Phase II study of adozelesin in untreated metastatic breast cancer.

Adozelesin is the first of a class of DNA-sequence-selective alkylating agents, the cyclopropa(c)pyrrolo(3,2-e)indol-4(5H)-ones (CPls), that have been shown to have of potent inhibitory properties of DNA synthesis. Based on preliminary data from phase I studies showing clinical activity in patients with breast cancer, we initiated a multicenter phase II study in untreated metastatic breast carcinoma. Adozelesin was administered at a starting dose of 150 microg/m2 as a single 10 min infusion per course, repeated every 4 weeks, for up to 1 year of treatment. It was planned that at least 25 patients should be accrued but the trial was stopped early because of slow accrual and lack of efficacy as demonstrated by the infrequency of objective responses. Seventeen patients were enrolled in this study, only 14 were evaluable, the following responses were observed: one partial response (7%), three stable diseases (22%) and 10 progressive diseases (71%). Myelosuppression was the most frequent adverse event; one patient died of pulmonary complications. We conclude that adozelesin has marginal efficacy in the treatment of metastatic breast cancer at the dosage and schedule used in this study.

Displaced Salter-Harris type I injury in a gymnast. A slipped capital humeral epiphysis?

The case of an adolescent Olympic-level gymnast with insidious onset shoulder pain is presented. Radiographic evaluation revealed bilateral physeal irregularities of the proximal humerus similar to those seen in Little Leaguer's shoulder. Roentgenograms of the involved shoulder also demonstrated Salter-Harris type I displacement at this physis and a slipped capital humeral epiphysis was diagnosed. A discussion reviewing proximal humeral physeal injury follows the case presentation.

Rehabilitation parameters in total knee replacement patients undergoing epidural vs. conventional analgesia.

Epidural analgesia for total knee replacement (TKR) surgery has been proposed as a means of enhancing patient comfort, thereby expediting rehabilitation and reducing hospital stay. This study was done to determine differences in rehabilitation parameters of range of motion and mobility in patients receiving epidural vs. conventional (intravenous) analgesia following TKR surgery. Chart reviews were done of 52 patients who underwent consecutive unilateral TKR, with 26 patients in each analgesia group. There were 21 males and 31 females, ages 24-88 years (median 65), with diagnoses of osteoarthritis (45), rheumatoid arthritis (4), and other (3). The surgeon, procedure, type of prosthesis, and physical therapy protocol were the same for all subjects. Demographics, range of motion, distance walked, assistance required for gait and transfers, assistive device, and exercise competence data were studied at the first postoperative day and at time of discharge. No significant difference was found in the length of stay at the p < .05 level. Significant differences at the first postoperative day favored the epidural group: in knee flexion range--median difference was 0.26 rad [95% confidence interval (CI): 0.09-0.52, p < .05] ie., 15 degrees (95% CI: 5-30); in total range of motion--median difference was 0.30 rad (95% CI: 0.09-0.58, p < .05), ie., 17 degrees (95% CI: 5-33); and in assistance required for gait and transfers (p < .05). At discharge, the epidural group required significantly less assistance (p < .05). There was a trend toward greater walking distance in the epidural group, who walked a median of 15.2 m farther than the conventional analgesia group.(ABSTRACT TRUNCATED AT 250 WORDS)

The use of epidural morphine in patients undergoing total knee arthroplasty.

Sixty-six patients undergoing total knee arthroplasty were offered epidural morphine as a method of postoperative analgesia. Of the 66 patients, 50 completed the minimum protocol of 3 days in a special epidural monitoring unit and were thus available for study. In this study group, 86% stated that they obtained 75-100% relief of pain with each epidural injection. Greater than 90% of the patients rated the overall experience with epidural analgesia as excellent or good. Ninety percent stated that they would choose epidural morphine analgesia again if given the choice. Nausea and vomiting were the most common adverse effects, occurring in 34%. One patient experienced respiratory depression, which was reversed with Narcan. The most frequent complaint related to the procedure itself was the use of an apnea monitor; 18% of the patients considered this monitoring device intolerable. The progress of total knee arthroplasties in the epidural unit was monitored by range of motion achieved. At 72 hours the average motion was 10 degrees-87 degrees and at the end of the hospital stay was 6 degrees-98 degrees. The total hospital bill for epidural morphine analgesic patients was $469 more than for a conventional arthroplasty patient, though the mean duration of hospital stay was 1.7 days less for the epidural morphine patients. Epidural morphine provided excellent but inconsistent postoperative pain relief. When relief was present, aggressive in-house rehabilitation could be instituted, and a shorter overall hospital stay was achieved when compared with conventional analgesia. Nonetheless, the related adverse effects and inconsistent pain relief on many patients may preclude the use of epidural morphine as a single postoperative analgesic agent.

The axillary nerve and its relationship to common sports medicine shoulder procedures.

Cadaveric dissections have demonstrated the precarious nature of the axillary nerve with relationship to three common sports medicine shoulder procedures: the anteroinferior acromioplasty and rotator cuff repair incision, the inferior capsular shift procedure, and the posterior portal for shoulder arthroscopy.

Hemodynamic and neural mechanisms of acute neurogenic hypertension in the rat.

Experiments were performed to test the hypothesis that acute hypertension caused by aortic baroreceptor deafferentation (ABD) is the result of sympathetic vasoconstriction. Cardiac output (CO), mean arterial pressure (MAP), and total peripheral resistance (TPR) were measured before and after ABD in anesthetized and conscious rats. The role of the sympathetic nervous system in acute ABD-induced hypertension was evaluated by examining the ability of adrenalectomy, adrenal demedullation, guanethidine or combined adrenal demedullation, and guanethidine pretreatment to prevent, and total autonomic blockade to reverse, ABD-induced hypertension. CO did not change significantly after ABD at any time, whereas MAP and TPR increased significantly (P less than 0.05). Only combined adrenal demedullation and guanethidine pretreatment prevented ABD-induced hypertension, and autonomic blockade normalized MAP in ABD rats. Normalization of blood pressure was the result of a decreased TPR. It is concluded that acute ABD-induced hypertension results from vasoconstriction caused by neurally released and/or circulating catecholamines.

Replacement of the patello-femoral joint with the total condylar knee arthroplasty.

We have studied 241 total condylar knee arthroplasties with replacement of the articular surface of the patella in 206 patients. The average age was 65 years. The technique of replacement of the patellofemoral joint emphasises realignment of the quadriceps mechanism, minimal excision of the patella to preserve subchondral bone, preservation of soft tissue attachments including the infrapatellar fat pad, and closure of the quadriceps without tension. The results of replacement have been good to excellent in 95 per cent of patients followed for two years or more. There were no subluxations, dislocations or fractures. Loosening was noted in one case associated with anterior knee pain. Discomfort was also noted with eccentric placement of the prosthesis where bone was left uncovered. We consider that routine replacement of the patello-femoral joint is advisable with total condylar knee arthroplasty.

Total knee arthroplasty in juvenile arthritis.

Sixteen patients with 29 knee arthroplasties due to juvenile arthritis were studied. Eight patients had been wheelchair-bound and were nonambulatory due to hip and knee involvement. Surgery was indicated for correction of deformity, decreased range of motion, and relief of pain. The average preoperative disability score was 40.3, and postoperative score was 79.9. Thirteen of the 16 patients also required bilateral hip replacement arthroplasty. The average hospital stay for bilateral knee arthroplasty under one anesthesia was 45.3 days. The average followup was 36 months with a range of 24 months to 7 years. The overall results were excellent in 13 knees, good in 11, fair in 3, and poor in 2. Ambulation improved in all but 2 of the knees. Of the 2 failures, 1 was due to deep infection and the other to severity of disease and poor cooperation of the patient, who remains wheelchair-bound.

Effect of forebrain lesions on response to chronic intraventricular angiotensin II.

We previously reported that chronic (10 days) intracerebroventricular (ivt) infusion of angiotensin II (ANG II) into conscious rabbits produced a significant rise in mean arterial pressure (MAP), water intake (WI), and urinary sodium excretion (UNaV), and a significant fall in plasma sodium (PNa) and potassium (PK) concentrations. Urinary potassium excretion (UKV) and body fluid volume were not changed significantly. In the present experiments, similar chronic infusions were carried out in intact rabbits and in rabbits with an electrolytic lesion placed in the anteroventral third cerebral ventricle (AV3V) region. Integrity of the AV3V area is essential for normal expression of a variety of acute physiological responses to ANG II injected into the brain. In rabbits with AV3V lesions, chronic ivt infusion of ANG II did not significantly alter MAP, but WI and fractional UNaV increased, and PNa decreased in a manner identical to that of sham-lesioned control rabbits. Plasma and extracellular fluid volumes increased, and body weight and food intake decreased in all rabbits during ANG II infusion, but to a slightly greater extent in the AV3V-lesioned rabbits. We conclude that an intact AV3V region is crucial for the hypertensive effect of chronic ivt fusions of ANG II in the rabbit but is not necessary for most of the fluid and electrolyte alterations associated with such infusions.

Tuberculosis in a rheumatoid patient. A case report.

A 72-year-old white woman with seropositive rheumatoid arthritis subsequently developed polyarticular tuberculosis. Clinical and radiographic evidence of deterioration of the right knee and left elbow was erroneously attributed to progressive rheumatoid arthritis. The diagnosis of a tuberculous infection was unduly delayed. Failure to recognize this infection might have been disastrous if a total knee arthroplasty had been performed as planned. This case illustrates the importance of awareness of other possible origins of joint destruction and infection in rheumatoid patients with rapid deterioration of joint function.

Methylmethacrylate stabilization for enhancement of posterior cervical arthrodesis in rheumatoid arthritis.

Stainless-steel wire, titanium mesh, and perforated titanium sheets and methylmethacrylate were used in conjunction with autogenous iliac-bone grafts to provide immediate stability in difficult or long posterior cervical fusions in eleven patients with rheumatoid arthritis, who were followed for three to 12.5 years. Two surgical techniques, using methylmethacrylate and metal supplementation of a traditional posterior cervical arthrodesis, are described. One technique includes the occiput, while the other consists of a long posterior fusion that excludes the occiput. In ten of the eleven patients, permanent radiographic stability was maintained as well as a significant reduction of pain and resolution of neural dysfunction. In the eleventh patient a cervical subluxation developed at the distal end of the rigidly fused segment, and eventually the patient died. Four patients who were seen early in the series had wound dehiscences, two of which were infected. Subsequently the methacrylate-metal composite was reduced in volume, and this problem did not recur. In summary, this technique has provided immediate internal splinting and avoided bulky external-fixation devices. It was most useful in fusions of the occiput to the upper part of the cervical spine, in long posterior cervical arthrodesis, and for the repair of pseudarthroses when traditional arthrodesis techniques had failed.

Complications of distal radial fractures: pins and plaster treatment.

Recent advances in the treatment of comminuted distal radial fractures has led to the use of pins and plaster, a concept described by many authors. This paper examines whether the use of pins and plaster maintains reduction of distal comminuted radial fractures, and, if so, if it is accomplished with a minimum of complications. With follow-up ranging from 1 month to 1 year following pin removal, 80 consecutive comminuted distal radial fractures treated with pins and plaster were analyzed for change in fracture reduction, associated injuries, and complications incurred during and as a result of the treatment mode. Thirty-three percent of our patients had some complications due to their pins and 16% required reoperation for carpal tunnel syndrome or replacement of loose pins, sequestrectomy, or extended treatment in long arm casts.

Influence of forebrain periventricular lesions on the development of renal hypertension in rabbits.

Ablation of tissue surrounding the anteroventral third cerebral ventricle (AV3V) has been demonstrated to prevent and reverse renal hypertension in the rat. The contribution of this brain area to the maintenance of hypertension in other species has not been examined. In the present investigation, an attempt was made to produce two-kidney, one clip renal hypertension in rabbits with histologically and functionally defined AV3V destruction. Electrolytic lesion of the AV3V in rabbits produced effects closely resembling those previously seen in rats: increased plasma volume and plasma sodium, temporary adipsia, no change in resting arterial pressure or heart rate, and significant attenuation of pressor responsiveness to angiotensin II (AII) delivered intracranially. However, the increase in arterial pressure observed over a 4-week period following the application of a 0.5 mm silver clip to the left renal artery (opposite kidney intact) was identical in 12 AV3V-lesioned and 12 sham-operated rabbits. Hypertension development was not accompanied by significant sodium retention, water retention, or plasma/extracellular fluid volume expansion in either group of rabbits. Pressor responses to intravenous infusions of AII and norepinephrine were identical in sham and AV3V-X rabbits. Thus, destruction of the AV3V, and the attendant reduction in the central pressor action of AII, does not alter the pattern of development of two-kidney, one clip renal hypertension in the rabbit. The contrasting results in rats and rabbits could be explained by the differing contribution of the area postrema to the pressor action of AII in the two species.

Continuous blood pressure measurement in rats with aortic baroreceptor deafferentation.

The purpose of this study was to determine if once-daily arterial pressure measurements are a reliable estimate of actual time-averaged arterial pressure in neurogenic hypertensive rats. Male rats were subjected to either aortic baroreceptor deafferentation (ABD, n = 10) or sham operation (SO, n = 10). One to 3 mo later, arterial pressure (AP) was recorded from a chronic indwelling catheter in each rat for 72 continuous hours. Subsequently, AP was determined once a day (10- to 30-min recording periods) in each rat for an additional 3 consecutive days. Continuous recording yielded an average mean arterial pressure (MAP) of 104 +/- 2 mmHg in SO rats and an average mean MAP of 120 +/- 3 mmHg in ABD rats. Standard deviation of MAP measured every 5 min for 24 consecutive hours (as an index of pressure lability) was 8.0 +/- 0.4 mmHg in SO rats and 14.4 +/- 1.3 mmHg in ABD rats. Both of the above differences were statistically significant (P less than 0.05). The average MAP from daily measurements in the same rats was 107 +/- 3 mmHg in SO rats and 124 +/- 3 mmHg in ABD rats. Average pressure values were not statistically different for the two measurement techniques in either group of rats. Overall, there existed a significant correlation (r = 0.64, P less than 0.01) between MAP measured continuously and daily in the 20 rats studied. We conclude that daily direct measurement of MAP in conscious ABD rats yields a satisfactory estimate of actual time-averaged MAP in these rats despite their markedly increased MAP lability.

Hip endoprosthesis stabilization with a porous low modulus stem coating: factors influencing stabilization.

A polytetrafluoroethylene/vitreous carbon porous material has been investigated as an alternative to acrylic for hip endoprosthesis fixation. This material, which is mechanically fused to the endoprosthesis stem, has been shown to promote soft-tissue ingrowth. In 29 patients receiving a porous-coated Thompson endoprosthesis, stabilization of the porous-coated stem as observed by acceptable clinical results occurred in only about 50%. Stabilization of porous-coated endoprostheses is unsatisfactory for the following reasons: lack of press-fit, inadequate prosthetic design, infection, and technical difficulties. The major cause of 40% failure in this series was an initially inadequate press-fit.