Non-Hodgkin's lymphomas of stage III extent. Is total lymphoid irradiation appropriate treatment?

Many investigators have regarded Stage III lymphomas as a generalized form of disease and have accordingly recommended systemic treatment programs. Between 1961 and 1973, 68 patients with clinical or pathologic Stage III non-Hodgkin's lymphomas were seen in the Division of Radiation Therapy at Stanford University Medical Center and were treated by high dose (3500 rads or more) total lymphoid radiation therapy only. Of the 17 patients who had a diffuse histologic pattern, the actuarial survival at 5 years was 39%, but only three patients have remained free of disease. In contrast, for the 51 patients who had a nodular histologic pattern, the actuarial survivals at 5 and 10 years were 75% and 65%, respectively. Corresponding relapse-free survivals for patients with nodular lymphomas were 43% and 33%, respectively. Of 28 patients who relapsed with nodular lymphomas, 18 (64%) had relapses confined to lymph nodes; six of these were extensions to previously unirradiated epitrochlear-brachial nodes. Seven of the 18 patients were treated only with further conventional external radiation therapy at the time of their relapses and remain free of disease for additional periods of 2 to 5 years. Hence, 30 of 51 (59%) patients with nodular lymphomas have thus far been controlled by high dose total lymphoid irradiation only. Over 90% of relapses among patients with nodular lymphomas were seen within the first 5 years. The data suggest that high dose conventional radiation therapy to incorporate not only the routine total lymphoid fields but also the epitrochlear, mesenteric, and Waldeyer's ring region has curative potential even in Stage III non-Hodgkin's lymphomas, especially in the nodular group.     

Interaction versus independence of startle-modification processes in the rat

The absolute bioavailability of quinidine was studied in 11 hospitalized patients. A 400-mg dose of quinidine gluconate was administered to each patient by intravenous infusion and as an oral solution. Drug treatments were separated by a 72-hr period. In 8 patients, peak plasma quinidine concentrations were reached in 65 min after the oral dose; in the remaining 3 subjects, peak concentrations were reached later. From the ratio of the total area under the plasma concentration-time curves (AUCoral/AUCir), the absolute bioavailability of quinidine ranged from 44% to 89% (mean, 72). In 8 patients, the ratio of the total amount of quinidine excreted in the urine in 48 hr (AUinfinity oral/AUinfinity ir) indicated that the extent of quinidine bioavailability varied form 47% to 96% (mean, 73). The predicted bioavailability of quindine due to first-pass effects was 76+/-11%. It is concluded that absorption after the oral solution was rapid and that the reduction of quinidine bioavailability was due to first-pass hepatic drug removal.     

Correction of postoperative metabolic alkalosis and renal failure by hemodialysis

Arylamidase activity in human endometrium tissue, uterine fluid, and serum in uterine dysfunction induced by a copper IUD, steroidal contraception, and lactational amenorrhea was investigated. Arylamidase activity in cell-free preparation of endometrium increased steadily from the early proliferative phase attaining the maximum level at the secretory phase. The activity in the uterine fluid and serum showed similar trends. In uterine dysfunction, the activity decreased in different conditions. The distribution of the enzyme activity in the particular and soluble fractions was within a close range (1.4 to 1.7), indicating the absence of transfer of enzyme from particulate to the soluble fraction. The administration (in vitro) of 10 -4 M estrogen and progesterone caused an increase in the activity. Substrate affinity values of the enzymes in both fractions remained unaffected while the catalytic phase values were altered indicating a qualitative difference in the 2 enzymes.     

Metabolic pathways of WR-2721 (ethyol, amifostine) in the BALB/c mouse

This study investigated the metabolism of the radio- and chemoprotector compound, WR-2721 [amifostine; s-2-(3- aminopropylamino)ethylphosphorothioate], in the Balb/c mouse. The latter was selected for these studies because considerable radiation protection data have been published for this mouse strain using the WR-2721 dose, route of administration, and optimal time for protection following intraperitoneal injection used herein. It is known that protection requires conversion of the parent drug to its free thiol metabolite, WR-1065, in cultured cells. Because it is possible that metabolites of WR-1065 could be involved in protection and because thiols are metabolically very reactive molecules, we investigated the metabolism of WR-2721 using electrochemical detection-HPLC methods. The following are the major findings in this study: 1) WR-2721 drug was rapidly cleared from the bloodstream. Blood concentration of the parent drug decreased 10-fold 30 min after administration from the maximal observed value at 5 min 2) WR-1065 rapidly appeared in the perchloric acid (PCA)-soluble fraction of normal solid tissues. The highest WR-1065 concentrations in liver and kidney were 965 and 2195 mumol/kg, respectively, 10 min after parent drug administration, whereas for heart and small intestine the highest values were 739 and 410 mumol/kg at 30 min. 3) WR-1065 accumulated in the PCA-soluble fraction of two experimental tumors at a lower rate than for the other tissues.(ABSTRACT TRUNCATED AT 250 WORDS)     

Long-term effects of pentobarbital anesthesia on the atrial natriuretic peptide system in rats

The midline fascial splitting approach is a modified midline approach to the iliac crest for bone graft that takes advantage of the anatomic planes between layers of the dorsal lumbar fascia. Two hundred consecutive grafts were taken by this technique with one superficial infection, two cases of serous hematoma, and three patients with significant postoperative pain at the harvest site, for an overall complication rate of 3%. In comparison, bone grafts were harvested from 200 consecutive patients by the midline subcutaneous approach to the iliac crest with 2 deep infections, 1 cluneal nerve injury, 15 patients with severe and disabling pain at the harvest site, and 12 patients with a serous hematoma, for an overall complication rate of 15%. The midline fascial splitting approach significantly reduced the incidence of postoperative serous hematoma (P < 0.007) as well as the incidence of significant and disabling pain (P < 0.001). In addition, the approach is simple, straightforward, anatomic, and decreases trauma to soft tissues.     

Radiotherapy for nasolacrimal tract epithelial cancer

PURPOSE: Tumors of the lacrimal sac are rare and have traditionally been treated surgically. We investigated the use of irradiation for treatment. METHODS AND MATERIALS: Three consecutive patients with primary epithelial cancer of the nasolacrimal apparatus were treated with irradiation. A tumor dose of 52-66 Gy was delivered with conventional fractionation to fields limited to the primary site and immediately surrounding tissues. RESULTS: Local tumor control was achieved in all three patients. Two patients subsequently developed metastatic cervical adenopathy; both were controlled with irradiation to the neck. One of these two died of distant metastases. Two patients are alive and well at 13 years and at 26 months. CONCLUSION: We conclude that epithelial lacrimal sac tumors are controllable by radiation therapy and with a good cosmetic result. Poorly differentiated lesions require elective cervical nodal irradiation.     

Grain dust-induced airflow obstruction and inflammation of the lower respiratory tract

To investigate the relationship between the physiologic and biologic effects of grain dust inhalation, we exposed 15 nonsmoking, nonasthmatic, nonatopic male grain handlers to buffered saline and aqueous corn dust extract by inhalation challenge in a crossover study. The inhalation challenges to buffered saline and corn dust extract were separated by at least 14 d. Compared with buffered saline, inhalation of corn dust extract resulted in significant airflow obstruction, which was observed within 30 min of exposure and persisted for 5 h. Inhalation of corn dust extract resulted in an acute inflammatory response characterized by higher concentrations of neutrophils (p = 0.001), IL-1 beta (p = 0.001), IL-1RA (p = 0.001), IL-6 (p = 0.001), IL-8 (p = 0.001), and TNF-alpha (p = 0.04) in bronchoalveolar lavage (BAL) fluid. mRNA levels specific for IL-1 beta, IL-1RA, IL-6, and IL-8 from cells present in the BAL fluid were significantly greater after challenge with corn dust extract than after challenge with buffered saline. Importantly, no significant differences were observed in the concentration of lymphocytes or eosinophils in the BAL fluid following inhalation of corn dust extract, and the concentrations of histamine and 15-HETE were similar in BAL fluid after the two challenges. The maximal percentage decrease in FEV1 was significantly associated with the absolute neutrophil concentration in the BAL fluid (p = 0.001), as well as the concentration of TNF-alpha (p = 0.03), IL-1 beta (p = 0.005), IL-1RA (p = 0.001), IL-6 (p = 0.001), and IL-8 (p = 0.001) in the BAL fluid.(ABSTRACT TRUNCATED AT 250 WORDS)     

Gadolinium-enhancement characteristics of magnetic resonance imaging in distinguishing herniated intervertebral disc versus scar in dogs

STUDY DESIGN: This study is an experimental investigation on the gadolinium contrast magnetic resonance imaging (MRI) in distinguishing sequestered disc fragment versus scar in dogs. The conspicousness of the disc fragment and signal intensities of the disc fragment and laminectomy scar were evaluated using gadolinium-enhanced MRI and histology. OBJECTIVES: This study investigated the effects of timing of gadolinium injections, gadolinium doses, and aging of scar or disc on the enhancement characteristics and conspicuousness of disc fragment in MRI. SUMMARY OF BACKGROUND DATA: Contrast-enhanced MRI has been frequently used as a procedure to evaluate patients with suspected recurrent herniated discs. In contrast-enhanced MRI, the postoperative scar tissue enhances to a greater extent than disc fragments. Previous reports suggest different contrast enhancement characteristics of scar depending on doses, timing of gadolinium, or maturity of scar. There are different compounds of gadolinium agents and different doses are becoming available. There is no previous report on the evaluation of gadolinium enhancement characteristics in dogs with concurrent herniated disc and scar. METHODS: Six conditioned Beagle dogs underwent hemilaminectomies and discectomies at the L3-L4 level. An autogenous disc fragment was obtained from the intervertebral disc of the tail. This disc fragment was placed anterolateral to the thecal sac, simulating a sequestered disc herniation. Three control animals underwent hemilaminectomies and discectomies alone. Each dog underwent MRI on a 1.5 Tesla scanner (3.0 mm slice in sagittal and axial projections with TR 500, TE 30 msec and high dose 0.3 mmol/kg of gadoteridol). Images were obtained at 15 days, 30 days, 60 days, and 90 days after surgery. At each imaging session, contrast enhancement was measured at 2 minutes, 25 minutes, and 45 minutes after gadolinium injection for kinematic analysis. Two animals at a time were killed on 30 days, 60 days, and 90 days postoperatively. Magnetic resonance imaging was done with conventional low dose 0.1 mmol/kg of gadopentetate at 15 days and before death. RESULTS: Results revealed that the difference of enhancement between disc and the scar and therefore conspicuousness of disc fragment was greater on 2-23-minute images as compared with 45- minute images, and the distinction decreased with aging of the scar. The high dose contrast-enhanced MRI increased signal intensities for both disc and scar. Conspicuousness of disc fragment seemed to be better with the high-dose gadolinium compound. CONCLUSIONS: In conclusion, contrast enhancement characteristics in MRI may depend on the timing of MRI after gadolinium injection, doses of gadolinium, and aging of scar or disc.