Immature teratomas of the genital tract in older women.

We report the clinicopathologic features of three women, 40 years of age or older, with malignant genital tract immature teratomas. All had FIGO stage III, grade II or grade III tumors. One tumor arose from the fallopian tube, the second from the ovary, and the third involved the cortical surfaces of both ovaries with minimal parenchymal involvement. The tumors weighed 1700, 5660, and 330 g and had histologic features similar to those generally seen in younger women. Two of the women died within 1 year of diagnosis. Interval growth of tumor after treatment with chemotherapy was documented in the third patient; she was reexplored and all of the excised tumor was composed of mature tissues. These cases affirm that, although rare, malignant germ cell tumors can occur in older peri- or postmenopausal women.

Experience with the P.A.S.-PORT venous access device in patients with gynecologic malignancies.

Experience with the P.A.S.-PORT, a peripherally implanted central venous access device, is evaluated in a retrospective review of 154 patients from July 1991 to June 1994. Blood could not be aspirated from six patients. Complications included temporary minor thrombophlebitis in seven patients (4.5%), symptomatic axillary or subclavian vein thrombosis in five patients (3.2%), clotted port in two patients (1.2%), port pocket cellulitis in two patients (1.2%), and fungal sepsis in two patients (1.2%). In six patients (3.8%) the P.A.S.-PORT had to be removed because of complications. The P.A.S.-PORT facilitated delivery of chemotherapy, parenteral nutrition, blood products, antibiotics, hydration, and blood sampling. It was demonstrated that the P.A.S.-PORT may be inserted and used with a low incidence of complications in gynecologic cancer patients.

Skeletal muscle of a growing organism has a greater transformation after electrical stimulation than adult skeletal muscle.

Six adult sheep and four newborn lambs (5 days old) were implanted with stimulator leads into the latissimus dorsi muscle and connected to a Myostim 7220 pacing system (Telectronics Pacing Systems, Inc., Englewood, CO). Electrical stimulation was started immediately after the operation. After 8 weeks of electrical stimulation, contractile force (CF) in adult sheep decreased to 76-81%, and to 78-82% in lambs. After 2 weeks' delay, CF in adults was 96-98%, and only 89-93% in lambs. After a 30 min intensive stress test, unconditioned control muscle lost 39% in lambs and 43% in adults. Muscle conditioned for 8 weeks lost 7-8% CF. However, after 2 weeks' delay, CF in adult muscle lost 33%, but only 12% in lambs. After cessation of electrical stimulation, the LDH-5 and LDH-1 + 2 fractions reverted to initial levels in adults, whereas in lambs, these levels continued to follow trends established during electrical stimulation. In both adults and lambs, the percent area occupied by the mitochondria increased during electrical stimulation by 6.9% in adults and 6.5% in lambs. After electrical stimulation cessation, the percent area in adults returned to baseline levels, whereas it continued to be elevated in lambs (3.3% vs 5.1%, respectively). The transformed muscle of the lamb did not revert to baseline levels after a delay period.

Magnesium sulfate reduces myocardial infarct size when administered before but not after coronary reperfusion in a canine model.

BACKGROUND: The role of magnesium in treating acute myocardial infarction (AMI) has been controversial. Several small clinical trials indicate that magnesium may have a role in treating AMI early, whereas the other results suggest that magnesium is of questionable benefit. METHODS AND RESULTS: We looked at the effect of magnesium on infarct size (IS) when given during a coronary occlusion and after reperfusion. Magnesium sulfate (6-mEq bolus plus 2 mEq/h for 5 hours) was given at 15 or 45 minutes of coronary occlusion or 15 minutes of reperfusion. The left anterior descending coronary artery was occluded for 90 minutes, followed by 300 minutes of reperfusion. IS to area at risk (IS/AR) was measured by planimetry after triphenyltetrazolium chloride staining. Collateral myocardial blood flow was measured with radioactive microspheres. The IS/AR ratio in the control group was 52.3 +/- 19.6% compared with 20.5 +/- 11.7% and 21.3 +/- 6.5% at 15 and 45 minutes of occlusion, respectively (P < .05). There were no significant differences in the reduction in IS at 15 and 45 minutes of occlusion. Although there was a reduction in the IS when magnesium was administered during reperfusion (38.2 +/- 13.4%), it was not statistically significant. There was no significant difference in the AR relative to the total left ventricular weight between the four groups. CONCLUSIONS: The data suggest that magnesium infusion during a coronary occlusion has a significant benefit in reducing the IS in this model. Magnesium may have a beneficial clinical role in AMI, especially if administered before reperfusion as a bolus followed by a constant infusion.

Is it possible to perform immediate cardiac assist using untrained latissimus dorsi muscle in a work-rest regimen?

The authors investigated what contractile force (CF) could be obtained from unconditioned latissimus dorsi muscle immediately after mobilization and for the 2 week vascular period of recovery. Latissimus dorsi muscle mobilization was performed on seven adult (4 experimental and 3 control) sheep leaving only the pedicle and the peripheral muscle intact. Telectronics stimulators (Myostim 7220; Teletronics Pacing Systems, Inc, Englewood, CO) were implanted. Immediately after mobilization 11-35% of the initial CF was lost. A 30 min fatigue test was performed 1 hr after mobilization (20 g/kg preload, 10 V, 10 Hz, 15 BPM, 6 impulses per burst) using a 1 min work-1 min rest regimen. Two sheep lost 2-12% of initial CF; two increased CF by 14-24%. At the end of the fatigue test, CF consisted of 74-89% of immobilized CF. Electrical stimulation training of the muscle was then initiated with the following regimen in the experimental animals only: 15 BPM, single impulses, 5 V, 10 Hz. Every day the muscle was exercised using a work-rest regimen to mimic cardiac assist, starting with 20 min on day 2, and increasing by 2 min per day until a total of 50 min was reached on day 16. All animals were retested for CF using a 42 min fatigue test on days 6, 11, and 16. On day 6, there was no fatigue evident in the experimental group during the 42 min test. CF after testing was 59-81% (mean 67%) of initial data. In the control group (animals with no electrical stimulation training protocol), CF decreased by 11% (from 64 to 53%). On day 11, there was no fatigue evident in the experimental group; CF in all animals increased by 2-8%. On day 16, there was also no fatigue evident in the experimental group; CF increased by 0-9%. An additional 20 min of continuous contraction (15 BPM) fatigue testing was performed on the muscle without rest between the tests. No fatigue was evident at the end of testing. Light microscopic analysis of latissimus dorsi muscle biopsy specimens taken on the days of testing showed no evidence of necrotic damage. Our investigations suggest that it may be possible to start muscle transformation immediately after mobilization and use the untrained latissimus dorsi muscle for cardiac assist immediately after surgery for short periods.

Force enhancement of skeletal muscle used for dynamic cardiomyoplasty and as a skeletal muscle ventricle.

Some patients with pre end-stage congestive heart disease do not receive a significant hemodynamic benefit from dynamic cardiomyoplasty because, during prolonged preoperative immobilization, their latissimus dorsi muscle (LDM) becomes extremely weak. It is the authors' hypothesis that the local administration of an anabolic steroid into an electrically stimulated LDM will produce a thicker and stronger muscle with significant resistance to fatigue. The electrical stimulation training protocol of sheep continued for 8 weeks. For localized anabolic steroid administration an osmotic pump was placed in a subcutaneous pocket and the catheter was introduced into the LDM. The contractile force of electrically stimulated and unstimulated control muscle was studied. Control data were calculated as 100% and all other data were corrected to control. After 4 weeks there was no decrease in contractile force. The change seen was from 88 to 100% with different preloads (10, 15, and 20 g/kg) and amplitudes of impulses (5 and 10 V). After 8 weeks, the LDM was more powerful than before electrical stimulation, with a change of 97-133%. Usually after 8 weeks of electrical stimulation alone, contractile force decreases to 70-75%. During a fatigue test (30 min, 100 bursts per minute, 10-25 Hz, ripple frequency, 10 V impulse amplitude) after 4 and 8 weeks of our protocol, the LDM lost only 12% of its initial force, whereas control muscle lost 40%. Thus local anabolic steroid administration makes the LDM stronger and more useful for cardiomyoplasty.

Endothelial cell seeding of latissimus dorsi muscle pouches.

The transformation of skeletal muscle tissue into a fatigue-resistant, autologous blood pump is being explored as an attempt to aid the failing heart. One of the options is to generate a pouch underneath the latissimus dorsi muscle, to connect an electrically conditioned muscle pouch to the circulation, and to use it as an autologous, contractile cardiac assist device. However, the potential of thrombus formation on the blood contacting surface, which is composed of fibrous material, might thwart the clinical usefulness of such skeletal muscle ventricles. We hypothesized that the thrombogenicity of these pouches could be reduced by lining their luminal surfaces with autologous endothelial cells. As a first step, we examined the feasibility of this approach under resting, nonbeating conditions. Using a multistage operative procedure, we isolated microvascular endothelial cells from canine adipose tissue and, after culturing these cells in the laboratory, seeded the autologous cells into preformed latissimus dorsi pouches in six mongrel dogs. Four to six weeks later the dogs were sacrificed and the ultrastructure of the pouches was examined by light and electron microscopy and by fluorescence techniques. The micrographs confirmed that the surfaces of seeded pouches, but not of the untreated controls, are lined with a continuous monolayer of functional endothelial cells, as assessed by the presence of several endothelial cell-specific markers. Current studies are under way to assess the thrombogenicity of these endothelialized skeletal muscle pouches.

Treatment of recurrent and metastatic endometrial carcinoma with cisplatin and doxorubicin.

Between April 1985 and February 1989, 19 patients with advanced or recurrent endometrial carcinoma were treated with the combination of cisplatin (50 mg/m2) and doxorubicin (50 mg/m2) administered intravenously every 21 days. Eight patients had Stage III disease, two had Stage IV and nine had recurrent cancer. Eleven patients had measurable disease at the start of therapy. There were 7 partial responses among the 19 patients, for an overall response rate of 36%. The median survival for the whole group was 17 months with a median progression free interval of 5 months. Patients without measurable disease at the onset of therapy had median survivals and progression free intervals which were significantly better than those patients with measurable disease, p < 0.011 and p < 0.025 respectively. Granulocytopenia (< 1000 microliters) occurred in 7 patients. No important thrombocytopenia, cardiotoxicity nephrotoxicity or neurotoxicity was observed. Emesis and alopecia occurred in all patients. No treatment related deaths were encountered.

Evaluating the flow characteristics of artificial pumping devices using nuclear scintigraphy.

The design and development of artificial blood pumps require qualitative and quantitative data relative to pump filling, ejection, and wall motion in order to optimize the design and maximize the pattern of blood flow through the pump. To assist in the development of an artificial heart, we utilized radionuclide scintigraphy and a high-resolution gamma camera to evaluate the flow patterns through the pump. We performed a comparative analysis of the flow patterns in a pneumatically driven ventricular assist device (Sarns/3M VAD) and the electrically driven Milwaukee Heart. These analyses disclose some significant differences between the two devices with regard to the blood sac compression patterns and ejection as well as valvular regurgitation. On the basis of these findings, nuclear scintigraphy for analyzing fluid shear stress and flow dynamics seems a useful technique for evaluating blood flow through artificial blood pumps. Because the procedure does not require a translucent casing or direct contact with the device being studied, it would be especially useful in evaluating artificial blood pumps implanted in patients with heart failure.

Morphology and integrity of endothelial cell monolayers inside a ventricle shaped perfusion chamber.

The long-term maintenance of patients with failing hearts on cardiac prostheses requires prevention of device related thromboembolic events. This challenge is being addressed by endothelialization of the blood sacs. However, the practice of establishing and maintaining a durable endothelial cell monolayer inside a beating prosthesis has not been fully realized. Thus, before exposing endothelial cell monolayers to the hemodynamics inside an artificial heart, the authors studied the effect of various flow patterns in a ventricle shaped chamber on the integrity and morphology of the endothelium. After 20 hours of superfusion by pulsatile flow, there were no denudation signs in the jet, where shear stress was 1.5 dynes/cm2. However, there was measurable damage to the monolayer close to the periphery of the eddies (turbulent flow) at 0.15 dynes/cm2. In either case, there were no signs of cell alignment with the flow, but there were changes in cell morphology compared with that of static control. These findings suggest that adjustment of endothelial cells in response to frictional forces occurs even at low shear stresses and that random velocity fluctuations might jeopardize the integrity of endothelial cell monolayers.

[Electrosurgical loop excision as diagnostic and simultaneously therapeutic intervention in cervical intraepithelial neoplasia]. / Elektrochirurgische Schlingenexzision als diagnostischer und gleichzeitig therapeutischer Eingriff bei der zervikalen intraepithelialen Neoplasie.

109 women referred to our center for colposcopy because of suspicious cervical cytology and in whom an abnormal epithelial pattern was diagnosed on colposcopy, or in whom a discrepancy between cytology and colposcopy was encountered, concomitantly underwent loop electrosurgical excision procedure as an outpatient procedure. All removed specimens were examined and no invasive cancer was found in any of them. No serious complications occurred. Ambulatory loop electrosurgical excision procedure appears to be a cost-effective and well tolerated treatment modality for the management of women with cervical intraepithelial neoplasia, with the advantage that this conservative procedure allows histologic examination of the removed tissue.

Experimental studies of pulsatile flow and endothelial cell adaptation in ventricle shaped cell culture chambers.

The authors' long-term research goal is to minimize the risk of thromboembolic complications in cardiac prostheses by lining blood contacting surfaces with a functional monolayer of autologous endothelial cells. These cells recognize changes in hemodynamics and can adapt effectively to experimentally manipulated flow conditions. By implication, the morphology of endothelial cells, in conjunction with their function, might serve as an indicator of the flow patterns in a particular location. It was hypothesized that, by understanding flow patterns at a given site, the local morphology and function of the endothelial cells in such a region could be predicted. To test this hypothesis, a series of ventricle shaped flow chambers were designed and perfused with pulsatile flow. The flow field in the chambers was studied by computer aided dye visualization and nuclear scintigraphy. The results showed that the large scale motion of the fluid in the cavity was highly coherent and consisted of distinct flow patterns. The temporal and spatial characteristics of the flow patterns, and their implications with respect to endothelial cell endurance in this in vitro environment, were examined in detail.

In vitro assessment of the Milwaukee Heart and right to left balance.

A new, electrically powered, total artificial heart, the Milwaukee Heart, has been developed. This device is undergoing testing in vitro. The unidirectional motion of the brushless DC motor (BDCM) affords easier motor control and reduces energy demand. Motors with a unidirectional motion have a longer life than those with bidirectional motion. This device requires less power due to the highly efficient mechanical design. It consumes 6.5 W of power at an average flow of 5 L/min into 100 mmHg of mean aortic pressure and 20 mmHg of mean pulmonary pressure. Pumping at 8 L/min it requires 9.6 W of power. The maximum pump flow is 10 L/min and overall efficiency is 20%. A slotted optocoupler is used to determine the position of the pusher plate at the start of left systole. The number of revolutions that the BDCM makes is counted from this position. There are 50 revolutions of the BDCM per stroke (using a 50:1 gear reducer connected to the motor). The position of the pusher plate is determined from the number of BDCM revolutions. Based on where the pusher plate encounters resistance from the bladder, the force on the left pump is increased or decreased. Left to right balance has been achieved by reducing the size of the right pusher plate in conjunction with varying right stroke volume. In vitro tests show that this new, electrically powered artificial heart provides reliable performance and satisfactory hemodynamic results.

High-dose-rate afterloading brachytherapy, external radiation therapy, and combination chemotherapy in poor-prognosis cancer of the cervix.

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.

A preliminary report of combination chemotherapy with cisplatin and mitomycin-C followed by radical hysterectomy or radiation therapy in patients with locally advanced cervical cancer.

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.

Combination chemotherapy for advanced adenocarcinoma of the cervix.

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.

Application of a new nuclear scintigraphy camera to evaluate flow and mechanical pumping of artificial hearts.

To assist in the development of an artificial blood pump, The Milwaukee Heart (MH-1), a new nuclear scintigraphy camera was used to study the wash-in and wash-out patterns of the MH-1. These studies indicate the MH-1 has an ejection fraction of 59.3%, with a stroke volume of 72 +/- 3 ml, and an afterload of 130 mmHg. Flow through the device is highly uniform, with no areas of stagnation. Regional ejection fraction images demonstrate homogeneous ejection from apex to base. The ability to scan through the first pass images allows study of wash-in, mixing, and wash-out of the tracer. In conclusion, this technique may provide a new approach to evaluating artificial heart pumps.

Coronary vasodilator reserve. Comparison of the effects of papaverine and adenosine on coronary flow, ventricular function, and myocardial metabolism.

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.