tbuckley/cabot-search huggingface dataset:
Bilateral germ cell testicular tumors in New Zealand: experience in Auckland and Christchurch 1978-1994.
Authors: B M Colls, V J Harvey, L Skelton, P I Thompson, C M Frampton
Journal: Journal of Clinical Oncology (1996)

PURPOSE The incidence of germ cell testicular tumors (GCTTs) is increasing world wide, and with effective treatment, the majority of patients are being cured. Thus, the clinical and social impact of a second testicular tumor is becoming more important. The frequency, cumulative risk, and relative risk of developing a second testicular cancer in New Zealand have been documented and compared with other reports. PATIENTS AND METHODS The records of 741 men presenting with germ cell testicular cancer in Auckland and Christchurch between 1978 and 1994 have been reviewed, and these data have been compared with data from other published studies. Cumulative risk was assessed by the Kaplan-Meier method. RESULTS Over 2% of the study population developed a second germ cell testicular cancer. The cumulative risk was 5.2% over 15 years. The relative risk of developing a contralateral testicular tumor is 27.5 times higher than age-matched New Zealand peers. These results match the only comparable report in the literature. Five of the 16 bilateral tumors (31%) were synchronous, which is a higher incidence than in any other reported series. There was no concordance of histology in the first and second tumors. Prior exposure to cisplatin combination chemotherapy did not prevent the development of a second tumor. CONCLUSION Men who are cured of a germ cell testicular cancer have a greatly increased risk of developing a second testicular cancer. Such patients should be informed of this risk and ideally kept under long-term surveillance.
Induction, transcription, synthesis, and adsorption of interleukin-1 by dialyzer membranes.
Authors: N D Vaziri, J Wang, T Cesario, S Yousefi, R Valenzuela, G Carandang
Journal: Journal of the American Society of Nephrology (1994)

This study was designed to dissect the direct effect of dialyzer membrane on interleukin-1 (IL-1) induction from those of complement activation, mechanical stimulation, acetate/bicarbonate and endotoxin diffusion, and cell type interactions. To this end, a suspension of P388D1 murine macrophages in a complement-free culture medium containing 10% heat-inactivated serum, a closed-loop system consisting of tubing alone or with a hollow-fiber cuprammonium cellulose (CU) or polyacrylonitrile (PAN) dialyzer, and a roller pump were used. The dialysate compartment was filled with the same medium and capped. Cell suspension was recirculated at 300 mL/min for 3 h. Cells and supernates were separated, and adhering proteins were eluted. All samples tested negative for endotoxin. IL-1 mRNA was greatest with CU, followed by PAN and tubing alone. IL-1 in the supernate was greater with CU than with either tubing alone or PAN (P < 0.005; analysis of variance), which showed comparable values. IL-1 eluted from loops was greatest with PAN dialyzers, followed by sets with CU dialyzers and tubing alone (P < 0.001; analysis of variance). Thus, both CU and PAN membranes directly induce IL-1. However, avid adsorption by PAN attenuates the rise in circulating IL-1.
Upper airway stimulation in OSA patients increases airway size in a dose-response manner
Authors: Olivier M. Vanderveken, Faiza Safiruddin, Johan Verbraecken, Kent Lee, Joachim Maurer, Paul Van de Heyning, Nico de Vries
Journal: European Respiratory Journal (2013)

Introduction: Upper airway stimulation (UAS) is a potential therapy for CPAP-refractory OSA by hypoglossal stimulation using an implantable, programmable neurostimulator. We tested whether increasing stimulation amplitude would increase palatal and tongue-base airway size during wakefulness and sedation.  Methods: Fifteen OSA patients had awake and drug-induced sleep endoscopy (DISE) at least 3 months after UAS system implantation (Inspire Medical Systems, Minneapolis, MN). Stimulation was applied at four increasing amplitudes: first sensation, tongue movement, PSG-titrated therapeutic, and sub-discomfort. Palatal and tongue-base cross-sectional area were measured and compared between periods with and without stimulation. Asterisk indicates p  Results: Twelve patients (all male, age: 51.2± 9.0 years) underwent DISE; fifteen patients (all male, age: 50.4 ±10.2 years) underwent awake laryngoscopy and eleven patients had both. During both awake and DISE, higher stimulation amplitudes had a graded response in enlarging airway size, with a larger percent increase during DISE.  The titrated amplitude increased airway size by ∼200% during DISE.  Conclusion: Upper airway stimulation increases airway size during awake and improves airway collapse during sedation. Increasing stimulation amplitudes enlarges both palatal and tongue-base airway size compared to periods of no stimulation in both awake and DISE.
Active sensitization of guinea-pig airways in vivo enhances in vivo and in vitro responsiveness
Authors: RL Featherstone, PA Hutson, ST Holgate, MK Church
Journal: European Respiratory Journal (1988)

A plethysmographic method was employed to assess the airway resistance of conscious, free-breathing guinea-pigs. Using this method animals sensitized by inhalation of ovalbumin and appropriate controls were assessed for their responsiveness to histamine and methacholine in vivo. The cough frequency on exposure to citric acid mist in the two groups was also assessed. Tracheal spirals from these animals were subsequently tested for their responsiveness to histamine, methacholine and prostaglandin D2 in vitro. Sensitization increased responsiveness to histamine, methacholine and citric acid in vivo but only histamine responses were affected in vitro. These changes were accompanied by a significant eosinophilia in the airways as assessed by bronchoalveolar lavage. We conclude that sensitization of the airways to ovalbumin results in responsiveness changes in bronchial smooth muscle accompanied by signs of airway inflammation.
U.S. Complicity and Japan's Wartime Medical Atrocities: Time for a Response
Authors: Katrien Devolder
Journal: The American Journal of Bioethics (2015)

Shortly before and during the Second World War, Japanese doctors and medical researchers conducted large-scale human experiments in occupied China that were at least as gruesome as those conducted by Nazi doctors. Japan never officially acknowledged the occurrence of the experiments, never tried any of the perpetrators, and never provided compensation to the victims or issued an apology. Building on work by Jing-Bao Nie, this article argues that the U.S. government is heavily complicit in this grave injustice, and should respond in an appropriate way in order to reduce this complicity, as well as to avoid complicity in future unethical medical experiments. It also calls on other U.S. institutions, in particular the Presidential Commission for the Study of Bioethical Issues, to urge the government to respond, or to at least inform the public and initiate a debate about this dark page of American and Japanese history.
Genetics of diabetic nephropathy.
Authors: H H Parving, L Tarnow, P Rossing
Journal: Journal of the American Society of Nephrology (1996)

Diabetic nephropathy is a clinical syndrome characterized by persistent albuminuria, a relentless decline in GFR, raised arterial blood pressure, and increased relative mortality for cardiovascular diseases. Diabetic nephropathy is a leading cause of end-stage renal failure. The pathogenesis of diabetic nephropathy is multifactorial, with contributions from metabolic abnormalities, hemodynamic alterations, and various growth factors and genetic factors. Epidemiologic and family studies have demonstrated that only a subset of the patients develop this complication that family clustering of nephropathy is present, and that ethnicity plays an important role in the risk of developing this kidney disease. Short stature and low birth weight are both associated with increased risk of developing diabetic nephropathy, supporting the hypothesis that genetic predisposition or factors operating in utero, in early childhood, or both contribute to the development of diabetic nephropathy. Studies elucidating phenotypic markers such as parenteral hypertension and systemic blood pressure elevation have yielded conflicting results. The contribution from elevated blood pressure only plays a minor role in the majority of the patients developing diabetic nephropathy. The majority of the studies have demonstrated increased sodium/lithium countertransport activity in insulin-dependent diabetes mellitus patients with nephropathy, whereas studies of this phenotypic marker in parents of patients with and without nephropathy have yielded conflicting results. Recently, studies of genetic markers involved in the regulation of blood pressure and levels of cardiovascular risk factors have been conducted. Several studies have demonstrated that the deletion polymorphism in the angiotensin-I-converting enzyme acts as a risk factor for cardiovascular disease in diabetic patients. However, a meta-analysis does not support the suggestion that this factor plays any role for the initiation of diabetic nephropathy. Similar negative results have been obtained in relation to polymorphisms of the genes encoding for angiotensinogen and the angiotensin II Type 1 receptor. However, studies in diabetic and non-diabetic glomerulopathies have clearly demonstrated a deleterious effect of the deletion polymorphism in the angiotensin-converting enzyme on the progression of kidney function.
ASH 2009 meeting report—Top 10 clinically oriented abstracts in chronic lymphocytic leukemia
Authors: Susan O'Brien
Journal: American Journal of Hematology (2010)

The 2009 American Society of Hematology annual meeting took place December 5-8, in New Orleans, Louisiana, USA.Official sources indicate over 20,000 people attended the meeting and more than 4,000 scientific abstracts were presented.Among the latter, close to 100 were in the category of BCR-ABL1-negative myeloproliferative neoplasms (MPN), including polycythemia vera, essential thrombocythemia and primary myelofibrosis.Here, I summarize and discuss the top 10 MPN abstracts, which I believe contain information that is immediately relevant to clinical practice.All 10 abstracts are published in full in the November 20, 2009 issue of Blood (volume 114, No. 22) and are identified here by their abstract numbers.
Photometric Cytodiagnosis of Vaginal Smears2
Authors: W. Sandritter, Bertha L. Lobel, G. Kiefer
Journal: JNCI Journal of the National Cancer Institute (1964)

With a cytophotometer 161 vaginal smears were investigated. Of 113 vaginal smears of Papanicolaou classes I and II, 9 were found in which 10 percent of the cells showed a dye content of the cell nuclei exceeding an arbitrarily chosen border line (24 arbitrary units). These cases of doubtful nature had been diagnosed as chronic inflammation. Thirteen smears of Papanicolaou classes III and IV (with one exception) showed more than 10 percent suspected cells (quota of error, 7.6%). All cases of Papanicolaou classes IV and V showed 12 to 84 percent cells exceeding the arbitrary border line. Measurements of the nucleic acid content in 142 carcinomas showed that only 1.4 percent malignant tumors had less than 10 percent cells with an increased nucleic acid content. Therefore, it is concluded that an automatic prescreening with a cytophotometer is advisable.
Adaptation to low-protein diets in renal failure
Authors: T H Goodship, W E Mitch, R A Hoerr, D A Wagner, T I Steinman, V R Young
Journal: Journal of the American Society of Nephrology (1990)

In normal subjects, short to intermediate responses to dietary protein restriction include decreased amino acid oxidation and protein degradation plus increased utilization of amino acids for protein synthesis; these responses are activated to improve amino acid utilization and nitrogen balance. To assess whether chronic renal failure (CRF) impairs the adaptive responses to a low-protein diet, we measured nitrogen balance and the kinetics of infused L-(15N,1-13C)leucine during fasting and feeding. In six adult CRF and four control (C) subjects, 0.6 (LP) and 1.0 (HP) g protein kg-1 day-1 diets were compared. LP reduced feeding stimulated oxidation of leucine by 26% in CRF and 33% in C (P = NS). During fasting, oxidation was unaffected by diet or CRF. For both groups, feeding suppressed protein degradation to the same extent; leucine incorporation into protein did not change. Nitrogen balance during the two diets was the same with C and CRF, as was protein balance estimated from results of measured leucine kinetics. Thus, patients with CRF can activate appropriate adaptive responses to LP inasmuch as reduced amino acid oxidation occurring with feeding and estimates of protein balance did not differ from control.
Effect of a surgical day unit on waiting lists
Authors: S Lakhani, R D Leach, P E M Jarrett
Journal: Journal of the Royal Society of Medicine (1987)

The effect of a surgical day unit (SDU) on the waiting lists of a busy district general hospital is reported over a 4-year period. During this time, 18 (15%) of the general surgical beds were closed for financial reasons. A real saving rather than an apparent one is reported due to the work expansion in the SDU.
Incidence of lung entrapment in malignant pleural effusion
Authors: Imran Bin Mohamed Noor
Journal: European Respiratory Journal (2012)

Introduction 

Lung entrapment is commonly seen in patients with empyema and complicated parapneumonic effusions. However, the incidence of lung entrapment is not well reported in malignant effusions. We intend to report the incident in our patient who underwent pleuroscopy in 2011.

Method 

A prospective observational study was performed on patients who underwent pleuroscopy in 2011 in Changi General Hospital (CGH). The findings on pleuroscopy were noted for all patients, in particular, the presence of lung entrapment. Biopsies of the parietal pleura were performed during plueroscopy. Patients with biopsies positive for malignant pleural effusion were included in our analysis.

Results 

In 2011, twenty four pleuroscopies performed in CGH. Fifteen (62.5%) were proven to have malignant pleural effusion on biopsy. Of these fifteen patients, 10 (66.7%) had lung carcinoma, 4 (26.7%) had breast carcinoma and the remaining patient (6.7%) had carcinoma of the cervix. Fourteen patients (93.3%) with malignant effusion were noted to have lung entrapment on pleuroscopy of various. Computed tomography scan (CT scan) of the lungs showed patency of the airway. However, bronchoscopy was not performed for these patients.

Conclusion 

The incidence of lung entrapment is high in our patients with malignant pleural effusion. This will have an impact on the long term management of such patients. Our finding would suggest that talc pleurodesis may not be the best treatment options. The use of an indwelling pleural catheter may be a better option for our patients with malignant pleural effusion.
First Intra-Patient Comparison of Antidepressant Use Among Tamoxifen Patients
Authors: L. Binkhorst, M. Bannink, P. De Bruijn, J. Ruit, H. Droogendijk, M. Lam, A. Jager, T. van Gelder, R.H.J. Mathijssen
Journal: Annals of Oncology (2014)
Pharmacokinetics of fluconazole in renal failure.
Authors: T Berl, K D Wilner, M Gardner, R A Hansen, B Farmer, B A Baris, W L Henrich
Journal: Journal of the American Society of Nephrology (1995)

Fluconazole (FLU) is a widely used antifungal agent. The multiple-dose pharmacokinetics of FLU in renal impairment have not been previously investigated. The following groups were studied: volunteers with creatinine clearances (CLcr, > 50 mL/min) of 107 mL/min, given a loading dose of 400 mg and a daily dose of 200 mg/day for 9 days (Group 1); subjects with CLcr between 21 and 50 mL/min with a mean of 38 mL/min, given a loading dose of 200 mg and a maintenance dose of 100 mg/day for 9 days (Group 2); subjects with CLcr between 11 and 20 mL/min with a mean of 14.8 ml/min, given a loading dose of 100 mg and a maintenance dose of 50 mg/day for 9 days (Group 3); and subjects on hemodialysis (three times per week) receiving a loading dose of 200 mg and then 100 mg after each of four dialysis sessions (Group 4) (N = 10 per group). After the administration of the loading dose on Day 1, the mean area under the curve (AUC) (0-24) measurements were approximately proportional to the dose of FLU and independent of renal function. After 10 days of FLU dosing, the mean renal clearance of FLU decreased as CLcr decreased for Groups 1 to 3, and the Day 10 mean half-lives were inversely related to mean CLcr (36.7 h in Group 1, 84.5 h in Group 2, and 101.9 h in Group 3). The mean AUC (0-24) on Day 10 was similar for Group 1 compared with Group 2, despite a reduction in the maintenance dose by 50%. (ABSTRACT TRUNCATED AT 250 WORDS)
Hyperoxia mediates barrier permeability dysfunction in 16HBE140- cells
Authors: Hanady Al-Shmgani, John Moody, Robert Sneyd, Roy Moate
Journal: European Respiratory Journal (2012)

Background:  Reactive oxygen species (ROS) induced by hyperoxia have been postulated to be responsible as mediators of oxidative stress and damage in human and experimental animal lung epithelium. This study aimed to determine the effects of hyperoxia on the tight junction associated protein ZO-1 in the human bronchial epithelial cell 16HBE140-, and the possibility of a protective role of antioxidant vitamins C and E.   Methods:  16HBE140- cells were cultured at a density of 2.5×10 5  cell/cm 2  in an air-liquid interface for 6 days where the transepithelial electrical resistance (TER) developed to 230 ± 28 Ω cm 2 . The experimental groups were divided into six sets, exposed for 24h to normoxia (21% O 2  ,  5% CO 2 ) as a control; hyperoxia (95% O 2,  5% CO 2 ); hyperoxia with 10 -7  M vitamin E (α-tocopherol); hyperoxia with 10 -  7  M vitamin C; hyperoxia with 10 -6  M vitamin C and hyperoxia with a combinations of vitamins E and C (10 -7 , 10 -6  M respectively). TER measurement, immunofluorescence staining of ZO-1 and RT-PCR to detect IL8, IL6, TNF-α and ZO-1 expression were used.   Results:  The reductions of the TER in hyperoxic groups (hyperoxia and hyperoxia with antioxidants) were associated with the reduction in the ZO-1 thickness and downregulation of ZO-1 expression compared with the control. In contrast, the expression of IL-8, IL-6 and TNF-α was upregulated in the hyperoxic groups compared with the control.   Conclusion:  Hyperoxia induced barrier integrity disruption represented by the decrease in TER and the reduction of ZO-1 levels is associated with an increased in the expression of pro-inflammatory cytokines IL-8, IL-6 and TNF-α. The antioxidant vitamins E and C had only a slight protective effect against hyperoxia damage.
Targeting CD38 with Daratumumab Monotherapy in Multiple Myeloma
Authors: Henk M. Lokhorst, Torben Plesner, Jacob P. Laubach, Hareth Nahi, Peter Gimsing, Markus Hansson, Monique C. Minnema, Ulrik Lassen, Jakub Krejcik, Antonio Palumbo, Niels W.C.J. van de Donk, Tahamtan Ahmadi, Imran Khan, Clarissa M. Uhlar, Jianping Wang, A. Kate Sasser, Nedjad Losic, Steen Lisby, Linda Basse, Nikolai Brun, Paul G. Richardson
Journal: New England Journal of Medicine (2015)

Multiple myeloma cells uniformly overexpress CD38. We studied daratumumab, a CD38-targeting, human IgG1κ monoclonal antibody, in a phase 1-2 trial involving patients with relapsed myeloma or relapsed myeloma that was refractory to two or more prior lines of therapy.In part 1, the dose-escalation phase, we administered daratumumab at doses of 0.005 to 24 mg per kilogram of body weight. In part 2, the dose-expansion phase, 30 patients received 8 mg per kilogram of daratumumab and 42 received 16 mg per kilogram, administered once weekly (8 doses), twice monthly (8 doses), and monthly for up to 24 months. End points included safety, efficacy, and pharmacokinetics.No maximum tolerated dose was identified in part 1. In part 2, the median time since diagnosis was 5.7 years. Patients had received a median of four prior treatments; 79% of the patients had disease that was refractory to the last therapy received (64% had disease refractory to proteasome inhibitors and immunomodulatory drugs and 64% had disease refractory to bortezomib and lenalidomide), and 76% had received autologous stem-cell transplants. Infusion-related reactions in part 2 were mild (71% of patients had an event of any grade, and 1% had an event of grade 3), with no dose-dependent adverse events. The most common adverse events of grade 3 or 4 (in ≥ 5% of patients) were pneumonia and thrombocytopenia. The overall response rate was 36% in the cohort that received 16 mg per kilogram (15 patients had a partial response or better, including 2 with a complete response and 2 with a very good partial response) and 10% in the cohort that received 8 mg per kilogram (3 had a partial response). In the cohort that received 16 mg per kilogram, the median progression-free survival was 5.6 months (95% confidence interval [CI], 4.2 to 8.1), and 65% (95% CI, 28 to 86) of the patients who had a response did not have progression at 12 months.Daratumumab monotherapy had a favorable safety profile and encouraging efficacy in patients with heavily pretreated and refractory myeloma. (Funded by Janssen Research and Development and Genmab; ClinicalTrials.gov number, NCT00574288.).
Autologous bone marrow transplantation in acute myeloid leukemia in first remission: results of a Dutch prospective study.
Authors: B Löwenberg, L J Verdonck, A W Dekker, R Willemze, F E Zwaan, M de Planque, J Abels, P Sonneveld, J van der Lelie, R Goudsmit
Journal: Journal of Clinical Oncology (1990)

Recent investigations have suggested a role for marrow ablative chemotherapy and radiotherapy given with autologous bone marrow transplantation (auto-BMT) in the treatment of acute myeloid leukemia (AML), but prospective studies have not been reported. We assessed the comparative values of auto-BMT and allogeneic marrow transplantation (allo-BMT) in 117 15- to 60-year-old consecutive patients (median, 43 years) with AML following remission-induction therapy. In 32 cases of the 90 (77%) complete responders, auto-BMT (nonpurged) was undertaken at a median of 3.8 months and in 23 eligible cases human leukocyte antigen (HLA)-matched allo-BMT occurred at 3.0 months after attainment of remission. Thus, nearly 60% of complete responders had access to transplantation, the others being withdrawn because of relapse, refusal, or other causes. Median time of regeneration to neutrophils 0.5 x 10(9)/L and platelets 20 x 10(9)/L were 39 and 63 days following auto-BMT versus 21 and 19 days after allo-BMT, respectively. AML relapse was the predominant cause of failure after auto-BMT (17 of 32) and procedure-related death was seen in three of 32 patients. The actuarial rates of relapse at 3 years are 60% (auto-BMT) and 34% (allo-BMT) (log-rank, P = .03). Patients treated with auto-BMT and allo-BMT have an overall survival of 37% and 66% at 3 years posttransplant, respectively (P = .05). Relapse-free 3-year survival rates are 35% and 51%, respectively (P = .12). Survival of the nongrafted complete responders is less than 10%. This study shows that allo-BMT in adult patients with AML in first complete remission (CR) results in more rapid hematopoietic reconstitution, is followed by fewer recurrences, and provides better survival than auto-BMT.