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Biomedical subjects

J M Klausner

Publications and source records attributed to J M Klausner.

At least 91 records · Page 5Linked to original sources
PubMed1988

Limb ischemia-induced increase in permeability is mediated by leukocytes and leukotrienes.

This study tests the role of white blood cells (WBC) and leukotrienes in mediating the increased microvascular permeability following ischemia and reperfusion. Anesthetized dogs (n = 23) underwent 2 hours of hind limb ischemia induced by tourniquet inflation to 300 mmHg. In untreated animals (n = 7), tourniquet release led after 5 minutes to a rise in plasma thromboxane (Tx) B2 levels from 360 to 1702 pg/ml (p less than 0.05); after 2 hours, lymph TxB2 concentration had risen from 412 to 1598 pg/ml (p less than 0.05). There were decreases in circulating WBC from 11,766 to 6550/mm3 and platelets from 230 to 155 x 10(3)/mm3. During reperfusion, popliteal lymph flow (QL) increased from 0.07 to 0.24 ml/hour (p less than 0.05), while the lymph/plasma (L/P) protein ratio was unchanged from 0.39, changes consistent with increased microvascular permeability. WBC depletion (n = 7) to 302/mm3 by hydroxyurea or nitrogen mustard attentuated (p less than 0.05) the reperfusion induced rise in plasma TxB2 from 91 to 248 pg/ml and prevented the increase in lymph TxB2 concentration. Within 5 minutes of tourniquet release WBC counts further decreased to 191/mm3 (p less than 0.05) and platelets declined from 175 to 93 x 10(3)/mm3 (p less than 0.05). QL increased from 0.07 to 0.12 ml/hour (p less than 0.05), lower than untreated animals (p less than 0.05), and the L/P protein ratio declined from 0.49 to 0.37 (p less than 0.05), dilutional changes consistent with increased filtration pressure but not permeability to protein. Pretreatment with the lipoxygenase inhibitor diethylcarbamazine (DEC) (n = 8) prevented the reperfusion-induced increase in plasma and lymph TxB2 levels (p less than 0.05) and the fall in WBC counts (p less than 0.05), while platelet counts declined from 381 to 210 x 10(3)/mm3 (p less than 0.05). QL rose from 0.09 to 0.23 ml/hour (p less than 0.05) during reperfusion, and the L/P protein ratio of 0.3 remained unchanged, a value lower than in untreated dogs (p less than 0.05). In two animals of each group, vascular recruitment was induced by tourniquet inflation to 50 mmHg. This led to a high QL of 0.25 ml/hour and a low L/P ratio of 0.18. In untreated animals during reperfusion, QL further increased to 1.3 ml/hour, and L/P ratio rose to 0.44, documenting increased vascular permeability. In contrast, reperfusion in leukopenic or diethylcarbamazine (DEC)-treated dogs with vascular recruitment, was not associated with increases in QL or the L/P protein ratio.(ABSTRACT TRUNCATED AT 400 WORDS)

6-Ketoprostaglandin F1 alpha↗
PubMed1988

Lower torso ischemia-induced lung injury is leukocyte dependent.

Lower torso ischemia leads on reperfusion to sequestration of polymorphonuclear leukocytes (PMN) in the lungs and increased permeability. This study tests the role of circulating leukocytes (WBC) in mediating this lung injury. Anesthetized sheep prepared with chronic lung lymph fistulae underwent 2 hours of bilateral hind limb tourniquet ischemia. In untreated controls (n = 7), 1 minute after reperfusion there were transient increases in mean pulmonary arterial pressure (MPAP) from 13 to 38 mmHg (p less than 0.05) and pulmonary microvascular pressure (Pmv) from 7 to 18 mmHg (p less than 0.05), changes temporally related to a rise in plasma thromboxane (Tx) B2 levels from 211 to 735 pg/ml (p less than 0.05). Lung lymph TxB2 levels rose from 400 to 1005 pg/ml at 30 minutes (p less than 0.05), and remained elevated longer than plasma levels. Lung lymph flow (QL) rose from 4.3 to 8.3 ml/30 minutes (p less than 0.05) after 30 minutes of reperfusion and remained elevated for 2 hours. The lymph/plasma (L/P) protein ratio was unchanged from 0.6, while the lymph protein clearance increased from 2.6 to 4.6 ml/30 minutes (p less than 0.05), suggesting increased microvascular permeability. WBC counts decreased within the first hour of reperfusion from 6853 to 3796/mm3 (p less than 0.05), and lung histology after 2 hours showed proteinaceous exudates and leukosequestration of 62 PMN/10 high-powered fields (HPF), higher than the 22 PMN/10 HPF (p less than 0.05) in sham animals (n = 3). Recruitment of the pulmonary vasculature by left atrial balloon inflation (n = 3) resulted in a rise in MPAP to 20 mmHg. After 3 hours of balloon inflation, QL stabilized at 9.8 ml/15 minutes, and a pressure-independent L/P protein ratio of 0.3 was achieved. During reperfusion, QL increased further to 11.2 ml/15 minutes, the L/P ratio rose to 0.56 and the calculated osmotic reflection coefficient decreased from 0.70 to 0.44, documenting an increase in lung microvascular permeability. In contrast to these untreated ischemic controls, sheep (n = 7) rendered leukopenic with hydroxyurea or nitrogen mustard and having a total WBC count of 760/mm3 and PMN count of 150/mm3 did not manifest reperfusion-induced increases in MPAP, Pmv, QL, lymph protein clearance, or lung lymph. TxB2 level (p less than 0.05). Plasma TxB2 levels rose slightly at 30 minutes from 199 to 288 pg/ml (p less than 0.05). Lung histology was normal. These data indicate that WBC mediate the ischemia-induced increase in pulmonary microvascular permeability.

Animals↗
PubMed1988

Delayed respiratory depression following fentanyl anesthesia for cardiac surgery.

High-dose fentanyl anesthesia is widely used in cardiac surgery. Its immediate side-effects are well known. However, its late adverse effect manifested by extreme truncal rigidity, decreased chest wall compliance, hypoventilation, respiratory acidosis and hemodynamic instability is not sufficiently appreciated. Of 380 patients who underwent aortocoronary artery bypass under high-dose (100 micrograms/kg) fentanyl anesthesia, 29 (7.6%) developed the sudden onset of extreme thoracic and abdominal rigidity, leading to respiratory depression 2 to 6 h postoperative, after an apparently normal recovery from the anesthesia. In 15 patients, a high plasma level of fentanyl (5.2 to 7.8 ng/ml) correlated with the clinical events. Administration of naloxone or a muscle relaxant rapidly reversed this late complication of fentanyl, thought to be due to re-entry of fentanyl into plasma from deposits in adipose tissue, muscle and the GI tract, leading to a secondary peak in plasma fentanyl. It is more likely to be encountered when hypothermia, rewarming, and acidosis occur in the postoperative period. Awareness of this life-threatening complication is critical in patients undergoing surgery with fentanyl anesthesia.

Aged↗
PubMed1988

Inhibition of thromboxane (Tx) synthesis by free radical scavengers.

Treatment with thromboxane (Tx) synthase inhibitors or free radical scavengers has been shown to afford protection from renal ischemia. Since free radicals are closely associated with thromboxane (Tx) synthesis, this study examines the thesis that free radical scavengers inhibit formation of Tx. Anesthetized rats (n = 42) underwent right nephrectomy. By random choice, before 45 min of left renal pedicle clamping, rats received: 0.5 ml dextrose placebo IV (n = 6); the hydroxyl radical scavenger dimethyl-thiourea (DMTU), 500 mg/kg IV (n = 10); or the superoxide scavenger superoxide dismutase (SOD), 24,000 Sigma Units (SU)/kg IV (n = 12). This dose of SOD was repeated before release of the clamp. Treatment with DMTU and SOD decreased plasma TxB2 levels following 5 min of reperfusion from 2,480 pg/ml in dextrose treated controls to 1,155 pg/ml (p less than 0.01) and 1,419 pg/ml (p less than 0.03), respectively. At 24 hr, DMTU and SOD therapy decreased creatinine from 3.0 mg/dl in controls to 1.6 mg/dl (p less than 0.01) and 2.1 mg/dl (p less than 0.05), respectively. At 24 hr, DMTU but not SOD decreased left renal weight from 113 to 94% (p less than 0.0003) of the weight of the previously removed right kidney, and histologically prevented acute tubular necrosis (p less than 0.05). In nephrectomized but nonischemic sham control rats (n = 7) plasma TxB2 and 6-keto-PGF1 alpha concentrations were 757 pg/ml and 82 pg/ml, creatinine level 0.9 mg/dl and kidney weight 94% of the previously removed right kidney.(ABSTRACT TRUNCATED AT 250 WORDS)

6-Ketoprostaglandin F1 alpha↗
PubMed1988

Selective lung leukosequestration after complement activation.

This study tests whether activated complement leads to a selective entrapment of polymorphonuclear leukocytes (PMN's) in the lungs. Awake sheep were infused for 5 min with zymosan-activated plasma (ZAP, 2.5 mg/ml) at a rate of 5 ml/min into the superior vena cava (IV, n = 4) or intra-arterially into the aortic arch or femoral artery (IA, n = 8). At the end of IV infusion, leukocyte counts fell from 8,862 to 1,631/mm3 (P less than 0.01). PMN counts across the lungs decreased by 74%. There were increases in plasma thromboxane (Tx) B2 from 114 to 2,733 pg/ml (P less than 0.01), mean pulmonary arterial pressure from 12 to 42 mmHg (P less than 0.01), and physiological shunt from 13 to 25% (P less than 0.05). Within 1 h lymph TxB2 levels had risen from 301 to 4,916 pg/ml (P less than 0.01), lung lymph flow (QL) rose from 3.7 to 11.1 ml/30 min (P less than 0.05), lymph-to-plasma protein ratio (L/P) remained unchanged at 0.63, and lymph protein clearance increased from 2.3 to 7.5 ml/30 min (P less than 0.05). Leukosequestration, quantitated by capillary PMN counting and by assaying the granulocyte marker myeloperoxidase, occurred relative to sham animals (P less than 0.05) in the lung and spleen but not in other organs. Intra-arterial ZAP infusion led to changes that were similar in magnitude and timing to the IV group.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Prolonged fever as a presenting symptom in adrenal tumors.

Four patients with adrenal tumors in whom prolonged fever was the foremost symptom are presented. Two of the patients had nonfunctional adrenocortical carcinoma, one had a pheochromocytoma without adrenergic hyperactivity, and in the fourth, an aldosteronoma was found. Only in 1 case was the tumor (pheochromocytoma) resectable and this patient became afebrile post surgery. A review of the literature revealed that fever is encountered in 6-10% of cases with adrenal tumors, sometimes as the first manifestation of disease. However, a survey of the large series of fever of unknown origin revealed no mention of adrenal tumors in that group of solid tumors which many cause prolonged fever.

Adrenal Gland Neoplasms↗
PubMed1987

Nail-bed melanoma.

In our series of 348 patients treated over a 10-year period, six (1.7%) had their primary lesions in the nail bed. Five of the subungual melanomas occurred in the toes and one in the thumb. Four of the lesions were of the acral lentiginous type. The delay in diagnosis was 7 months to 6 years. Four of the patients presented with advanced, neglected tumors. One had distant metastases at diagnosis. The treatment was mainly surgical. Digital amputation was carried out for local control. Five patients underwent lymph node dissection and in three of them regional metastases were found. Of the four patients with regional and distant metastases at the time of diagnosis, three died within 6 to 60 months and the fourth is alive with metastatic spread. Of the two patients with melanoma confined to the nail bed, one is free of disease 50 months following diagnosis and the other suffered from a local recurrence and has been free of disease for 30 months following wide excision and limb perfusion.

Aged↗
PubMed1987

Surgical approach to malignant melanoma in the gastrointestinal tract.

The gastrointestinal (GI) tract is a common site for malignant melanoma. Diagnosis of lesions in the GI tract is usually delayed until complications occur, such as obstruction, bleeding, or perforation of the GI tract. Of 348 patients with malignant melanoma treated during a 10-year period, 11 had GI involvement either in a metastatic form or as a primary melanoma. Three of these patients were treated surgically for metastatic lesions in the small bowel causing intussusception, two for peritonitis secondary to perforation of the small bowel, and one for massive bleeding from metastatic melanoma in the stomach. Another patient had a primary melanoma in the esophagus and underwent esophagectomy. Three patients had primary melanomas of the anal canal and one of the rectum. Three of them underwent abdominoperineal resections, and two had bilateral groin dissection in addition. Six of the patients are alive 6 months to 4 years following diagnosis. The remaining five died of metastatic melanoma from 6 months to 4 years post-surgery.

Adult↗
PubMed1987

Gangrene of the lower limbs in diabetic patients: a malignant complication.

Diabetic foot lesions are a common medical problem with major socioeconomic impact. Gangrene is usually a late and sometimes fatal complication. A series of 118 diabetic patients who underwent amputation of the lower limb at our institution over a 10 year period has been presented. Forty-two patients underwent amputation of the toes or part of the foot, 48 underwent below-knee amputation, and 18 underwent above-knee amputation. In 24 (20.3 percent), the necrotic process advanced postoperatively and necessitated additional amputation. The average hospital stay was 33.6 days. Twenty-eight patients (23.7 percent) died during the postoperative period, and the main cause of death was sepsis. Patients who presented with extensive gangrene had a higher mortality rate. There was no correlation between mortality and the duration of conservative treatment, number of repeated operations, the treatment of diabetes before hospitalization, onset of symptoms, or status of the peripheral pulses. The solution to the problem is early and vigorous preventive treatment. This could be accomplished through highly specialized clinics within the community.

Aged↗
PubMed1987

Training aids for instruction in the initial management of injury casualties and in resuscitation procedures.

Practical experience in the initial treatment of injured patients is not easily available to the medical student. The small number of injured patients available for observation in a short time, the fact that the patients do not necessarily arrive in regular teaching hours, and the large number of students present in teaching groups compound this difficulty. Specialized instruction in these subjects is therefore important. The acquisition and use of teaching aids facilitate precise and efficient presentation of the material. We present teaching aids specifically prepared for instruction in the initial management of the injured and in resuscitation procedures. These aids include a library of video recordings documenting important emergency procedures, a TV camera used for filming these procedures, a collection of slides on the subject of emergency medicine and recent injuries, mannequins for instruction in cardiopulmonary resuscitation (CPR), utilization of the hospital's animal research laboratory for instruction in critical procedures such as venous cutdown, chest drainage, etc., and simulated computer programs.

Animals↗
PubMed1987

Rectoscopic decompression of acute recto-sigmoid obstruction.

Effective non-operative decompression of a low obstruction of the colon can sometimes be accomplished by inserting a tube into the rectum and threading the tip up to a point proximal to the obstruction (1). Failure of this non-surgical decompression would require emergency surgery--either a diverting colostomy or a two-stage resection. A new non-surgical treatment performed on a patient with an obstructive tumor of the recto-sigmoid is described. Decompression of the obstructed bowel was achieved with a rectal tube introduced over a flexible guide wire proximal to the obstruction with the aid of a rectoscope, following which a one-stage procedure--an anterior resection was performed in one patient, while the other was referred for oncological treatment.

Acute Disease↗
PubMed1987

Gastrointestinal anastomotic healing during treatment with perioperative 5-fluorouracil.

This clinical study examines the influence of perioperative administration of 5-fluorouracil (5-FU) on gastrointestinal anastomotic healing. Intravenous 5-FU, 10 mg/kg body weight, was started during surgery and continued for 9 days only when advanced cancer was detected. A total of 32 gastric and enteric anastomoses were performed. All 32 patients with anastomoses recovered without any clinical evidence of leakage. Side effects attributed to 5-FU appeared in five patients, usually in a mild form of diarrhea and vomiting. On the whole, the course of recovery of this group was no different than expected from patients with advanced malignancy undergoing extensive surgery. Based on this, it appears that 5-FU administration during and immediately after surgery has no deleterious effect on the gastrointestinal tract.

Aged↗
PubMed1987

Conventional fractionation radiotherapy combined with 5-fluorouracil for metastatic malignant melanoma.

Clinical and experimental data suggest a synergistic antitumoral effect with the combined treatment of radiotherapy and 5-fluorouracil (5-FU) serving as a radiosensitizer. This combined modality was studied in 30 malignant melanoma patients with advanced locoregional or isolated, bulky, soft-tissue or visceral metastases. All patients were symptomatic, pain being the chief complaint, followed by symptoms related to large tumors. Treatment was given on an ambulatory basis, twice weekly, and consisted of 5-FU, 500 mg/m2 administered in 8-h i.v. drip infusion, followed by radiotherapy 8 h after completion of the 5-FU administration. 60Co teleunit, delivering 400 rad per dose per fraction, was given over 6 1/2 weeks to a total of 5,200 rad. The overall response rate was 70% (21 of 30 patients). Three patients (10%) achieved a complete response lasting from 3 to 11 months, and 18 (60%) achieved a partial response lasting from 3 to 13 months. The response rate was 82% for skin, 75% for lymph node, and 43% for visceral metastases. Symptomatic relief was obtained in 83% (25 of 30) of the patients. This palliative therapy was well-tolerated, and patients were able to maintain their routine lifestyles throughout. Only in one patient was 5-FU abandoned after 3 weeks, due to cardiac ischemia. Similar response rates have only been achieved with radiotherapy alone employing individual fractions of 600 rad or higher. Since the 5-FU we added is known to have a very limited effect on malignant melanoma, this study suggests its potential as a radiosensitizer in malignant melanoma.

Abdominal Neoplasms↗
PubMed1987

Effect of OKY 046, a thromboxane synthase inhibitor, on lung vascular permeability after pulmonary embolism in sheep.

OKY 046, a specific thromboxane synthase inhibitor, was used to investigate whether large pulmonary emboli, like microemboli, cause an increase in thromboxane A2 and an associated increase in vascular permeability in sheep. Nineteen sheep were anaesthetised and had cannulas inserted into the afferent lymphatic of the caudal mediastinal lymph node and pulmonary and carotid arteries. Several days later the animals were pretreated with placebo or OKY 046 0.4 mg/kg one hour before being given clotted blood 0.5 g/kg intravenously. After embolisation in the control animals mean pulmonary artery pressure (MPAP) rose from 12 to 34 mm Hg and pulmonary artery wedge pressure (PAWP) fell from 4.4 to 1.5 mm Hg; the cardiac index did not change but the physiological shunt (QS/QT) rose from 17% to 50%. One hour after embolisation the platelet count fell from 76 to 32 x 10(6)/l whereas at 15 minutes thromboxane B2 rose from 116 to 560 pg/ml in plasma and from 324 to 795 pg/ml in lymph (p less than 0.05). By 2 hours the concentration of thromboxane B2 was higher in lymph than in plasma. Lymph flow rose from 8.7 to a maximum of 27.3 ml/h at 15 minutes but despite the increase in flow the lymph:plasma (L:P) protein ratio did not fall, indicating an increased permeability of the blood vessels to protein. Pretreatment with OKY 046 inhibited the rise in plasma and lymph thromboxane B2, and limited the rise of QS/QT. The changes in MPAP, PAWP, cardiac index, platelet count, lymph flow, and L:P protein ratio, however, were no different from those in untreated sheep. These results indicate that a large pulmonary embolus leads to an increase in plasma and lung lymph thromboxane A2, which moderates the rise in QS/QT in part but not the increase in vascular permeability.

Acrylates↗
PubMed1986

Active immunotherapy of human solid tumor with autologous cells treated with cholesteryl hemisuccinate. A Phase I study.

A marked increase in specific immunogenicity of tumor cells is induced upon incorporation of cholesteryl hemisuccinate (CHS) into the cell membrane, which presumably promotes the expression of latent tumor-associated antigens. Immunotherapy with CHS-treated and irradiated tumor cells as vaccine was found to be very effective in various murine experimental tumors and in eliciting delayed-type hypersensitivity in cancer patients. Based on these findings, we have carried out a Phase I study on 21 patients with solid tumor who had exhausted standard therapeutic options. All participating patients were examined by conventional physical and clinical tests prior and during the study. The immunotherapy regimen for most patients consisted of an intramuscular injection of 2 X 10(7) CHS treated and irradiated autologous tumor cells given at 2-week intervals. Variations on this regimen were mostly due to the lack of sufficient number of cells. None of the patients displayed evidence of toxicity or any other local or systemic adverse effects. In seven patients, regression of tumor mass was observed. In six of nine patients who were tested for delayed-type hypersensitivity against their CHS treated tumor cells, a significant increase in skin reaction was observed after immunotherapy. The lack of any adverse reaction in this treatment, in addition to the observed positive clinical and immunologic response in advanced cancer patients, indicate a safe therapeutic potency which is planned to be investigated in the subsequent clinical studies.

Cholesterol Esters↗