Biomedical subjects
Publications and source records attributed to C W Christensen.
A patient with advanced adenocarcinoma of the cervix was treated only with cisplatin and mitomycin C (MMC). The regimen achieved a complete response, confirmed by chest radiograph and computed axial tomography scan, lasting 50 months. The patient is alive with recurrent disease 59 months after diagnosis. No severe drug-related toxicity occurred.
Neoadjuvant chemotherapy with cisplatin and mitomycin-C was used in the primary treatment of 17 patients with locally advanced cervical cancer (stages Ib-IIIb; tumor diameter greater than 5 cm) prior to definitive local treatment with radical hysterectomy or radiotherapy. Thirteen of the seventeen patients (76.5%) responded to initial chemotherapy, permitting a radical hysterectomy in ten patients. At histologic examination of the surgically resected primary tumor and lymph nodes, complete pathologic responses were found in 2 patients and partial pathologic responses in 8 patients. The median follow-up time is 14.5 months with a median survival for all patients of 52 weeks. All responders are alive. No therapy-related deaths, major complications, or delay in treatment occurred. Neoadjuvant chemotherapy with mitomycin-C and cisplatin is feasible and may be of benefit for patients with locally advanced cervical cancer.
Fourteen patients with poor-prognosis cervical cancer were treated with concurrent chemotherapy (cisplatin and mitomycin-C), external radiation therapy (RT), and high-dose-rate (HDR) brachytherapy. Pelvic RT was delivered as (a) external-beam radiation (four-field box technique, 40.0 Gy), (b) brachytherapy using HDR 60Co or 192Ir (3.80 Gy/fraction, thrice weekly; total dose, 46.83 Gy) with intrauterine stent, and (c) parametrial boost using an AP field with custom-fabricated step wedges. Post-radical-hysterectomy patients received 50.40 Gy external RT and 3.23 Gy/day vaginal cylinder HDR at 1/2-cm depth (total dose, 16.15 Gy). Complete clinical and radiographic response was noted in all evaluable patients who are alive with no evidence of disease, 3 to 27 months after completion of therapy (median, 9 months). Toxicity consisted of grade 2 to 3 hematologic toxicity (4 patients) and nausea and vomiting in all, but grade 3 in only 2 patients. One patient had grade 2 diarrhea. The only major complication (small bowel obstruction) occurred in a patient with lupus vasculitis. This pilot study demonstrates the feasibility of this regimen in an outpatient setting with acceptable toxicity. More prolonged follow-up of our patients is required to determine its impact on long-term survival.
To evaluate coronary flow reserve during cardiac catheterization, intracoronary adenosine and papaverine have been used in the clinical setting. Although papaverine maximizes coronary blood flow, it induces several toxic side effects that reduce its desirability as a coronary dilator. This investigation was designed to compare the subselective intracoronary administration of papaverine with that of adenosine in an animal model. In dogs (n = 34), we studied the effects of each agent on hemodynamics, regional myocardial blood flow, contractility (sonomicrometric and echocardiographic), metabolism (coronary arterial and venous lactate and tissue high-energy phosphates), and electrocardiographic (ST and QT intervals) parameters. Barbiturate and morphine anesthesia/analgesia was induced, and a left thoracotomy was performed. An arterial shunt was created from the left carotid artery to the left anterior descending coronary artery. Two separate groups were studied: group 1 (n = 16) for regional myocardial blood flow and mechanical function and group 2 (n = 18) for biochemical measurements. Adenosine (67 +/- 2 micrograms/min) or papaverine (6 +/- 1 mg/min) was infused into the coronary shunt at a rate of 0.5 + 0.1 ml/min for a maximum duration of 3.5 minutes. Regional myocardial blood flows were determined at control (predrug) and maximal coronary flow using radiolabeled microspheres. All hemodynamic, wall motion, biochemical, and electrocardiographic parameters were also measured at these times. Both drugs produced comparable increases in total and regional coronary blood flows (adenosine, 1.21 +/- 0.15 to 4.83 +/- 0.36 ml/min/g; papaverine, 1.21 +/- 0.05 to 4.89 +/- 0.28 ml/min/g) upon infusion into the left anterior descending coronary artery. Papaverine produced significant (p less than 0.05) changes in subendocardial ST segment electrocardiogram (-2.5 mm), QT prolongation (8 +/- 2%), myocardial creatine phosphate (47% decrease), and coronary sinus serum lactate (277% increase) compared with control. In addition, intracoronary papaverine induced an abnormal contractile pattern. No significant changes in any of these parameters (i.e., ST segment, QT prolongation, myocardial creatine phosphate level, or lactate level) were observed with intracoronary adenosine infusions. We conclude that intracoronary adenosine is comparable to papaverine for maximizing coronary blood flow without the deleterious properties observed with intracoronary papaverine.
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We investigated the ability of two new coronary perfusion catheters to maintain regional myocardial blood flow throughout a 90-minute period of occlusion. In 21 dogs (group I = total occlusion control; group II = reperfusion catheter; group III = autoperfusion balloon catheter) we studied regional blood flow, distal coronary perfusion pressure, infarct size, and red blood cell hemolysis after placement of either catheter into the left anterior descending coronary artery. Regional (microsphere) blood flow showed a reduction in transmural blood flow during occlusion in comparison to baseline values (1.07 +/- 0.12 to 0.81 +/- 0.11 and 1.01 +/- 0.16 to 0.73 +/- 0.08 ml/min subendocardial perfusion for groups II and III, respectively). Comparable changes in blood flow were observed in the subepicardial and midmyocardial regions. Distal coronary perfusion pressures were reduced by 26% and 28% for groups II and III, respectively. Both catheters prevented significant infarction and maintained adequate regional myocardial blood flow throughout the 90-minute period of occlusion without significant complications of clotting or destruction of erythrocytes.
Six patients with metastatic ovarian cancer with extensive involvement of the pelvic and/or para-aortic lymph nodes underwent surgical debulking with the Cavitron Ultrasonic Surgical Aspirator. Intraoperative and postoperative morbidity was minimal. It is suggested that this technique may be used for cytoreductive surgery in combination with standard surgical techniques.
Cisplatin-induced nausea and vomiting occurs both acutely and over a prolonged period of time. These symptoms may be incapacitating and are frequently given as a reason to discontinue therapy. We compared prochlorperazine and transdermal scopolamine when added to a standardized metoclopramide antiemetic regimen. Twenty-seven patients receiving cisplatin at 100 mg/m2 were randomly assigned to one of the two treatment arms. Patients were observed during chemotherapy and answered a standard questionnaire 24-26 hours later. Among similar treatment groups no differences were seen regarding the number of emetic events, level of nausea, degree of sedation or overall acceptability of one treatment arm or another. While not superior to prochlorperazine, transdermal scopolamine is a useful antiemetic agent and can be combined with metoclopramide in an attempt to reduce cisplatin-induced nausea and vomiting. Further evaluation of this approach is needed.
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The purpose of this investigation was to determine the subtypes of alpha adrenoceptors present in human saphenous vein and to determine if there is a large receptor reserve for phenylephrine as has been demonstrated in canine saphenous vein. The subtypes of alpha adrenoceptors found in isolated human saphenous vein were determined using selective alpha-1 and alpha-2 adrenoceptor agonists and antagonists. Prazosin, a selective alpha-1 antagonist, produced a parallel shift of the concentration response curve to phenylephrine, a selective alpha-1 agonist, with no significant reduction in the maximal response. Yohimbine, a selective alpha-2 antagonist, produced a parallel shift of the concentration response curve to B-HT 920, a selective alpha-2 agonist, with no reduction in the maximal response. The pA2 values obtained for prazosin and yohimbine in human saphenous vein agreed closely with corresponding values obtained in canine saphenous vein. These results demonstrate that both alpha-1 and alpha-2 adrenoceptors exist in human saphenous vein. Phenoxybenzamine (10(-7) M), an irreversible alpha-1 adrenoceptor antagonist, markedly reduced the maximal response produced by phenylephrine, an agonist with high intrinsic activity, with no significant shift in the concentration response curve in human saphenous vein, suggesting that there was little or no alpha-1 receptor reserve for phenylephrine. The sensitivity of alpha-1 versus alpha-2 adrenoceptor-mediated vasoconstrictor responses to nitroglycerin were compared in human and canine saphenous veins. In both species, nitroglycerin blocked the vasoconstrictor response produced by stimulation of alpha-2 adrenoceptors to the same degree.(ABSTRACT TRUNCATED AT 250 WORDS)
We examined the influence of glass bead embolization and oleic acid, dextran, and imipramine infusion on the pulmonary uptake of trace doses of [3H]serotonin and the extravascular volume accessible to [14C]antipyrine in anesthetized dogs. Embolization and imipramine decreased serotonin uptake by 53 and 61%, respectively, but no change was observed with oleic acid or dextran infusion. The extravascular volume accessible to the antipyrine was reduced by 77% after embolization and increased by 177 and approximately 44% after oleic acid and dextran infusion, respectively. The results suggest that when the perfused endothelial surface is sufficiently reduced, as with embolization, the uptake of trace doses of serotonin will be depressed. In addition, decreases in serotonin uptake in response to imipramine in this study and in response to certain endothelial toxins in other studies suggest that serotonin uptake can reveal certain kinds of changes in endothelial function. However, the lack of a response to oleic acid-induced damage in the present study suggests that serotonin uptake is not sensitive to all forms of endothelial damage.
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It has been suggested that the peptides alpha-metanocyte stimulating hormone (alpha-MSH) and MSH-release inhibitory factor (MIF-1) may alter adenosine-3', 5'-cyclic monophosphate (cAMP) metabolism [13,26]. Normal and hypophysectomized (hypoxed) rats were administered saline (controls IP daily X 3), alpha-MSH (80 mug/kg IP daily X 3) or MIF-1 (1 or 10 mg/kg IP daily X 3) and sacrificed 30 min after the third injection in a focused microwave oven (1.5 KW; 2-3 sec). Various brain areas were then assayed for cAMP levels after each treatment. The occipital cortex area was the only area to show consistent changes in both normal and hypoxed rats after alpha-MSH treatment. These findings were replicated for the occipital cortex in a second group of normal and hypoxed rats which were similarly treated. The results suggest a correlation between the rise in cAMP found and reported changes in visual acuity and attention in rats and human after treatment with alpha-MSH [8,14, 23].
Previous reports have indicated that alpha-MSH release inhibiting hormone (MIF-1) increased the behavior occurring as a result of the dihydroxyphenylalanine (DOPA) potentiation test [3,7]. This study was undertaken to see whether dopamine (DA) or norepinephrine (NE) levels likewise increased in the test animals. The DOPA potentiation test was performed as follows: 2-4 hr before behavior measurement, 40 mg/kg of the monoamine oxidase inhibitor pargyline HCl was given orally. Two hr later this was followed by the intraperitoneal (IP) injection of MIF-1 at doses of 0.1, 0.3 or 1.0 mg/kg. Behavioral measurement was begun after the IP injection of 200 mg/kg of dl-DOPA 1-2 hr after the MIF-1. The parameters included social interaction, aggressiveness, fighting, ataxia, jumping, defecation, urination and salivation. The animals were beheaded while the behavior was still increased and the striatal area removed, placed in aluminum foil, and kept at -50 degrees C until assayed. In general, especially among the younger animals, a significant correlation (p=0.05 to p=0.01) was found between the increased behavioral responses to MIF-I and the rise in DA. Because of a few exceptions to this correlation the possibility is suggested that MIF-I might also affect behavior by acting directly on the postsynaptic membrane thus bypassing any change in NE or DA which is known to increase cycli AMP in the striatum.