[Health condition of female aerobic dance instructors. Subjective symptoms and related factors].

Aerobic dance has recently become popular in all age groups, but the injuries among full-time and part-time aerobic dance instructors have rarely been pointed out in Japan. In this study the subjective symptoms of 63 female instructors in Gifu area were evaluated through health questionnaire. As a control group, 94 female students of the same age group were also included to compare the prevalence of subjective symptoms. Multiple logistic regression analysis was applied to observe the relation between instructors' symptoms and working conditions. The following results were obtained: 1) Complaints of leg and foot pain and laryngeal discomfort were significantly greater in instructors than in students even after adjusting for age and participation in other sports. 2) A significant positive relation was found in instructors between the frequency of dance lessons (times/wk) and various symptoms (calf pain, foot pain, sore throat, and hoarse voice) after adjusting for age and participation in other sports. These results suggest that leg and foot pain and laryngeal discomfort are characteristic symptoms of aerobic dance instructors. Consideration should be made to adjust the frequency of dance lessons in order to reduce these symptoms.


[A simple method for measuring cleaning solvent in air by gas detector tube for ethyl acetate].

A simple method for measuring cleaning solvent in air by gas detector tube for ethyl acetate was evaluated with regard to basic performance such as sensitivity, precision, discolor tone and effect of temperature. Satisfactory results were obtained with regard to sensitivity, precision, discolor tone in the indicator and stability of discolored length. Range of measurable concentration by the present method was about 25-800 mg/m3. It was found necessary in the present method to make temperature correction. It was concluded from these results that the present method is useful for measuring cleaning solvent in air. However, positive effect on discolored length was found by vapor of toluene and ethyl acetate when they coexisted. No effect on discolored length was found by vapor of acetone, methanol or trichloroethylene.


[Sex difference in free erythrocyte protoporphyrin (FEP) level. I. Sex difference in FEP level in healthy rural residents].

FEP and other hematological parameters were measured in 157 healthy rural residents (98 females and 59 males). The mean FEP in females was higher than in males (p less than 0.05); mean +/- SD = 62.98 +/- 19.36 and 54.57 +/- 21.20 micrograms/dl.pcv, respectively, although both of the means were within normal limits. There was no significant sex difference in erythrocyte ALA-D activity. Whole blood lead (Pb-B) level in females showed a tendency to be lower than in males, but there was no significant sex difference in erythrocyte lead level. The mean value of hematocrit (Ht), hemoglobin (Hb) and iron in serum (Fe-S) were lower in females than in males (p less than 0.01). Serum GOT and GPT level tended to be lower in females than in males (0.05 less than p less than 0.1). There was hardly any significant relationship between Pb-B and each parameter of lead exposure, because the subjects in this study were only rural residents with no occupational lead exposure and with their Pb-B levels being extremely low. As for the parameters of anemia, Fe-S was positively correlated with Ht and Hb level and negatively correlated with FEP level. By sex, Fe-S was correlated with Ht and FEP level only in females. As for the possible reasons why FEP level in females in higher than in male, women tended to have iron-deficiency induced by blood loss due to menstruation, pregnancy, and difference in dietary pattern from males.


[Sex difference in free erythrocyte protoporphyrin (FEP) level. II. Sex difference in FEP level in rats exposed to lead].

An experimental study on Donryu rats was primarily carried out to elucidate sex difference in FEP level. Each of 33 male and 33 female rats was divided into 3 groups; that is, control group (5% glucose solution only), low lead dose group (Pb 0.5 mg/kg.BW) and high lead dose group (Pb 5 mg/kg.BW). Lead was injected intraperitoneally once a week for 6 wk. FEP, Ht, urinary coproporphyrin (CP-U), delta-aminolevulinic acid (ALA-U) and porphobilinogen (PBG-U) were determined once every two weeks for 6 wk, and whole blood lead (Pb-B) at the end of the experiment. Mean value of Ht was lower in females than in males throughout the period of the experiment in almost all groups. Pb-B level of all groups and erythrocyte Pb level of high dose group were higher in males than in females. FEP level without lead injection and with low lead exposure was higher in males than in females. By analysis of variance for gain from initial FEP level, only the low lead dose group demonstrated a significant sex difference (p less than 0.01); the female group tended to increase, while the male group maintained a constant level. Furthermore, FEP/Pb-B ratio in females was higher than in males only for the high dose group. The changes in ALA-U in male and female rats were comparable to those in FEP. Unlike FEP and ALA-U, CP-U level was higher in males than in females only for the high lead dose group. In this study using rats, sex difference in FEP level was different from that in human.(ABSTRACT TRUNCATED AT 250 WORDS)


[Total aortic arch graft replacement using a prosthetic graft with three branches for acute type A aortic dissection].

Between March 1991 and August 1991, six consecutive patients underwent the replacement of the both ascending aorta and total aortic arch using a prosthetic graft with three branches for acute type A aortic dissection involving the aortic arch. Preoperative complications included cardiac tamponade in 5 cases, aortic regurgitation in 2, and shock state in 3. All operations were performed with the aid of extracorporeal circulation, selective cerebral perfusion, and open aortic anastomosis within 3 days after the onset. One patient died of rupture of the aortic anastomosis secondary to mediastinitis two weeks after the operation. All patients gained their own consciousness after the operation without any serious cerebral complications. The present data suggest that acute type A aortic dissection involving the aortic arch could be treated by replacing both the ascending aorta and aortic arch using a prosthetic graft with three branches with an aid of the extracorporeal circulation, selective cerebral perfusion and open distal anastomosis.


[Postoperative respiratory dysfunction in patients with Stanford type A aortic dissection].

Between 1986 and 1990, 24 patients with Stanford type A dissection (acute; 14, chronic; 10) underwent surgery through median sternotomy. The patients were divided into two groups by a duration of postoperative ICU stay for respiratory care. Six patients in the long-period group stayed in ICU for more than 15 days and 18 patients in the short-period group stayed for less than 15 days after surgery. Acuity of disease, age, sex, operation time, pump time, aortic clamp time, lowest esophageal temperature, amount of blood transfusion, arch manipulation for cerebral perfusion with or without arch reconstruction, occurrence of phrenic nerve palsy and other postoperative complications, postoperative cardiac, hepatic and renal functions were compared between two groups. Conclusions are as follows: 1) Arch manipulation for cerebral perfusion with or without arch reconstruction, phrenic nerve palsy, other complications (pericardial and pleural fluid accumulation, recurrent nerve palsy, postoperative bleeding and coronary spasm) and high serum creatinine level were main factors for prolonged postoperative ICU stay for respiratory care and 2) arch manipulation in the patients with chronic type A aortic dissection induced high incidence of phrenic nerve palsy.


[Total aortic arch replacement through a median approach].

Seven patients underwent total aortic arch replacement only through a median approach since March 1990, in our institute. The woven Dacron graft with three side arm branches were used. After the proximal anastomosis at the ascending aorta, open distal anastomosis at the descending aorta was performed in five cases, under circulatory arrest of the lower body using separate perfusion to the brain. In two cases with true aneurysms involving the aortic arch, occlusion balloon catheters were employed for distal anastomosis. The anastomosis of the arch vessels was performed after coronary reperfusion. There was no early operative death, and our results demonstrate that total arch replacement can be safely accomplished through a median approach with an acceptably low operative risk.


[Basic study of myocardial coagulation by intraoperative laser ablation: in the presence and absence of blood].

To investigate whether the efficacy of laser ablation therapy is affected by the color of the target organ, we irradiated 9 canine hearts through the epicardium with Nd-YAG laser (200 J, 400 J), and compared coagulated myocardial volume in the beating heart (reddish) with that in the stopped heart (whitish) infused with 0 degrees C saline (cardioplegic model) via a coronary artery. The coagulated myocardial volume of the beating heart was significantly larger than that of the arrested heart, indicating the YAG laser energy is absorbed by red myocardium to greater extent than it is by white myocardium. In conclusion, during intraoperative laser ablation, the presence or absence of blood in cardiac tissue is an important factor for safe irradiation.


[Autogenous pericardial patch augmentation of the anastomotic orifice of Blalock-Taussig shunt].

Our recent experiences of the autogenous pericardial patch augmentation of Blalock-Taussig anastomotic orifice are reported. In Case 1, the direct suture between the left subclavian artery and the left pulmonary artery was difficult on the anterior wall because of the shortness of the left subclavian artery. Therefore, a piece of the patient's own pericardium was excised and sutured anteriorly between the two vessels by interrupted 7-0 polypropylene sutures. A 19 months postoperative angiogram showed so-called parrot-beaking of the subclavian artery probably due to tension, but there was no distortion or stenosis of the pulmonary artery. In Case 2, the right subclavian artery distal to the bifurcation of the vertebral artery was longitudinally split measuring approximately 2.5 cm in length, and widened by a piece of the autogenous pericardium in a wedge shape. Then, it was anastomosed to the right pulmonary artery without undue tension. Seven months postoperatively the patient died from severe AV valve regurgitation. The autopsy showed widely patent anastomosis and good healing as well as slight expansion of the pericardial patch but without aneurysm formation. In Case 3, the same operation as in Case 2 was performed. A 6 months postoperative angiogram showed no stenosis or distortion of either the subclavian or the pulmonary artery. Although it is premature to draw any conclusion, the use of the autogenous pericardium may be indicated to widen the anastomotic orifice of Blalock-Taussig shunt without sacrificing the length of the subclavian artery even in small infants or neonates.


[Surgical treatment of total anomalous pulmonary venous connection Darling type Ib using pedicled right atrial flap].

A one-month-old baby with total anomalous pulmonary venous connection (TAPVC) type Ib underwent a total correction with a pedicled right atrial (RA) flap, which was made by incising the RA wall in a quadrangular configuration. The common pulmonary vein (PV) was cut back into the left atrium (LA). Then the RA flap was sutured along the limbus of PV recess and atrial septal defect (ASD) to create a new pulmonary venous channel. The defect in the RA wall was directly closed without any prosthetic patch. Absorbable sutures (# 6-0 PDS) were used throughout. Postoperative course was uneventful and echocardiogram showed widely opened PV channel draining into the LA. We think that this procedure could be applied in various types of total and partial anomalous pulmonary venous connection, avoiding pulmonary venous obstruction on the assumption that the RA flap should grow.


[Surgical treatment of dissecting aortic aneurysm using GRF glue].

A 62-year-old woman underwent primary anastomosis for dissecting aortic aneurysm (DeBakey IIIb) using GRF glue. GRF glue consists of mixture of gelatin and resorcin. The mixture is hardened by the addition of medical formaldehyde. Resorcin is diphenole which reacts with formaldehyde, creating tridimentional network. Primary anastomoses were performed after the lumen of dissected aorta was adhered with GRF glue. It appears that primary anastomosis using GRF glue is a simpler and safer operative method for dissecting aortic aneurysm.


[Report of three cases of emergency surgical salvage for acute pulmonary embolism].

Pulmonary embolism (PE) is one of the increasing diseases in Japan, which is aggravated rapidly and early diagnosis is necessary to improve its prognosis. We experienced three cases of successful surgical salvage. It is emphasized that the Doppler ultrasonic echocardiography plays important part in diagnosing PE early and noninvasively. Namely, it shows a appearance of acute cor pulmonale, and is usually able to guess the pulmonary artery pressure by using the simplified formula of Bernoulli's equation. We believe that the surgical pulmonary embolectomy under the cardiopulmonary bypass should be immediately considered in case of unsatisfactory conservative thrombolytic therapy.


[Surgical treatments of emphysematous giant bullae accompanied with severe bronchial asthma].

Two operative cases of emphysematous giant bullae of the lung accompanied with bronchial asthma were reported. Case 1: A 41-year-old man suffering from dyspnea and fever-up was diagnosed as emphysematous giant bullae of the right lung accompanied with severe bronchial asthma. Preoperative examination revealed severe hypoxemia (PO2 46 mmHg) and mixed type ventilatory disorder; VC 1.68 t (41%), FEV1.0 0.59 l (35%). On the first anesthesia, operation was postponed by the severe asthmatic attack and circulatory collapse. After the complete prevention of the attack by giving corticosteroid (25 mg/day) for two weeks, resection of giant bullae could be performed safely. Case 2: A 31-year-old man complaining wheeze was diagnosed as emphysematous giant bullae of bilateral upper lobes of lung accompanied with bronchial asthma. Preoperative and intraoperative states were uneventful, though, on the day after the operation, asthmatic attack occurred due to the difficulty in expectation of sputa. It took 12 hours and many kinds of drugs to improve the respiratory state. In the patients of bronchial asthma, preoperative sufficient suppression of hyperreactivity of airway tracts and postoperative careful treatment to avoid asthmatic attack seem to be indispensable.


[Limits of duration of chest tube drainage in the first episode of spontaneous pneumothorax].

We treated three patients with spontaneous left pneumothorax who underwent a long period of chest tube drainage before surgery. Case 1 was a 61-year-old man. On day 13 after drainage started, much air leakage occurred and surgery was done the next day. Case 2 was a 57-year-old man. Drainage failed to allow the air leakage to seal. The patient did not consent to surgery for about a month, but on day 38 after drainage started, he underwent surgery. Case 3 was a 19-year-old man. First, chest tube drainage was successful and he was extubated on day 16. However, pneumothorax recurred the next day. Liver dysfunction delayed surgical treatment, and the patient underwent surgery on day 54 after the first drainage. Postoperatively, he developed wound infection of the chest tube route and aseptic pleurisy of unknown origin. Limits of duration of unsuccessful chest tube drainage for the first episode of spontaneous pneumothorax are controversial. These cases suggest that when two weeks of chest tube drainage is unsuccessful, surgery should be undertaken in view of postoperative complication and social indications.


[Combined revascularization of coronary and femoral arteries].

A 63-year-old male patient with both coronary artery disease and leg ischemia was successfully treated with a combined procedure. Coronary arteries were bypassed with the saphenous vein graft and in situ left internal mammary artery, and bilateral femoral arteries were bypassed with expanded polytetrafluoroethylene grafts descended from the ascending aorta through the preperitoneal abdominal wall tunnel. After this procedure he experienced neither angina nor claudication.


[A case of enchondroma protuberance with destroying the rib bone].

A 42-year-old female was referred to our hospital because of a tumor shadow in the right lung fields. Tomography revealed a tumor which had destroyed the right 4th rib. Under the diagnosis of malignant tumor, she was treated by radical en bloc excision. The pathological diagnosis was enchondroma.


[A case of invasive thymoma which had grown in the SVC via left innominate vein through thymic vein].

A 66-year-old male was referred to our department with mediastinal tumor. The chest X-ray and the chest CT showed a large tumor adjacent to pulmonary artery and descending aorta. Cavogram revealed a filling defect of the SVC. He underwent complete resection of the tumor, resection of the SVC and reconstruction of the SVC with ringed PTFE. The main tumor was 12 x 7 cm in size and the tumor in the SVC was 20 x 15 mm in size. Histopathological findings showed a lymphocytic thymoma. Compact invaded nest of tumor cell was found in the innominate vein. The tumor in the SVC was invasive to the intima of the SVC, but its media and adventure were intact. This case is rare among patients with invasive thymoma as far as the growth is concerned.


[A case of incomplete endocardial cushion defect with mirror-image dextrocardia, IVC defect and azygos connection].

A case of incomplete endocardial cushion defect associated with mirror-image dextrocardia, IVC defect and azygos connection is reported. Intracardiac defect was corrected under moderate hypothermia with cardiopulmonary bypass. Three venous drainage cannulas were necessary to be indwelled into SVC, hepatic vein and right common iliac vein to maintain adequate venous drainage for extra-corporeal circulation. Thus, anomaly of venous system, which is commonly associated with mirror-image dextrocardia, must be recognized correctly and prepared before intracardiac correction.


[Chemo-thermotherapy of radiation-induced squamous cell carcinoma in anterior chest wall].

A 62-year-old woman had visited our hospital with the large and deep ulcer formation on the left anterior chest wall. A biopsy of the ulcerous lesion established the diagnosis of a squamous cell carcinoma which might be induced by the irradiation after mastectomy. Although a wide resection of the chest wall including left arm was performed, it was impossible to resect completely. After then, she had operations for local recurrence for three times in three years. However, cure was not obtained, and residual lesions gradually enlarged and all layers of the anterior chest wall was replaced with tumor tissues. Conventional chemotherapy using ftorafur and mitomycin C was not effective. Therefore, we tried combined therapy with intravenous administration of cisplatin (CDDP) and vindesine (VDS), and local hyperthermia using radiofrequency (RF) wave. A total number of 11 courses of this treatment modality was carried out at once a week intervals. The tumor-temperature was maintained at the range of 40-43 degrees C for 40 min in each treatment session. Chemotherapeutic agents were administered simultaneously with hyperthermia. After these treatments, the recurrent tumor was markedly reduced, and epithelization of the ulcer was recognized from the surrounding normal skin. The residual tumor was then resected completely. The operative wound was successfully closed by surrounding normal tissue mobilization. She is in good postoperative condition. We concluded that the chemo-thermotherapy is safe and promising therapeutic modality for such invasive squamous cell carcinoma, and the normal tissues are not affected. Furthermore, this approach will expand the scope of radical resection for such an uncontrollable tumor.


[A surgical repair of complete endocardial cushion defect associated with single atrium, persistent left superior vena cava draining into the left atrium, hemiazygos connection and double orifice mitral valve].

Successful surgical repair of a 1-year-old girl of complete endocardial cushion defect associated with single atrium, persistent left superior vena cava draining into the left atrium, hemiazygos connection and double orifice mitral valve was reported. We repaired the endocardial cushion defect by using an endocardial cushion prosthesis and a new atrial septum was created to allow the left superior vena cava draining into the right atrium. We made no treatment for the accessory mitral valve orifice because of no regurgitation.


[A case report: an elderly patient surviving conservative surgical repair of ventricular septal perforation (VSP) with using Swan-Ganz catheter in order to close VSP temporarily].

A 81-year-old female was referred to our hospital for VSP. Preoperative catheterization showed that pulmonary arterial pressure (PAP) was 50 mmHg over in systole, and L-R shunt rate was 63.4%. In spite of any medications under intraaortic balloon pumping, hemodynamics was gradually worsened. And so Swan-Ganz catheter was inserted into right ventricle via VSP retrogradely in order to close VSP with the balloon of the catheter. PAP decreased to about 40 mmHg in systole and L-R shunt rate became to 49.7% by this method. This treatment could conserve the surgical repair for 5 days and the operation was performed on 22 days after the onset of VSP. It is very important to be able to conserve VSP operation by using Swan-Ganz catheter to close VSP temporarily.


[A successful surgical case of acute myocardial infarction in total obstruction of the left main coronary arterial ostium].

Cardiogenic shock due to acute myocardial infarction in an 81-year-old man with total obstruction of the left main coronary arterial ostium was successfully treated with coronary artery bypass grafting. Although this procedure was successful there are some problems in the surgical management of this condition with regard to myocardial protection and preoperative evaluation of poorly visualized left coronary system. It is necessary to infuse first a large volume of high pressure cardioplegic solution and then follow it with another infusion of the solution, through the vein graft, at the regular volume and pressure. Furthermore, the complete revascularization of the left coronary system by vein grafts is recommended.


[A case of emergency operation of entrapped intra-aortic balloon].

We report a case of emergency operation for entrapped intra-aortic balloon. The cause of entrapment of balloon was formation of a clot inside the balloon, which necessitated surgical removal. When intra-aortic balloon rupture by contact of calcific atheromatous plaque, the alarm is not often triggered. In this case, perforation is diagnosed by the presence of blood in the tube connecting the balloon. It is recommended that the balloon should be removed at the presence of blood in the tube.


[Pseudocoarctation associated with dissecting aneurysm of the aorta: a case report].

A case of pseudocoarctation with dissecting aneurysm of the ascending aorta and arch is reported. A 49-year-old man was admitted with chest pain and loss of consciousness. Angiogram showed kinking of the aortic isthmus and dissecting aneurysm of the ascending aorta. There was no pressure gradient between arms and legs. Prosthetic graft replacement of the ascending aorta was successfully performed by the use of total cardiopulmonary bypass with moderate hypothermia. Etiology of the development of pseudocoarctation is unknown, however, hypothesis that embryological abnormality of the aortic arch is one of the contributing factors has been widely accepted. This case was accompanied by bicuspid aortic valve. It is suggested that the developmental etiology of this case seems to be similar to that of classical coarctation of the aorta. Development of the dissecting aneurysm is supposed to be due to hypertension of the upper body during exercise, even though there is no pressure gradient at rest.


[Preoperative preparation and surgical treatment of elderly and very old patients with abdominal hernia].

On the basis of analysis of the results of treatment of 312 elderly and senile patients with abdominal hernia, it was established that performance of adequate preoperative preparation permitted considerable extension of indications for the operation. Contraindications for surgical treatment of such patients should be established after performance of preoperative preparation with regard for indices of external respiration and hemodynamics.


[The use of sonic waves in the treatment of motor disorders of the upper alimentary canal in the early postoperative period].

The effect of sonic waves on motor activity of the stomach, duodenum, extrahepatic bile ducts in 152 patients at the early postoperative period was studied. Motor activity was assessed on the basis of findings of clinical investigations, electrogastroenterography, balloon tensiomanometry, cholangiodebitomanometry. It was established that influencing with the sonic waves with a frequency of 2.5 kHz, intensity of 0.66 W/cm2 2 times a day for 10-15 min within 1-3 days contributed to rapid stable restoration of motor activity of the upper alimentary canal in 86.6% of the patients.


[Surgical technique and approaches in orthotopic liver transplantation].

The first clinical experience with orthotopic transplantation of the liver was summarized. Within the period of from February 1990 to May 1991, 8 operations were performed, including one retransplantation of the liver. The peculiarities and variants of surgical technique, general principles of the performance of operation, methods for vascular and biliary reconstruction are presented. After the operation, 3 patients are alive, no surgical complications were observed.


[Formation of closed aseptic anastomosis of the hollow organs with the use of laser].

The authors modified the method for formation of aseptic anastomosis, using radiation of the CO2-laser and neodymium-doped YAG laser. The techniques for placing the enteroenteric anastomosis, gastroentero- and cholecystojejunoanastomosis are presented. Reduction in incidence of inflammatory and purulent postoperative complications has been achieved.


[Surgical treatment of patients with obstructive jaundice].

The results of treatment of 481 patient operated on for obstructive jaundice have been analysed. In 388 (80.7%) patients, jaundice was caused by non-tumor lesion of the bile ducts. At the peak of jaundice, operated on were 312 (64.9%) patients, who experienced no benefit from conservative therapy. The tactics for operative intervention was chosen individually with regard for the cause of jaundice, concomitant pathology and age of a patient. The main cause of death was the aggravating hepato-renal failure due to prolonged jaundice and late hospitalization.


[Use of acelysin solution in the treatment of acute purulent inflammatory diseases of soft tissues].

The authors have successfully used for local treatment of purulent wounds a new preparation acelysin. In animals with the induced abscesses, under the influence of acelysin, more rapid recovery than in the control group of animals treated with hypertonic sodium chloride solution, dioxidine solution was achieved. The effectiveness of treatment was judged by duration of the course of a wound process, findings of morphologic, cytologic and bacteriologic studies. Use of acelysin solution in 24 patients with suppuration of an operative wound has confirmed its effectiveness.


[Effectiveness of ultraviolet irradiation of the blood of patients with purulent inflammatory diseases and its effect on the natural resistance].

In the complex treatment of 121 patient with purulent-inflammatory diseases with the aim of detoxication, reinfusion of the blood irradiated with ultra-violet rays was used. Judgment about the effectiveness of treatment was based on the findings of clinical and laboratory studies. There were no complications. In 8 patients, a hyperthermal reaction occurred. Under the influence of irradiation, a quantity of the natural killer cells has normalized, while in the control group, it was smaller than in healthy subjects.


[Surgical treatment of inguinal hernias in elderly and very old patients].

The results of surgical treatment of inguinal hernias in 315 war veterans, including 260 the elderly and senile, have been analysed. All the patients underwent the elective operations. Four (1.2%) patients developed complications after the operation, there were no lethal outcomes. The authors came to a conclusion about the expediency to perform elective herniotomy in elderly and senile patients even in presence of concomitant diseases.


[Significance of the separate symptoms in acute appendicitis].

On the basis of the experience with treatment of 19,346 patients with acute appendicitis, the authors have established that pain in the right inguinal region, rigidity of muscles of the anterior abdominal wall, and a Volkovich-Kocher symptom were the most informative symptoms. The Shchetkin-Blumberg symptom caused by the development of an inflammatory process in the peritoneum is not an appendicular symptom; the Rovzing, Voskresensky, Obraztsov symptoms, not being the specific symptoms of acute appendicitis, are of essential informative value only in combination with the other symptoms of the disease.


[Treatment of ligature fistulas after appendectomy].

On the basis of clinical examples, the danger of ambulatory treatment of a ligature fistula is shown. To prevent its development, a care of tissues is necessary: in cases of technical difficulties, a wound should be widened, fat and muscles isolated, a wound before closure needs mandatory irrigation with antiseptic solutions. Ineffectiveness of conservative treatment of a fistula during 1-2 weeks requires the operative intervention in a specialized department with excision of purulent necrotic masses and ligature which maintains the inflammation. Before wound closure, a perforated drain for flowing irrigation should be established.


[Foreign bodies in the rectum and colon].

On the basis of analysis of treatment of 80 patients with foreign bodies of the rectum and colon, the volume and character of the therapeutic measures required were defined. The endoscopic methods for removal of the foreign bodies, peculiarities of extraction of the large foreign bodies are presented. The cases of penetration of the foreign bodies into the colon via a natural, or artificial intestinal fistula are described.


[Intratissue electrophoresis in patients with appendicular colic and a preliminary diagnosis of non-destructive acute appendicitis].

The possibility of the use of intratissue electrophoresis in patients with presumptive diagnosis of acute appendicitis was studied. Use of the method suggested contributes to enhancing the effectiveness of the treatment performed, prevents unsubstantiated performance of appendectomy, shortens time patients stay in a hospital. The long-term results of treatment with the use of intratissue electrophoresis are better than those in use of the existing methods of dynamic observation (parenteral administration of spasmolytic and desensitizing agents).


[Reconstruction of the anus in marginal necrosis of the lowered intestine after abdominal-anal resection].

The experience with treatment of a most frequent complication after abdomino-anal resection with bringing down the intestine--marginal necrosis of a xenotransplant--is summarized. The expediency of individual approach to the choice of treatment is noted. Active therapeutical tactics is suggested.


[Diagnosis and therapy of acute hemorrhoids].

The analysis of the results of treatment of 137 patients with acute hemorrhoids was carried out. A typical hemorrhoidal analysis was noted in 83.5% of the patients. Operated on were 129 (94.1%) patients, including 27 (20.9%)--at day 3-4 after hospitalization. Duration of hospital stay of the patients operated on after short-term preparation was 9.2 days. This figure is 4.1 days less than that in patients operated on in a delayed order.


[One-stage surgery of hemorrhoids complicated with fissure in ano].

The data on incidence of detection of associated rectal diseases--hemorrhoids and anal fissures--are presented. The indications for operative treatment are considered, a method suggested by the authors for surgical treatment of the mentioned diseases, which was used in 62 patients, is described. Use of the improved operative technique contributed to reduction in number of complications. Duration of treatment has shortened by 7 days.


[Surgical treatment of chronic paraproctitis].

The experience with operative treatment of 974 patients with chronic paraproctitis has been summarized. After the operations for intrasphincter fistula, 1% of the patients developed a disease recurrence, 0.5%--incompetence of the anal sphincter; for transsphincteric fistula--2.6 and 1.9%, respectively, for extrasphincteric fistula--5.7 and 5.2%. A fistula excision into the intestinal lumen is an operation of choice in intra- and transsphincteric fistula. In extrasphincteric fistula, fistula excision, plastic transfer of mucosa for closure of its internal opening with preservation of the anal sphincter should be performed. In presence of the extensive scars and purulent leaks, a ligature should be added to fistula excision.


[Acute intestinal obstruction caused by gallstones in aged patients].

The results of treatment of 6 patients operated on for acute ileus caused by a gallstone have been analysed. The authors consider the elderly and senile age not to be a contraindication for operation.


[Computerized tomography of the organs of the small pelvis in children with anorectal atresia].

In 12 children with the different forms of anorectal atresia, for studying the state of a sphincter apparatus of the rectum and assessment of quality of its bringing down into the perineum after proctoplasty, computerized tomography of the organs of a small pelvis was used. Underdeveloped and undifferentiated musculus levator ani in children with high anorectal atresia and fistula to the urinary bladder was revealed. The method permits to establish exact location of the intestine brought down relative to musculus levator ani and external anal sphincter.


[Myelodysplastic diseases in childhood].

The myelodysplastic syndromes (MDS) are a group of hematopoietic neoplasms characterized by ineffective hematopoiesis and a high risk of transformation in acute leukemia. Pathogenesis and clinical course of these disorders are heterogenous. MDS is unusual in childhood, and differential diagnosis is specially broad in this age group. Allogenic bone marrow transplantation is the treatment of choice. Therapy with hematopoietic growth factors can overcome the maturation defect of the malignant clone in some instances. Multicenter studies are necessary to accumulate sufficient data on pathogenesis, clinical course and treatment results of MDS in childhood.


[Experiences with modified BFM protocols in the treatment of children with acute lymphoblastic leukemia (ALL) in East Germany 1981-1991].

Between September and August 1991 818 previously untreated children and adolescents up to 18 years of age with acute lymphoblastic leukemia were entered into two modified BFM-protocols. Patients with B-ALL were excluded. From 1981 to 1987 524 patients were entered into the randomized multicenter study ALL VII/81 (modified ALL-BFM 81 protocol). Patients were divided into three risk groups standard (SR), medium (MR), high risk (HR) using the BFM risk factor. In a connecting study from 1988 to 1991 294 patients were registered on the stratified and randomized multicentric trial ALL VIII/87 (modified ALL-BFM 86 study). The main modification in study ALL VII/81 concerned the duration of treatment. Patients were randomized into two groups. The first group received as a late reinduction protocol III and then therapy was stopped. The second group received 6-MP and MTX for another six months. The other whole treatment strategy of ALL-BFM 81 was adopted. In protocol ALL VIII/87 the only modification was the reduction of the MTX dosage from 5 g/m2 to 1 g/m2 with an infusion time of 24 hours (leucovorin rescue 15 mg/m2 after 48 and 54 hours). The probability of the event-free-survival (EFS) for study ALL VII/81 was 59%. CNS events were significantly more frequent in standard risk patients with intermediate dose MTX (4 x 0.5 g/m2) compared with the irradiation group (18 Gy). The EFS for SR patients amounts to 61%, for MR patients to 59% and for HR patients to 36%. There was no significant difference of EFS for the two groups with different duration of therapy.(ABSTRACT TRUNCATED AT 250 WORDS)


[Is the pharmacokinetic profile of cytarabine clinically relevant?].

Cytarabine (Ara-C) is a cytotoxic agent which is rapidly metabolized and thus has a short half-life. Consequently, variations of infusion time influence directly the plasma level over time. Individual differences in plasma level courses with identical dosage are irrelevant regarding treatment response. Several studies, however, reported correlation of the leukemic cells' ability to build and retain the metabolite Ara-C-triphosphate (Ara-CTP) intracellularly with clinical response to therapy. The half-life of the intracellular Ara-CTP concentration in myelogenic blasts (AML) is lower than in blasts from children with acute lymphoblastic leukemia (common-ALL). The varying dosage recommendations of conventional (CD), intermediate (ID) and high-dose (HD) Ara-C therapy are based on considerations of cellular pharmacology. ID and HD Ara-C therapy schedules are designed to overcome well-known resistance phenomena thus providing high intracellular Ara-CTP concentrations.


[Effect of dose intensity and therapy-induced leukocytopenia in intensive therapy on the prognosis of acute lymphatic leukemia in childhood. Results in 213 patients of the COALL-85 study].

Dose intensity (DI) plays an important role in the treatment of neoplastic diseases. The individual DI within a protocol may vary considerably and thus may be an important prognostic factor. In 213/305 patients treated in the cooperative study COALL-85 for childhood acute lymphoblastic leukemia the following parameters of individual therapy intensity were analyzed: Total time for intensive treatment, cumulative doses of single drugs, mean relative dose (= relation between received and prescribed doses of all drugs), mean relative dose intensity ( = mean relative dose/time) as well as frequency and duration of leukocytopenia. Therapy for LR (low-risk) and HR (high-risk) patients were separately analyzed by both life-table method and multivariate regression analysis. Neither length of time, mean relative dose intensity nor the other parameters had any significant influence on prognosis within the HR protocol. The only significant prognostic factor was the remission status on day 28 (p less than 0.001 in multivariate analysis). In contrast patients treated with the LR protocol had significantly fewer relapses if treatment resulted in leukocytopenic episodes (probability for event free survival (EFS) = 0.76 in patients with one or two leukocytopenic episodes compared to 0.52 in patients with none). Patients with a mean relative dose greater than 0.9 showed a higher EFS of borderline significance than patients with mean relative dose less than = 0.9 (0.72 vs 0.49, p = 0.09). We would like to conclude, that treatment protocols with very intensive and prolonged combination chemotherapy have a certain margin of safety in DI without disadvantage for the patient.(ABSTRACT TRUNCATED AT 250 WORDS)


[Effect of cranial irradiation on rate of recurrence in children with acute myeloid leukemia. Initial results of the AML-BFM-87 study. The AML-BFM Study Group].

Study AML-BFM-87 compared prospectively if cranial irradiation could be abandoned by adding two blocks of intensification with high dose ARA-C and VP-16 after consolidation and furthermore, improve prognosis compared to study -83. 210 children were enrolled in study AML-BFM-87 until March 31, 1991. 164 (78%) achieved complete remission. Probabilities for event-free survival (EFS) and event-free interval (EFI) of 5 years were: .45 (SD .04) and .57 (SD .05). In the first 2.5 years of the study irradiation was randomized (n = 31), selected or refused (n = 24). However, during this period irradiation was mandatory in patients with leukocyte count greater than 70,000/mm3, and also in children with initial CNS involvement. Since July 1989 prophylactic cranial irradiation was abandoned. Patients of the group with mandatory irradiation (n = 39) presented with more unfavourable risk parameters than the group of non-irradiated children, who were enrolled in the study after randomisation had been stopped. Nevertheless, results showed in randomized and selected patient groups as well as in the total cohort a longer relapse-free interval (RFI) in irradiated (n = 66) compared to non-irradiated (n = 94) patients (RFI of 5 years: .70, SD .04 vs. .51, SD .07, p less than .05). Relapses in non-irradiated children occurred mainly in the bone marrow and less often in the CNS. The increase in relapse rate was seen especially in non-irradiated patients of the low risk group as defined in study AML-BFM-83 (RFI: .40, SD .14 vs. .79, SD .09 with irradiation, p less than .01). In the high risk group, however, the differences were not significant. Our results suggest that cranial irradiation is an important part of therapy in childhood AML, and that the good prognosis of the low risk group in study AML-BFM-83 was probably based on the combination of intensive chemotherapy and cranial irradiation.


[Comparison of chemotherapy alone with allogeneic bone marrow transplantation in first full remission in children with acute myeloid leukemia in the AML-BFM-83 and AML-BFM-87 studies--matched pair analysis].

16 patients of studies AML-BFM-83 and -87 with allogeneic bone marrow transplantation (BMT) in first complete remission (CR) were compared with matched controls with postremission chemotherapy (CT-MC). CT-MC were selected from 250 non-grafted patients with a minimum of remission duration corresponding to the median interval between remission and allogeneic BMT (7.3 and 3.6 months in studies BFM-83 and BFM-87). Matched pair criteria according to prognostic significance were: blast cell reduction day 15 in bone marrow, FAB subtypes, white blood cell count, age, and time to CR. Therapy results in BMT and CT-MC groups were comparable: 2 relapses and 2 treatment-related deaths after BMT vs. 5 relapses. The probability for event-free interval of 9 years was: .73 (SD .12) in the BMT group vs. .67 (SD .12) in the CT-MC group. Early and late toxicity was higher in the BMT group. 3 children of the BMT group had tolerable or severe sequelae (convulsive seizures, hemiparesis). Currently, there is no advantage for allogeneic BMT in first CR according to our results. Only high risk patients should be grafted as soon as possible after achieving CR.


[Treatment of recurrence of acute myeloid leukemia in childhood. A retrospective analysis of recurrence in the AML-BFM-83 study].

Complete remission (CR) rates of 80% are achieved with the AML-BFM protocols but one third of patients relapse within the first three years. There are few reports of treatment of relapsed childhood AML, and these deal with the evaluation of new drugs for frontline therapy. We performed a retrospective analysis to investigate how patients previously treated with the AML-BFM-83 protocol were treated after relapse and how many long term remissions were achieved. 48 of 139 patients relapsed after having achieved complete remission with the AML-BFM-83 protocol which consists of continous infusion of ARA-C 100 mg/m2 day 1-2, ARA-C 200 mg/m2 day 3-8, Daunorubicin 60 mg/m2 day 3, 4, and 5, and VP-16 150 mg/m2 day 6, 7, and 8, and an 8 week consolidation therapy consisting of Prednisolone, Thioguanine, Vincristine, ADR, ARA-C, Cyclophosphamide, intrathecal ARA-C and cranial irradiation followed by maintenance therapy. Duration of first remission ranged from 1.5 months to 66.3 months. Excluding 5 children with either isolated or combined extramedullary relapses and another 4 patients for missing data, 39 children were evaluable. 20 children received no therapy or palliative therapy while 16 patients received chemotherapy and another 3 children were transplanted in relapse. Although 9 different intensive chemotherapy regimens were used for reinduction, a high number (12 of 16 = 75%) of second complete remissions was achieved. Several therapeutic options were used to maintain a second remission: regular maintenance therapy (7 patients), allogeneous bone marrow transplantation (BMT) (2 patients), autologous BMT (3 patients).(ABSTRACT TRUNCATED AT 250 WORDS)


[Changes in blood coagulation in treatment with ALL-BFM-90 and NHL-BFM-90 protocols].

1. Treatment according to the ALL/NHL-BFM 90 protocol I (induction phase) caused multiple and severe coagulation changes in all 14 patients of our study. Glucocorticoids alone made Fibrinogen drop to 148 mg/dl, AT III and Protein C rise to 136% or even 179% respectively. After day 12, immediately following the start of therapy with Coli-Asparaginase (ASP), fibrinogen continued to drop to reach its lowest average value of 46 mg/dl on day 24. Anticoagulant factors like plasminogen (lowest average value: 36%), AT III (47%) and Protein C (93%) dropped abruptly. These alterations were reversed after discontinuation of Glucocorticoids and ASP. During consolidation (protocol II) similar alterations are observed as in protocol I when Glucocorticoids are applied alone. However, after Erwinia-ASP there is no fall in AT III, plasminogen, and Protein C as is observed in protocol I with Coli-ASP. 2. Severe hemorrhages or thromboses are uncommon as compared to the degree of coagulation changes which can be regularly observed. Complications occur more often in girls. Most of them are seen during the 2nd or 3rd week of simultaneous ASP-Glucocorticoid therapy. 3. To avoid twofold alteration of hemostasis it should be considered to apply Glucocorticoids and ASP separately and to replace Coli-ASP by Erwinia-ASP. The efficacy of prophylactic replacement of decreased coagulation factors has not yet been confirmed. Immunologic and infectious side effects have to be taken into consideration. 4. More definite recommendations can be given when each suspected bleeding and/or thrombosis is confirmed by imaging procedures, when it is documented and registered, and when coagulation studies are performed during the critical phase.


[Clinical experiences with adrenaline as therapy and prevention of E. coli-L-asparaginase-induced anaphylaxis].

Management of E.-coli L-asparaginase induced anaphylaxis mainly consists of application of i.v. epinephrine but also in the withdrawal of this drug. Despite of this firm recommendation we have shown in 7 patients with E. coli L-asparaginase induced anaphylaxis, that further application of the drug is possible in the presence of a continuous epinephrine infusion (0.01-0.02 mg/kg) started one hour before and finished one hour after the concomittant infusion of the E.-coli L-asparaginase. In none of the patients there was a second event of anaphylaxis even though most of the patients still had to continue on E.-coli L-asparaginase with an average of more than 6 infusion.


[German multicenter thalassemia study. Concept and initial results].

At present more than 300 children and adolescents with Thalassaemia major are living in the FRG. The purpose of this project is--for the first time--to apply a standardized therapy protocol to these patients, to prove its effectivity and study side-effects. The multi-center study started in April 1991. The therapy is based on periodical transfusion of erythrocytes in order to keep haemoglobin (Hb) concentration (= basic Hb-value) above 10.5 g/dl, and daily application of Desferal, 40 mg/kg bw s.c. for iron elimination. Until Nov. 30, 1991 74 patients from 31 different childrens hospitals entered the study. Preliminary results after evaluation of the basic questionnaires can be summarized as follows: 1. The majority of patients if not too old to highly profit from improvement of therapy; 2. In 40.9% of these patients HbF concentration was higher than 15%, which indicates a suboptimal transfusion therapy; 3. At least 30% of patients need intensified iron elimination. Even these preliminary data demonstrate the necessity to improve the therapy of Thalassaemia major in Germany. The goal is to include all affected patients in the study and so optimize long term results concerning quality of life and prognosis.


[Early neuroblastoma detection in Germany. On the status of the Hamburg-Stuttgart cooperative pilot study].

In Germany, a pilot study for the early detection of neuroblastoma was initiated at the beginning of 1991 in the regions of Hamburg and Stuttgart. The aims of the study are: (1) to develop an infrastructure for neuroblastoma screening, (2) to test the methodology, (3) to determine the compliance rate, (4) to collect data for a future epidemiological study. At 6 months of age, the parents are contacted by general practitioners and private pediatricians within the framework of the routine infant surveillance. The parents are informed about the pilot study and given a sampling kit. A simple urine sample is required, which is collected on a test strip, dried and sent to the test center. From the eluate, the levels of Vanillymandelic acid (VMA) and Homovanillic acid (HVA) are estimated by high performance liquid chromatography (HPLC). The results are sent to the practitioner. In cases of insufficient samples or raised values, the parents are asked for a second sample. If a raised value is comfirmed, clinical investigation including abdominal ultrasound and chest X-ray is carried out. From 2-12/1991, 27,282 samples were examined. There were 1326 (4.86%) insufficient samples and 644 (2.36%) samples retested because of raised initial VMA/HVA levels. 45 (0.15%) children were clinically examined. Until now 2 of them have still elevated levels without evidence of tumor and 2 others have evidence of a tumor which has not been proven to be neuroblastoma. These first results are encouraging with respect to the feasibility of carrying out a neuroblastoma screening program in Germany. It is to early to assess the compliance rate.


Thyroid function in premature infants.

The present study was performed using the simultaneous assays of free T4 and TSH levels in dried blood spots of filter paper for mass-screening of inborn errors of metabolism in order to clarify the thyroid function of premature infants. The subjects were divided in three groups: A group infants less than 1500 g at birth (n = 34, 27.4 +/- 2.6 weeks of gestational age), B group infants from 1500 to 2500 g at birth (n = 104, 35.6 +/- 2.4 weeks) and C group infants over 2500 g at birth (n = 490, 39.0 +/- 1.2 weeks). TSH levels were 4.51 +/- 3.03, 2.62 +/- 2.24 and 2.84 +/- 2.06 microU/ml in A, B and C group respectively and significant difference was recognized in group A and C. Free T4 levels were 0.71 +/- 0.42, 1.81 +/- 0.96 and 2.15 +/- 0.67 ng/dl, in group A, B and C respectively, and significant differences were recognized in all three groups. There was positive correlation between free T4 levels and gestational ages (Y = -2.413 +/- 0.11725X, r = 0.206, p less than 0.05).


A novel type of regulatory protein for the GDP/GTP exchange reaction of rho p21, a ras p21-like small GTP-binding protein, in rabbit intestine.

A novel regulatory protein for rho p21, a ras p21-like GTP-binding protein (G protein), was purified from the cytosol fraction of rabbit intestine. This protein, designated as rho GDP dissociation inhibitor (GDI), regulated the GDP/GTP exchange reaction of rho p21 by inhibiting the dissociation of GDP from and subsequent binding of GTP to it. rho GDI did not affect the GTPase activity of rho p21. rho GDI formed a complex with the GDP-bound form of rho p21 but not the GTP-bound form. rho GDI was inactive for other small G proteins including ras p21, smg p21 and smg p25A. These results indicate that rho GDI is a novel type of regulatory protein for the GDP/GTP exchange reaction of rho p21.


[The IgG subclass level in children and adolescents with malignant diseases].

Children with malignant disease have an increased risk for bacterial infections. We investigated a possible correlation between septic episodes and decreased IgG subclass levels in 63 patients. At diagnosis 13 of 50 children showed decreased IgG subclass levels: 10x IgG4, 2x IgG1, and 1x IgG3 + IgG4 were reduced. Bone marrow infiltration by tumor cells did not increase the frequency of subclass reductions (4/25 with, 9/25 without bone marrow infiltration). The time course of subclass levels was followed during 37 febrile episodes (mainly fever of unknown origin, septicemia, pneumonia) of 23 children under cytostatic therapy. 6 patients showed transient low IgG subclasses: 2x IgG4, 1x IgG1, 1x IgG3, 1x IgG2 + IgG4, and 1x IgG1 + IgG3 + IgG4. Children with decreased IgG subclass levels appeared to occur more independently of leucopenia. In general, febrile episodes in children with subclass decreases did not last a longer period and did not occur more frequently than in children without IgG subclass deficiencies. In conclusion, the determination of IgG subclasses in cancer children at diagnosis or during chemotherapy did not add substantial information of prognostic or therapeutic relevance.


[The "Lower Saxony/Northern Rhine-Westphalia" Neuroblastoma Screening Project: on the need for epidemiologic comparison].

The proof for the general evolution of metastatic neuroblastoma from localized disease by a low-speed process is lacking. The epidemiological approach would require the decrease of neuroblastoma related mortality by reduction of the number of metastatic cases per population unit as a result of a screening program. During 1983 through 1990 the neuroblastoma incidence in the FRG was 0.85-1.09 cases per 100,000 children less than 15 years of age. The mortality rate ranged between 0.25 and 0.49 deaths per 100,000 children. The project "Niedersachsen/Nordrhein-Westfalen" started April 1st, 1992 and is investigating urinary catecholamine metabolite excretion in infants at the age of 10-12 months and for a second time in toddlers at 17-19 months. The target population includes 24.7 million inhabitants with 267,000 births per year. The urine sampled on filter paper is analyzed using thin layer chromatography. Positive and questionable positive results are confirmed by HPLC and GC-MS. The aim of the study is to demonstrate the feasibility of the chosen approach. Furthermore first epidemiological data will be obtained. Until a population-based study on neuroblastoma mortality in screened versus controlled populations has proven the usefulness of the screening it cannot be recommended as a general service to the public.


Long-term preservation of canine pancreas by a new simple cold storage method using perfluorochemical--the two-layer cold storage method (Euro-Collins' solution/perfluorochemical).

Long term preservation of canine pancreas by a new simple cold storage method using perfluorochemical (PFC), two-layer (Euro-Collins' solution (EC)/PFC) cold storage method, was tested in the canine model of segmental pancreas autotransplantation. The functional recovery of the graft preserved by this method (group 1) was determined by daily fasting blood glucose concentration and intravenous glucose tolerance test at two weeks after autotransplantation and compared with simple cold storage with EC (group 2), cold storage in EC with simple bubbling of oxygen (group 3), and control (no preservation) (group 4). Maintenance of normoglycemia at least 5 days after transplantation was considered a success of preservation. The functional success rates after 24 hour preservation were 4/4 (100%), 4/4 (100%) and 4/5 (80%) for groups 1, 2 and 3 respectively, and the functional success rates of groups 1, 2 and 3 after 48 hour preservation were 5/6 (86%), 1/5 (20%) and 1/5 (20%) respectively. In addition the functional success rates after 72 hour preservation were 6/6 (100%), 0/6 (0%) and 0/5 (0%) for groups 1, 2, and 3 respectively. It was clear that the two-layer cold storage method had made it possible to preserve the canine pancreas for up to 72 hours although the upper limit of reliable preservation time of groups 2 and 3 was 24 hours. The mean K value of group 1 after 72 hour preservation was 1.78 +/- 0.42 compared with 2.05 +/- 0.32 of group 4 at two weeks after transplantation. Biopsies of grafts of group 2 and 3 after 72 hours preservation showed remarkable autolytic changes in exocrine and endocrine tissues. In contrast, biopsies of grafts of group 1 after 72 hour preservation showed almost normal architecture in both tissues. In addition, biopsies of 72 hour preserved grafts of group 1 at 4 weeks after autotransplantation showed almost normal pancreatic architecture with minimal fibrotic changes in the exocrine tissue. This study demonstrated the possibility of long-term preservation of the pancreas for transplantation.


Function of the post-translationally modified C-terminal region of rho p21.

rhoA p21, a ras p21-like small GTP-binding protein, purified from bovine aortic smooth muscle is similarly modified at its C-terminal region as described for ras p21s. In this study, I examined the role of the post-translational modifications of the C-terminal region of rhoA p21 by comparing bovine rhoA p21 with bacterially-produced rhoA p21 because the bacterial protein was not modified. Bovine rhoA p21 bound to plasma membranes, but bacterial rhoA p21 did not. Both the stimulatory and inhibitory GDP/GTP exchange proteins for bovine rhoA p21 were inactive for bacterial rhoA p21. On the other hand, the GTPase activating protein for bovine rhoA p21 was also active for bacterial rhoA p21. These results indicate that the post-translational modifications of the C-terminal region of bovine rhoA p21, which are absent in bacterial rhoA p21, are essential for its interaction with membranes and the stimulatory and inhibitory GDP/GTP exchange proteins but not with the GTPase activating protein.


Weakness of thigh muscles in individuals sustaining anterior cruciate ligament injury.

The purpose of this study was to assess the quadriceps and hamstrings muscle strength deficits at different knee flexion angles (30 degrees and 60 degrees) in individuals who had sustained anterior cruciate ligament (ACL) injury, who had never had thigh muscle strengthening exercise. Isometric (0 degree/sec) and isokinetic (60 degrees/sec and 180 degrees/sec) torque measurements were performed on sixty-six patients (29 males and 37 females) with chronic ACL insufficiency. Significant strength deficits of the quadriceps and hamstrings muscles in injured knees were found at both 30 degrees and 60 degrees of knee flexion in three testing conditions (0 degree/sec, 60 degrees/sec, and 180 degrees/sec). In the comparison of torque production at 30 degrees and 60 degrees knee flexion angles, for the male group, significantly greater deficits of the quadriceps torque were found at 60 degrees knee flexion than at 30 degrees knee flexion in the isometric and isokinetic 60 degrees/sec testing modes. For the female group, significantly greater deficit of the quadriceps torque was found at 60 degrees knee flexion than at 30 degrees knee flexion only in isokinetic 60 degrees/sec. There was no significant difference of the hamstrings torque deficit between 30 degrees and 60 degrees knee flexion in any testing modes. In the comparison of isometric and two isokinetic testing modes (60 degrees/sec and 180 degrees/sec), for the male group, significantly greater deficits of the quadriceps torque were found at 30 degrees knee flexion in isokinetic 180 degrees/sec and at 60 degrees knee flexion in isokinetic 60 degrees/sec as compared to the isometric test. There was no statistical difference in the hamstrings torque values. For the female group, significantly greater deficits of the quadriceps and hamstrings torque were found at 30 degrees knee flexion in isokinetic 60 degrees/sec and at 60 degrees in isokinetic 60 degrees/sec and 180 degrees/sec as compared to the isometric test. It was concluded that long lasting instability without any muscle exercises may result in the weakness of not only the quadriceps muscle but also even hamstrings muscle, and that the quadriceps strength might be more susceptible to ACL insufficiency at 60 degrees knee flexion angle than at 30 degrees knee flexion angle, whereas, the hamstrings did not show any angular-specific torque deficits. These findings might resulted from characteristics of torque-curves of the quadriceps and hamstrings muscles.(ABSTRACT TRUNCATED AT 400 WORDS)


Cell-kinetics and biochemical pharmacology of methotrexate and 6-mercaptopurine in human malignant T-lymphoblasts.

The cell-kinetics and biochemical pharmacology of simultaneous and sequential combination treatment with 0.02 microM methotrexate (MTX) and 2 microM 6-mercaptopurine (6MP) were studied in MOLT-4 malignant T-lymphoblasts. The results were compared with our data from earlier studies of separate treatment with these antimetabolites. A synergistic effect of combination treatment could be demonstrated, based on the inhibition of purine de novo synthesis by both agents, on DNA and RNA synthesis, on the incorporation of 6-thioguanine nucleotides into DNA and RNA, and on inhibition of cell growth and clonal growth. The synergistic effects of combination treatment with MTX and 6MP will only be available in malignant lymphoblasts, and will be absent in normal bone marrow cells and normal lymphocytes, because the activity of purine de novo synthesis in these cells is absent or low. Based on the synergistic effects of MTX and 6MP and the good penetration of both agents in the cerebrospinal fluid, the Dutch Childhood Leukemia Study Group presently performs a randomized study during protocol M of the BFM/DCLSG-ALL-90 protocol comparing the results of 4 times each two weeks 24 hr intravenous administration of MTX (5 g/m2) versus intravenous MTX, immediately followed by 24 hr intravenous administration of 6MP (1.3 g/m2). The pharmacokinetics and intracellular biochemical pharmacology of 6MP in lymphocytes will be studied, comparing intravenous administration and low dose oral administration.


Chest roentgenographic techniques for demonstrating human lung tumour xenografts in nude rats.

Roentgenographic techniques were investigated for imaging orthotopic lung tumours in anaesthetized nude rats endobronchially implanted with human lung cancer cells. A conventional radiographic unit with a dual-screen, double-emulsion film mammographic receptor produced images preferable to those from a mammographic unit because of superior resolution. Typical exposure factors were 300 mA, 29 kVp, and 17 ms at a focus-film distance of 76 cm with a 2.11 by 2.41 mm effective focal spot and inherent filtration of 1.2 mm aluminium. Sensitivity for tumour detection was 0.93 for 59 animals with pathologically proved tumours and 0.96 for 54 animals with tumours larger than 4 mm or 50 mg. For 24 pathologically tumour-free animals, specificity was 1.00. For 55 animals radiographically judged to have tumours, positive predictive value was 1.00. For all 83 animals, accuracy was 0.95. This technique effectively demonstrates orthotopic human lung tumours in nude rats and should be useful for noninvasive monitoring of tumour presence, location, size, and changes in size.


Effects of urethane, alphaxolone/alphadolone, or halothane with or without neuromuscular blockade on survival during repeated episodes of global cerebral ischaemia in the rat.

The effect of 4 anaesthetic regimens on blood pressure and survival was investigated during repeated episodes of cerebral ischaemia in the rat induced by diathermy of the vertebral arteries and reversible occlusion of the carotid arteries. The best results were obtained with inspired halothane with neuromuscular blockade and artificial ventilation, followed in order by halothane, intravenous alphaxolone/alphadolone, and intraperitoneal urethane with spontaneous ventilation.


Euonymus europaeus lectin as an endothelial and epithelial marker in canine tissues.

The Euonymus europaeus agglutinin (EEA) is an endothelial marker in mammalia. In canine tissues, 4 types of endothelial cells (general, nervous, arterial, hepatic) were identified by the presence of the EEA receptor and by its sensitivity to neuraminidase enhancement. In adult dogs, EEA binding saccharides had endothelial or epithelial distributions and reactivities similar to those described for human tissues. Different EEA reactivities were observed between fetal, neonatal and adult canine tissues mainly at the arterial level. These findings suggest that the development of the binding sites is not identical in dog and man. Related lectins and monoclonal antibodies were used to characterize the EEA binding site, and the probable structure of the EEA binding saccharide in endothelial cells appeared to be alpha Gal (1,3) beta Gal (1,4) GlcNAc.


[Ifosfamide and the metabolites of side chain oxidation--excretion in urine in various pediatric therapeutic protocols].

The precondition for the antineoplastic effect of ifosfamide (Ifo) is the oxydation of the oxazaphosphorine ring system. The 'ring oxidation' by several steps leads to the formation of alkylating mustard. A second metabolic pathway results in the cytostatically inactive metabolites 2- and 3-deschlorethyl-ifosfamide (2-, and 3-d-Ifo). This 'side chain oxidation' plays a quantitatively more important role with ifosfamide than with cyclophosphamide. The urinary excretion of unmetabolized Ifo and of 2- and 3-d-Ifo, which represents the amount of Ifo not activated, has been investigated by capillary gaschromatography in 18 treatment cycles of 14 children with various therapeutic schedules (800, 2000 and 3000 mg/m2 given as bolus, over 1 h or as continuous infusion for 2 respectively 5 days). The total cumulative excretion during 12 completely sampled cycles ranged from 27 to 50% of the given Ifo. Between 14 and 34% could be detected as IFO, 9 to 29% as 3-d-Ifo and 2 to 8% as 2-d-Ifo. In 4 children the amount of 'side chain oxidized' IFO exceeded the amount of unmetabolized Ifo. 24 hours after the end of therapy excretion is nearly complete. No relationship between the excreted amount of unmetabolized Ifo, 2-d-Ifo and 3-d-Ifo and the dose schedule could be determined. There was no clearcut dependency between cumulative dose, the children got in the past, and formation of 2- and 3-d-metabolites.


A method for hyperthermic treatment of mouse skin.

The Sencar mouse skin system is a recognized model for tumour initiation, promotion and progression. The current interest in the effect of hyperthermia on this multi-stage tumorigenesis model prompted the need for a technique to accurately heat a section of dorsal skin of a large number of mice for 30 min per heat treatment. In the technique described, experimental groups of 25 female Sencar mice were treated at 7-8 weeks of age under general methoxyflurane anaesthesia. Treatment consisted of the application of initiating and/or promoting agents with or without hyperthermia. For hyperthermic skin treatments, each group of mice was placed onto a platform in a water bath so that the dorsal skin of the mice was in contact with 44 degrees C temperature controlled water.


The lipid composition of milk from mice fed high or low fat diets.

Total fatty acids and the proportions of methyl esters of individual fatty acids were measured in mouse milk. Pregnant mice were fed either a high fat (HF) diet or a low fat (LF) diet from 14 days of gestation. After parturition, each dam was milked once a day for a period of 18 days. The mean total fatty acid concentration over the entire study period was 110 mg/g of milk (approximately 11.7% fat as triglyceride) for both dietary treatment groups. During days 2 to 6 postpartum, the mean total fatty acid concentration for dams fed HF diet was lower than for the LF group. Although the concentration of total fatty acids of mouse milk was not affected by the level of dietary fat fed to the dam, several variations in the proportions of individual fatty acids were observed.


Monitoring of blood gas parameters and acid-base balance of pregnant and non-pregnant rabbits (Oryctolagus cuniculus) in routine experimental conditions.

Blood gas parameters and acid-base balance values were determined in adult pregnant New Zealand rabbits (Oryctolagus cuniculus) in standard laboratory housing conditions and during anaesthesia with an association of ketamine-chlorpromazine, administered before surgical procedures. All the variables were also studied in adult non-pregnant female, used as controls. No differences in pH, sO2c, O2Hb, COHb, sO2m and a-vDO2 were found between pregnant and non-pregnant rabbits in physiological conditions and during anaesthesia. Ketamine-chlorpromazine and pregnancy seemed to change the other parameters used to assess the acid-base balance and the oxygenation conditions. Anaesthesia affected only Hb, O2Ct, O2Cap, CcO2 and P50. The additive effect of pregnancy and anaesthesia modified pCO2, pO2, HCO3-, TCO2, BEb, SBC, BEecf, A-aDO2, RI, MetHb, RHb, CaO2 and CvO2. The patterns described are close to those of other species, suggesting the New Zealand rabbit might be a reliable animal model for monitoring selected variables.


Spontaneous inclusion body hepatitis in young tamarins: I. Morphological study.

Over a period of 4 years approximately 60% of the new born and juvenile animals in a breeding colony of tamarins (Saguinus fuscicollis) died a sudden death. Histological examination at necropsy revealed interstitial hepatitis in 22 of the 30 young animals of the present study. The hepatocytes contained intranuclear inclusion bodies in 12 of the 22 cases. Upon ultrastructural examination, tubulovesicular structures and amorphous material were found in the nuclei. The endoplasmic reticulum had proliferated and was closely associated with undulating curved membranes. These morphological alterations resemble those reported in chimpanzees experimentally infected with NANB hepatitis viruses.


Sex ratio and mortality in a laboratory colony of the common marmoset (Callithrix jacchus).

In a retrospective study sex ratio and mortality were analysed in a captive colony of common marmosets (Callithrix jacchus). Seven hundred and thirty-five infants in 294 litters (20 singletons, 119 twins, 140 triplets, 14 quadruplets) out of 57 breeding females were evaluated. The sex ratio at birth was 0.95 males:1.0 females. The frequency of males and females, as well as the sex composition of twins and triplets confirm the assumption of dizygotic twinning in the common marmoset. According to age at death, 9 categories were differentiated, with perinatal mortality being the highest. Once early infancy had passed the probability of a common marmoset infant of our colony reaching childhood is nearly 95%. Sixty per cent of all liveborn infants survived beyond 18 months. Mortality of infants at birth from primiparous mothers did not differ from that of pluriparous females, nor did the survival rate of infants with the filial generation the respective female had reached (F1 to F6). Females with a high ratio of triplets and quadruplets had a lower reproductive success than females with a majority of singleton or twin deliveries. Differential mortality between males and females was not observed. The frequency of stillbirths was not strongly related to parity, but was to litter-size. Most stillborn babies were seen in sets of quadruplets, most abortions in singletons. A normal socialization in a stable social environment, as well as not pairing the animals before they are fully adult, are considered important factors in good breeding success and infant survival.


Epidemiology of Rocky Mountain spotted fever in South Carolina, 1985-1990.

By analyzing three different sources of data including DHEC reported cases, hospital discharge data, and death certificates, our study reveals that RMSF is endemic in South Carolina particularly in the Piedmont area and that underreporting of RMSF in South Carolina is likely. The incidence and case fatality rates of RMSF derived from hospital discharge data are higher than these rates derived from cases reported to DHEC. Physicians should be aware of the endemicity of RMSF in South Carolina and should include it in the differential diagnosis of any case of fever of unknown origin especially during the spring and summer seasons regardless of the history of a tick bite.


Managing agitation in the critical care setting.

Pharmacologic control of the agitated ICU patient requires preliminary assessment of the underlying causes of agitation. Reversal of correctable abnormalities, consideration of drug reaction, withdrawal and pain management should be addressed first. Delirium is the most common cause of agitation in the ICU and often has multiple causes. Pharmacologic management of agitation can be safely accomplished by intravenous haloperidol with or without lorazepam, as outlined above.


Heterogeneity in gastric carcinoma with special reference to DNA content and mitotic activity: histopathologic differentiation.

DNA ploidy and mitotic activity were microspectrophotometrically investigated in 46 patients with gastric carcinoma. Measurements of DNA content and mitotic index (M.I.) were examined in the mucosal, submucosal, muscularis propria, and serosal layers of tumors, respectively. The frequency of cells with values exceeding hexaploid chromosome (6c) and mitotic counting analysis revealed a significant higher value in serosa, compared with findings in the mucosa. This tendency was not evident in cases of a differentiated type adenocarcinoma but was noted in those with the undifferentiated type. There were 37 tumors (80.0%) with the same DNA distribution patterns in every layer of the stomach (homogeneous DNA ploidy). Heterogeneity of DNA ploidy was observed in nine tumors (20.0%). Carcinoma with a heterogeneous DNA ploidy manifested a significantly higher incidence of metastasis to the lymph nodes than did those with homogeneous type. Characteristically, there was venous permeation preponderance in the differentiated type and peritoneal dissemination preponderance in the undifferentiated type. This evidence of DNA heterogeneity in gastric carcinoma tissues suggests a possible correlation with the metastatic behavior.


Atrophic chronic gastritis and esophagogastric anastomotic leak after resection and reconstruction for esophageal carcinoma.

The incidence of anastomotic leakage after esophagectomy for cancer and reconstruction with the stomach was analyzed with respect to the presence of coexistent atrophic chronic gastritis (ACG). Of a total of 28 operated esophageal cancer patients with ACG, 6 patients developed an anastomotic leak at the cervical esophagogastrostomy (21%). Of a total of 8 operated esophageal cancer patients none of the patients developed an anastomotic leak. The ACG positive and the ACG negative patients were found to be well matched for age, sex, type of operation, transplant route, level of the anastomoses, and suture technique, and all were operated on by the same surgeons. The difference in leakage rate did not reach statistical significance.


Flow cytometric DNA analysis of hepatic tumours on ultrasound-guided fine-needle aspirates.

A study was performed on a nonconsecutive series of 51 patients in order to assess the feasibility, reliability, and usefulness of flow cytometric (FCM) DNA analysis of samples obtained from benign and malignant hepatic tumours by means of ultrasound-guided fine-needle aspiration (UG-FNA). Cytological and often histological confirmation of the nature of the lesion was obtained in all cases from an expert pathologist. For FCM DNA analysis in 32 cases, it was also possible to use samples obtained at surgery from the actual tumours. There were no post UG-FNA complications, either early or late. It was possible to perform FCM DNA analysis on 6/7 (85.7%) of the benign tumour aspirates and all 44 (100%) coming from the malignant tumours. All the benign tumours showed a DNA-diploid pattern, while the DNA content was aneuploid in 91% of the malignant tumours. Apart from one case, the results of the FCM DNA analysis of the samples removed at surgery were the same as those obtained from the aspirates (97%). FCM DNA analysis on UG-FNA samples from hepatic tumours is a fairly simple, reproducible, well-tolerated technique; it does not involve risks if performed by skilled operators and, since it can be easily repeated even on small tumours, it is a suitable method for monitoring hepatic metastases during chemotherapy.


Effect of liposomal interleukin-2 on ascites-forming rat hepatoma.

Interleukin-2 was entrapped in liposomes (Lip-IL-2) and injected into rats. The intraperitoneal injection of Lip-IL-2 into rats bearing an ascites-forming rat hepatoma (AH-66) significantly increased the survival time when compared with rats administered free IL-2 or saline-containing liposomes. The number of peritoneal exudate cells (PEC) increased markedly after intraperitoneal injection of Lip-IL-2 and consisted mainly of macrophages. The level of tumor necrosis factor alpha (TNF-alpha) and the intensity of free radicals increased in the ascites at 48 hrs after Lip-IL-2 administration, whereas TNF-alpha was not detected and the intensity of free radicals did not increase after free IL-2 administration. Our findings suggested that entrapment of IL-2 into liposomes enhanced its potential for cancer therapy, presumably by activating macrophages to produce TNF-alpha and free radicals.


Posthemipelvectomy hernia.

We present four patients who developed posthemipelvectomy hernias. Identified etiologic factors include infection at the time of hemipelvectomy, radiation therapy, and excessive weight gain. Two patients were reconstructed using local tissues, and two required prosthetic materials. There were no hernia recurrences, although two patients died of recurrent cancer.


The value of nuclear morphometry in the management of patients with colorectal polyps that contain invasive adenocarcinoma.

Haggitt's classification is a useful guide in the management of patients with large bowel polyps which contain invasive adenocarcinoma in that patients with levels 1 to 3 require no operation. Nuclear morphometry has been shown to be a useful prognostic discriminant for patients with invasive carcinoma of the large bowel. The nuclear shape factor of 44 polyps with invasive carcinoma was studied to determine whether this parameter was of value to define those patients with Haggitt level 4 who should have a resection. The shape factor of 50 interphase nuclei was obtained through the use of image analysis by tracing the nuclear profiles as digitized on a video screen. The nuclear shape factor was defined as the degree of circularity of the nucleus, a perfect circle recorded as 1.0. Our previous experience showed a nuclear shape factor greater than 0.84 was associated with a poor outcome. The overall mean shape factor was 0.71 (0.59-0.85). There was a tendency for the patients with residual disease to have values in the upper range. Our findings suggest that nuclear morphometry fails to add any predictive information in this clinical situation.


Quality of life in bone tumor patients comparing limb salvage and amputation of the lower extremity.

In 33 long-term survivors of lower extremity bone cancer quality-of-life data were studied following limb salvage compared to amputation. Self-report questionnaires, semistructured interviews and visual analog scales were used to measure psychoneurotic and somatical distress, activities of daily living, self-esteem, and adjustment to illness. Fourteen patients with limb salvage (age 13-56 years, median 24) and 19 patients with an amputation (age 21-53 years, median 27) were evaluated 2-17 years (median 10 years) after surgery. The differences between the two groups were not statistically significant. However, physical complaints were reported more often by limb salvage patients, whereas the amputees showed a trend toward lower self-esteem and isolation in social life, due to their disability. Both groups felt equal diminution of quality of life and disability as measured on the visual analog scale. These findings could support the cosmetic advantage of limb salvage compared to amputation.


Late relapse and mortality in stage I large bowel cancer.

The outcome was determined for patients with Stage I cancers of the large bowel (colon, rectum, and anus) who were treated from 1982-1989. In 119 consecutive patients, the 5-year survival was approximately 70% (72% by the absolute direct method; 67% by the actuarial life table method). Although the overall 5-year survival was similar to numerous other published reports, it was disturbing to observe that 41% of the living patients had relapsed. Furthermore, although 88/119 (67%) were alive at last report, 2-7 years after treatment, only 23 (19%) were believed to be free of cancer. We conclude that follow-up for more than 5 years and the assessment of disease-free survival are required to evaluate the outcome from Stage I large bowel cancer.


A 94 year old male stage IV breast cancer patient showing complete remission under tamoxifen treatment after operation.

A 94 year old man with an invasive ductal carcinoma of the breast (T4N2M1, stage IV), underwent a modified radical mastectomy to improve his quality of life. The estrogen receptor status of both the breast tumor and the metastatic axillar lymph nodes was high. Immunohistochemical staining for epidermal growth factor, epidermal growth factor receptor, or c-erbB-2 protein was negative. The patient received only tamoxifen continuously for 3 months, and later apparently showed a complete remission. Therefore, in advanced male breast cancer with a high estrogen receptor status, operation in conjunction with hormone therapy may lead to a favorable result in some cases.


Axillary node dissection for early breast cancer: some is good, but all is better.

Optimal management of the axillary lymphatics in breast cancer patients remains a contentious subject. Axillary recurrence, while infrequent, may have very significant clinical consequences in the affected patient. Axillary sampling, partial and total axillary lymphadenectomy, radiotherapy, and surgery plus radiotherapy are discussed with attention to efficacy in prevention of axillary recurrence, accuracy of nodal staging, and morbidity. The incidence of axillary recurrence decreases and accuracy of staging increases with the number of lymph nodes resected. There is little difference in incidence of morbidity between partial and total axillary lymphadenectomy. Radiotherapy is not as effective as lymphadenectomy for regional disease control and, when administered following a surgical staging procedure, increases the risk of lymphedema of the ipsilateral upper extremity and, in patients undergoing breast-conserving surgery, the ipsilateral breast. We believe that total axillary lymphadenectomy provides optimal regional disease control and axillary staging with morbidity comparable to that of partial lymphadenectomy.


Influence of continuous positive airway pressure on sleep apnea-related desaturation in sleep apnea patients.

To investigate the influence of nasal continuous positive airway pressure (CPAP) on apnea-related desaturation, we compared the sleep apnea-related desaturations obtained during a polysomnographic study before and during nasal CPAP in 15 sleep apnea patients. An individual desaturation curve was determined with a regression analysis by plotting the lowest SaO2 value reached during each apnea against its duration; these data were collected throughout the night. At baseline, we only considered the apneas with a preapneic SaO2 value greater than 90% and a minimal SaO2 value above or equal to 60%. For the CPAP study, the preapneic SaO2 value also had to be within 2% the baseline value for the apneas to be retained. Due to the restriction criteria imposed to characterize apnea-related SaO2 falls, residual apneas still had to be recorded with CPAP. These data were analyzed separately for obstructive apnea for non-rapid eye movement (REM) and REM sleep stages. A desaturation curve was obtained from 10 sec to a variable upper limit that corresponded to the longest apnea duration commonly reached during both baseline and CPAP for a given apnea-type and sleep stage. The individual apnea-related SaO2 fall was characterized by measuring a desaturation area corresponding to the area under the curve. It was expressed in % SaO2/sec of apnea. CPAP reduced the number of apneas per hour of sleep from 37.5 +/- 6.5 (mean +/- SEM) to 14.3 +/- 3.7 (p = 0.001), and improved the whole night SaO2 level as estimated by a cumulative SaO2 curve. The mean apnea duration was reduced from 22.9 +/- 1.5 sec at baseline to 16.8 +/- 0.5 sec during CPAP therapy (p = 0.005). The preapneic SaO2 value was 94.8 +/- 0.3% at baseline and 95.5 +/- 0.2% during CPAP (p = 0.5). The desaturation area decreased from 267 +/- 48% SaO2/sec at baseline to 152 +/- 41% SaO2/sec during CPAP (p less than 0.001). We conclude that CPAP improves the apnea-related desaturation independently of the shortening of apneas and of any difference in the preapneic SaO2 value.


Effect of hydralazine on vascular mechanics in a canine lobar preparation of pulmonary embolism.

We studied the effect of hydralazine (H) on pulmonary vascular mechanics in an isolated, in situ, canine lobe model of normal and increased pulmonary vascular resistance (Rp) produced by Gelfoam embolization (GE). Pulmonary pressure-flow (P-Q) curves from 24 lobes were obtained at baseline and after each intervention. Hemodynamic parameters for analysis included: the mean critical closing pressure (Ppai), vascular conductance (1/Rp), lobar flow (QL), and the pulmonary inflow pressure (Ppa) at different levels (50, 100, 200, 400, and 600 ml/min) of a fixed flow. After the preparation was stabilized, the 24 lobes were classified into 2 groups. For group 1 (n = 8) we studied the effect of H on the normal pulmonary vasculature. In group 2 (n = 16) we studied the effect of GE. Following GE, this group was further divided in half. For group 2A (n = 8) we followed the natural history of GE with measurements at 15 and 60 min. For group 2B (n = 8) measurements were done 15 min after GE and repeated again 15 min after the infusion of H. For group 1 lobes, H promoted a significant decrease (p less than 0.001) in Ppa at fixed flows of 200, 400, and 600 ml/min compared to baseline, with no change in Ppa for flows below 100 ml/min. QL and 1/Rp increased (p less than 0.01), and there was not any significant change in Ppai. In group 2A lobes, GE produced an increase in Ppa at all levels of flow (p less than 0.01), QL and 1/Rp decreased (p less than 0.05), and there was an increase in Ppai (p less than 0.05). These changes remained stable over the 60 min of observation. For group 2B lobes, GE produced the same hemodynamic changes as in group 2A, and the infusion of H caused a decrease in Ppa at flows between 100 and 300 ml/min. (p less than 0.01) with no change in Ppa at flows below 100 ml/min. QL and 1/Rp increased (p less than 0.01) and Ppai did not change compared to 15 min after GE. We conclude that in the normal canine pulmonary vasculature as well as in the model of GE, H decreased Rp and did not affect mean critical closing pressure, all of which may be explained by an increase in vascular conductance due to an increase in vascular distensibility.


Granulocyte-macrophage colony-stimulating factor modulation of the inhibitory effect of transforming growth factor-beta on normal and leukemic human hematopoietic progenitor cells.

Experiments were undertaken to investigate the molecular basis of primitive hematopoietic progenitor cell regulation in both the long-term culture system and in methylcellulose, particularly with a view to characterizing factors either able or unable to influence the behaviour of primitive leukemic cells from patients with chronic myeloid leukemia (CML). Long-term cultures of CML cells with or without irradiated normal marrow feeder layers were initiated from peripheral blood cells of CML patients with high white blood cell counts. Three weeks later the effect of exogenously added transforming growth factor-beta 1 (TGF-beta 1) on progenitor cycling status was examined. A single addition of 5 ng/ml TGF-beta 1 was able to reversibly arrest the otherwise uninterrupted turnover of primitive leukemic erythroid and granulopoietic progenitors for a period of up to 7 days both in the presence and absence of a normal adherent cell population. When TGF-beta 1 was incorporated into methylcellulose cultures, its ability to inhibit colony formation by CML progenitors showed the same differential activity on primitive cell types exhibited by normal progenitors. Dose-response curves for analogous populations of normal and leukemic cells were indistinguishable. Increasing the concentration of granulocyte-macrophage colony-stimulating factor (GM-CSF) in methylcellulose colony assays decreased the sensitivity displayed by normal clonogenic cells to TGF-beta 1 and no differences were detectable when CML cells were used in such regulator competition experiments. These findings support a general model of primitive hematopoietic cell regulation in which entry into S-phase is determined at the intracellular level by multiple convergent pathways that may deliver either positive or negative signals from activated cell surface receptors for distinct extracellular factors. The present study shows for the first time that primitive CML progenitors exposed to TGF-beta 1 in vitro can be transiently blocked in a noncycling state for several days without loss of viability and that the mechanisms responsible for the emergence and maintenance of a clonal population of CML cells in vivo do not appear to involve changes in their sensitivity to TGF-beta 1. It is thus unlikely that the heightened proliferative activity exhibited by primitive CML progenitors both in vivo and in long-term culture can be explained by an abnormality in the intracellular mechanisms normally activated by TGF-beta 1 receptor-ligand binding. We suggest that primitive CML cells are either defective in their ability to see (or activate) endogenously produced TGF-beta 1, or are defective in their responsiveness to another, undefined, regulator.


Post-remission therapy of acute myelocytic leukemia in adults: curability breeds controversy.

The curability of acute myelocytic leukemia (AML) in adults relies upon two treatment strategies. The first is induction therapy to effectively reduce the patient's leukemia burden and allow for recovery of normal hematopoiesis. Once this is achieved and the patient enters a complete remission, further potentially curative post-remission therapy can be administered. Induction therapy has not changed significantly over the past two decades, relying primarily on conventional-dose cytarabine and an anthracycline combination. Post-remission therapy, on the other hand, has changed with the introduction of more intensive and aggressive cytoreductive treatment as well as utilization of myeloablative regimens followed by either allogeneic or autologous bone marrow transplantation (BMT). The scope of this review is to evaluate the different curative post-remission treatment approaches for adult patients with AML. Discussions will focus on younger patients (less than 65 years) with responsive disease who enter a complete remission and then have post-remission therapy options available to them. Often, decisions concerning post-remission therapies are based solely on age and the availability of compatible donors; however, since understanding of the biology of leukemia has expanded and treatment strategies have improved, our ability to recommend particular treatment approaches has also evolved. We are now in a position to recommend therapeutic options based on disease and host characteristics.


Co-induction of c-fos and junB during the latent period preceding commitment of Friend erythroleukemia cells to differentiation.

Chemically induced differentiation of Friend murine erythroleukemia cells (F-MELC) is a multistep process with a latent period of about 12 h preceding irreversible commitment to terminal maturation. To gain understanding of the early genetic response of F-MELC to the dimethyl sulfoxide (DMSO) inducer of F-MELC differentiation, we have investigated by Northern blot analysis the expression of fos and jun family genes that encode components of the transcription factor AP-1 complex. Our results show that c-jun mRNA is not detected at any time in untreated and DMSO-treated F-MELC. In contrast, DMSO-induced differentiation of F-MELC is associated with an early and transient induction of c-fos and junB mRNAs by 2 to 8 h treatment while in presence of dexamethasone, an inhibitor of F-MELC commitment, c-fos mRNA is not detected and junB mRNA remains at basal levels. junD mRNA is detected at low levels in untreated F-MELC and remains unchanged during DMSO treatment. Furthermore, DMSO treatment in a F-MELC cell line resistant to DMSO-differentiation does not result in an early induction of c-fos and junB mRNAs. Taken together, these results indicate that the DMSO-induced F-MELC differentiation is accompanied by an early co-induction of c-fos and junB during the latent period preceding the commitment to erythroid maturation.


Factors affecting the in vitro evolution of a myeloma cell line.

A continuously growing plasma cell line has been established from the bone marrow of a multiple myeloma patient. Initial growth of the cells was dependent on the presence of bone marrow stromal cells. Following initial outgrowth the cells were maintained by transfer onto non-autocthonous bone marrow stromal cultures. Following approximately one year of continuous growth, a subline was derived which could be grown independently of feeder cells. These stromal-cell-independent myeloma cells nevertheless retained dependence for a growth factor present in stromal-cell-conditioned media. The relevant factor in the conditioned media was determined to be interleukin-6 (IL-6). The cells also ultimately became independent of the conditioned media. These latter cells were shown to contain mRNA for IL-6 and eventually began to secrete IL-6. This cell line has thus progressed from complete dependence on stromal cells to IL-6-dependent growth in the absence of stromal cells to complete self sufficient growth. This in vitro progression may reflect an in vivo pattern of myeloma development.


Possible correlation between fusion pattern of BCR/ABL mRNA and clinical response to alpha-interferon in chronic myelogenous leukemia.

Twenty six patients with Philadelphia chromosome (Ph1) positive chronic myelogenous leukemia (CML) treated with IFN-alpha were classified on the basis of the fusion pattern of BCR/ABL chimeric mRNA determined by a reverse-transcriptase-polymerase chain reaction (RT-PCR) method. The relationship between the fusion pattern of BCR/ABL mRNA and the clinical outcome was also analysed. Twelve patients showed M-bcr exon 3/ABL exon 2 (B3/A2) chimeric mRNA and nine had M-bcr exon 2/ABL exon 2 (B2/A2) mRNA. Eleven of the 12 patients with B3/A2 achieved complete hematological response with IFN-alpha therapy, as did three of the nine patients with B2/A2. The mean duration to blastic crisis was significantly longer in the B3/A2 patients (mean 52.4 months) than in the B2/A2 patients (mean 26.2 months) (p less than 0.01). These results suggest that the fusion pattern of BCR/ABL mRNA may affect the therapeutic response to IFN-alpha and clinical outcome in CML patients.


Interleukin-2 induction of lymphokine-activated killer activity in the peripheral blood of an acute lymphoblastic leukaemia patient--case study.

In this case study an acute lymphoblastic leukaemia (ALL) patient relapsing after autotransplant had remission reinduced with chemotherapy and consolidated after initial response by a course of therapy with recombinant interleukin-2 (rIL-2) given subcutaneously. Immunological parameters measured during therapy demonstrated an increase in the numbers of T cells and in lymphokine-activated killer (LAK) cell activity against autologous leukaemic blasts and LAK-sensitive cell lines. The therapy was well tolerated and administered on an out-patient basis. The patient has remained in haematological remission for over twelve months. Sustained remissions have not been observed previously in relapsed transplant patients using chemotherapy alone. The data suggests that rIL-2 deserves further evaluation in ALL patients who are immunologically intact with residual disease after primary or secondary chemotherapy.


Development of T-cell leukaemia in an ataxia telangiectasia patient following clonal selection in t(X;14)-containing lymphocytes.

Ataxia telangiectasia is a rare inherited and progressive neurological disorder in which patients show an unusual predisposition to T-cell leukaemia. We report here observations on a patient with a large cytogenetically abnormal clone showing a single t(X;14)(q28;q11) translocation which conferred a proliferative advantage on the cells. The further evolution of this clone to cytogenetically more complex clones of lymphocytes was seen in the patient. She subsequently developed a rapidly progressing T-cell leukaemia, with a CD4+CD8+ T-cell phenotype, about five years after the first appearance of additional chromosome translocations in the clone cells.