tbuckley/cabot-search huggingface dataset:
Association of<i>Ureaplasma urealyticum</i>in the Placenta with Perinatal Morbidity and Mortality
Authors: Ruth B. Kundsin, Shirley G. Driscoll, Richard R. Monson, Ching Yeh, Stella A. Biano, William D. Cochran
Journal: New England Journal of Medicine (1984)

We investigated the presence of ureaplasmas, mycoplasmas, chlamydiae, fungi, aerobic and anaerobic bacteria, and cytomegalovirus in fetal membranes and evaluated their association with perinatal morbidity and mortality. We cultured 801 placentas from three groups of subjects (144 who died in the perinatal period, 452 neonates admitted to the intensive-care unit, and 205 controls). Ureaplasma urealyticum, Mycoplasma hominis, or both were isolated from 21 per cent of placentas of premature and term infants who died in the perinatal period, 25 per cent of those admitted to intensive care, and 11 per cent of controls. Gestational age and birth weight were inversely related to isolation of ureaplasma, and chorioamnionitis was positively related to isolation. The presence of ureaplasmas in the placenta suggests the transcervical migration of these microorganisms from the lower genitourinary tract. These data show a strong association between ureaplasma infection of the placenta and low birth weight of the neonate and suggest that the association is causal.
Case 15-1993
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, William F. McNeely, Betty U. McNeely, Cheryl J. Bunker, Christophe Girardet
Journal: New England Journal of Medicine (1993)

Presentation of CaseA 58-year-old man was admitted to the hospital because of recurrent gastrointestinal bleeding.The patient had been in stable health until 27 months earlier, when hematochezia developed. His physician found that he was depressed and anxious. Physical examination was negative; a stool specimen was negative for occult blood. The hematologic and blood-chemical laboratory findings throughout the patient's course are presented in Table 1 and Table 2, respectively. An upper gastrointestinal series showed only a small hiatus hernia. Examination with a fiberoptic colonoscope to the level of the cecum revealed no abnormality. Ferrous sulfate was prescribed.The patient was then well . . .
State Practice Environments and the Supply of Physician Assistants, Nurse Practitioners, and Certified Nurse-Midwives
Authors: Edward S. Sekscenski, Stephanie Sansom, Carol Bazell, Marla E. Salmon, Fitzhugh Mullan
Journal: New England Journal of Medicine (1994)

Most proposals to increase access to primary care in the United States emphasize increasing the proportion of generalist physicians. Another approach is to increase the number of physician assistants, nurse practitioners, and certified nurse-midwives.We analyzed variations in the regulation of nurse practitioners, physician assistants, and certified nurse-midwives in all 50 states and the District of Columbia. Using a 100-point scoring system, we assigned numerical values to specific characteristics of the practice environment in each state for each group of practitioners, awarding a maximum of 20 points for legal status, 40 points for reimbursement for services, and 40 points for the authority to write prescriptions. We calculated coefficients for the correlation of summary measures of these values within states with estimates of the supply of practitioners per 100,000 population.There was wide variation among states in both practice-environment scores and practitioner-to-population ratios for all three groups of practitioners. We found positive correlations within states between the supply of physician assistants, nurse practitioners, and certified nurse-midwives and the practice-environment score for the state (Spearman rank-correlation coefficients, 0.63 [P < 0.001], 0.41 [P = 0.003], and 0.51 [P < 0.001], respectively). Positive associations were also found in the states between the supply of generalist physicians and the supply of physician assistants (r = 0.54, P < 0.001) and nurse practitioners (r = 0.35, P = 0.014). Nevertheless, in the 17 states with the greatest shortages of primary care physicians, favorable practice-environment scores were still associated with higher practitioner-to-population ratios for physician assistants (r = 0.68, P = 0.003), nurse practitioners (r = 0.54, P = 0.026), and certified nurse-midwives (r = 0.42, P = 0.09).State regulation of physician assistants, nurse practitioners, and certified nurse-midwives varies widely. Favorable practice environments are strongly associated with a larger supply of these practitioners.
An <i>in-vitro</i> model of the effects of pH on cisplatin-induced nephrotoxicity
Authors: S. B. Elharran, M. Molepo, F. H. Shirazi, R. Goel
Journal: Journal of Clinical Oncology (2005)

2077 Background: There is evidence that acidic conditions potentiate the cytotoxicity of Cisplatin (Cp) (F. Tanaka et al, Hearing Research: 177, 2003, 21–31). However, little is known about the effects of pH on Cp nephrotoxicity in humans. It was indicated that the proximal renal tubules in humans are more affected by Cp cytotoxicity than the distal renal tubules (G. Daugaard et al, Clin Pharmacol Ther.: 44(2), 1988,164–172). We hypothesize that pH variations in renal tubules are important modulators of Cp nephrotoxicity. Methods: LLC-PK1 (porcine proximal) and MDCK (canine distal) renal tubular epithelium cells were used as in-vitro models to investigate the effect of pH variations on Cp-induced nephrotoxicity. The IC50 of Cp at different pHs after one-hour exposure was determined for these two cell lines using the MTT assay. For LLC-PK1 cells, C-14 thymidine assay was used to examine the effect of Cp on DNA synthesis, and Platinum (Pt) uptake was measured by atomic absorption spectroscopy. Similar experiments are ongoing for MDCK cells. Results: The IC50 of Cp for LLC-PK1 cells at pH 6.0, was 33 μM Cp. The IC50s for MDCK cells was 75 μM (n=3, P< 0.005, r2=0.98). The table below shows the results of LLC-PK1 cells as a function of extracellular pH (pHe) (n=3, P<0.005). Standard errors are not listed, to save space. The highest inhibition in DNA synthesis (12%±3 SD, P<0.0001), and the highest uptake of platinum (Pt) (180ng/106 cells) were detected at pH 6.0 compared to the other pH values tested. Conclusions: These cells developed maximal Cp-induced cytotoxicity at pHe=6.0. This cytotoxicity in LLC-PK1 cells is correlated with intracellular Cp uptake, and with inhibition of DNA synthesis. If impairment of DNA synthesis is ultimately found to be the mechanism of clinical Cp-induced nephrotoxicity, then strategies can be developed to overcome this process, and improve the therapeutic index of Cp. No significant financial relationships to disclose.
Clinical Course of Retrovirus-Associated Adult T-Cell Lymphoma in the United States
Authors: Paul A. Bunn, Geraldine P. Schechter, Elaine Jaffe, Douglas Blayney, Robert C. Young, Mary J. Matthews, William Blattner, Samuel Broder, Marjorie Robert-Guroff, Robert C. Gallo
Journal: New England Journal of Medicine (1983)

We studied the clinical features of 11 patients with adult T-cell lymphoma associated with the human T-cell lymphoma virus. The patients were predominantly young, black, and born in the southeastern United States. They had an aggressive course, with the rapid onset of disseminated skin lesions or symptoms related to hypercalcemia and other metabolic disturbances, or both. Common findings included rapid enlargement of peripheral, hilar, and retroperitoneal lymph nodes, with sparing of the mediastinum; invasion of the central nervous system, lungs, or gastrointestinal tract; and opportunistic infections. A paraneoplastic syndrome characterized by increased bone turnover, abnormal bone scintigraphy, and hypercalcemia was present in all patients. Intensive combination chemotherapy produced prompt complete clinical remissions, which were generally of short duration. Similar features have been described in patients in Japan and the West Indies who had adult T-cell lymphoma, which is also associated with the human T-cell lymphoma virus. This syndrome should be suspected in patients presenting with the acute onset of widespread T-cell lymphoma in association with metabolic bone disease and hypercalcemia. The presence of the syndrome can be confirmed by appropriate serologic and virologic studies.
Case 25-2009
Authors: Harold J. Burstein, Irene Souter, Helen Anne D'Alessandro, Dennis C. Sgroi
Journal: New England Journal of Medicine (2009)

A 36-year-old woman was seen in the multidisciplinary breast cancer clinic of this hospital for management of hormone-receptor–positive breast cancer. She had a 1.4-cm, grade 2 of 3, infiltrating ductal carcinoma that was positive for estrogen-receptor protein and progesterone-receptor protein and negative for human epidermal growth factor receptor type 2, with micrometastases to 1 of 13 axillary lymph nodes detected by immunohistochemical analysis. A management decision was made.
Safety and Efficacy of Obinutuzumab Plus Bendamustine in Previously Untreated Patients with Chronic Lymphocytic Leukemia: Subgroup Analysis of the Green Study
Authors: Stephan Stilgenbauer, Osman Ilhan, Darius Woszczyk, Christoph Renner, Eva Mikuskova, Sebastian Böttcher, Eugen Tausch, Tom Moore, Nicola Tyson, Helena Adamis, Véronique Leblonde, Francesc Bosch, Robin Foà
Journal: Blood (2015)
Residual Disability in Survivors of Stroke — The Framingham Study
Authors: Glen E. Gresham, Therese E. Fitzpatrick, Philip A. Wolf, Patricia M. McNamara, William B. Kannel, Thomas R. Dawber
Journal: New England Journal of Medicine (1975)

Of 123 survivors of documented completed stroke from the Framingham Cohort, 119 received objective evaluations of functional status along with an equal number of controls matched for age and sex. Of the stroke survivors, 16 per cent were institutionalized, 31 per cent dependent in self-care, and 20 per cent dependent in mobility. In addition, 71 per cent had decreased vocational function, and 62 percent decreased socialization outside the home. Each of these frequencies was significantly greater than the corresponding rate in the control group.
High TOP2A mRNA expression occurs in the absence of TOP2A or ERBB2 gene amplification
Authors: M. Gehrmann, T. Fischbach, J. Hengstler, C. von Toerne, H. Kölbl, M. Schmidt
Journal: Journal of Clinical Oncology (2008)

22057 Background: Topoisomerase II alpha, encoded by TOP2A, is the putative molecular target of anthracycline drug action. Recently, it has been shown that TOP2A gene amplification occurs almost exclusively in conjunction with ERBB2 amplification. Since no benefit of anthracylines was observed in ERRB2 negative patients it was hypothesized that any anthracycline benefit might be restricted to those patients with TOP2A and ERBB2 co-amplification. Since alternative treatment options exist for ERBB2 positive breast cancer, the role of anthracycline-based therapy in the adjuvant treatment of breast cancer has been questioned Methods: In a series of 53 formalin-fixed paraffin-embedded (FFPE) tissue samples from patients with invasive breast carcinomas we analysed TOP2A and ERBB2 gene amplification as well as RNA expression. Amplifications were determined using the HER2 FISH pharmDx™ kit and the TOP2A FISH pharmDxTM kit (both from DakoCytomation, Denmark A/S, Glostrup). In addition, RNA was isolated from corresponding formalin fixed tumors and TOP2A and ERBB2 expression was determined by real time RT-PCR. Results: Neither ERBB2 nor TOP2A amplifications were detected in 40 samples (75.5%). ERBB2 and TOP2A co-amplification was observed in six samples (11.3%). Additional six samples showed ERBB2 but no TOP2A amplification (11.3%). Only one sample (1.9%) exhibited TOP2A amplification without concomitant ERBB2 amplification. ERBB2 m-RNA expression was distinctly higher in ERBB2 amplified compared to non-amplified tumors. In contrast, a considerable fraction of TOP2A non-amplified tumors showed a similar high TOP2A mRNA expression as TOP2A amplified or TOP2A/ERBB2 co-amplified tumors. Conclusions: Our data confirm that TOP2A amplification predominantly occurs as co-amplification with ERBB2. However, TOP2A gene amplification is not a prerequisite for high TOP2A RNA expression. Therefore, it should be considered that anthracylines might still be a valuable treatment option in ERBB2 negative tumors with high TOP2A mRNA expression. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Siemens Medical Solutions Diagnostics
Ehlers–Danlos Syndrome
Authors: Reed E. Pyeritz
Journal: New England Journal of Medicine (2000)

The first comprehensive description of a syndrome comprising laxity and fragility of the skin associated with hypermobility of the large joints was published in 1892 by Tschernogobow1 in Moscow. With remarkable insight, he interpreted the cause of the phenotype as a systemic defect in connective tissue. However, as is common in medicine, those who came later are immortalized in the eponym, in this case Ehlers2 and Danlos,3 Danish and French dermatologists, respectively, who published their observations independently in the first decade of the 20th century.The familial nature of these clinical associations was demonstrated in 1949,4 and soon thereafter Jansen . . .
Abstract PD2-08: Potential role of prolactin signaling in development and growth of the lobular subtype of breast cancer
Authors: S Oesterreich, TA Katz, G Logan, K Levine, A Nagle, Z Huo, GC Tseng, H Rui, AV Lee, LM Butler
Journal: Cancer Research (2016)

Abstract Invasive lobular carcinoma (ILC) is the eighth most frequently diagnosed cancer in any organ, and accounts for 8-11% of breast cancer. This histological subtype is characterized by loss of E-cadherin, and favorable prognostic factors, such as low Ki67 and high rates of ER/PR-positive tumors. Only recently is the lobular subtype gaining recognition as a distinct disease, displaying a unique growth pattern, unique molecular changes in addition to loss of E-cadherin, and evidence for late recurrences and reduced response to targeted endocrine therapy. It is widely accepted that a late age at first full term birth (FFTB) increases a women's risk for breast cancer. Interestingly, several published epidemiological studies have shown that the increased risk after a late age at FFTB is preferential for the lobular subtype of breast cancer compared to the ductal subtype. We therefore hypothesized that pregnancy hormones like prolactin play an integral role in the development and progression of ILC. Interrogation of the Cancer Genome Atlas (TCGA) data revealed a high expression of milk protein genes as well as prolactin signaling molecules, specifically Stat5a and Stat5b in lobular carcinomas compared to ductal carcinomas. We developed a lactation score including 7 milk protein genes and found that in the TCGA data set ILC tumors have a significantly higher lactation score than IDC tumors. Additionally, we found that ILC cell lines express increased prolactin receptor mRNA and protein levels compared to IDC cell lines. Prolactin treatment in ILC and IDC cells reveals divergent signaling pathways - prolactin stimulates ERK activation in IDC but not ILC cells. We are currently further delineating the prolactin signaling pathways, and resulting phenotypes, comparing ILC and IDC cells. We expect these experiments to move the field forward by establishing a relationship between prolactin and lobular carcinoma. Citation Format: Oesterreich S, Katz TA, Logan G, Levine K, Nagle A, Huo Z, Tseng GC, Rui H, Lee AV, Butler LM. Potential role of prolactin signaling in development and growth of the lobular subtype of breast cancer. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr PD2-08.
Soundings: Sorry to bother you but . . .
Authors: Trisha Greenhalgh
Journal: BMJ (2001)

The doorbell always rings with particular urgency on those rare occasions when I've just found half an hour between paperwork and bedtime and curled myself up in a big armchair with a book. This time, it was a nervous, housewifely woman in a pinny who looked young and indecisive enough to be my daughter.

“You don't know me, but I live at number 121. It's a bit of an emergency.”

Like most people who live within gasping distance of a doctor, the residents of our street have an uncanny homing instinct for my porch. Furthermore, their own GPs are allegedly “unavailable” in the evenings and “don't do Sundays.” A few years ago the chap from across the way chose to have his aortic dissection on the pavement outside. I didn't notice him at all until I was pulling out of the drive, and when I screeched to a halt and leapt out of the car my husband assumed I'd run him over.

A dozen of what the police euphemistically call onlookers quickly gathered, four of whom independently responded to my request for a soluble aspirin in a mug (OK, but the patient had complained of central chest pain). The rest were offering general advice on managing the acutely indisposed. I was not to move him.

Someone began a discussion about whether the recovery position was on the left or the right side. But the old lady from on the corner scotched them all by saying: “Look, she's not St John's, she's a proper doctor.”

If asked at parties, I usually say I'm a journalist or an aerobics teacher, but with this recent incident still in my mind, I knew there was no use grasping at an alter ego. I took a deep breath and faced up to the nervous wreck on my doorstep.

“Yes, I am.”

I prepared myself for a mercy dash to dislodge a fishbone from one of her dinner guests, sedate a terminally insomniac toddler or resuscitate granny.

“Well, my dog got something in her paw yesterday. Mrs Dean told me to give her half an aspirin, and when I did that she went to sleep and she's been like it for 48 hours.”

I couldn't believe my luck.

“Ah, well you've been given the wrong directions. See that far house down on the left with the light on in the attic? Don't tell him I told you, but the vet lives there.”
Quinolone-Resistant<i>Campylobacter jejuni</i>Infections in Minnesota, 1992–1998
Authors: Kirk E. Smith, John M. Besser, Craig W. Hedberg, Fe T. Leano, Jeffrey B. Bender, Julie H. Wicklund, Brian P. Johnson, Kristine A. Moore, Michael T. Osterholm
Journal: New England Journal of Medicine (1999)

Increasing resistance to quinolones among campylobacter isolates from humans has been reported in Europe and Asia, but not in the United States. We evaluated resistance to quinolones among campylobacter isolates from Minnesota residents during the period from 1992 through 1998.
Bioprinting Organotypic Hydrogels with Improved Mesenchymal Stem Cell Remodeling and Mineralization Properties for Bone Tissue Engineering
Authors: Daniela Filipa Duarte Campos, Andreas Blaeser, Kate Buellesbach, Kshama Shree Sen, Weiwei Xun, Walter Tillmann, Horst Fischer
Journal: Advanced Healthcare Materials (2016)

3D-manufactured hydrogels with precise contours and biological adhesion motifs are interesting candidates in the regenerative medicine field for the culture and differentiation of human bone-marrow-derived mesenchymal stem cells (MSCs). 3D-bioprinting is a powerful technique to approach one step closer the native organization of cells. This study investigates the effect of the incorporation of collagen type I in 3D-bioprinted polysaccharide-based hydrogels to the modulation of cell morphology, osteogenic remodeling potential, and mineralization. By combining thermo-responsive agarose hydrogels with collagen type I, the mechanical stiffness and printing contours of printed constructs can be improved compared to pure collagen hydrogels which are typically used as standard materials for MSC osteogenic differentiation. The results presented here show that MSC not only survive the 3D-bioprinting process but also maintain the mesenchymal phenotype, as proved by live/dead staining and immunocytochemistry (vimentin positive, CD34 negative). Increased solids concentrations of collagen in the hydrogel blend induce changes in cell morphology, namely, by enhancing cell spreading, that ultimately contribute to enhanced and directed MSC osteogenic differentiation. 3D-bioprinted agarose-collagen hydrogels with high-collagen ratio are therefore feasible for MSC osteogenic differentiation, contrarily to low-collagen blends, as proved by two-photon microscopy, Alizarin Red staining, and real-time polymerase chain reaction.
Occult tumor contamination of hematopoietic stem-cell products does not affect clinical outcome of autologous transplantation in patients with metastatic breast cancer.
Authors: B W Cooper, T J Moss, A A Ross, J Ybanez, H M Lazarus
Journal: Journal of Clinical Oncology (1998)

To determine whether occult tumor contamination of autologous bone marrow or peripheral-blood progenitor cells (PBPC) influences clinical outcome after high-dose chemotherapy in patients with stage IV breast cancer.We used an immunocytochemical assay capable of detecting one tumor cell in 5 x 10(5) hematopoietic cells to analyze bone marrow and/or PBPC collections obtained from 57 consecutive women with chemotherapy-sensitive metastatic breast cancer who received high-dose chemotherapy. The influence of occult tumor on time to progression, overall survival, and first site of recurrence (old or new) was studied.Twenty-three of 57 (40%) patients received bone marrow (n=6) or peripheral-blood progenitor collections (n=17) that contained microscopic cancer. Median time to progression and overall survival were 9 and 22 months in patients who did not receive infused tumor cells, compared with 10 and 24 months, respectively, in those who received occult tumor (P=not significant [NS]). Worse survival, but not time to progression, was observed in six patients who received > or = 2/100,000 tumor cells. Regardless of whether occult tumor was infused, the majority of relapses occurred in prior, rather than new sites of disease. Three patients who received stem-cell products contaminated by microscopic breast cancer remain free from progression at 21+, 47+, and 52+ months.Microscopic tumor was frequently detected by immunocytochemistry in hematopoietic stem-cell products, but did not predict for inferior treatment outcome in this cohort of patients with metastatic breast cancer. Quantitative information regarding infused tumor burden may have prognostic significance.
Double-Blind Studies on the Use of Steroids in the Treatment of Acute Hemarthrosis in Patients with Hemophilia
Authors: C. T. Kisker, Carolyn Burke
Journal: New England Journal of Medicine (1970)

Two double-blind studies showed the clinical effectiveness of a five-day course of corticosteroid treatment of acute hemarthrosis in boys with hemophilia. When antihemophilic factor or plasma thromboplastin component was given repeatedly until return of joint function was judged complete, significantly less replacement therapy of this type was needed if corticosteroids were added to the regimen. When replacement therapy was limited to a single dose of 25 units of antihemophilic factor per kilogram 89 per cent of patients in the corticosteroid group responded favorably, whereas 34 per cent of those in the control group needed additional replacement for complete return of joint function. Immobilization and splinting were not used in the treatment of the joint. These measures tend to weaken the surrounding muscle structure and thereby increase the amount of physical therapy and time needed before ambulation and complete return of function are possible.