation (Radiation Therapy Oncology Group #85-26) with conventional fractionation (1.8 CGE/day, 5 fractions/week). All treatments were planned using the three-dimensional (3D) planning system developed at the Massachusetts General Hospital, and the dose was delivered using opposed lateral fields for the photon component and a noncoplanar isocentric technique for the proton component. Clinical symptoms of TL damage were classified into 4 grades. Computerized tomography (CT) and magnetic resonance imaging (MRI) scans were evaluated for white matter changes. Abnormalities associated with persistent or recurrent tumor were distinguished from radiation-induced changes. TLs were delineated on the original scans of the 10 patients with damage and those of a group of 33 patients with no clinical or MRI evidence of injury. Dose distributions were calculated and dose-volume histograms were obtained for these patients. RESULTS: Of the patients, 10 developed TL damage, with bilateral injury in 2 and unilateral injury in 8. The cumulative TL damage incidence at 2 and 5 years was 7.6 and 13.2%, respectively. The MRI areas suggestive of TL damage were always separated from the tumor bed. Symptoms were severe to moderate in 8 patients. Several baseline factors, tumor- or host-related, were analyzed to evaluate their predictivity for TL damage: age, gender, tumor site, histology, type of presentation, type and number of surgical procedures, primary tumor volume, prescribed dose, normal tissue involvement, and volume of TL receiving doses ranging between 10 and 50 CGE or more. Only gender, in a univariate analysis (log rank) was a significant predictor of damage (0.0155), with male patients being at significantly higher risk of TL injury. In a stepwise Cox regression that included gender as a variable, no other baseline variable improved the prediction of damage. CONCLUSIONS: The 2- and 5-year cumulative TL damage rates were 7.6 and 13.2%, respectively. Despite the different TL damage rates related to age, tumor volume, number of surgical procedures prior to radiation therapy, and prescribed doses to the tumor, only gender was a significant predictor of damage (p = 0.0155) using a univariate (log rank) test. Chordomas and chondrosarcomas of the base of the skull may represent an interesting model to evaluate the TL damage rates because of their extradural origin, displacing the white matter instead of infiltrating it as gliomas do, because of their longer local recurrence-free survival other than gliomas and other brain tumors and because of the high doses of irradiation delivered to the target volume to obtain local control.
STUDY DESIGN: A case of intrapelvic aneurysm is reported. It is as an example of one of the many extraspinal causes of sciatica. OBJECTIVE: To demonstrate the importance of clinical examination in the assessment of patients with sciatic, despite continuing improvements in methods for imaging the spine. SUMMARY OF BACKGROUND DATA: Extraspinal conditions cause sciatic in a rare but recognized group of patients. Their clinical symptoms can be very similar to those of patients with sciatic from lumbar disc protrusion. METHODS: The clinical appearance, investigation, and treatment of a patient with an internal iliac artery aneurysm causing sciatic are discussed. RESULTS: Surgical treatment of the patient's aneurysm resulted in relief of the symptoms of sciatica. CONCLUSIONS: Although these cases are unusual in isolation, together they represent an important group. When a patient has sciatica, the clinician looks first to the spine for the origin of symptoms. Extraspinal causes are often not considered in the differential diagnosis. This oversight may be compounded by observation of asymptomatic disc protrusions on computed tomographic and magnetic resonance studies. The importance of clinical history and examination in the diagnosis of these lesions cannot be overemphasized.
To determine the changes in capillary perfusion, which occur with elevated tissue pressure, and to highlight the relationship between systemic blood pressure and compartment pressure, we designed an experiment that allowed direct observation of the microcirculation of skeletal muscle under normal and increased compartment pressures. In each of 10 anesthetized rats, the cremaster muscle was exposed and suspended in a transparent pressure chamber. In vivo videomicroscopy was then performed and blood pressure was monitored via left carotid artery cannulation. Two sets of data for each animal were obtained: deltaP (mean arterial pressure compartment pressure) at which the muscle capillary blood flow was completely arrested, and the number of capillaries per 10,000 square micrometers of skeletal muscle with blood flowing at compartment pressures of 0, 15, 30, 45, and 60 mm Hg. Capillary blood flow stopped at a deltaP of 25.5 mm Hg +/- 14.3 SD. We found that capillary blood flow, as measured by the number of capillaries with blood flow per 10,000 square micrometers, decreased significantly (P < 0.05) as compartment pressure reached 15, 30, 45, and 60 mm Hg, when compared to 0 mm Hg; there was no vessel collapse at these pressures. These data show that increasing compartment pressure reduces the number of perfused capillaries per unit area, and that there is complete cessation of muscle capillary blood flow when the compartment pressure is within about 25 mm Hg of the mean arterial pressure.
We studied the electrophysiological effects of E 4031, given in a dose ascending manner (1.5, 3.0, and 6.0 micrograms/kg over 5 min followed by 0.1, 0.2, and 0.4 microgram/kg per min for 60 min, respectively) to 19 volunteers. There were significant, dose related linear increase in QT and QTc intervals, in atrial functional and effective refractory periods (ERPs) at a paced cycle length of 400 ms, and in ventricular functional and ERPs at a paced cycle length of 600 ms. There was no significant change in the AH and HV intervals or QRS duration. No significant proarrhythmic or other side effects were encountered during the administration of the drug. E 4031 prolongs atrial and ventricular refractoriness without significantly affecting AV or intraventricular conduction, consistent with selective Class III properties. At the doses used in the present study, intravenous infusion of E 4031 appears to be safe and well tolerated.
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Twenty-four Sprague-Dawley rats underwent exploration and exposure of the sciatic nerve, followed by sham isolation, irrigation, and subsequent wound closure (Group 1); barrier vein wrapping of the nerve using glutaraldehyde-preserved allograft inferior vena cava (Group 2); or barrier vein wrapping of the nerve with femoral vein autograft from the contralateral extremity (Group 3). Four months later, the rats were sacrificed and the nerves fixed in situ in buffered glutaraldehyde. Sections proximal, mid-portion, and distal to the barrier and vein wrap were fixed with osmium tetroxide, epon embedded, stained with toluidine blue, and studied under x200 and x400 light microscopy. Epineural scar formation increased 10 times in Group 2, compared to Group 3 (p < 0.0001). Epineural thickness and the number of degenerating axons did not differ significantly among all groups. Inflammatory cells in Group 2 increased 100 times, compared to Group 3 (p < 0.0001). Continuing with the underlying epineural layer was apparent grossly and microscopically with all allografts, but with no autografts. Thus, glutaraldehyde-preserved allograft vein wraps appear to incite a marked inflammatory response, with epineural scarring and adherence to the underlying nerve, while autograft vein wraps do not.
A growing body of experimental data indicates that the "no-reflow" phenomenon is a type of reperfusion injury in skeletal muscle which may, in part, be mediated by oxygen free radicals, and thus may be attenuated by using agents that scavenge or inhibit formation of these reactive oxygen metabolites. This study was undertaken to assess the efficacy of recombinant human manganese superoxide dismutase (rhMnSOD) in reducing reperfusion injury in skeletal muscle. The specific advantage of this agent over other SOD types is a much longer plasma half-life (5 to 7 hr), allowing better equilibration between extra- and intracellular compartments. The rat cremaster model was used to study "no-reflow" in skeletal muscle. Reperfusion injury in the muscle was assessed by fluorescein dye perfusion, myocyte creatine phosphokinase (CPK) release, and contractile function in response to electrical field stimulation. Compared with untreated saline control animals, those treated with rhMnSOD after 5 hr of cremasteric ischemia, had a significantly higher percentage area of blood reflow (78 percent +/- 6 percent of normal), a greater percentage tetanic (66 percent +/- 9 percent of normal) and twitch (56 percent +/- 9 percent of normal) contractile strength, and less CPK release (21.5 percent higher than pre-reperfusion baseline CPK levels) (p < 0.05). Untreated saline control CPK release (21.5 percent higher than the prereperfusion level. Animals treated with allopurinol also had a significantly higher percentage twitch contraction (47 percent +/- 14 percent of normal) and a lower CPK release (11.1 percent of the prereperfusion value) 45 min after reperfusion than untreated saline controls.(ABSTRACT TRUNCATED AT 250 WORDS)
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This study was designed to evaluate the effect of transfusion guidelines on perioperative blood usage with a view to identifying a protocol for transfusion therapy in our hospital. Eighty consecutive patients with normal haemoglobin concentrations presenting for total hip arthroplasty were studied. The maximum allowable blood loss (MABL) was calculated for each patient using the formula of Kallos et al. Blood loss up to this value was replaced with Haemaccel. When the MABL was reached, a haematocrit (Hct) was performed and blood was given if the Hct was less than 30 in men and 27 in women. Otherwise replacement was with Haemaccel. All postoperative complications, duration of hospital stay, and physiotherapy compliance assessments were recorded. A discharge Hct > 36% was the criterion for overtransfusion. The results were compared with findings from a retrospective group before the introduction of these guidelines. Analysis of the data demonstrated a reduction in the frequency of transfusion (97% vs 32% P < 0.05), the volume transfused (2.7 vs 1.3 units P < 0.05), and the incidence of overtransfusion (45% vs 5% P < 0.05) between the two groups of patients. There was no difference between the groups in complication rate, duration of hospital stay or physiotherapy scoring. We conclude that the introduction of guidelines for transfusion in total hip arthroplasty patients has produced a marked reduction in blood usage in our hospital without detrimental effect.
Of 271 patients with primary colorectal cancer, 70 (26%) had detectable hepatic metastases. A primary tumour resection was possible for 225 (83%) of patients overall. Of the 46 patients with non resectable tumours, 38 (82%) had hepatic metastases. 23 (33%) of the patients with Dukes' D tumours died perioperatively relative to 13 (6%) of those with localised tumours (p < .001). Seventeen (70%) of the twenty three patients with Dukes' D cancers who died perioperatively had locally advanced disease but were not obstructed and had neither a resection or a stoma performed. Perioperative mortality is unacceptably high in patients with hepatic metastases but may be reduced by more specialised investigation of patients with suspected advanced disease to assess the degree of local dissemination and liver seeding prior to considering laparotomy.
175 patients referred for arthroscopy were studied prospectively to assess the accuracy of clinical examination supplemented by standard radiology in the evaluation of knee symptoms. Clinical diagnosis of medial meniscal tears was inaccurate while greater confidence could be placed in the diagnosis of anterior cruciate ligament and lateral meniscus tears. Clinical accuracy rates could be improved if patients with minimal symptoms were excluded from arthroscopy examination.
The histological subgroups of primary gastric tumours presenting to one surgical unit over two successive six year periods were analysed and the therapeutic value of gastric resection assessed. An increased incidence of gastric lymphoma (13% relative to 5%) occurred in the second six year period. This increase could not be attributed to improved morphological or histochemical techniques. The diagnosis of lymphoma was confirmed preoperatively in 13 (94%) of the 14 patients by a combination of multiple endoscopic biopsies and brush cytology. Five of the six patients who underwent a potentially curative resection are tumour free at a mean follow-up of four years. Histological grading, whether high or low, had no bearing on survival. Gastric lymphoma is increasing in incidence and should be considered in the evaluation of gastric tumours as surgical resection at present offers the best prospect of long term survival.
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Cardiac transplantation has become the treatment of choice for end stage heart disease. In 1990 2,000 transplants were performed worldwide. Orthopaedic Surgeons will be asked with increasing frequency to evaluate and treat bone and soft tissue problems with these patients. Orthopaedic service at the Mater Hospital has been involved in the follow-up treatment of orthopaedic complications in 46 transplant patients over a six year period. Thirty eight were male and eight were female. The ages were between 12 years and 65 years (mean 44.3). Nine (20%) of these patients developed thirteen orthopaedic complications: A vascular Necrosis of the hip (AVN) (4), Soft tissue infections (3), Osteoporosis (2), Stress Fractures (2), Osteomyelitis (1) and Ostomalacia (1). The mode of presentation, investigation and management of orthopaedic problems particular to these patients is described. Most patients who develop bony complications have had increased doses of steroids for episodes of rejection. This study highlights the special features of this patient population that require modification of the treatment approach such as the need to avoid the drug Erythromycin and the increased risk of AVN of the hip in patients who require high dose steroids.