tbuckley/cabot-search huggingface dataset:
Partial Ankyrin and Spectrin Deficiency in Severe, Atypical Hereditary Spherocytosis
Authors: T L Coetzer, J Lawler, S C Liu, J T Prchal, R J Gualtieri, M C Brain, J V Dacie, J Palek
Journal: New England Journal of Medicine (1988)

HEREDITARY spherocytosis is a common form of hemolytic anemia that is heterogeneous in terms of its clinical presentation, molecular basis, and inheritance.1 The primary defect is thought to reside in the red-cell membrane skeleton, a submembranous network composed mainly of spectrin, actin, and proteins that migrate on gel electrophoresis as bands 4.1 and 4.9 (proteins 4.1 and 4.9).2 Visualization of the skeleton by electron microscopy has revealed a primarily hexagonal lattice of fibers of spectrin tetramers linked to junctional complexes containing actin and proteins 4.1 and 4.9.3 4 5 The skeleton is attached to the membrane by ankyrin (protein 2.1), which connects . . .
Evidence for X-Linked Dominant Inheritance of Ornithine Transcarbamylase Deficiency
Authors: Elizabeth M. Short, Harold O. Conn, Philip J. Snodgrass, Alexander G.M. Campbell, Leon E. Rosenberg
Journal: New England Journal of Medicine (1973)

The mode of Inheritance of ornithine transcarbamylase deficiency was studied in four kindreds, each containing one or more affected children with ammonia intoxication. In two families a total of eight males died in the neonatal period, three of whom had virtually complete absence of activity of this hepatic enzyme. Three families contained female probands with partial deficiency whose hyperammonemia was controlled by dietary protein restriction. All the fathers of affected children had normal activity whereas two mothers had partial deficiency. No such deficiency could be documented in the other two mothers, each with only a single affected female child. On the basis of this study and a genetic analysis of previously reported families, ornithine transcarbamylase deficiency is believed to be inherited as an X-linked dominant trait leading to lethal neonatal hyperammonemia in affected hemizygous males and partial enzyme deficiency with variable severity of hyperammonemia in affected heterozygous females.
Soundings: Dangerous places
Authors: James Owen Drife
Journal: BMJ (2005)

Risky destinations bother me less as I get older. Uzbekistan, a few months ago, felt safe. I heard the president was autocratic but relatively restrained in comparison with his neighbour in Turkmenistan, who has closed all regional hospitals and renamed January after himself.

A British passport, a World Health Organization schedule, and a police checkpoint outside our hotel gave me a sense of reassurance. The only time I felt anxious in Tashkent was when the lobby filled up with GIs. Hey, with y'all here, we're a target.

Nepal, several weeks later, was equally undemocratic. The king had seized power, apparently exasperated by parliament's failure to quell Maoist insurgency. Outside the royal palace, wary sentries crouched behind sandbags. On the streets, one blown-out shop was being repaired but otherwise life was normal. We checked our email in internet cabins to the sound of traffic tooting outside.

These two countries, north and south of the mountains, had much in common. Each had once been part of an empire whose influence could still be felt. In Tashkent we lectured through Russian translators. In Kathmandu schoolchildren wore English-style uniforms, and the local radio, playing requests, broke into “Happy Birthday.”

Both places inspire heartache in the visitor. Uzbekistan has ancient, evocative architecture and markets almost unchanged since Marco Polo's day. Nepal has the Himalayas: the tourist flights at dawn are stunning, I'm told. These timeless countries could be magnets for visitors. Instead, men shoot one another.

Doctors in both places are wonderfully hospitable, but their official salaries are too small to live on. Compromises have to be made, and the rural poor lose out on medical care. Slowly you realise that this is normal across much of the world.

Neither country is in fact dangerous for foreigners. It is the natives who are at risk, especially the women. In Nepal one in 135 pregnancies ends in the mother's death.

When you check on the internet you can easily find data on a nation's population, economics, and oil reserves. Webmasters could help by making the maternal mortality rate a headline statistic. It is a clear indicator of how civilised a country is. Who knows, it might shame some autocrats into action.
Is adult sleep apnea seasonal
Authors: Neil M. Skjodt, Ronald S. Platt
Journal: European Respiratory Journal (2014)

BACKGROUND : Multiple authors have shown paediatric sleep apnoea is seasonal reflecting respiratory infections. Other authors have speculated from animal data that obesity may reflect seasonal changes in leptin metabolism.   AIMS:  To determine seasonality, if any, in sleep polygraphy referral rates, body mass index, neck circumference, clinical risk of sleep apnea, perceived sleepiness, and sleep apnea severity in adult subjects.   METHODS:  A convenience sample of 1000+ adults referred for screening sleep polygraphy (www.sagatech.ca) were categorized by month of referral, body mass index (BMI), neck circumference, pre-test probability of sleep apnoea, Epworth score, and estimated sleep apnoea severity. Visual trends in monthly variation were confirmed if monthly variables were outside the sample interquartile range.   RESULTS:  Polygraphy referrals were triphasic with March, June, and September peaks. Synchronous March to April and September to October increases in BMI (1.5 to 2 kg/m2) and Epworth score (1 to 1.5 points corresponding to the known clinically significant difference) occurred without seasonal variations in neck circumference, pre-test risk of sleep apnoea, or polygraphy-estimated respiratory disturbance index.   CONCLUSIONS : Synchronous spring-fall biphasic peaks in obesity and sleepiness occurred without seasonal variation in sleep apnoea risk or severity in a large adult sample. We will expand our analysis to a larger sample (20 000+) and other adult samples to confirm seasonal obesity and sleepiness.   FUNDING:  RCPSC and MITACS.
Pulseless Disease and Carotid-Artery Thrombosis
Authors: Richard Warren, Leonard J. Triedman
Journal: New England Journal of Medicine (1957)

ARTERIAL reconstruction by thrombendarterectomy or grafting has been widely and successfully used for obliterative arteriosclerosis of the abdominal aorta and its branches. This has naturally stimulated efforts to apply the same principles to other important arteries similarly involved. In reviewing descriptions of such conditions interfering with the blood supply to the brain and the upper extremities, one frequently encounters the terms "pulseless disease" and "carotid-artery thrombosis."Pulseless DiseaseIn 1908 Takayusu,1 a Japanese ophthalmologist, first reported a syndrome characterized by occlusion of the main arterial trunks from the aortic arch. Since that time several case reports and reviews have appeared . . .
Desensitization to Walnut and Test Tree Nuts during a Double Blind, Placebo Controlled Walnut Oral Immunotherapy Trial
Authors: Amy M. Scurlock, Mallikarjuna R. Rettiganti, Anne M. Hiegel, Amika Sood, Caroline Daniel, Sarah E. Beckwith, Jessica L. Bettis, James D. Sikes, Suzanne E. House, Jennifer N. Payne, Robbie D. Pesek, Tamara T. Perry, Peggy L. Chandler, Josh L. Kennedy, Chunqiao Luo, Lynn Christie, Stacie M. Jones
Journal: Journal of Allergy and Clinical Immunology (2016)
Appendectomy does not decrease the risk of future colectomy in UC: results from a large cohort and meta-analysis
Authors: Alyssa Parian, Berkeley Limketkai, Joyce Koh, Steven R Brant, Alain Bitton, Judy H Cho, Richard H Duerr, Dermot P McGovern, Deborah D Proctor, Miguel D Regueiro, John D Rioux, Phil Schumm, Kent D Taylor, Mark S Silverberg, A Hillary Steinhart, Ruben Hernaez, Mark Lazarev
Journal: Gut (2016)

<h3>Objectives</h3> Early appendectomy is inversely associated with the development of UC. However, the impact of appendectomy on the clinical course of UC is controversial, generally favouring a milder disease course. We aim to describe the effect appendectomy has on the disease course of UC with focus on the timing of appendectomy in relation to UC diagnosis. <h3>Design</h3> Using the National Institute of Diabetes and Digestive and Kidney Diseases Inflammatory Bowel Disease Genetics Consortium database of patients with UC, the risk of colectomy was compared between patients who did and did not undergo appendectomy. In addition, we performed a meta-analysis of studies that examined the association between appendectomy and colectomy. <h3>Results</h3> 2980 patients with UC were initially included. 111 (4.4%) patients with UC had an appendectomy; of which 63 were performed prior to UC diagnosis and 48 after diagnosis. In multivariable analysis, appendectomy performed at any time was an independent risk factor for colectomy (OR 1.9, 95% CI 1.1 to 3.1), with appendectomy performed after UC diagnosis most strongly associated with colectomy (OR 2.2, 95% CI 1.1 to 4.5). An updated meta-analysis showed appendectomy performed either prior to or after UC diagnosis had no effect on colectomy rates. <h3>Conclusions</h3> Appendectomy performed at any time in relation to UC diagnosis was not associated with a decrease in severity of disease. In fact, appendectomy after UC diagnosis may be associated with a higher risk of colectomy. These findings question the proposed use of appendectomy as treatment for UC.
Pathogenesis of Hereditary Vitamin-D-Dependent Rickets
Authors: Donald Fraser, Sang Whay Kooh, H. Peter Kind, Michael F. Holick, Yoko Tanaka, Hector F. DeLuca
Journal: New England Journal of Medicine (1973)

Requirements of vitamin D2, vitamin D3, 25-hydroxyvitamin D3 and 1α,25-dihydroxyvitamin D3 were studied in five patients with vitamin-D-dependent rickets, a recessively inherited form of vitamin-D-refractory rickets. Massive doses of vitamin D2 (1.25 to 2.50 mg per day), vitamin D3 (1.25 mg per day) and 25-hydroxyvitamin D3 (0.4 to 0.9 mg per day) were required to heal the rachitic lesions, but minute doses of 1α,25-dihydroxyvitamin D3. (1.0 μg per day) promptly initiated healing. The dosage of 1α,25-dihydroxyvitamin D3 was probably in the physiologic range for the human infant — evidence against target-cell unresponsiveness. Our data suggest that conversion of vitamin D to 25-hydroxyvitamin D was normal in our patients, but that a block was present in subsequent conversion to 1α,25-dihydroxyvitamin D, the active metabolite. We postulate, therefore, that vitamin-D-dependent rickets is an inborn error of vitamin D metabolism due to a genetic defect in 25-hydroxycholecalciferol-1-hydroxylase, the enzyme responsible for the production of 1α,25-dihydroxyvitamin D. (N Engl J Med 289:817–822, 1973)
Activated Prothrombin Concentrate for Patients with Factor VIII Inhibitors
Authors: Elizabeth M. Kurczynski, John A. Penner
Journal: New England Journal of Medicine (1974)

Abstract Activated prothrombin concentrate, a complex containing prothrombin, factors VII, IX, X, and XI, was used successfully for the treatment of hemorrhagic episodes in eight patients with factor VIII inhibitors. Six had hemophilia A, and two were women with acquired inhibitors. Partial thromboplastin times decreased immediately after infusion of the complex, and remained low for as long as 24 hours. Prothrombin times decreased also, whereas factor X rose 200 to 300 per cent, and factor VII levels increased by as much as 2000 per cent. Although thrombotic complications can occur after infusions of regular prothrombin complex preparations, none developed with the activated concentrate. Fibrin split products were found in two patients in titers of 1:5 and 1:40. This complex appears to offer effective control of severe hemorrhage in patients with factor VIII inhibitors. (N Engl J Med 291:164–167, 1974)
Risk factors for lymph node and distant metastasis in colorectal carcinoids: An analysis of nationwide registry in Japan over 15 years
Authors: T. Konishi, T. Watanabe, T. Muto, K. Kotake, H. Nagawa
Journal: Journal of Clinical Oncology (2006)

3620 Background: No global consensus has been established on the crucial determinants of metastasis in colorectal carcinoids. This study aims to determine the predictive factors for lymph node (LN) and distant metastasis, and to provide strategic model for the treatment of this uncommon disease. Methods: All patients diagnosed as carcinoids from 1984 to 1998 were extracted from the nationwide database, “Multi-Institutional Registry of Large-Bowel Cancer in Japan”, which covers almost 10% of all colorectal cancers in Japan. Risk factors for metastasis were analyzed among colorectal carcinoids undergoing surgery. Results: Among 90,057 cases of colorectal tumors registered from 1984 to 1998, a total of 345 cases of carciniods were identified. All cases were from the Asian population. The site distribution consisted of the ileum 3 (0.9%), appendix 8 (2.3%), colon 28 (8.2%) and rectum 304 (88.6%). Among colorectal carcinoids, a total of 263 cases undergoing surgery were eligible for the analysis (colon 23, rectum 240). Overall incidence of LN and distant metastasis were 29% and 7%, respectively. Univariate analysis showed that age&gt;55, tumor size, tumor invasion≥T2, and lymphovascular invasion were associated with LN metastasis as well as distant metastasis. Multivariate analysis revealed that tumor size&gt;10mm and lymphovascular invasion (LVI) were independently predictive of LN metastasis, while tumor size&gt;20mm was a single risk factor for distant metastasis. Notably, tumors not larger than 10mm and without LVI exhibited no LN metastasis ( Table ). Conclusions: Tumors not larger than 10mm and without LVI could be curatively treated by endoscopic resection or transanal excision. However, tumors larger than 10mm or those with LVI should undergo radical surgery for LN dissection. Furthermore, tumors larger than 20mm carry a high risk for distant metastasis, and require close follow-up even without evident metastasis at the time of surgery. [Table: see text] No significant financial relationships to disclose.
Local Injections of Hydrocortisone as a New and Effective Treatment for Strictures of the Urethra and Meatus
Authors: Charles D. Bonner, Melvin K. Lyons, Daniel Shields
Journal: New England Journal of Medicine (1955)

STRICTURES of the human urethra are of three types: inflammatory, traumatic and congenital. The basic histology1 common to all strictures is a proliferation of fibroblasts in the tunica propria. This progresses to the point where the elastic tissue and muscle fibers of this area are destroyed and replaced by fibroblasts. In extreme cases the mucosa and corpus spongiosum are also replaced. In inflammatory strictures, the proliferation is accompanied by a marked infiltration of leukocytes. This infiltration takes place to a much less degree in traumatic strictures and is entirely absent in congenital strictures.The clinical course, treatment, complications and prognosis . . .
Urokinase-type plasminogen activator (uPA) and its inhibitor PAI-1 for improved management in node-negative (N0) breast cancer: Experiences from the ongoing multicenter trial NNBC 3-Europe
Authors: M. M. Persing, D. Paepke, M. Schmidt, C. Veyret, D. Augustin, A. Guerts, P. M. Martin, G. von Minckwitz, C. Thomssen, N. Harbeck
Journal: Journal of Clinical Oncology (2007)

11081 Risk-assessment in N0 breast cancer is still controversial. In line with St. Gallen, only few patients (pts) are considered at such low risk of relapse, that adjuvant chemotherapy could be avoided. Various groups have started clinical trials aimed at improved risk-assessment by gene or protein analysis of the primary tumor. We launched the NNBC 3-Europe trial asking the following questions: Is the identification of low- risk pts by the invasion markers uPA and PAI-1 more effective than by St. Gallen criteria? Is adjuvant chemotherapy using an anthracycline- taxane sequence superior to standard FEC in N0 high-risk pts? The centres of the NNBC 3 trial had to choose their mode of risk- assessment (either St. Gallen criteria or uPA/PAI-1) prior to recruitment. High-risk pts receive chemotherapy randomly assigned to FEC-100*3 followed by Docetaxel-100*3 (FEC-Doc), or FEC-100*6. No adjuvant chemotherapy is given to low-risk pts. Pts with hormone receptor positive tumors receive standard endocrine therapy. To date, 1206 pts in 57 centres have been registered. Using fresh frozen tumor tissue, uPA and PAI-1 are tested in nine laboratories; inter-laboratory quality assurance is performed. In 141 of 1188 evaluable pts, St Gallen criteria were used. In the biological risk-assessment group, 150 of 1047 tumors (14.3%) were well differentiated, thus regarded as low-risk. Using both, tumor grade and uPA/PAI-1, 35.3% of the pts were considered low-risk, whereas the remaining 64.7% high-risk pts received adjuvant chemotherapy (FEC-Doc, n=334, or FEC, n=343). Multicenter prospective risk assessment based on testing of fresh frozen (or paraffin- embedded) tumor tissue is sophisticated. All trials with similar approach (MINDACT, TAILORx) had a long preparation phase including thorough assay validation. The ongoing NNBC-3 trial demonstrates that inclusion of pts based on testing of fresh frozen material is feasible in a routine setting. Risk-group distribution is as expected. The study is planned to recruit 5,700 pts and it is performed in cooperation with the EORTC Patho-Biology Group, the German AGO Breast Group, and the German Breast Group (GBG). Unrestricted grants by Sanofi-Aventis and Pfizer. [Table: see text]
Morbidity and survival of 32 recurrent ovarian cancer patients treated with aggressive cytoreductive surgery followed by intraperitoneal hyperthermic chemoperfusion
Authors: S. D. Richard, N. Gusani, H. J. Zeh, C. Colovos, S. W. Cho, D. L. Bartlett, R. P. Edwards
Journal: Journal of Clinical Oncology (2007)

16078 Background: Cytoreductive surgery followed by intraperitoneal hyperthermic chemoperfusion (CS/IPHC) has shown increased survival for patients with recurrent and persistent GI malignancies with peritoneal dissemination. We present our preliminary experience with CS/IPHC as palliative therapy for recurrent ovarian cancer treated at a single institution. Methods: A retrospective review of CS/IPHC for women with recurrent or persistent epithelial ovarian carcinoma previously treated with platinum/taxane chemotherapy at a single institution from 2002–2006 was performed. Each patient had an attempted optimal surgical debulking (volume of residual disease &lt;1 cm) prior to chemoperfusion. IPHC was performed on all patients for 100 minutes at temperatures between 40–42°C with either mitomycin C (40 mg/m 2 ) or cisplatin (100 mg/m 2 ). Post-surgical complications were evaluated. End points analyzed included morbidity, progression free survival, and over all survival. Results: Thirty-two patients were identified, with optimal cytoreductive surgery obtained in 26 (81.3%). Procedures required for cytoreduction included omentectomy (n=16), splenectomy (n=14), colonic resection (n=14), small bowel resection (n=13), ileostomy (n=9), hepatic resection (n=5), partial gastrectomy (n=5), and diaphragmatic stripping (n=3). Over-all morbidity was 65.6%, with major morbidity of 9.4%. There were three mortalities within sixty days of operation. Common morbidities included neutropenia (n=5), ileus (n=5), pleural effusions (n=4), and sepsis (n=4). Median length of stay was 11 days (6 to 47). Nineteen patients had a documented recurrence with a median progression free survival of 8 months (1 to 22). Median survival was 13 months (1 to 54) for these patients with recurrent end stage ovarian cancer. Conclusions: CS/IPHC is associated with high morbidity, but acceptable mortality. In a subset of patients, survival is improved compared to historical controls for recurrent ovarian cancer. A randomized phase II study is planned based on this data. No significant financial relationships to disclose.
A Cytokine Working Group phase II study of temozolomide (TMZ), thalidomide (THAL) and whole brain radiation therapy (WBRT) for patients with brain metastases from melanoma
Authors: M. B. Atkins, J. Sosman, S. Agarwala, T. Logan, J. Clark, M. Ernstoff, D. Lawson, J. Dutcher, G. Weiss, W. Urba, K. Margolin
Journal: Journal of Clinical Oncology (2005)

7552 Background: The combination of TMZ and THAL was reported to produce a high response rate (RR) including shrinkage of CNS disease in patients (pts) with metastatic melanoma (Hwu et al JCO 21:3351). We tested the efficacy of a regimen involving TMZ/THAL and WBRT in pts with brain metastases from melanoma. Methods: Pts with melanoma and MRI documented brain metastases received WBRT, 30 Gy in 10 fractions days 1–5 and 8–12; TMZ 75mg/m2/day weeks 1–6; THAL 100 mg po/day weeks 1–4, then escalated by 100 mg/day at weeks 5, 7, and 9 as tolerated to a maximum of 400 mg/day. CNS and systemic tumor response was assessed at wk 10. Pts without CNS or clinically significant systemic progression received additional cycles of TMZ (same dose) and THAL (MTD from cycle 1) at 10 wk intervals. Pts with prior cytotoxic chemotherapy, WBRT or THAL were ineligible. Prior focused RT was permitted for oligometastatic CNS disease. Results: 40 pts (25 M/ 15 F), median age 49 (range 28–81), ECOG PS 0/1 (20/20) were enrolled in the protocol. The majority of pts had brain metastases documented on routine staging head scan. Sites of systemic disease included: lung (28 pts), LN (17), soft tissue (14), liver (14), bone (7), adrenal (6), other (5); number of non-CNS disease sites were: 0 (1 pt), 1 (6), 2 (11), ≥ 3 (18), NA (4). Prior therapy: none (22 pts), IFN (5), vaccine (5), other cytokine (2); 7 pts had received focused RT to isolated CNS lesions (7). 3 pts had CNS responses (1 CR, 2 PR) (RR 7.5%)-all unconfirmed by repeat scan; 7 pts had stable CNS disease at 10 weeks. No pts exhibited a systemic response. Only 4 pts received 2 cycles of therapy and just 1 received 3. Median TTP was 10 wks (range 1–30 wks); median overall survival (OS) was 4 mos (range 0.5 -12 mos). Grade 3–4 side effects included DVT (3 pts), PE (1), myelosuppression (2), CNS events (8), cardiac (3). 18 pts (45%) required admission for side effects (7) and/or symptomatic disease progression. Conclusions: Median OS of pts with brain metastases from melanoma treated with TMZ/THAL and WBRT is comparable to that of other treatments with few clinically meaningful responses. Other treatment approaches are clearly necessary for this pt population. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Celgene