shukoor65/lab-rag-model huggingface dataset:
A new anticancer drug delivery system for the management of carcinomatous peritonitis. To develop a new drug delivery system for the treatment of carcinomatous peritonitis, we constructed 5-fluorouracil poly L-microcapsules (5Fu-mc) by the organic phase separation technique and examined their drug-releasing capacities and anticancer effects. The microcapsules consisted of in vitro dissolvable polymolecular poly L-lactic acid and 5-fluorouracil (5Fu). The 5Fu-mc was about 200 microns in diameter and had a 5Fu content of about 40% (weight/weight). 5Fu-release time from the microcapsules was about 50 hours in vitro and about 48 hours in vivo. After the release of the 5Fu, the poly L-lactic acid was metabolized very slowly in the peritoneal cavity. The 5Fu-mc caused fewer side effects than the equivalent dose of a 5Fu solution. In addition, macroscopic and microscopic examinations of various abdominal organs revealed no toxic effects from the microcapsules. After administration of 5Fu-mc into the abdominal cavity of rats with AH-130 carcinomatous peritonitis, the 5Fu concentration remained at a high level for an extended period in the ascites but fell rapidly to low levels in the plasma. In conclusion, the present studies indicated that the 5Fu-mc were much more effective in prolonging the life of tumor-bearing hosts while producing less systemic side effects than a 5Fu solution.
New recurring chromosomal translocations in childhood acute lymphoblastic leukemia. We identified seven new recurring translocations among 483 cases of acute lymphoblastic leukemia (ALL) with adequate chromosome banding studies. Four were apparently balanced [t(1;3)(p34;p21), t(7;9)(p15;p23-p24), t(12;13)(p13;q14), t(17;19)(q22;p13)], while three were unbalanced with the formation of a dicentric chromosome [dic(7;9)(p13;p11), dic(7;12)(p11;p12), and dic(12;17)(p11;p11-p12)]. One translocation was observed in five cases, two in four cases, and the remaining four in two cases each. The modal chromosome numbers in these 21 cases were 45 (n = 11), 46 (n = 8), and 47 (n = 2). Eight of the 11 cases with a dicentric chromosome had a modal number of 45. Only a single translocation was found in 14 cases (67%), representing the sole structural abnormality in six cases. In three of the seven translocation subgroups, the blast cells were consistently of B lineage (pre-B, early pre-B, or both); in all others, they represented both the B and T lineages. The small size of these subgroups prevented definitive clinical correlations, although it may be important that two of the four cases with a t(17;19) and an early pre-B-cell immunophenotype had disseminated intravascular coagulation, an event usually observed in acute promyelocytic leukemia or T-cell ALL. These findings add substantially to the existing list of nonrandom chromosomal translocations in childhood ALL and may help to explain the genetic alterations leading to the loss of normal growth control mechanisms in this disease.
Proportionate mortality trends: 1950 through 1986 Mortality trends in the United States from 1950 through 1986 were analyzed for the conditions that are or have recently been among the six leading causes of death. The age-adjusted mortality rate for all causes has decreased from 841.5 to 541.7 per 100,000 population. Cause-specific, age-adjusted mortality rates have declined from 1950 through 1986 for cerebrovascular disease, injuries, perinatal conditions, heart disease, and influenza and pneumonia. Time trends in the proportion of persons dying of each of these diseases, however, have varied; the proportion dying of cerebrovascular disease, injuries, and perinatal conditions has decreased, and the proportion of persons dying of heart disease and influenza and pneumonia has remained fairly stable from 1950 through 1986. During this same time, age-adjusted death rates have increased for chronic obstructive pulmonary disease and have remained fairly stable for malignant neoplasms, while the proportions of persons dying of chronic obstructive pulmonary disease and malignant neoplasms have increased dramatically. For people aged 35 to 64 years, malignant neoplasms have now overtaken heart disease as the leading cause of death. For those aged 65 years and older, heart disease remains the leading cause of death, accounting for almost 50% of all deaths in persons 85 years and older.
Hyperoxia prevents hypoxia-induced bronchial hyperreactivity via a cyclooxygenase-independent mechanism. We tested the hypothesis that prior exposure to alveolar hyperoxia prevents the hypoxia-induced enhancement of bronchial reactivity, possibly via a cyclooxygenase-dependent mechanism. In 15 sheep, specific lung resistance (sRL) was measured before and after 30 min of exposure to either air or a hypoxic gas mixture (13% O2). The sheep then inhaled 50 breaths of aerosolized 5% histamine solution (n = 9) or 10 breaths of 2.5% carbachol solution (n = 9), and measurements of sRL were repeated. On subsequent days the above protocols were repeated after a 30-min exposure to hyperoxia (O2 greater than or equal to 95%), without or after pretreatment with indomethacin (2 mg/kg). After air-sham exposure, carbachol and histamine increased mean sRL to 370 +/- 40 (SE) and 309 +/- 65% of baseline, respectively. Exposure to the hypoxic gas mixture had no effect on baseline sRL but enhanced the airway responsiveness to carbachol and histamine; mean sRL increased to 740 +/- 104 and 544 +/- 76% of baseline, respectively (P less than 0.05). Prior 30-min exposure to hyperoxia prevented the hypoxia-induced enhancement of bronchial reactivity to carbachol (sRL = 416 +/- 66% of baseline) and histamine (sRL = 292 +/- 41% of baseline) without affecting the airway responsiveness to these agents after air. Pretreatment with indomethacin did not reverse the protective effects of hyperoxia or the hypoxia-induced enhancement of bronchial reactivity. We conclude that 1) prior exposure to alveolar hyperoxia prevents the hypoxia-induced enhancement of bronchial reactivity and 2) neither the protective effects of hyperoxia nor the hypoxia-induced enhancement of bronchial reactivity is mediated via a cyclooxygenase-dependent mechanism.
Pathophysiology of myocardial perfusion in hypertension. Chronic and acute hypertension have multiple untoward effects on the coronary circulation, several of which may either mimic or markedly worsen the clinical manifestations of coronary artery disease. Early after the onset of left ventricular hypertrophy secondary to hypertension, coronary vasodilator reserve is significantly impaired. During cardiac hypertrophy secondary to hypertension, the coronary arteries fail to enlarge in concert with ventricular enlargement. This failure results in a relative decrease by approximately 50% in the ratio of epicardial vessel diameter to the mass of myocardium perfused. The lower range of coronary subendocardial autoregulation is altered by chronic renovascular hypertension. A variety of vascular smooth muscle homeostatic mechanisms are abnormal in genetic models of hypertension, as is endothelium-dependent vascular relaxation. Acute hypertension may enhance constriction to serotonin, most likely through the release of potent vasoconstrictor substances from leukocytes and platelets that adhere to the endothelium as a result of endothelial damage. Finally, many of the consequences of myocardial infarction are worsened in the setting of hypertension and left ventricular hypertrophy.
Homing and progression patterns of childhood acute lymphoblastic leukemias in severe combined immunodeficiency mice. The aim of this study was to analyze the homing and progression patterns of childhood acute lymphoblastic leukemias (ALL) in mice with severe combined immunodeficiency (SCID). Upon intraperitoneal (IP) transfer, cells from relapse samples of three children with T-lineage ALL spread hematogenously and infiltrated the non-lymphoid and/or lymphoid organs with a pattern reminiscent of the human clinical disease. These mice either died or were killed in extremis at a mean of 9 weeks. Moreover, cell lines established in vitro from two of these samples manifested identical homing and progression in the SCID mouse as compared with the original patients' cells. Thus, long-term culture of the primary leukemic T cells did not alter their invasive potential and migration pattern. When engrafted IP, three cell lines established from pre-B-ALL cases displayed primarily a lymphatic spread with induction of local tumor masses and kidney/liver nodules. Mice were killed at 11 to 13 weeks, but had not developed imminently fatal leukemia. However, when transferred intravenously, one pre-B ALL cell line was able to spread hematogenously and to infiltrate both lymphoid and non-lymphoid tissues. Overall, these data demonstrate that the SCID mouse provides an efficient and reproducible model to study the pathogenesis of childhood ALL, and may be a suitable system for evaluating therapy.
Hemilaryngectomy for salvage of radiation therapy failures. Radiation therapy has been the treatment most frequently used for early vocal cord cancer with surgery usually in the form of total laryngectomy held in reserve as a salvage option. We report our experience in selected patients who, having failed radiation therapy for their early vocal cord cancers, underwent frontolateral hemilaryngectomy as attempted salvage surgery. Between 1977 and 1986, fourteen patients at the University of Pittsburgh Eye and Ear Hospital underwent hemilaryngectomy for salvage of their stage I vocal cord squamous cell carcinoma after full-course radiation therapy had been unsuccessful. Over this same time period, 77 patients underwent total laryngectomy for salvage of radiation therapy failure. Three patients failed hemilaryngectomy, two of whom were ultimately salvaged with total laryngectomy. Thus a 79% salvage rate was achieved with hemilaryngectomy with an average followup of 90 months. The overall cure rate was 93% (13 of 14) with voice preservation in 86% (12 of 14). Decannulation, postoperative infection, and initiation of oral intake were not influenced by age. Such problems occurred more often in patients undergoing radiation therapy compared to those undergoing hemilaryngectomy without previous radiation therapy. These results indicate that hemilaryngectomy may be used for the salvage of radiation therapy failures of stage I vocal cord carcinoma with good success and without undue morbidity.
Ig repertoire of human polyspecific antibodies and B cell ontogeny. A total of 463 EBV Ig-secreting clones were derived from embryonic tissues, cord blood, and adult peripheral blood. Subcloning and analysis of the H and K loci (germline vs rearranged DNA status) of 44 primary clones insured clonality in at least 92% of cases. Whatever the cell origin, a somewhat constant proportion of clones (i.e., 11 to 16%) expressed polyspecific antibodies when tested on a panel of nine Ag, including self-Ag. The VH and VK repertoires have been studied using VH1-VH6 and VK1-VK4 family-specific probes. For all EBV clones the VH and VK utilization was similar to that of the normal untransformed population. A correlation was observed between the level of expression and the gene number for VH, whereas a clear distortion appeared for VK. Moreover, the usage pattern of VH and VK families of the polyspecific clones did not significantly differ from that of clones of unknown specificity, suggesting that polyspecificity was not linked to a restricted repertoire.
Prospective randomized evaluation of two regimens for converting from continuous to intermittent feedings in patients with feeding gastrostomies. Forty enterally fed male patients were randomized to one of two regimens designed to determine the better means of converting them from continuous to intermittent enteral feedings. All patients received a nutritionally complete iso-osmolal 1 kcal/cc formula containing 6 g of nitrogen/L beginning on the second postgastrostomy day. Half of the patients (20) were randomized to a discontinuous regimen abruptly changing from continuous to gradually increasing intermittent feedings until reaching their nutritional goals. Intravenous fluids were given to maintain normal fluid balance. The other 20 patients were randomized to an overlapping regimen, receiving continuous feedings at a decreasing rate while intermittent feedings were progressively increased. Intravenous fluids were used during the first three stages only. There were no significant differences (p less than 0.05) in major diagnosis, type of gastrostomy, age, weight, height, admission or discharge serum albumin concentration, calculated basal energy expenditure (BEE), or nutrient goals (1.5 X BEE, 1.5 g of protein/kg per day).
Severe 5-fluorouracil toxicity secondary to dihydropyrimidine dehydrogenase deficiency. A potentially more common pharmacogenetic syndrome. This study describes the inheritance of a defect in pyrimidine catabolism and its association with drug-induced toxicity in a patient receiving 5-fluorouracil (FUra) as adjuvant chemotherapy for breast carcinoma. The study population included the affected patient (proband), nine of her blood relatives, and seven healthy volunteers. The activity of dihydropyrimidine dehydrogenase (DPD), the initial enzyme of pyrimidine (and FUra) catabolism, in peripheral blood mononuclear cells was measured in each subject by a specific radiometric assay using FUra as the substrate. The proband had no detectable DPD activity. When enzyme levels in the proband and relatives were compared with that in controls, an autosomal recessive pattern of inheritance was demonstrated. This is the third patient with severe FUra toxicity secondary to an alteration in pyrimidine catabolism and the second from our clinic population suggesting that the frequency of this genetic defect may be greater than previously thought. Monitoring DPD activity may be important in the management of patients experiencing severe toxicity secondary to FUra chemotherapy.
Characterization of liver epithelial cells transfected with myc and/or ras oncogenes. While many liver tumors contain activated myc and ras oncogenes, the mechanisms by which these genes contribute to cellular transformation is poorly understood. Activated versions of the cellular oncogenes, c-myc and/or c-H-ras were transfected into normal rat liver epithelial cells to identify cellular pathways that are altered in the cells containing the oncogenes. The results of these and other investigations indicate that the biological properties associated with the transfection of c-myc include immortalization, reduced contact inhibition of growth, activation of phospholipase A2-mediated pathways, increased sensitivity to transformation with a ras gene, and greatly increased sensitivity to growth factors. The biological properties associated with the transfection of the ras gene include morphological transformation, anchorage-independent growth, tumorigenicity, increased phosphatidylinositol metabolism, the induction of growth-factor processing and secretion, which leads to (exogenous) growth factor-independent tumor growth, and a marked resistance to normal inhibitors of growth such as TGF-beta. It is proposed that the complementary actions of the myc and ras genes in cellular transformation may be related to the ras-induced secretion of autocrine growth factors by cells sensitized to their effects by the myc gene. The increased stimulus for growth coupled to a ras-induced insensitivity to growth inhibitors may lead to clonal expansion of these cells and tumor development.
Necrolytic migratory erythema: dyskeratotic dermatitis, a clue to early diagnosis. A 57-year-old woman with a 6-year history of a dermatitis that evolved into typical necrolytic migratory erythema is reported. Four biopsy specimens were obtained in 5 years. The early lesions revealed superficial perivascular inflammation in the dermis, minor epidermal spongiosis, and scattered dyskeratotic cells in the upper epidermis. The differential diagnosis of this pattern of dyskeratotic dermatitis, particularly in a chronic eruption, should include consideration of hyperglucagonemia and the possibility of an associated pancreatic islet cell tumor.
Correlation of occult clonogenic leukemia drug sensitivity with relapse after autologous bone marrow transplantation. Despite initial complete remission rates exceeding 70%, the majority of patients with acute myeloid leukemia (AML) and adults with acute lymphocytic leukemia (ALL) eventually relapse. Improving the therapeutic results in acute leukemia requires detecting, and understanding the biology of, the minimal residual leukemia remaining after therapy and responsible for relapse. To investigate the biologic relevance of an in vitro assay for clonogenic leukemia (leukemia colony-forming units [CFU-L]) as a measure of minimal residual leukemia, we studied 58 consecutive patients with acute leukemia in complete remission undergoing autologous bone marrow transplantation (BMT) with cyclophosphamide-based therapy. CFU-L were cultured from the pretransplant remission marrows in 45 of 58 patients: 35 of 43 patients with AML and 10 of 15 with ALL. Clonal rearrangements, identical to the patients' overt leukemia when available, were detected in the occult CFU-L from four of the eight patients with ALL in whom adequate DNA for analysis could be obtained from the CFU-L. None of the uncultured pretransplant remission marrows from the 15 ALL patients showed clonal gene rearrangements. We also determined the in vitro sensitivity of the occult CFU-L to 4-hydroperoxycyclophosphamide (4HC), and correlated these results with the outcome of the patients. The sensitivity of the occult CFU-L to 4HC was the only factor that predicted relapse following BMT. The actuarial probability of relapse was 18% in the 23 patients whose CFU-L were sensitive to 4HC compared with 77% in the 22 patients whose CFU-L were resistant (P less than .001). The only factor that influenced the CFU-L sensitivity to 4HC was the type of leukemia. The CFU-L from the AML patients were more sensitive to 4HC than the CFU-L from the ALL patients (P = .001). Occult CFU-L genetically and functionally represent occult leukemia. Therefore, the CFU-L assay should provide a means for studying the biology of minimal residual leukemia and improving the therapeutic results in patients with acute leukemia.
Intraoperative colonic lavage and primary anastomosis in nonelective colon resection. In selected individuals requiring emergency colon resection, intraoperative colonic lavage with primary anastomosis represents a safe alternative to staged reconstruction. This procedure achieves excellent mechanical preparation of the colon, facilitates safe anastomosis, and avoids the disadvantages associated with multistaged operations. At our institution, 25 patients requiring urgent segmental resection of the left colon have undergone intraoperative colonic lavage. Primary anastomosis without fecal diversion has been performed in 21 of these patients. Obstruction of the large intestine was the indication for operation in 56 percent of the patients in this series. Ten patients (40 percent) required laparotomy for an acute intra-abdominal inflammatory process. No post-operative deaths have occurred in our series, and no patient has sustained clinically evident anastomotic leakage. A pelvic abscess developed in one patient after sigmoid colectomy for diverticulitis. Three patients required treatment for wound infection. Based on our results, we recommend resection with intraoperative colonic lavage and primary anastomosis as the preferred treatment for the majority of patients requiring nonelective segmental left colon resection.
Scrapie-infected spleens: analysis of infectivity, scrapie-associated fibrils, and protease-resistant proteins. Scrapie-associated fibrils (SAF) and protease-resistant proteins (PrP) were isolated from spleens and brains of clinical animals (mice and hamsters) from three scrapie agent-host strain combinations, and their concentrations were compared with infectivity levels. The spleens of infected animals contained lower levels of infectivity, PrP, and SAF than did brains. Regardless of the route of infection, both SAF and infectivity were detected in spleen before brain. Infectivity increased in brains and spleens of 139A-infected mice before the detection and increase in SAF, suggesting that the synthesis of SAF and PrP may not be the limiting factor in agent replication. In contrast to those in ME7- and 263K-infected animals, the Western blot profiles for PrP from brain and spleen of 139A-infected mice exhibited distinct differences. Results indicate that SAF and PrP found in the spleens are both organ- and scrapie strain-specific.
Randomized study on the effect of collagen impregnation of knitted Dacron velour aortoiliac prostheses on blood loss during aortic reconstruction. Intraoperative blood loss is an important factor in reconstructive surgery for aortoiliac disease because it is clearly associated with an increase in the operative morbidity and mortality rates. To minimize intraoperative blood loss, a blood-tight vascular prosthesis has been developed by impregnating a knitted Dacron prosthesis with bovine collagen. To study a potential reduction of intraoperative blood loss using these collagen-impregnated prostheses, we conducted a prospective randomized trial involving the collagen-impregnated prosthesis and its non-impregnated substrate, the Dacron knitted non-impregnated prosthesis. During a 2.5-year period, 123 consecutive patients (undergoing 81 procedures for aneurysmal disease and 43 procedures for occlusive disease) were admitted for elective aortic reconstructive surgery. Equal numbers of the two prostheses were randomly implanted. Various parameters were monitored: intraoperative blood loss before aortic cross-clamping (phase 1), during implantation of the prosthesis (phase 2) and after release of aorta cross-clamping (phase 3); the number of intraoperative and postoperative blood transfusions; and, finally, all preoperative and intraoperative factors that might contribute to intraoperative blood loss. A significant overall difference in intraoperative blood loss between the collagen-impregnated (2425 ml) and the non-impregnated (1907 ml) group was found (P = 0.003). However, this difference could not be attributed to collagen impregnation because no statistically significant difference in blood loss was found in the relevant period of operation (phase 3). Similar results were observed in patients operated on for both aneurysmal and occlusive disease (2600 versus 2195 ml and 2105 versus 1344 ml respectively).
A clinicopathologic study of 153 cases of complete hydatidiform mole (1980-1990): histologic grade lacks prognostic significance. Although the significance of histologic grading in hydatidiform mole has previously been investigated, most studies evaluated patients treated before 1975. Since 1975, many advances have been made in the understanding and treatment of hydatidiform mole, including the division of molar pregnancy into complete and partial hydatidiform mole. We retrospectively studied 153 cases of complete hydatidiform mole diagnosed and treated at the Brigham and Women's Hospital between 1980-1990 to determine the current prognostic significance of histologic grading in this disease. The histologic grade (based on the criteria of Hertig and Sheldon) was compared with the subsequent clinical course, including the rates of spontaneous remission, persistent gestational trophoblastic tumor, metastatic disease, "high-risk" metastatic disease, chemotherapy resistance, and survival. The histologic grade of the original complete hydatidiform mole did not correlate significantly with any index of clinical outcome evaluated.