bluuebunny/crossref_metadata_2025 huggingface dataset:
Prevention of Fetal Death in the Antiphospholipid Antibody Syndrome
Authors: Cowchock S
Published: January 2017

The first treatment of pregnant women with antiphospholipid antibody syndrome (APLS) employed high doses of corticosteroids, plus low dose aspirin, with the goal of suppressing production of the autoantibody. Corticosteroids (usually prednisone), even when much lower doses are used, and even when tapered after midpregnancy, have been associated with significant maternal and obstetric risks and side effects: the most important are osteomalacia and preterm delivery (often precipitated by premature rupture of the membranes).

Since the publication of a randomized trial demonstrating equivalent live birth rates of about 75% whether heparin or prednisone was used for treatment (plus low dose aspirin), the use of adjusted doses of heparin, together with low dose aspirin, has replaced prednisone for treatment of pregnant women; although prednisone may still be needed to treat manifestations of associated autoimmune disorders. A recent randomized trial has shown that the addition of heparin to aspirin is probably superior to treatment with aspirin alone. To achieve prophylactic levels of plasma heparin equivalent to those measured in patients who are not pregnant and are treated with the usual dose of standard heparin of 5000 IU every 12 h, the heparin dose required for treatment of pregnant women is usually higher. For that reason, heparin doses should be adjusted using the nadir APTT, or better plasma heparin measured by a factor Xa inhibition assay at the 2 h post-injection peak.

Although low molecular weight heparin has been shown to be useful in prevention of fetal resorption in a mouse model, and appears to be equally safe for treatment of pregnant women, we still have no published data to show therapeutic equivalency, with respect to treatment of APLS-complicated pregnancy, to standard heparin preparations, and none that demonstrate any lower risk for the complication of most concern when heparin is given to pregnant women—osteopenia. Similarly, intravenous infusion of gamma globulins (IVG) appears on the basis of case reports to be effective additional treatment in cases where standard therapy has failed. Gamma globulin preparations contain anti-idiotypic antibodies that have been shown to bind to patient antiphospholipid antibodies. The place for the addition of IVG to standard therapy has not been defined, but clinically significant and corticosteroid-resistant thrombocytopenia complicating antiphospholipid antibody syndrome might be one indication for primary treatment with IVG ± low dose aspirin.

Overall, live birth rates in most treatment studies are in the range of 70–80%. The reported birth rate information, however, cannot be compared between studies. None of the studies reported have used tools such as logistic regression analysis to allow for such significant predictors of live birth as the number of prior miscarriages, maternal age, medical history, or a history of fetal death (loss of a viable and chromosomally normal fetus after the 10th gestational week).
A Biographical Note on Marcel Proust's Professor Cottard
Authors: Pearn John
Published: January 2017

A medical practitioner, Professor Cottard, features in Marcel Proust's À la recherche du temps perdu, which has been described as one of the supreme achievements of world literature. Proust modelled the character of Cottard on the real-life Parisian neurologist and psychiatrist Dr Jules Cotard (1840–1889). Marcel Proust's father, Dr Adrien Proust, was an eminent Parisian surgeon and a contemporary of Cotard. A review of the biographical literature (in French) relating to Dr Jules Cotard and an analysis of his published work (in English and French) have revealed a striking parallelism between the lives of the fictional Cottard and Jules Cotard.
Henry Naunton Davies (1827–1899): A Devoted Family Doctor and a Brave Rescuer
Authors: Roberts Shirley
Published: January 2017

Henry Naunton Davies lived and practised in the Rhondda valley, in Wales. In 1877 a local coalmine became suddenly flooded, and 14 men were trapped. Davies made a valuable contribution to the rescue effort, and was subsequently awarded the British Medical Association's Gold Medal for Distinguished Merit (he was the first recipient of that honour).
“Let Right Be Done”: Unprofessional Conduct, Reputations and Injustices, and Their Effect on the Life of the Surgeon James Fitzjames Fraser West (1833–1883)
Authors: Goodman Geraldine M
Published: January 2017

Unprofessional behaviour was still common when James Fitzjames Fraser West first qualified in 1854. The paper covers the ugly dispute that occurred in 1857, when West was appointed honorary surgeon at Queen's Hospital in Birmingham. West's reputation did not suffer any long-term harm, however, and he went to his grave a much-respected man.
Sir William Jenner (1815–1898) and Queen Victoria
Authors: Seddon David
Published: January 2017

This biographical note outlines the work of Sir William Jenner (1815–1898), court physician 1861–93 and President of the Royal College of Physicians 1881–8. He was the first to distinguish between typhoid and typhus both clinically and pathologically.
Self-Sampling in Screening to Reduce Mortality from Colorectal Cancer: A Qualitative Exploration of the Decision to Complete a Faecal Occult Blood Test (FOBT)
Authors: O'Sullivan I , Orbell S
Published: January 2017

Objective:

To explore beliefs that might impact upon public reactions to a proposed population level faecal occult blood test (FOBT) screening invitation and acceptability of completing an FOBT home self sampling kit.

Methods:

Four focus groups were conducted to explore men and women's beliefs about colorectal cancer risk, their understanding of screening and reactions to an FOBT kit. Participants were shown a kit and permitted to examine it during the focus groups.

Results:

Colorectal cancer is viewed as having severe quality of life impacts and is commonly regarded as being caused by diet. Faecal blood is an expected symptom. A home self-sampling kit is viewed as highly acceptable, but some concerns were raised about collecting and storing faecal matter.

Conclusions:

The main implications for public education arising from the analysis were firstly, that communications regarding the potential to avoid quality of life impacts of colorectal cancer may motivate participation; secondly, that public education might address the ability of the test to detect asymptomatic abnormalities, in particular occult (as opposed to visible) blood; thirdly, in order to prevent avoidance responses to fear, communications need to emphasise that many abnormal test outcomes will not be cancer and early treatment may prevent cancer and associated adverse quality of life impacts; fourthly, that uptake may be promoted by emphasising messages that the test kit is very convenient; and finally, that instruction leaflets might minimise procedural concerns by suggesting simple and easy methods to collect and store faecal samples.
Overdiagnosis in Screening: Is the Increase in Breast Cancer Incidence Rates a Cause for Concern ?
Authors: Paci E , Warwick J , Falini P , Duffy S W
Published: January 2017

Objectives:

To estimate the degree of overdiagnosis of breast cancer in a mammographic screening programme.

Setting:

A mammography service screening programme in Florence, Italy.

Methods:

We studied the incidence of breast cancer in Florence between 1990 and 1999, following the introduction of screening in 1990. Incidence of breast cancer in this period was compared with incidence between 1985 and 1989, before the introduction of screening. It was necessary to estimate the number of cancers that would have arisen in the absence of screening, but after the end of followup (31 December 1999), so that these were not misclassified as overdiagnosed tumours. Around 60,000 women aged 50–69 were invited for screening during the period of study.

Results:

There were 2780 breast cancers diagnosed during the period of study (2626 were invasive). There was no significant evidence of overdiagnosis of invasive cancers. When invasive and in situ cancers were considered together, around 5% of cases were overdiagnosed.

Conclusions:

There is a small amount of overdiagnosis of ductal carcinoma in situ in mammography screening; however, this should not deter women from being screened. Training and practice in mammographic screening should emphasise detection of small, invasive lesions. Research into the natural history and treatment of the disease should aim at minimising overtreatment of those in situ lesions that are less likely to progress to invasive disease.
Cost Analysis in a Population Based Screening Programme for Colorectal Cancer: Comparison of Immunochemical and Guaiac Faecal Occult Blood Testing
Authors: Castiglione G , Zappa M , Grazzini G , Sani C , Mazzotta A , Mantellini P , Ciatto S
Published: January 2017

Objective—

To compare the costs of colorectal cancer (CRC) screening by two faecal occult blood tests (FOBT)—namely, Hemoccult (guaiac based) and reversed passive haemagglutination (RPHA) tests. RPHA was interpreted according to two positivity thresholds (+ or +/-).

Methods—

Attenders performed both tests. Subjects with a positive FOBT test were invited to have a complete exploration of the colon. The total costs for every 10 000 screened subjects and costs for each unit of result (screened subject, or patient with adenoma/s or cancer detected) were calculated for both tests.

Results—

8353 subjects were enrolled. A total of 2109 repeated screening after two years. RPHA(+ and +/-) showed the highest and RPHA(+) the lowest positivity rate at first screening. The Hemoccult positivity rate was highest at repeat screening. Total costs of screening by RPHA(+ and +/-) were highest as this method had the highest recall rate. Screening by RPHA(+) was the least costly. Costs for each screened subject were highest for RPHA(+ and +/-) and lowest for RPHA(+). Costs for each cancer detected were lowest for RPHA(+) and highest for Hemoccult or RPHA(+ and +/-) in subjects aged > 49 or < 50, respectively. Costs for subjects with detected adenoma/s of > 9 mm were lowest for RPHA(+ and +/-) and highest for Hemoccult. At repeat screening total costs of RPHA(+ and +/-) were lower than at first screening, whereas for each subject with cancer or adenoma/s costs were increased.

Conclusions—

Our data confirm that screening by RPHA is more cost effective than by Hemoccult.
Interval Breast Cancers in the NHS Breast Screening Programme: Does the Current Definition Exclude Too Many?
Authors: Faux A M , Richardson D C , Lawrence G M , Wheaton M E , Wallisconsultant M G
Published: January 2017

Objectives—

To examine the impact of the definition of interval breast cancers on interval cancer rates arising from the prevalent (first) screening round.

Design—

Interval breast cancers arising from the prevalent (first) screening round at the Warwickshire, Solihull and Coventry Breast Screening Unit (17 April 1989 to 31 March 1992) were identified by comparison of data held at the unit with records at the West Midlands Cancer Intelligence Unit. Exclusion criteria used in National statistics were applied to this sample to quantify their impact on achieved interval cancer rates. The round lengths experienced by individual women at the unit were determined from the prevalent and incident invitation dates for 155 women with incident (re-screen) breast cancers detected in the second round.

Setting—

Warwickshire, Solihull and Coventry Breast Screening Unit. Subects—59 017 women screened between 17 April 1989 and 31 March 1992 with a negative screening result and 155 women with incident screen detected cancers.

Results—

A total of 278 interval cancers were identified, giving an overall rate from the prevalent screening round of 47.1/10 000 women screened. Of these, 213 met the criteria used in the definition of interval cancers for National statistics and were termed “core” interval cancers. The overall “core” interval rate was 36.1/10 000 women screened, similar to interval cancer rates found in the north west of United Kingdom. Thus applying commonly used exclusion criteria produced a 23.4% reduction in the apparent interval cancer rate, with the largest decrease resulting from the exclusion of cancers arising at 36 months or more from the last screen.

Conclusions—

The exclusion criteria used in the definition of interval cancers have a significant impact on observed interval cancer rates. Of particular concern is the exclusion in the current National definitions of cancers arising at 36 months or more from the last screen, which may mask a problem with significant implications for the success of the NHSBSP.
Globalization, Innovation, and Regional Development
Authors: Gordon Richard , Kimball Linda
Published: January 2017

Contemporary theoretical and empirical analysis of globalization and regionalization have remained relatively separate from each other: globalization is assumed precisely to transcend nation-state and region while industrial districts are presumed to be relatively self-contained. In contrast to these views, this paper examines the changing dynamics and new reciprocal interdependence of regional and innovation networks in Silicon Valley: integration with global networks has become essential to the long-term viability of regional innovation processes within the infamous region. The paper also summarizes how structural transformations have led to a new understanding of internationalization, transnationalization, and globalization in the world economy, and describes the problems with prevailing state-led counter movements to these processes. It then introduces a new model of problem-solving growth in a context of globalization, and suggests the need for the facilitative state whose role will be a new form of interstitial participation.
The Real Crisis of Silicon Valley: A Retrospective Perspective
Authors: Castells Manuel
Published: January 2017

Ten years ago, Silicon Valley was the leading pole in the world of high technology development and was headed for a potential regional crisis. Two major issues were at stake: first, “the applications gap,” the need to diffuse technological applications throughout society, beyond the limits of corporate uses and military equipment, to match the extraordinary development of technological innovation; and second, the lack of social conditions for Silicon Valley's entrepreneurs to constitute themselves into a visionary class able to restructure society around its interests, coinciding with the interests of development of such a technological innovation. The industry had to become demand-driven, rather that supply-induced.

Today, the Valley has rebounded and repositioned itself, without fulfilling the conditions of this “social” model. Uses of information technology exploded in all realms, along the lines of networking activities. But how to explain this phenomenon? The answer lies in the research and theorization that Richard Gordon conducted during the last decade of his life. Silicon Valley was, and is, a milieu of innovation. It was, and is, also a network of firms and entrepreneurs. But it is something else — in Richard Gordon's words, the collaborative partnerships that linked up the regional production system and the extra-regional environment in a context of global exchanges. Gordon's theory of Silicon Valley is the missing link without which various interpretations of this most important case of regional development are only partial.
Ifosfamide-Induced Neurotoxicity: A Case Report and Review of the Literature
Authors: Miller Lisa J. , Eaton Virginia E.
Published: January 2017

OBJECTIVE:

To review published abstracts, journal articles, and case reports for evidence of ifosfamide-induced neurotoxicity in both adult and pediatric populations.

DATA SOURCES:

Peer-reviewed journal articles (October 1985 through August 1990) obtained through a computer literature search, with subsequent bibliography scanning.

STUDY SELECTION:

We identified 34 reports that specifically addressed neurotoxicity related to ifosfamide therapy. By consensus of the authors, 8 of these reports were excluded due to a small study population, duplication or age of data.

DATA EXTRACTION:

Studies were assessed by the first author and verified by the second author. Several colleagues also contributed to the analysis.

DATA ANALYSIS:

Risk factors and mechanisms behind this potentially fatal neurotoxic reaction remain speculative and, in some cases, contradictory. The predictive capability of a published nomogram is restricted by differences in dosage regimens and encephalopathic classifications. Currently, the best prevention against neurotoxicity is little or no use of concurrent medications that have central nervous system effects.

CONCLUSIONS:

Further studies should address the influence of other nephrotoxic agents (e.g., cisplatin, aminoglycosides) on the incidence of ifosfamide-induced neurotoxicity.
A Computerized Intensive Care Unit Order-Writing Protocol
Authors: Halpern Neil A. , Thompson Robert E. , Greenstein Robert J.
Published: January 2017

OBJECTIVE:

To present a computerized intensive care unit order-writing protocol.

DESIGN:

Descriptive report.

SETTING:

Eight-bed surgical intensive care unit, Department of Surgery, Department of Veterans Affairs Medical Center, Bronx, NY.

METHODS:

IBM-based, computer network program that provides user-friendly, logical, and comprehensive organ-system order sequences for patient management.

RESULTS:

Since July 1988, an order program that stresses (1) improved and more efficient patient care, (2) the use of program-integrated automatic safety features, (3) the substitution of computer entry for handwriting, and (4) the assurance that physicians deliver obligatory care in a logical organ-system—based progression has been implemented.

CONCLUSIONS:

The order protocol system presented is simple to introduce and operate, has minimal training and technical requirements, and is demonstrably reliable.
Fulminant Hepatic Failure Possibly Related to Ciprofloxacin
Authors: Grassmick Bradford K. , Lehr Victoria Tutag , Sundareson Alistair S.
Published: January 2017

OBJECTIVE:

To report a case of hepatic failure in a patient who was receiving oral ciprofloxacin.

DATA SOURCES:

Case reports, review articles, and relevant laboratory studies identified by MEDLINE.

DATA EXTRACTION:

Data were abstracted from pertinent published sources by one author and reviewed by the remaining authors.

DATA SYNTHESIS:

A 66-year-old man was admitted for hip arthroplasty and developed fulminant hepatic failure during oral ciprofloxacin therapy. Ciprofloxacin was started on postoperative day 13 for treatment of a urinary tract infection. Over the next three days he became confused and hypoglycemic. His prothrombin time increased to >90 s. Serum aspartate aminotransferase and alanine aminotransferase concentrations were markedly elevated. The patient died on postoperative day 20. Postmortem examination of the liver revealed extensive centrilobular necrosis. A skin biopsy was consistent with a drug reaction. It is unknown whether the patient had received a quinolone compound in the past or had a history of exposure to hepatotoxins.

CONCLUSIONS:

It cannot be concluded that ciprofloxacin directly caused hepatic failure in this patient. It is possible that the drug evoked a hypersensitivity reaction or exacerbated a preexisting hepatotoxicity. A detailed patient history and evaluation of hepatic function should be obtained prior to initiating ciprofloxacin therapy. A nonquinolone antimicrobial may be a safer alternative for patients with hepatic dysfunction.
Drug- and Chemical-Induced Aseptic Meningitis: A Review of the Literature
Authors: Marinac Jacqueline S.
Published: January 2017

OBJECTIVE:

The primary objective of this article is to provide readers with case reports of drug- or chemical-induced aseptic meningitis (DCAM) described in the medical literature. Background information regarding the classification of DCAM, incidence, proposed mechanisms, associated risk factors, clinical management, and sequelae is presented.

DATA SOURCES:

A MEDLINE search was used to identify pertinent background literature and case reports of DCAM.

DATA EXTRACTION:

All case reports of DCAM involve anecdotal information. A critical analysis of a causal relationship to the implicated drug or chemical and the appearance of meningeal involvement is presented. Animal data are included when pertinent.

DATA SYNTHESIS:

DCAM is a rare adverse event associated with numerous agents. Patients present with a variety of clinical signs and symptoms and laboratory findings of cerebral spinal fluid, when obtained, vary greatly. Most patients fully recover without sequelae.

CONCLUSIONS:

Numerous drugs and chemicals have been implicated in the medical literature as producing DCAM. Two proposed mechanisms of DCAM have been theorized: a delayed hypersensitivity-type reaction and direct meningeal irritation. The nonsteroidal antiinflammatory drugs, certain antibiotics, radiographic agents, and muromonab-CD3 have been most frequently implicated. There appears to be an association between the occurrence of the hypersensitivity-type reactions and underlying collagen vascular or rheumatologic disease.
Methemoglobinemia in a Patient Undergoing Gastrointestinal Endoscopy
Authors: Bhutani Anjali , Bhutani Manoop S. , Patel Rajesh
Published: January 2017

OBJECTIVE:

To report a case of methemoglobinemia induced by benzocaine in a patient undergoing gastrointestinal endoscopy.

CASE SUMMARY:

Before undergoing an upper gastrointestinal endoscopy, a 15-year-old girl received 20% benzocaine as a spray, to locally anesthetize the pharyngeal mucosa. Thirty minutes after the endoscopy, the patient suddenly became cyanotic, short of breath, and comatose. She was intubated and transferred to the intensive care unit. Her blood methemoglobin concentration was 54 percent. The patient was treated with intravenous methylene blue. Four hours later she was extubated. She was alert, awake, and asymptomatic.

DISCUSSION:

This is the fourth reported case of methemoglobinemia induced by benzocaine spray in patients undergoing gastrointestinal endoscopy. Pathways for the formation of methemoglobin in the body are reviewed. Intravenous methylene blue is the drug of choice for this condition, and produces rapid and dramatic reversal of methemoglobinemia.

CONCLUSIONS:

It is common to use benzocaine spray prior to upper gastrointestinal endoscopy. Benzocaine rarely induces methemoglobinemia in these patients. Prompt diagnosis and treatment with intravenous methylene blue is warranted in such cases.
Randomized, Controlled Trial of Transdermal Clonidine for Smoking Cessation
Authors: Hilleman Daniel E. , Mohiuddin Syed M. , Delcore Michael G. , Lucas B. Daniel
Published: January 2017

OBJECTIVE:

To determine the efficacy and safety of clonidine versus placebo in smoking cessation.

DESIGN:

Single-center, randomized, double-blind, parallel-design comparison of transdermal clonidine with behavior modification, transdermal clonidine without behavior modification, placebo with behavior modification, and placebo without behavior modification.

SETTING:

Outpatient, university-based ambulatory care facility.

PATIENTS:

One hundred fifty generally healthy, highly nicotine-dependent cigarette smokers.

INTERVENTION:

Clonidine was given as the transdermal patch initiated 72 hours prior to smoking-cessation attempts and continued for six weeks thereafter. Clonidine was given at a dose of 0.2 mg/d for patients weighing more than 150 pounds (>67.5 kg) and at a dose of 0.1 mg/d for patients weighing less than 150 pounds (<67.5 kg). Behavior modification consisted of a total of 12 one-hour structured group training sessions. Patients not receiving behavior modification received printed material, which included the “Help Quit Kit” and the “I Quit Kit” from the American Cancer Society.

MAIN OUTCOME MEASURES:

Smoking-cessation rates were assessed at 6, 12, 24, and 52 weeks of follow-up. In addition, adverse reactions to clonidine or placebo were evaluated.

RESULTS:

Clonidine with behavior modification was statistically superior to the other three treatment groups but only at 6 weeks of follow-up. There were no differences in smoking-cessation rates among any of the treatment groups at any other follow-up intervals. Patients receiving behavior modification, regardless of whether they received clonidine, had better quit rates than patients not receiving behavior modification at all follow-up times except 52 weeks. Women receiving clonidine had significantly better quit rates than men receiving clonidine at all follow-up visits. Clonidine was associated with a significantly higher incidence of adverse effects than placebo (52 vs. 11 percent). However, the number of smokers withdrawing from the study was not greater with clonidine compared with placebo (9 vs. 7 percent, respectively).

CONCLUSIONS:

Clonidine is probably not effective as a pharmacologic adjunct to behavior modification in smoking cessation. It may have a potential role in women smokers who do-not respond to or cannot tolerate more traditional smoking-cessation therapies.
Interpretation of Simulation Studies for Efficient Estimation of Population Pharmacokinetic Parameters
Authors: Ette Ene I. , Kelman Andrew W. , Howie Catherine A. , Whiting Brian
Published: January 2017

OBJECTIVE:

To develop new approaches for evaluating results obtained from simulation studies used to determine sampling strategies for efficient estimation of population pharmacokinetic parameters.

METHODS:

One-compartment kinetics with intravenous bolus injection was assumed and the simulated data (one observation made on each experimental unit [human subject or animal]), were analyzed using NONMEM. Several approaches were used to judge the efficiency of parameter estimation. These included: (1) individual and joint confidence intervals (CIs) coverage for parameter estimates that were computed in a manner that would reveal the influence of bias and standard error (SE) on interval estimates; (2) percent prediction error (%PE) approach; (3) the incidence of high pair-wise correlations; and (4) a design number approach. The design number (Φ) is a new statistic that provides a composite measure of accuracy and precision (using SE).

RESULTS:

The %PE approach is useful only in examining the efficiency of estimation of a parameter considered independently. The joint CI coverage approach permitted assessment of the accuracy and reliability of all model parameter estimates. The Φ approach is an efficient method of achieving an accurate estimate of parameter(s) with good precision. Both the Φ for individual parameter estimation and the overall Φ for the estimation of model parameters led to optimal experimental design.

CONCLUSIONS:

Application of these approaches to the analyses of the results of the study was found useful in determining the best sampling design (from a series of two sampling times designs within a study) for efficient estimation of population pharmacokinetic parameters.
Acetylcysteine as a Cytoprotective Antioxidant in Patients with Severe Sepsis: Potential New Use for an Old Drug
Authors: Dasta Joseph F. , Henderson Alan , Hayes Peter
Published: January 2017

OBJECTIVE:

To stimulate debate regarding a potential new use for acetylcysteine as a cellular antioxidant in severely septic patients with systemic inflammatory response syndrome (SIRS).

DATA SOURCES:

A MEDLINE review of published animal, human, and laboratory studies relating to the cytopathogenic effects of active radicals in SIRS and the protective effects of acetylcysteine and glutathione.

STUDY SELECTION:

Few studies were available so all studies pertinent to the objective were reviewed.

DATA EXTRACTION:

Clinical and basic science data from the available trials of the effects of acetylcysteine on active radical production or active radical cell injury were extrapolated to predict the effect of acetylcysteine on human sepsis.

DATA SYNTHESIS:

Severe sepsis is a major cause of SIRS. Much of the cellular injury associated with SIRS is mediated by active radicals produced by inflammatory cells that overwhelm endogenous antioxidants. Reduced glutathione is a crucial intracellular antioxidant that becomes depleted during SIRS. Regeneration of glutathione can be achieved by acetylcysteine, which unlike glutathione itself penetrates cells. In animal models of sepsis and lung injury, acetylcysteine mitigates the cytopathologic effects of SIRS. In humans, clinical benefit has been demonstrated in the SIRS of established fulminant hepatic failure.

CONCLUSIONS:

The data do not as yet lead to any firm conclusions regarding the value of acetylcysteine in the management of SIRS in severe sepsis. The animal and human studies are, however, sufficiently encouraging to warrant formal trials to test the hypothesis that acetylcysteine therapy has a cytoprotective effect in sepsis.
Comparison of Fluid Volumes with Whole Bowel Irrigation in a Simulated Overdose of Ibuprofen
Authors: Olsen Keith M. , Gurley Bill J. , Davis George A. , Archer Scott R. , Ma Frank H. , Ackerman Bruce H.
Published: January 2017

Objective:

To determine the effect of 2 different fluid volumes of polyethylene glycol whole bowel irrigation (WBI) solution on absorption of an ingested toxin in a simulated overdose model.

Design:

Prospective, randomized, crossover trial.

Setting:

Clinical research unit.

Participants:

Nine adult men.

Interventions:

On 2 separate days, volunteers ingested approximately 75 mg/kg of ibuprofen. In treatment 1, 30 minutes after ingestion of ibuprofen, a 3-L WBI at 2 L/h was begun. This procedure was repeated in treatment 2 with an 8-L WBI administered at 2 L/h. Fourteen timed serum samples were collected prior to and after drug ingestion for a 24-hour period and analyzed for ibuprofen concentration. The peak serum concentration, time to peak concentration, total area under the serum concentration-time curve (AUC), clearance, and volume of distribution were compared.

Results:

The mean ± SD AUCs did not differ between the 3-L (1185.3 ± 216.9 mg·h/L) and 8-L (1153.5 ± 251.5 mg·h/L) treatments (p = 0.710). Time to peak serum concentration, peak serum concentration, clearance, and volume of distribution were comparable for the 2 treatments (p > 0.05).

Conclusions:

These data indicated that a total WBI volume of 3 L would be expected to perform as well as 8 L administered at the same rate. We recommend that further research define the optimal dose of WBI in acute ingestion of toxins.
Adjuvant Therapy of Node-Negative Breast Cancer
Authors: Hall Philip D. , Lesher Beth A. , Kneuper Hall Rayna
Published: January 2017

Objective:

To present the controversies regarding adjuvant cytotoxic chemotherapy or hormonal therapy in patients with node-negative breast cancer, and to evaluate the use of prognostic factors in identifying patients with node-negative breast cancer who will benefit from adjuvant therapy.

Data Source:

A MEDLINE search was performed to identify pertinent primary literature and review articles. Articles also were identified through Current Contents, textbooks, and bibliographies of selected articles.

Data Extraction:

The most recent clinical trials that evaluated cytotoxic chemotherapy or hormonal therapy in patients with node-negative breast cancer were chosen. Recent review articles and clinical trials that analyzed prognostic factors also were evaluated.

Data Synthesis:

The treatment of patients with node-negative breast cancer remains controversial. Approximately 60–80% of patients with this diagnosis will be alive 10 years after initial treatment without adjuvant therapy. The use of chemotherapy or hormonal therapy in node-negative disease increased after the 1988 National Cancer Institute Clinical Alert. Since that time, the research in node-negative breast cancer has focused on identifying prognostic factors and evaluating new treatment regimens. It is hoped that prognostic factors will help direct treatment decisions by identifying subgroups of patients who may benefit from adjuvant therapy. Prognostic factors currently being evaluated include tumor size, hormonal receptors, ploidy status, S-phase fraction, and cathepsin D.

Conclusions:

Many patients with node-negative breast cancer will be cured by local therapy alone. Even so, up to 58% of node-negative patients may develop recurrent disease. Reduction of breast cancer recurrence in patients with node-negative breast cancer has been documented as a result of adjuvant chemotherapy or tamoxifen. Of utmost priority is the identification of patients with node-negative breast cancer at highest risk for recurrence so that they may receive appropriate adjuvant therapy with curative intent, while sparing patients at lower risk for recurrence the toxic effects and financial burden incurred by unnecessary adjuvant treatment.
Recurrent Methicillin-Resistant Staphylococcus Aureus Osteomyelitis: Combination Antibiotic Therapy with Evaluation by Serum Bactericidal Titers
Authors: Aspinall Sherrie L , Friedland David M , Yu Victor L , Rihs John D , Muder Robert R
Published: January 2017

Objective:

To report on a patient with recurrent methicillin-resistant Staphylococcus aureus (MRSA) osteomyelitis and bacteremia successfully treated with combination antibiotic therapy.

Case Summary:

Two sets of blood cultures from a 55-year-old man with fever, malaise, and low back pain grew MRSA. Radiologic studies of the spine showed bony changes consistent with osteomyelitis. Soon after completing 6 weeks of vancomycin, the patient experienced a recurrence of back pain. Laboratory values included an increase in the sedimentation rate to 53 mm/h and positive blood cultures for MRSA. Vancomycin, gentamicin, and rifampin were administered for 8 weeks. Serum inhibitory and bactericidal titers were more than 1:1024 for both the peak and trough concentrations. Radiologic studies of the spine showed healing osteomyelitis. Two years after completion of antibiotic therapy, the infection has not recurred.

Discussion:

Antibiotic therapy alone was attempted because the patient was considered a risky surgical candidate. Serum inhibitory and bactericidal titers documented the high in vivo activity of the vancomycin, gentamicin, and rifampin combination. Initiation of vancomycin therapy led to disappearance of the fever and back pain. Cure was documented by sustained normalization of the erythrocyte sedimentation rate and radiologic evidence of healing.

Conclusions:

Combination antibiotic therapy with vancomycin, rifampin, and low-dose gentamicin (1 mg/kg q12h) may be useful for deep-seated tissue infection caused by MRSA.
Exogenous Surfactant Use in Neonates
Authors: Ishisaka Denis Y
Published: January 2017

OBJECTIVE:

To review exogenous surfactant use in the treatment of respiratory distress syndrome (RDS) in premature neonates.

DATA SOURCES:

A MEDLINE search and extensive review of journals was conducted to identify the information for this review from 1983 to 1995 using the following key words: prematurity, surfactant, clinical trials, beractant, Survanta, colfosceril, Exosurf, and neonatal respiratory distress syndrome.

STUDY SELECTION AND DATA EXTRACTION:

All articles were considered for possible inclusion in the review. Emphasis was placed on controlled studies involving beractant and colfosceril palmitate.

DATA SYNTHESIS:

Results of published clinical trials using beractant or colfosceril palmitate in premature infants at risk for RDS have shown improvement in the need for supplemental oxygen and ventilatory support over the course of RDS and a reduction in pneumothorax. However, there was little impact on the incidence of intraventricular hemorrhage. Clinical trials studying the treatment of established RDS have also shown similar improvements. In a comparison of prophylactic versus late treatment, no distinct advantage of preventive treatment was found, except among infants less than 26–28 weeks gestation. Single- versus multiple-dose studies have shown no specific advantage of more than two doses of colfosceril palmitate. A comparison trial of beractant and colfosceril palmitate has shown no difference in outcome. Long-term follow-up studies have been encouraging among infants being treated with exogenous surfactant.

CONCLUSIONS:

The use of beractant and colfosceril palmitate in premature infants has clearly decreased morbidity and mortality associated with RDS. Only one trial has compared the efficacy of beractant with that of colfosceril in the treatment of RDS. There does not appear to be a distinct advantage of one product over another. Early treatment of infants at highest risk for RDS, those less than 26–28 weeks gestation, seems to be beneficial over waiting for RDS to progress in severity. Further research needs to be performed to determine the optimal dosing and timing of these agents, as well as comparative trials studying efficacy. Criteria for use of these products need to be further defined to decrease the incidence of unnecessary treatment.
The Cholesterol Controversy
Authors: Geurian Kristi L
Published: January 2017

OBJECJIVE:

To provide information about the controversy associated with lowering of cholesterol concentrations to preventcoronary heartdisease(CHD).

DATA SOURCFS:

Studies, review articles, and editorials identified from MEDLINE searches (from 1966 to 1995) and bibliographies of identified articles.

STUDY SELECTION:

Studies, review articles, and editorials addressing controversial issues related to cholesterol lowering.

DATA EXTRACTION:

Pertinent information was selected and the data synthesized into a review format.

DATA SYNTHESIS:

Hypercholesterolemia is a well-known CHD risk factor. Reduction of serum cholesterol concentrations has been shown to reduce the incidence of CHD. Unfortunately, cholesterol lowering also appears to increase the risk for cancer, accidental and violent death, stroke, and oddly enough, CHD when certain medications are used.

CONCLUSIONS:

Significant reductions in serum cholesterol concentrations can be achieved with cholesterol-lowering interventions. However, the benefits associated with cholesterol reduction may not outweigh the risks in all patients with hypercholesterolemia. Cholesterol-lowering interventions should be recommended with caution in patients at increased risk for cancer, stroke, and depression. Caution should also be used when recommending fibric acid derivatives for patients with existing CHD.
Severe Vaginal Bleeding Associated with Recombinant Interferon Beta-1B
Authors: Pakulski Leslie A , DiMarco Linda M
Published: January 2017

OBJECTIVE:

To report a case of severe vaginal bleeding associated with interferon beta-1b (IFN-β).

CASE SUMMARY:

A 19-year-old white woman diagnosed with multiple sclerosis was treated with IFN-β 4 million IU every other day for 1 month. After 1 month, the dosage was increased to 8 million IU. The patient subsequently experienced severe vaginal bleeding. Because her hemoglobin was 3.9 g/dL, she was admitted to the hospital for treatment and observation. IFN-β was discontinued and she was treated with conjugated estrogens and received 2 units of packed red blood cells. The bleeding ceased and the patient was discharged in stable condition.

DISCUSSION:

Menstrual disorders of mild-to-moderate severity were reported during clinical trials with IFN-β. This is the first case report regarding severe vaginal bleeding probably associated with IFN-β. The mechanism for development of IFN-β-reiated menstrual disorders is unknown.

CONCLUSIONS:

Reports of menstrual disorders associated with recombinant IFN-β are rare; however, clinicians should be aware that this complication can occur. Should menstrual disorders occur with no other etiologic factors identified, IFN-β should be discontinued, with improvement expected shortly thereafter.
Tissue Oxygenation and Skin Blood Flow in the Diabetic Foot: Responses to Cutaneous Warming
Authors: Boyko Edward J. , Ahroni Jessie H. , Stensel Victoria L.
Published: January 2017

We previously reported an unexpected statistically significant decline in the mean transcutaneous partial pressure of oxygen (TcPO2) with cutaneous warming from 37°C to 44°C on the plantar diabetic foot, as opposed to the expected increase seen at the dorsal sites. To elucidate this relationship we compared changes with cutaneous warming in TcPO2 and skin circulation measured by laser Doppler flowmetry on the right plantar foot surface of 20 consecutive subjects.

Neuropathy by monofilament testing was present in 55% of the cases. Right dorsal foot TcPO2 increased with cutaneous warming from 37°C to 44° by a mean change of +43.6 ± 20.7 mmHg (± standard deviation) in 95% of the cases. In 42% of cases right plantar first metatarsal head TcPO2 fell with warming from 37°C to 44°C by a mean change of −10.7 ± 7.6 mmHg. In the remaining 58% of cases right plantar first metatarsal head TcPO2 rose by 6.8 ± 6.3 mmHg. In 95% of cases right plantar great toe laser Doppler perfusion units (LDPU) increased with warming from 36°C to 44°C by a mean change of +50.4 ± 37.1. Blood flow measured by laser Doppler flowmetry increased in 95% of the subjects with heating. The finding that blood flow was increased with warming contradicts the hypothesis that arterioles in the plantar great toe cannot vasodilate in response to thermal stimuli.

This finding supports the hypothesis that the decline in TcPO2 with warming might be due to an increase in epidermal oxygen consumption that exceeds the increase in oxygen delivery due to increased blood flow. The pathological mechanisms behind microvascular dysfunction in skin microcirculation in the diabetic foot need further investigation.
Benefits of Early Prosthetic Management of Transtibial Amputees: A Prospective Clinical Study of a Prefabricated Prosthesis
Authors: Schon Lew C. , Short Kelly W. , Soupiou Olga , Noll Kenneth , Rheinstein John
Published: January 2017

To evaluate the use of an immediate postoperative prosthesis (IPOP) for transtibial amputees, we compared patient outcomes from a prospective clinical study of 19 patients managed with an IPOP with those of a retrospective review of a matched historic control group of 23 patients managed with standard soft dressings. Data were analyzed with the Student's t-test, and significance was set at P=0.05. The IPOP patients had no surgical revisions, whereas the patients with standard soft dressings had 11. This was a significant difference. IPOP patients also had significantly fewer postoperative complications and shorter times to custom prosthesis than did controls.
Elongation Behavior of Calcaneofibular and Cervical Ligaments in a Closed Kinetic Chain: Pathomechanics of Lateral Hindfoot Instability
Authors: Martin Lewis P. , Wayne Jennifer S. , Owen John R. , Smith Robert T. , Martin Sidney N. , Adelaar Robert S.
Published: January 2017

Numerous reconstructive procedures are performed to correct both ankle and subtalar instability after trauma although the precise pathology which results in this chronic instability and pain is not yet known. This study examined the role of the calcaneofibular (CLFL) and cervical ligaments (CRVL) during physiologic loading and demonstrated the effect of CLFL deficiency on the CRVL. Talar and subtalar tilt as well as inversion range of motion before and after CLFL sectioning were studied. Eleven osteoligamentous fresh frozen cadaver legs were used in which each foot was taken through six positions: neutral, 35° plantarflexion, dorsiflexion, inversion, plantarflexion-inversion, and dorsiflexion-inversion. The CLFL and CRVL stretched the greatest in dorsiflexion-inversion. The most Interesting finding was that the CRVL was elongated relative to neutral in all other test positions of the foot. However, the CLFL was shortened relative to neutral in plantarflexion and plantarflexion-inversion. In the CLFL deficient state, CRVL ratios demonstrated significant increases in length of the CRVL. Talar tilt increased on average more than 9° with CLFL deficiency (p<0.008) while subtalar tilt did not change significantly. The maximum tibiocalcaneal angle, recorded for dorsiflexion-inversion, increased more than 5° after sectioning the CLFL (p<0.05).
Outcome of Surgical Treatment of Tarsal Tunnel Syndrome
Authors: Sammarco G. James , Chang Laurette
Published: January 2017

One hundred and eight ankles in 72 patients were evaluated from July 1986 to July 1997 with clinical findings and positive electrodiagnostic studies of tarsal tunnel syndrome. Clinical data included physical findings, subjective complaints, duration of symptoms, trauma history, steroid injections, nonsteroidal use and workman's compensation involvement. Associated medical conditions included diabetes, back pain and arthritis. Sixty-two patients underwent tarsal tunnel release, with 13 of them bilateral. There were 44 females and 18 males, 35 right feet and 40 left feet. The average age was 49 years. Preoperative symptom duration was 31 months. Average length of follow-up was 58 months. Average time for return to usual activity was nine months. All patients had at least a 12-month follow-up, and compared with both (Maryland Foot Score) MFS and AOFAS postoperative scores. Preoperative MFS scores obtained prior to 1994, were 61/100 (average), and postoperative MFS scores were 80/100 (average). Postoperative AOFAS scores were 80/100 (average). Patients with symptoms less than one year had postoperative MFS/AOFAS scores significantly higher than those with symptoms greater than one year. The most common surgical findings included arterial vascular leashes indenting the nerve and scarring about the nerve. Varicosities and space occupying lesions were present also. The outcome of surgery was not affected by the presence or absence of trauma. Patients with tarsal tunnel syndrome warrant surgery when significant symptoms do not respond to conservative management. Meticulous surgical technique must be followed. Improvement in foot scores is predictable even when a discrete space-occupying lesion is not present and when symptoms have been present for periods of greater than one year.
Biomechanical Comparison of Two Fixation Methods for First Metatarsophalangeal Joint Arthrodesis
Authors: Molloy Sean , Burkhart Bradd G. , Jasper Louis E. , Solan Matthew C. , Campbell John. T. , Belkoff Stephen M.
Published: January 2017

Purpose:

The aim of this study was to compare the mechanical stability of two methods of fixation for arthrodesis of the hallux metatarsophalangeal joint: a technique using an intramedullary screw and a standard technique using crossed interfragmentary compression screws.

Methodology:

The metatarsophalangeal joint was mechanically evaluated in cantilever bending using a servohydraulic testing machine. Differences in stiffness and strength parameters between the two techniques were checked for significance (P<0.05) using a paired t-test.

Results:

Fixation provided by the intramedullary screw was stiffer and stronger than that from crossed compression screws.

Conclusions:

The stronger and stiffer intramedullary screw technique offers mechanical advantages over the crossed interfragmentary screw technique.