tbuckley/cabot-search huggingface dataset:
Magnetic resonance imaging of the bone marrow (MRBM) as an outcome measure for patients with metastatic prostate cancer
Authors: G. A. Gignac, M. J. Morris, L. H. Schwartz, E. Lis, H. I. Scher
Journal: Journal of Clinical Oncology (2006)

14521 Background: Previously we have shown that the distribution of osseous metastases in prostate cancer (PC) matched the distribution of the normal adult marrow. Over 90% of advanced PC patients have disease in bone. Imaging the marrow has the potential to allow detection of metastases before osseous response has occurred and provides a three dimensional volumetric measure that can be quantified and monitored serially for changes over time. We are examining the use of MRBM as an indicator of treatment effect in patients with metastatic PC. Methods: Patients with PC and 2 or more MRBM surveys were identified and extracted from a database of all patients at MSK who have had radiologic studies. Cases were further identified on the basis of having metastatic disease, followup MRBM within 4–7 months, concurrent PSA and bone scans. MRI reports were stratified as either “progression” or “stable/improved” assuming a clinician would change therapy if progression was documented. PSA was similarly recorded, using a definition of ≥ 25% increase from baseline to indicate progression. Bone scans were stratified on the basis of new lesions verses no new lesions. Results: Twenty-five patients were eligible for review with a median baseline PSA of 7.34 ng/ml (0.05–473 ng/ml). Average percent change of PSA at followup was 651% (0–11033%). Treatment included: hormones (11), chemotherapy (5), calcitriol (4) and observation (5). The change in MRBM was concordant in 73% of patients with progression by PSA. These results are demonstrated below in the Table. Conclusions: MRBM is a novel means to assess metastatic disease to bone. This preliminary analysis suggests that MRBM can be early indicator of treatment failure. We plan to explore it prospectively as an outcome measure for PC using a lesional analysis. Grant Support: PEPSICO, PCF, NCI 102544, CA102544 and 5T32CA09207. [Table: see text] [Table: see text]
A pilot study of suramin in the treatment of progressive refractory follicular lymphomas
Authors: R V La Rocca, M R Cooper, C A Stein, D Kohler, M Uhrich, E Weinberger, C E Myers
Journal: Annals of Oncology (1992)

Ten patients with progressive follicular lymphomas (seven with follicular mixed lymphomas, three with follicular, small cleaved cell lymphomas) with clinical indications for systemic therapy received parenteral suramin. Each had failed from one to six prior chemotherapeutic regimens and three had in addition received prior radiation therapy. All had measurable disease and nine of the ten had documented bone marrow involvement at the start of therapy. Suramin was administered at an initial infusion rate of 350 mg/m2/day, which was then modified on the basis of subsequent weekly plasma suramin concentrations in order to reach a final plasma concentrations of 250-350 micrograms/ml. Treatment cycles were repeated at eight week intervals. Nine of ten patients are evaluable for response. Five of nine evaluable patients achieved a partial remission as defined by a greater than 50% decrease in the sum of the product of all measurable lesions. Sites of response include: Peripheral (five patients) and central (four patients) adenopathy, disappearance of biopsy-proven skin involvement (one patient), malignant pleural effusions (one patient) and shrinkage of an enlarged spleen (two patients). Disappearance of B symptoms occurred in the one responder with these symptoms. Response duration varied from 3 to 9 months (mean 5.6 months) with time to subsequent systemic therapy varying from 5 to 12 months (mean 8 months). Drug related toxicity included the development of polyradiculopathy (one case), liver function abnormalities (three cases), thrombocytopenia (five cases), vortex keratopathy (two cases) and bacterial infection (two cases). We conclude that suramin has significant activity against follicular lymphomas refractory to standard chemotherapy and that its precise role in the treatment of lymphoproliferative neoplasms in general warrants further investigation.
Case 16-1999
Authors: David A. Chad, Nancy L. Harris
Journal: New England Journal of Medicine (1999)

Presentation of CaseA 71-year-old, right-handed man was admitted to the hospital because of progressive muscle weakness and difficulty swallowing.The patient had been well until one year earlier, when he had several bouts of pulmonary and paranasal-sinus infections that were treated with amoxicillin. Nine months before admission, his voice was becoming progressively softer and hyponasal. Two months later, muscle weakness developed in the arms and legs, especially on the right side, and subsequently worsened, with loss of muscle bulk. Five months before admission, the patient began to have falls because of a right footdrop, and he had occasional leg . . .
Fish-Tank Granuloma
Authors: S F Wolfe, A W Gurevitch
Journal: New England Journal of Medicine (1997)

Figure 1. A 22-year-old man lacerated the back of his left index finger while cleaning his fish tank. When seen three months later, he had a verrucous, crusted plaque at the site of the injury and two subcutaneous nodules along the line of lymphatic drainage. He was afebrile and asymptomatic but was concerned about the nodules. A punch biopsy of the border of the plaque was obtained. Half was sent for routine histologic analysis and staining for acid-fast bacilli; the results of both were nondiagnostic. The other half was sent for mycobacterial culture at 30 to 33°C, which revealed Mycobacterium . . .
Indolent<i>Staphylococcus albus</i>or<i>aureus</i>Bacteremia after Ventriculoatriostomy
Authors: Robert T. Schimke, Paul H. Black, Vernon H. Mark, Morton N. Swartz
Journal: New England Journal of Medicine (1961)

NEUROSURGICAL procedures designed for the alleviation of hydrocephalus have become increasingly successful in the past four years. In 1957 Pudenz et al.1 described a new technic (ventriculoatriostomy) for shunting cerebrospinal fluid from the cerebral ventricles into the right atrium. The unique innovation employed was the inclusion of a one-way valve that allowed cerebrospinal fluid to pass into the right atrium through a system of subcutaneously placed catheters connecting a cerebral ventricle with the right atrium via the jugular vein. Anderson2 has reported 24 satisfactory results in a series of 36 cases in which this procedure was performed. It is significant . . .
RTOG 0436: A phase III trial evaluating the addition of cetuximab to paclitaxel, cisplatin, and radiation for patients with esophageal cancer treated without surgery.
Authors: David H. Ilson, Jennifer Moughan, Mohan Suntharalingam, Adam Dicker, Lisa A. Kachnic, Andre A. Konski, Bapsi Chakravarthy, Chris Anker, Harish V. Thakrar, Naomi Horiba, Vivek Kavadi, Melvin Deutsch, Adam Raben, Kevin S. Roof, John H. Suh, Jondavid Pollock, Howard Safran, Christopher H. Crane
Journal: Journal of Clinical Oncology (2014)

4007 Background: RTOG 0436 is a randomized Ph III trial evaluating cetuximab added to concurrent chemoradiation for patients (pts) undergoing non-operative management of esophageal carcinoma (EC). Methods: Pts with biopsy proven squamous cell or adenocarcinoma of the esophagus (T1N1M0; T2-4 AnyN M0; Any T/N M1a) were randomized to weekly concurrent cisplatin (50 mg/m2), paclitaxel (25 mg/m2) for 6 weeks and daily radiation 50.4 Gy/1.8 Gy fractions ± weekly cetuximab (400 mg/m2 day 1 then weekly 250 mg/m2) for 6 weeks. Pts were stratified by histology, tumor size (< 5 cm vs > 5cm) and the status of celiac lymph nodal involvement. Overall survival (OS) was the primary endpoint, with a planned accrual of 420 pts to detect an increase in 2-year OS from 41% to 53%; 80% power and 1-sided 0.025 alpha. An interim analysis of cCR was planned for the first 150 of each histology. Results: The study accrued 344 pts from 2008-2013 and 328 were eligible. Based on interim analyses, the study stopped accruing adeno pts in 5/2012 and SCC pts in 1/2013. Pts were well matched for pretreatment characteristics: 80% T3/4 disease, 66% N1, and 19% celiac nodes. Grade 3/4/5 treatment (tx) related AEs were 45%, 22%, 4% in Arm 1 (cetuximab) and 49%, 17%, 1% in Arm 2 (no cetuximab). A cCR rate of 56% was observed in Arm 1 vs 59% in Arm 2 [p=0.72]. No differences were seen in cCR between tx arms for either histology. The 12 and 24 mo OS rates for cCR pts were 79% and 58% vs 53% and 30% for those with residual disease [p<0.0001]. Median follow-up for all pts is 15.4 mos. The 12 and 24 mo OS (95% CI) for Arm 1 is 64% (56%, 71%) and 44% (36%, 52%) vs 65% (57%, 72%) and 42% (34%, 50%) for Arm 2 [p=0.70]. Adeno pts (n=203) had a 12 and 24 mo OS of 65% and 43% for Arm 1 vs 64% and 41% for Arm 2 [p=0.37]. The 12 and 24 mo OS for the 125 SCC pts was 62% and 46% for Arm 1 vs 67% and 43% for Arm 2 [p=0.97]. Conclusions: Cetuximab added to chemoradiation did not improve OS. There were no differences in cCR rates by tx arm. These results add to the growing body of literature indicating no benefit for current EGFR targeted agents in the tx of unselected patients with EC. Supported by RTOG CA21661 and CCOP CA3742 NCI grants and Bristol Myers Squibb. Clinical trial information: NCT00655876.
Comparative analysis of bone marrow (BM) micrometastasis (M) with sentinel lymph node (SLN) status in early breast cancer (BRCa)
Authors: M. P. Patel, S. Saha, S. Ali, D. Iddings, D. Wiese, H. Sankaran, M. Arora, T. Singh, T. Branigin, K. Barber
Journal: Journal of Clinical Oncology (2007)

508 Background: While sentinel lymph node (SLN) metastasis (mets) and bone marrow (BM) micrometastases (M) provide prognostic information in breast cancer (BRCa) patients (pts), a definitive relationship between the two has not yet been proven. We hypothesize that the presence of BMM may not infer an increased risk of SLN mets due to differences in their mechanisms of spread. Methods: We conducted a 6-year retrospective study of 251 T1/T2 BRCa pts who underwent bilateral iliac crest bone marrow aspiration, SLN mapping, and either lumpectomy, partial mastectomy, modified radical mastectomy, or total mastectomy by a single surgeon. BM samples were examined for micrometastases by Automated Cellular Imaging System using Chroma Vision Cytokeratin Detection Kit to detect cells expressing CK 8 as defined by CAM 5.2 monoclonal antibody. Pts with BMM underwent repeat BM analysis after completion of adjuvant chemotherapy. Data was collected for SLN, BM, ER/PR and HER2/neu status. Results: There were 251 consecutive pts entered into the study. Of these, 27.5% (69/251) had SLN mets and 9.6% (24/251) had BMM. Of the pts with SLN mets, 11.6% (8/69) had BMM vs. 88.4% (61/69) with no BMM ( Table ). In pts with ER/PR negative (-ve) BRCa, 7.1% (2/28) had BMM vs. 92.9% (26/28) with no BMM and 25% (7/28) had SLN positive (+ve) vs. 75% (21/28) SLN -ve pts ( Table ). Of the pts with HER2/neu +ve BRCa, 13.1% (8/61) had BMM vs. 86.9% (53/61) with no BMM and 26.2% (16/61) were SLN +ve vs. 73.8% (45/61) SLN -ve pts. After completion of adjuvant chemotherapy all pts with BMM (n=24) converted to BM -ve status. Conclusions: No correlation was identified between BMM and SLN status in T1 and T2 BRCa pts. This study suggests that BMM can occur independently of SLN status. Furthermore, (-ve) ER/PR and (+ve) HER2/neu status did not have a direct correlation with either BMM or SLN mets. Pts with BMM status may benefit from adjuvant therapy. Long-term implications of BM (+ve) have to be evaluated by larger multi- center trials. [Table: see text] No significant financial relationships to disclose.
Low-Molecular-Weight Heparin
Authors: Edwin W. Salzman
Journal: New England Journal of Medicine (1986)

Heparin, the familiar anticoagulant, is a naturally occurring sulfated glycosaminoglycan that for commercial purposes is extracted from bovine and porcine lung or intestine; it was originally purified from the liver (hence its name). A highly charged anion, heparin has many biologic activities aside from retarding blood clotting, but that is its only practical clinical indication at present. Its anticoagulant action reflects its ability to accelerate the formation of a molecular complex between a protein constituent of normal plasma, antithrombin III, and serine proteases of the intrinsic coagulation system, thus blocking the enzymatic activity of the clotting factors. The term "antithrombin . . .
The Demonstration of Porta-Pulmonary Anastomoses in Portal Cirrhosis with the Use of Radioactive Krypton (Kr<sup>85</sup>)
Authors: Stanley Shaldon, John Caesar, Livio Chiandussi, Harry S. Williams, Eli Sheville, Sheila Sherlock
Journal: New England Journal of Medicine (1961)

VENOUS anastomoses connecting the portal and pulmonary veins have been shown in cirrhotic patients by post-mortem injection,1 and there has been considerable speculation concerning their possible significance in life, particularly as a cause of arterial oxygen unsaturation and finger clubbing in patients with cirrhosis.2 3 4 5 Radioactive krypton (Kr85) solution, when injected into a peripheral vein, is blown off in the expired air as it reaches the alveolar surface of the lungs (Fig. 1). This has led to its use to demonstrate intrapulmonary arteriovenous shunts, which would allow krypton to bypass the alveoli and so reach a peripheral artery. In normal . . .
Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia syndrome
Authors: Giulio Rossi, Alberto Cavazza, Paolo Spagnolo, Nicola Sverzellati, Lucia Longo, Agita Jukna, Gloria Montanari, Cristiano Carbonelli, Giada Vincenzi, Giuseppe Bogina, Renato Franco, Marcello Tiseo, Vincent Cottin, Thomas V. Colby
Journal: European Respiratory Journal (2016)

The term diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) may be used to describe a clinico-pathological syndrome, as well as an incidental finding on histological examination, although there are obvious differences between these two scenarios. According to the World Health Organization, the definition of DIPNECH is purely histological. However, DIPNECH encompasses symptomatic patients with airway disease, as well as asymptomatic patients with neuroendocrine cell hyperplasia associated with multiple tumourlets/carcinoid tumours. DIPNECH is also considered a pre-neoplastic lesion in the spectrum of pulmonary neuroendocrine tumours, because it is commonly found in patients with peripheral carcinoid tumours. In this review, we summarise clinical, physiological, radiological and histological features of DIPNECH and critically discuss recently proposed diagnostic criteria. In addition, we propose that the term “DIPNECH syndrome” be used to indicate a sufficiently distinct patient subgroup characterised by respiratory symptoms, airflow obstruction, mosaic attenuation with air trapping on chest imaging and constrictive obliterative bronchiolitis, often with nodular proliferation of neuroendocrine cells with/without tumourlets/carcinoid tumours on histology. Surgical lung biopsy is the diagnostic gold standard. However, in the appropriate clinical and radiological setting, transbronchial lung biopsy may also allow a confident diagnosis of DIPNECH syndrome.
Anemia and FOLFOX chemotherapy for colorectal carcinoma
Authors: S. Taylor, C. Ho, F. Hu, J. Barnett, B. Melosky
Journal: Journal of Clinical Oncology (2005)

3684 Background: Advanced cancer is frequently associated with anemia which can significantly contribute to overall morbidity in those patients. Anemia has also been associated as a prognostic factor in tumors such as lung, ovarian and head and neck. However research of anemia in colorectal cancer is more limited and mostly refers to treatments with conventional protocols involving 5-FU plus leucovorin but there has been not data regarding the incidence of anemia in more recent therapies such as FOLFOX 6. This retrospective study will determine the prevalence and degree of anemia in patients with metastatic colorectal carcinoma being treated with oxaliplatin based chemotherapy. Methods: A retrospective chart review was performed identifying all patients treated for colorectal carcinoma with first or second line FOLFOX 6 chemotherapy in 2003 at the four British Columbia Cancer Agency cancer centres in British Columbia Canada. Baseline hemoglobin and all hemoglobin levels while on chemotherapy and including two weeks after finishing chemotherapy were selected. Results: 183 patients received FOLFOX chemotherapy in 2003, of which 173 had baseline Hgb available. Mean Hgb at baseline was 124 g/L and 64% (110/173) of patients had a hemoglobin level greater than 120 g/L Mean number of cycles delivered was seven. During chemotherapy, 63% (115/183) of patients had a Hgb level of less than or equal to 120 g/L. However 22% (41/183) patients had documented hemoglobin less than or equal to 100 g/L. Only 14% (26/183) had hemoglobin levels less than or equal to 90 g/L where one may intervene with blood transfusion. Conclusion: Patients with metastatic colorectal cancer being treated with oxaliplatin chemotherapy have a high rate of mild anemia but 22% may require anemia management and 14% may need to be transfused if early intervention is not possible. Its believe that this information may help to anticipate anemia management in this type of patients. No significant financial relationships to disclose.
Familial Idiopathic Hypercalciuria
Authors: Fredric L. Coe, Joan H. Parks, Eddie S. Moore
Journal: New England Journal of Medicine (1979)

The frequency of hypercalciuria was determined in the families of nine hypercalciuric patients with idiopathic hypercaliuria who formed recurrent calcium oxalate renal stones. Idiopathic hypercalciuria occurred in 26 of 73 relatives, in three consecutive generations of two families and in two successive generations of four other families. Multiple siblings or children of the probands were affected in three families. Nineteen of 44 first-degree relatives (43 per cent) had idiopathic hypercalciuria, as compared to seven of 29 (29 per cent) other relatives; there was no relation to age or sex. Renal stones were formed by 19 of the 44 first-degree relatives but by none of the others; nine of the 19 were women. We conclude that there is a familial form of hypercalciuria, which appears to be transmitted as an autosomal dominant trait. Stone disease is frequent in first-degree relatives, and affects both sexes equally.
Adaptation by Deletogenic Replication Slippage in a Nascent Symbiont
Authors: Adam L. Clayton, D. Grant Jackson, Robert B. Weiss, Colin Dale
Journal: Molecular Biology and Evolution (2016)

As a consequence of population level constraints in the obligate, host-associated lifestyle, intracellular symbiotic bacteria typically exhibit high rates of molecular sequence evolution and extensive genome degeneration over the course of their host association. While the rationale for genome degeneration is well understood, little is known about the molecular mechanisms driving this change. To understand these mechanisms we compared the genome of Sodalis praecaptivus, a nonhost associated bacterium that is closely related to members of the Sodalis-allied clade of insect endosymbionts, with the very recently derived insect symbiont Candidatus Sodalis pierantonius. The characterization of indel mutations in the genome of Ca. Sodalis pierantonius shows that the replication system in this organism is highly prone to deletions resulting from polymerase slippage events in regions encoding G+C-rich repetitive sequences. This slippage-prone phenotype is mechanistically associated with the loss of certain components of the bacterial DNA recombination machinery at an early stage in symbiotic life and is expected to facilitate rapid adaptation to the novel host environment. This is analogous to the emergence of mutator strains in both natural and laboratory populations of bacteria, which tend to reach high frequencies in clonal populations due to linkage between the mutator allele and the resulting adaptive mutations.
Case 6-1967
Authors: Edward F. Bland, Benjamin Castleman
Journal: New England Journal of Medicine (1967)

Presentation of Case First admission. An eighty-three-year-old Chinese man was admitted to the hospital because of vomiting.Six years previously he had come to the Medical Clinic because of a dizzy spell. There was no previous history of cardiac disease. Physical examination at that time disclosed cardiac enlargement, a Grade 2 systolic murmur at the base of the heart with transmission to the carotid vessels and a Grade 3 blowing decrescendo diastolic murmur along the left sternal border. An electrocardiogram (Fig. 1) showed a normal rhythm at a rate of 90 and was within normal limits. X-ray films and . . .
A Short-Term Study of the Safety, Pharmacokinetics, and Efficacy of Ritonavir, an Inhibitor of HIV-1 Protease
Authors: Sven A. Danner, Andrew Carr, John M. Leonard, Leah M. Lehman, Francesc Gudiol, Juan Gonzales, Antonio Raventos, Rafael Rubio, Emilio Bouza, Vicente Pintado, Antonio Gil Aguado, Juan Garcia de Lomas, Rafael Delgado, Jan C.C. Borleffs, Ann Hsu, Joaquin M. Valdes, Charles A.B. Boucher, David A. Cooper
Journal: New England Journal of Medicine (1995)

Reverse-transcriptase inhibitors have only moderate clinical efficacy against the human immunodeficiency virus type 1 (HIV-1). Ritonavir is an inhibitor of HIV-1 protease with potent in vitro anti-HIV properties and good oral bioavailability.We evaluated the antiviral activity and safety of ritonavir in a double-blind, randomized, placebo-controlled phase 1 and 2 study of 84 HIV-positive patients with 50 or more CD4+ lymphocytes per cubic millimeter. The patients were randomly assigned to one of four regimens of ritonavir therapy, or to placebo for four weeks and then (by random assignment) to one of the ritonavir regimens.During the first 4 weeks, increases in CD4+ lymphocyte counts and reductions in the log number of copies of HIV-1 RNA per milliliter of plasma were similar among the four dosage groups, but in the three lower-dosage groups there was a return to base-line levels by 16 weeks. After 32 weeks, in the seven patients in the highest-dosage group (600 mg of ritonavir every 12 hours), the median increase from base line in the CD4+ lymphocyte count was 230 cells per cubic millimeter, and the mean decrease in the plasma concentration of HIV-1 RNA (as measured by a branched-DNA assay) was 0.81 log (95 percent confidence interval, 0.40 to 1.22). In a subgroup of 17 patients in the two higher-dosage groups, RNA was also measured with an assay based on the polymerase chain reaction, and after eight weeks of treatment there was a mean maximal decrease in viral RNA of 1.94 log (95 percent confidence interval, 1.37 to 2.51). Adverse events included nausea, circumoral paresthesia, elevated hepatic aminotransferase levels, and elevated triglyceride levels. Ten withdrawals from the study were judged to be related to ritonavir treatment.In this short-term study, ritonavir was well tolerated and had potent activity against HIV-1, but its clinical benefits remain to be established.
Hemochromatosis Presenting as Acute Liver Failure after Iron Supplementation
Authors: Francisco Pérez Roldán, Ana Amigo Echenagusia, Pedro González Carro
Journal: New England Journal of Medicine (1998)

To the Editor: Hemochromatosis is an autosomal recessive disorder of iron overload caused by a mutation of the HFE gene on the short arm of chromosome 6. The principal clinical features are diabetes mellitus, cirrhosis, hypogonadism, and cardiac failure,1,2 and the age at clinical presentation is usually 40 years or older.1 We report a case of acute liver failure after iron supplementation in the setting of unrecognized hemochromatosis. A 29-year-old woman was admitted to the hospital because of a two-day history of jaundice, asthenia, hypercholuria, and hypocholia. The patient had been well until two months before admission, when she . . .