shukoor65/lab-rag-model huggingface dataset:
A novel vitamin D3 analog, 22-oxa-1,25-dihydroxyvitamin D3, inhibits the growth of human breast cancer in vitro and in vivo without causing hypercalcemia. Although 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] has been shown to inhibit the growth of certain malignant cells, its hypercalcemic effect has prevented clinical application. We have recently developed a novel vitamin D3 analog, 22-oxa-1,25-(OH)2D3 (OCT), that is capable of promoting differentiation and inhibiting proliferation without inducing hypercalcemia. The present study was undertaken to determine whether OCT could be applied for the treatment of breast cancer with or without estrogen receptor (ER). OCT inhibited the proliferation of both ER-positive (MCF-7, T-47D, and ZR-75-1) and ER-negative breast cancer cells (MDA-MB-231 and BT-20) in vitro in a time- and dose-dependent manner, as determined by cell number and [3H]thymidine uptake. The antiproliferative effect was observed with a concentration as low as 10(-11) M OCT, and treatment of MCF-7 cells with 10(-8) M OCT for 8 days caused more than a 50% reduction in cell number compared with that of vehicle-treated cells. OCT was approximately 1 order of magnitude more potent than 1,25-(OH)2D3 in inhibiting the proliferation of MCF-7 cells. The in vivo effect of OCT was examined in athymic mice implanted with ER-negative MX-1 tumor, which was established as the xenograft derived from human breast carcinoma. Intratumor administration of OCT three times a week remarkably delayed the growth of MX-1 tumor in a time- and dose-dependent manner. The antitumor effect of 1 microgram/kg BW OCT was greater than that of 500 microgram/kg BW adriamycin, and the relative tumor weights in each group on day 26 were 29.7% and 50.5% of that in the vehicle-treated group, respectively. The effects of OCT and adriamycin were additive, and the relative tumor weight after 26 days of combined treatment was 21.7% of that in the vehicle-treated group. Oral administration of OCT was also effective, and the relative tumor weight in the OCT-treated group (1 microgram/kg BW) was 54.6 +/- 0.1% (mean +/- SEM) of that in the vehicle-treated group. Neither intratumor nor oral administration of OCT raised the serum calcium level in these animals. These results demonstrate that OCT is a potent inhibitor of the proliferation of breast cancer cells with or without ER and that OCT inhibits the growth of breast cancer in vivo without inducing hypercalcemia. We suggest that OCT may provide a new strategy for the treatment of breast carcinoma regardless of ER status.
PEG ileus. A new cause of small bowel obstruction. A case of small bowel obstruction due to a lodged percutaneous endoscopic gastrostomy tube inner bumper is described. Most probably inner bumper lodgement in the terminal ileum is related to its size. Laparotomy was required to remove the bumper and relieve the obstruction. We suggest that all percutaneous endoscopic gastrostomy bumpers be retrieved endoscopically when the PEG tube is removed or replaced unless a collapsible inner bumper is used.
A phase II study of the combination of carboplatin and ifosfamide in previously untreated metastatic small cell lung carcinoma. This Phase II study evaluated the combination of two active agents in small cell lung carcinoma (SCLC): carboplatin and ifosfamide. Thirty previously untreated patients (27 men and 3 women) with a median age of 59 years were included in this study. Twelve patients had one metastatic site and 18 had two or more metastatic sites. The median performance status was 80%. The chemotherapy (CT) regimen administered during the course of this study consisted of carboplatin (300 mg/m2) and ifosfamide (4 g/m2) plus mesna every 4 weeks. All 30 patients were evaluable: 1 achieved a complete remission (CR) and 18 achieved a partial remission (PR) (objective response rate, 63%). The median response time was 3 months and the median survival time was 8 months (range, 1 to 25+ months). Bone marrow toxicity was Grade III in three patients and Grade IV in four patients. The carboplatin and ifosfamide combination was well tolerated. No cross-resistance with the doxorubicin and etoposide regimen was established because 4 of 11 patients responded to this combination (+/- cisplatin) after failing to respond to the ifosfamide and carboplatin regimen. The ifosfamide and carboplatin combination may be considered for inclusion in non-cross-resistant alternating CT schedules.
A simple method for biliary-enteric anastomosis and chronic bile diversion in the rat. A simple method of biliary-enteric anastomosis, without the use of surgical microscopy, is described. There were no signs of cholestasis after 3 mo of follow-up. A modified procedure using a silicone elastomer catheter as a stent for the biliary-enteric anastomosis resulted in biliary obstruction within 3 wk after surgery. Our experimental bile duct implantation technique is a simple and useful experimental method for the investigation of chronic biliary diversion and biliary physiology. Additionally, it can be performed safely and easily in a rodent model without sophisticated microscopic techniques.
Unwashed filtered shed blood collected after knee and hip arthroplasties. A source of autologous red blood cells. We evaluated the results of twelve hematological and plasma protein determinations in 450 to 500-milliliter volumes of shed blood that had been collected with or without acid-citrate-dextrose anticoagulant (National Institutes of Health Formula A) from knees and hips during the first twelve hours after arthroplasty. We also evaluated the effects on the recipients when the blood was used for reinfusion. The findings in the units that had been obtained in less than four hours, in between four and six hours, and in more than six hours after the arthroplasty were similar whether or not the acid-citrate-dextrose anticoagulant had been used. The mean values for the collected units were: in the blood, a concentration of hemoglobin of 115 grams per liter, a hematocrit of 0.34, a white blood-cell count of 4.8 x 10(9) per liter, and a red blood-cell count of 3.7 x 10(12) per liter, and, in the plasma, a level of hemoglobin of 160 grams per liter, a level of fibrinogen of less than 0.2 gram per liter, a level of factor-V clotting protein of less than 10 per cent of normal, a level of factor-VIII clotting protein that was 45 per cent of normal, a level of antithrombin III that was 45 per cent of normal, a level of plasminogen that was 55 per cent of normal, a level of protein C that was 100 per cent of normal, and a level of fibrin-degradation products of 1000 micrograms per milliliter of plasma. The clinical response of the patient was assessed after the reinfusion of a total of 205 units of unwashed shed blood into 153 patients. In addition, in 126 of the 153 patients, hematological and plasma-protein measurements were analyzed before the autotransfusion and one and twenty-four hours afterward. Each of these patients had received one to four units of shed blood that had been filtered but not washed. Only two (2 per cent) of the ninety-nine patients who received shed blood that had been collected six hours or less after the operation had a febrile reaction, whereas twelve (22 per cent) of the fifty-four patients who received blood that had been collected six to twelve hours after the operation had such a reaction.(ABSTRACT TRUNCATED AT 400 WORDS).
Motor inhibition from the brainstem is normal in torsion dystonia during REM sleep. The maintenance of axial atonia during REM sleep was monitored in 14 patients with primary torsion dystonia, 10 patients with secondary torsion dystonia, and 10 normal subjects using submental EMG and video EEG telemetry. The excitability of the corticospinal tract during REM sleep was also assessed using scalp magnetic stimulation in seven patients and three controls. During REM sleep dystonic patients had well maintained atonia evidenced by infrequent bursts of submental activity, no episodes of complex semi-purposeful behaviour and reduced motor responses to magnetic stimulation. These findings suggest that the inhibitory centres in the region of the locus coeruleus and their descending pathways to the spinal alpha motor neurons are intact in torsion dystonia.
Lateral parascapular extrapleural approach to the upper thoracic spine. The upper thoracic vertebrae are difficult to approach surgically because of the narrowing of the thoracic inlet, the proximity of the brachial plexus, and the parascapular shoulder musculature. A novel lateral parascapular extrapleural approach to the upper thoracic vertebrae is described. The parascapular shoulder musculature (trapezius, levator scapulae, and rhomboid muscles) is reflected off the spinous processes to the scapula as a musculocutaneous flap, preserving the neurovascular supply. The paraspinal musculature is mobilized and retracted, and the upper dorsal ribs are removed with caution to avoid injury to the C-8 and T-1 nerve roots. The rami communicantes are transected, and the sympathetic chain is displaced anterolaterally. The T2-4 vertebrae can be approached unobstructed. The T-1 nerve root obstructs posterolateral access to the T-1 vertebra, necessitating an inferolateral approach underneath the T-1 nerve root axilla. Four patients with compressive myelopathy from upper thoracic vertebral metastases underwent neural decompression, vertebral reconstruction, and posterior spinal fixation with this approach. Their postoperative neurological status was either unchanged or improved. Complications included radiographic pleural effusion and superficial wound dehiscence; one patient required posterior spinal reinstrumentation for progressive kyphosis. One patient developed pneumonia 7 days postoperatively which was unresponsive to appropriate treatment. It is believed that the anatomical limitations to this region have been overcome, and that excellent exposure of the T1-4 vertebrae for neural decompression and vertebral reconstruction can be performed safely. A major advantage is that posterior spinal fixation can be carried out simultaneously.
Disulfiram implant: a double-blind placebo controlled follow-up on treatment outcome. Seventy-six alcohol-dependent patients participated in a study of the clinical effect of implanted disulfiram (DS). The patients were randomized to a DS group (n = 40), receiving a subcutaneous abdominal implantation of 10 x 100 mg DS tablets and a placebo group (PL group) receiving an implantation of 9 x 100 mg calcium phosphate tablets together with one calcium phosphate tablet containing 1 mg DS. Both groups believed they were receiving DS. At admission there was no significant difference between the DS and PL groups with regard to demographic characteristics, psychosocial adjustment, drinking variables, medical disorders, or laboratory results. After a study period of approximately 300 days, 63 patients (33 DS; 30 PL) were assessed using a battery of tests. There was no significant difference between the groups with regard to reduction in average alcohol consumption, number of days to the first alcohol intake after implantation, or level of psychosocial function. Nevertheless, both groups reduced their ethanol consumption significantly, probably due to the psychological deterrent effect. The DS implant did result in a significantly higher incidence of wound complications. This study does not support the idea that a 1-g DS implant has any significant clinical effect different from the implant containing only 1 mg DS (placebo).
Effect of cardiopulmonary support on regional and global left ventricular function during transient coronary occlusion. The ability of extracorporeal cardiopulmonary support (CPS) to unload the left ventricle and reduce ischemic dysfunction during transient coronary occlusion was studied in 10 anesthetized dogs. Three serial 60-second circumflex coronary artery occlusions were performed with CPS initiated only during the second occlusion. CPS significantly reduced preocclusion systolic blood pressure, blood pressure x heart rate double-product, circumflex blood flow, left ventricular end-diastolic pressure (LVEDP), peak negative dP/dt, and left ventricular systolic thickening. Circumflex occlusion caused changes in LVEDP and left ventricular wall thickening that were similar regardless of the presence or absence of CPS. These data suggest that CPS unloads the left ventricle during myocardial ischemia but does not prevent regional or global myocardial dysfunction.
Clinical features and results of therapy for children with paraspinal soft tissue sarcoma: a report of the Intergroup Rhabdomyosarcoma Study. Soft tissue sarcomas of the paraspinal region comprised 3.3% (56 of 1,688) of the patients entered and eligible on Intergroup Rhabdomyosarcoma Studies I (IRS-I) and II (IRS-II) (1972 to 1984). These lesions tended to be greater than 5 cm in diameter at diagnosis, invaded the spinal extradural space, and were of the extraosseous Ewing's sarcoma or undifferentiated sarcoma subtype in 55% (30 of 56) of the cases. Patients with tumors in clinical groups II, III, and IV were treated with radiotherapy (XRT) and vincristine-dactinomycin (VA) or VA plus cyclophosphamide (VAC) +/- doxorubicin. Clinical group I patients treated on IRS-II did not receive XRT, while those on IRS-I were randomized to receive VAC +/- XRT. Forty-four of the paraspinal patients (79%) achieved a complete response (CR) compared with 77% (1,260 of 1,632) for patients with disease in other sites. Twenty-seven patients (55%) subsequently relapsed (five local, three regional, four local and distant, and 14 distant). The proportion of patients surviving 5 years by clinical group (stage) from I to IV were 50%, 50%, 62%, and 27%, respectively. Paraspinal patients had somewhat poorer survival than patients with disease in other sites, both in IRS-I and IRS-II; the percentage of paraspinal patients surviving 5 years was 50% and 52% for IRS-I and IRS-II, respectively, whereas these percentages were 55% and 63% for patients with disease in other sites. Histology did not influence the CR rate, but unexpectedly, patients who had embryonal rhabdomyosarcoma (RMS) had the poorest overall survival rate. We concluded that patients with paraspinal lesions may require extended-field radiation therapy to reduce the high local failure rate and more intensive chemotherapy to achieve better local and systemic tumor control.
Etiology of autism: genetic influences. In summary, there are a few specific genetic conditions that can be associated with autism. Among cases of unknown etiology, there is ample evidence for a higher genetic liability to autism in siblings of autistic probands than expected from the population prevalence. It appears likely that both parents and siblings have a higher liability for social and cognitive deficits that are milder but conceptually similar to those found in autism. Others factors may alter this underlying genetic liability such as sex, IQ, and prenatal and perinatal injury. In the future, genetic analyses and genetic linkage studies will need to consider using a broader definition of the autism phenotype to include not only autism but severe cognitive and social deficits. The exact genetic mechanisms and genes involved are the subject of current investigations by several research groups. Investigations in this area are likely to continue to provide important information about the causes of autism.
Renovascular hypertension: predicting surgical cure with exercise renography. Renal artery stenosis with resultant renovascular hypertension has attracted clinical attention because the disease is potentially curable and because numerous diagnostic and therapeutic modalities compete for clinical acceptance. An exercise-mediated disturbance of renal hippurate transport was recently described, and has been implicated as having a role in nephrogenic fixed hypertension. To predict the final course of renovascular hypertension before operation we carried out a prospective study with the goal of verifying the predictive value of exercise hippurate scintigraphy. The study was to test the hypothesis that patients with disturbance of renal hippurate transport (pathologic renogram) induced by exercise would have stabilized hypertension and would continue to be hypertensive after operation. Thirty-one patients with hypertension who had unilateral or bilateral renovascular stenosis documented on angiography were referred to rest and exercise hippurate scintigrams before operation. The results of the examinations at rest served as standard and were compared with the exercise scintigrams. In 19 of the 31 (61%) patients a disturbance of transrenal hippurate transport evolved during exercise, whereas 12 (39%) patients failed to respond to exercise with altered hippurate kinetics. Twenty-six patients went on to renovascular operations; five had percutaneous transluminal angioplasty. Revascularization results differed markedly when the blood pressure response of patients with positive results on exercise (abnormal) and patients with negative results on exercise (normal) were compared. Ten of 12 patients with hypertension who had normal exercise renograms were cured. In comparison, blood pressure values were little influenced by therapy in patients with an abnormal response, where 17 of 19 patients continued to have hypertensive disease after therapy.
Report of the Council on Scientific Affairs: ultrasonic imaging of the heart: report of the Ultrasonography Task Force. The use of ultrasonography in cardiology has progressed so dramatically that not only is anatomic information available but information can also be derived about cardiac hemodynamics. Applications range from intravascular ultrasonic imaging of coronary atherosclerosis to predictions of the severity of fetal valvular pulmonic stenosis detected in utero. We reviewed cardiac ultrasonography as utilized in B-mode imaging, pulsed and continuous-wave spectral Doppler, and Doppler color flow mapping. We reviewed specialized areas, including stress echo for wall motion analysis, valvular and congenital heart disease applications, and new applications in intraoperative, transesophageal, contrast echography, coronary imaging, and fetal echocardiography. Finally, future applications of quantitative flow mapping and intraluminal and interventional ultrasonography were considered along with the required technological advances.
Unproven methods of cancer management. Livingston-Wheeler therapy. Livingston-Wheeler's cancer treatment is based on the belief that cancer is caused by a bacterium she has named Progenitor cryptocides. Careful research using modern techniques, however, has shown that there is no such organism and that Livingston-Wheeler has apparently mistaken several different types of bacteria, both rare and common, for a unique microbe. In spite of diligent research to isolate a cancer-causing microorganism, none has been found. Similarly, Livingston-Wheeler's autologous vaccine cannot be considered an effective treatment for cancer. While many oncologists have expressed the hope that someday a vaccine will be developed against cancer, the cause(s) of cancer must be determined before research can be directed toward developing a vaccine. The rationale for other facets of the Livingston-Wheeler cancer therapy is similarly faulty. No evidence supports her contention that cancer results from a defective immune system, that a whole-foods diet restores immune system deficiencies, that abscisic acid slows tumor growth, or that cancer is transmitted to humans by chickens.
Tube feeding-related diarrhea in acutely Ill patients. Acutely ill patients received tube feeding for an average of 15.8 days and, on average, 35% of those days were spent in the intensive care unit (ICU). Patients were prospectively assigned either a fiber-free formula (FFF-OSMOLITE HN, Ross; n = 50) or a fiber-supplemented (soy polysaccharide 14.4 g/L) formula (FSF = JEVITY, Ross; n = 50). Diarrhea was defined as three or more loose or watery stools per day and occurred in 30% of all patients. Diarrhea developed in 29 (41%) of the 71 patients who received antibiotics during, or within 2 weeks prior to, the feeding period, whereas only 1 (3%) of the 29 patients not receiving antibiotics developed diarrhea (p less than 0.005); and this patient developed diarrhea on the day of death. Among the 30 patients with diarrhea, stool Clostridium difficile (CD) toxin was positive in 15 (50%), negative in 11 (37%), and was not measured in four. The mean serum albumin was significantly lower in patients with diarrhea (2.43) than in those without diarrhea (2.75) (p = 0.043). There were no significant differences in age, sex, diagnoses, number of feeding days, and percent ICU days between patients with and without diarrhea. While not statistically significant, patients who received FSF were observed to have a lower incidence of diarrhea, a lower percentage of diarrhea days per total feeding days, and a lower frequency of positive CD toxin assays than patients who received FFF. In this patient population, antibiotic usage was the factor most strongly associated with diarrhea during tube feedings.
Factors affecting decisions to institutionalize demented elderly. This study followed 321 community-based patients with documented dementias, 22% of whom were institutionalized after 1 year. Multivariate analyses indicated that none of the patient characteristics, such as level of cognitive, psychiatric, or neurological impairment, predicted institutionalization. Social psychological characteristics, type and number of caregivers, and subjective caregiver distress did predict which patients were ultimately institutionalized. Implications for treatment planning are discussed.
Hyperfractionated radiation therapy in brain stem tumors. Results of treatment at the 7020 cGy dose level of Pediatric Oncology Group study #8495. Between May 1986 and February 1988, 57 patients were accrued to the second dose level of a Phase I/II Pediatric Oncology Group (POG) study exploring the use of hyperfractionated radiation therapy (HRT) in children with high-risk brain stem tumors. Local fields were treated with fraction sizes of 117 cGy given twice daily, with a minimum interfraction interval of 6 hours, to a total dose of 7020 cGy in 60 fractions over 6 weeks. Information regarding clinical status during HRT was available for 55 patients (44 [80%] improved, 6 remained stable, and 5 deteriorated). Results of initial and follow-up computed tomography (CT) scan and/or magnetic resonance imaging (MRI) were available for review for 52 patients. One patient had a complete response (CR) to treatment, 3 had a partial response (PR) (more than 50% response), and 40 remained stable, for a total response rate (CR + PR + stable) of 77%. Median time to disease progression was 6 months. Median survival time was 10 months. Survival rate was 39.6% (standard error [SE] = 6.6%) at 1 year and 23% (SE = 5.8%) at 2 years. Complications of treatment included an enhanced skin reaction in six patients and otitis media and/or externa in nine. One patient bled into tumor shortly after completion of HRT, and three had intralesional necrosis. Five patients continued taking steroids for protracted periods in the face of improved clinical and/or radiologic findings. Complications related to the use of steroids included opportunistic infections, impaired glucose tolerance, hypertension, osteoporosis, and significant mood changes. In no patient was there evidence of any late injury attributable to HRT. When compared with results of treatment with HRT at a lower dose level (6600 cGy), there appears to be a trend toward improved survival at 7020 cGy despite a less favorable patient population at the higher dose level. A second dose escalation to 7560 cGy in 60 fractions over 6 weeks has been implemented as planned.