Medical Era Research Articles

Walking the tightrope

Most Canadians have long-standing familiarity with images of Jean Francois Gravelet crossing the Niagara River (Niagara, Ontario) on a tightrope on June 30, 1855. Pictures of the famous incident show the ‘Great Blondin’, as he was known, balanced precariously over the Niagara River Gorge. In fact, the Great Blondin made many crossings of ever increasing difficulty, either by walking, running or cycling. On one occasion, he pushed a wheelbarrow to the centre of the rope where he stopped, cooked and ate an omelette made on a small stove. The culmination of his efforts came with carrying his manager across in a special shoulder harness. We have chosen Blondin’s feats as a metaphor for the hazards of drug prescribing for children. How good is this metaphor? Even funambulists, or tightrope walkers, do not venture forth without some substantial aids. For starters, they have the fundamental support of a stout rope or wire, and a balancing bar that serves to distribute the risk. Often they enjoy the additional security afforded by a safety net. Those who prescribe drugs for infants and children enjoy far less tangible support and, in many cases, lack the safety net that might be provided through research. It is a fact almost as astonishing as the achievements of Blondin that, 100 years into the modern medical era, children are still treated in most parts of the world without the benefit of adequate scientific evidence to support therapeutic decisions. Unfortunately, prescribers have been left to be guided by anecdotal advice and their own therapeutic intuition. Not only are prescribers deprived of new therapeutic guidance, they must frequently fall back on knowledge acquired at an earlier time, which is almost certainly past its ‘best before date’. Many have estimated that medical knowledge expires at a rate of 25% per decade after the time that it is acquired. Of course, some might argue that at least an additional 25% of medical knowledge is incorrect at the moment when teaching occurs. Can we do more to protect infants and children who require modern therapy? Daredevilry in therapeutics is not an admirable activity, but neither is therapeutic nihilism defensible. All practitioners who serve childhood populations can and must contribute to the creation of new knowledge that will guide future treatment guidelines. Their impact will come through participation in clinical trials addressing major therapeutic questions, and through careful objective reporting of adverse events in keeping with the approaches highlighted by two of the articles in the present theme issue. Two common scenarios of therapeutic interventions in children are also addressed in the present issue. One is vaccination pain management, where we learn that pharmacological intervention is effective, but even more effective if combined with non-pharmacological approaches. The other is the use of acetaminophen. In fact, it makes us nervous to know that we know so little about this old remedy. Above all, physicians and pharmacists who care for children must become more effective advocates for their charges. One hundred years of waiting for improvements in the environment for a choice in childhood therapies is simply too long. A society that can afford billions of dollars for the purchase of fighter jets can surely afford to provide better evidence-based care for its children, and indirectly for the more than two billion children living outside our borders. The continuing feat of attempting to walk the paediatric therapeutic tightrope will not be applauded by future generations who will be left deprived of safe and effective treatments.

Invasive fungal sinusitis in patients with hematological malignancy: 15 years experience in a single university hospital in Taiwan

BackgroundRisk factors and outcomes in hematological patients who acquire invasive fungal sinusitis (IFS) are infrequently reported in the modern medical era.MethodA retrospective study of hospitalized patients with hematological disease was conducted at National Taiwan University Hospital between January 1995 and December 2009.ResultsClinical characteristics and outcomes with their associated radiographic and microbiological findings were analyzed. Forty-six patients with IFS and 64 patients with chronic non-invasive sinusitis were enrolled as comparsion. IFS developed more commonly in patients with acute myeloid leukemia (AML) and with prolonged neutropenia (absolute neutrophil count less than 500/mm3 for more than 10 days) (p < 0.001). Aspergillus flavus was the most common pathogen isolated (44%). Serum Aspergillus galactomannan antigen was elevated in seven of eleven patients (64%) with IFS caused by aspergillosis but negative for all three patients with mucormycosis. Bony erosion and extra-sinus infiltration was found in 15 of 46 (33%) patients on imaging. Overall, 19 of 46 patients (41.3%) died within 6 weeks. Patients with disease subtype of AML (p = 0.044; Odds Ratio [OR], 5.84; 95% confidence interval [95% CI], 1.02-30.56) and refractory leukemia status (p = 0.05; OR, 4.27; 95% CI, 1.003-18.15) had worse prognosis. Multivariate analysis identified surgical debridement as an independent good prognostic factor (p = 0.047) in patients with IFS.ConclusionsPatients of AML with prolonged neutropenia (> 10 days) had significantly higher risk of IFS. Early introduction of anti-fungal agent and aggressive surgical debridement potentially decrease morbidity and mortality in high risk patients with IFS.

A New Appraisal of Combined Treatments for PTSD in the Era of Psychotherapy Adjunctive Medications

Combinations of pharmacologic and psychosocial interventions have garnered much enthusiasm over the past 30 years. Unfortunately, this enthusiasm is often disproportionate to the empirical support for these approaches. However, a new wave of basic, translational, and clinical research has demonstrated that the use of some substances—themselves having little to no therapeutic benefit—may help to increase or potentiate the effectiveness of certain psychological treatments. While these drugs have shown promise in the treatment of other anxiety disorders, they have yet to be thoroughly studied in PTSD populations. This article will describe the movement towards the use of pharmacologic substances as adjuncts to psychotherapy and will describe the rationale, initial support, implications, and future directions of their use in the treatment of PTSD.

Psychopharmacology and Mental Health Practice: An Important Alliance

Many mental health professionals are concerned about an increasingly "medicalized" society, driven in part by significant growth in biomedical research and biological perspectives on psychological disorders. The modern medical era, which has endorsed reductionism as the principal way of viewing many health conditions, offers many options for treating psychiatric diagnoses. Pharmacology is a major influence in psychiatric treatment decisions, and despite questions by mental health practitioners about reliance on drugs (Murray, 2009), psychopharmacology provides helpful alternatives. However, pharmacological options for mental health concerns should not be considered in isolation, and the use of drug treatments for cognitive, emotional, and behavioral disorders warrants careful contextual analysis. Mental health practitioners are encouraged to view pharmacology within a comprehensive sociohistorical framework that recognizes the value of a reductionist perspective as part of psychology's rich cognitive and behavioral contributions to contemporary mental health assessment and intervention.

Multiple Sclerosis Therapeutic Pipeline: Opportunities and Challenges

The year 2010 marked the beginning of the era of oral medications for the treatment of multiple sclerosis, with the approval of dalfampridine to improve walking and fingolimod as the first oral disease-modifying agent. This review provides an overview of these and other emerging therapies, with an emphasis on the opportunities for new treatment paradigms they have the potential to offer, followed by a discussion of the challenges they will pose in the new era of multiple sclerosis management. Therapeutics in late-stage development for MS include non-selective immunosupressants, targeted immune-modulators, and monoclonal antibodies. Oral agents including cladribine, teriflunomide, laquinimod, and dimethyl fumarate, as well as monoclonal antibodies alemtuzumab, daclizumab, and rituximab are considered. Potential side effects and adverse event monitoring, including opportunistic infections, emergent malignancies, and other systemic consequences of immunosuppression are discussed in a unified section. Challenges of optimally staging, sequencing, and combining treatments in the expanding multiple sclerosis armamentarium are discussed. This review emphasizes the multifactorial decision making that these new therapeutics will warrant in terms of patient selection and personalization/individualization of therapy, and the increasingly interdisciplinary approach that will be necessitated by the new generation of agents.

Histological and histochemical changes in placenta of diabetic pregnant females and its comparision with normal placenta

Objective To investigate the histological and histochemical changes in placenta of diabetic pregnant females and compare them with normal placenta. Methods The histological and histochemical features of 60 placenta, 30 obtained from normal pregnant females and 30 from diabetic pregnant females, were studied. These placenta were obtained from Department of Obstetrics and Gynaecology, GSVM Medical College Kanpur and ERA's Lucknow Medical College and Hospital Lucknow. Results On histological examination, the diabetic placenta showed increased syncytial knots, fibrinoid necrosis, trophoblastic basement membrane thickening, villous stromal fibrosis, villous oedema, crowding of villi, thickening of vessel wall and fibrin deposition. On histochemical study it was found that the PAS reactivity was stronger in diabetic placenta as compared to normal. Sudan Black reactivity was higher among diabetic placenta in comparison to normal placenta. Conclusions It is concluded that distinct histological and histochemical changes could be seen in placenta of diabetic pregnant females.

Pentalogy of Cantrell with a Single-Ventricle Cardiac Defect: Collaborative Management of a Complex Disease

We present a case of ectopia cordis with a complex single-ventricle congenital heart defect in association with pentalogy of Cantrell. Management by a skilled multidisciplinary team was critical for patient survival. Early fetal diagnosis and the use of advanced imaging techniques allowed adequate time for planning and identified critical anatomic details. Preserving the heart's natural covering, performing cardiac surgery without cardiopulmonary bypass, and using catheter intervention decreased the risk to the patient. Complete coverage of the defect was achieved using skin generated with tissue expanders. This case illustrates the importance of collaboration when caring for infants with critical, high-risk disease and highlights the increased potential for survival with complex ectopia cordis in the current medical era.

Intraarterial nimodipine for the treatment of symptomatic vasospasm after aneurysmal subarachnoid hemorrhage: A preliminary study

Despite dramatic advances in all medical era, cerebral vasospasm is still the major complication in patients with subarachnoid hemorrhage (SAH). The purpose of this study was to assess the influence of intraarterial (IA) nimodipine in the treatment of symptomatic vasospasm and in preventing neurological disabilities. We retrospectively reviewed 10 patients of SAH who received IA nimodipine in 15 procedures. The decision to perform angiography and endovascular treatment was based on the neurological examination, brain computed tomography (CT) and CT-angiography. The procedure reports, anesthesia records, neurological examination before and after the procedure, brain imaging and short- and long-term outcome were studied. The average dose of nimodipine was 2 mg. The median change in mean arterial pressure at 10 min was -10 mmHg. No significant change of heart rate was observed at 10 min. There was radiological improvement in 80% of the procedures. Neurological improvement was noted after eight out of 12 procedures when nimodipine was used as the sole treatment and after 10 out of 15, overall. Six patients clinically improved after the treatment and had good outcome. In one patient, an embolus caused fatal anterior and middle cerebral arteries infarction. There was no other neurological deficit or radiological abnormality due to the nimodipine treatment itself. Low-dose IA nimodipine is a valid adjunct for the endovascular treatment of cerebral vasospasm. Beneficial effects are achieved in some patients, prompting a prospective control study.

Razi's description and treatment of facial paralysis.

In the modern medical era, facial paralysis is linked with the name of Charles Bell. This disease, which is usually unilateral and is a peripheral facial palsy, causes facial muscle weakness in the affected side. Bell gave a complete description of the disease; but historically other physicians had described it several hundred years prior although it had been ignored for different reasons, such as the difficulty of the original text language. The first and the most famous of these physicians who described this disease was Mohammad Ibn Zakaryya Razi (Rhazes). In this article, we discuss his opinion.

Acute Migraine Therapy: New Drugs and New Approaches

Opinion StatementThe conceptual shift of our understanding of migraine from a vascular disorder to a brain disorder has dramatically altered the approach to the development of new medicines in the field. Current pharmacologic treatments of acute migraine consist of nonspecific and relatively specific agents. Migraine-specific drugs comprise two classes, the ergot alkaloid derivatives and the triptans, serotonin 5-HT1B/1D receptor agonists. The ergots, consisting of ergotamine and dihydroergotamine (DHE), are the oldest specific antimigraine drugs available and are considered relatively safe and effective. Ergotamine has been used less extensively because of its adverse effects; DHE is better tolerated. The triptan era, beginning in the 1990s, was a period of considerable change, although these medicines retained vasoconstrictor actions. New methods of delivering older drugs include orally inhaled DHE and the transdermal formulation of sumatriptan, both currently under study. Novel medicines being developed are targeted at neural sites of action. Serotonin 5-HT1F receptor agonists have proven effective in phase II studies and have no vascular actions. Calcitonin gene-related peptide (CGRP) receptor antagonists are another promising nonvasoconstrictor approach to treating acute migraine. Olcegepant (BIBN4096BS) and telcagepant (MK-0974) have been shown to be safe and effective in phase I, II, and (for telcagepant) phase III clinical trials. Other targets under investigation include glutamate (AMPA/kainate), TRPV1, prostanoid EP4, and nitric oxide synthase. With new neural targets and the potential for therapeutic advances, the next era of antimigraine medications is near.

Issues in cervical cancer incidence and treatment in HIV

Cervical disease burden continues to be especially high in HIV-infected women, even in the era of effective antiretroviral medications. This review discusses the multiple issues surrounding HIV-associated cervical cancer. Also, the unique treatment-related issues in HIV-associated cervical cancer are addressed. The incidence of invasive cervical cancer has remained stable in industrialized nations; however, it is only estimated in developing countries secondary to a relative lack of data collection and registries. Trends in HIV-associated cervical cancer have changed in the highly active antiretroviral therapy (HAART) era. Recent molecular pathways suggest that the natural progression of human papillomavirus infection, the causal agent in all cervical cancers, may be related to immune system dysfunction as well as HIV/human papillomavirus synergistic mechanisms. When highly active retroviral therapies are used, invasive cervical cancer treatments are impacted by concomitant drug toxicities that could potentially limit therapeutic benefit of either HAART or the standard of care treatment for locally advanced cervical cancer, concomitant chemoradiotherapy. The significance and care of the patient with invasive cervical cancer is becoming a geographically relevant phenomenon such that it may be time to re-address the global definition. Further studies in treatment issues and drug-drug interactions with cervical cancer treatments in the setting of HIV are paramount.

Integrated optical tools for minimally invasive diagnosis and treatment at gastrointestinal endoscopy

Over the past two decades, the bulk of gastrointestinal (GI) endoscopic procedures has shifted away from diagnostic and therapeutic interventions for symptomatic disease toward cancer prevention in asymptomatic patients. This shift has resulted largely from a decrease in the incidence of peptic ulcer disease in the era of antisecretory medications coupled with emerging evidence for the efficacy of endoscopic detection and eradication of dysplasia, a histopathological biomarker widely accepted as a precursor to cancer. This shift has been accompanied by a drive toward minimally-invasive, in situ optical diagnostic technologies that help assess the mucosa for cellular changes that relate to dysplasia. Two competing but complementary approaches have been pursued. The first approach is based on broad-view targeting of "areas of interest" or "red flags." These broad-view technologies include standard white light endoscopy (WLE), high-definition endoscopy (HD), and "electronic" chromoendoscopy (narrow-band-type imaging). The second approach is based on multiple small area or point-source (meso/micro) measurements, which can be either machine (spectroscopy) or human-interpreted (endomicroscopy, magnification endoscopy), much as histopatholgy slides are. In this paper we present our experience with the development and testing of a set of familiar but "smarter" standard tissue-sampling tools that can be routinely employed during screening/surveillance endoscopy. These tools have been designed to incorporate fiberoptic probes that can mediate spectroscopy or endomicroscopy. We demonstrate the value of such tools by assessing their preliminary performance from several ongoing clinical studies. Our results have shown promise for a new generation of integrated optical tools for a variety of screening/surveillance applications during GI endoscopy. Integrated devices should prove invaluable for dysplasia surveillance strategies that currently result in large numbers of benign biopsies, which are of little clinical consequence, including screening for colorectal polyps and surveillance of "flat" dysplasia such as Barrett's esophagus and chronic colitis due to inflammatory bowel diseases.

Treatment of Acute Retinal Necrosis

To compare outcomes from patients with acute retinal necrosis (ARN) treated in the acyclovir-only era with those treated in the era of newer antiviral therapies, identify variables affecting outcomes in ARN, and evaluate strategies for fellow eye prophylaxis. Multicenter, nonrandomized, retrospective, interventional series. A cohort of 58 patients diagnosed with ARN by a retina specialist at 1 of 4 referral centers between 1981 and 2008. The cohort was divided into 2 subgroups: patients treated during the acyclovir-only era (n = 36) and patients treated during the current era of newer antiviral medications (n = 22). Intravenous, oral, or intravitreal antiviral medications, including acyclovir, valacyclovir, famciclovir, valganciclovir, ganciclovir, and foscarnet; prophylactic laser retinopexy; aspirin; oral steroids. Visual acuity, retinal detachment, and fellow eye involvement. A wide range and combination of antiviral agents are currently used for initial and long-term treatment of ARN. Outcomes from the newer antivirals era were similar to those achieved during the acyclovir-only era. In both groups, the incidence of 20/200 or worse visual acuity was 24% per person-year (P = 0.91). The prevalence of retinal detachment was approximately 50% in each group (P = 0.59). No variables, including prophylactic laser retinopexy, were associated with risk of retinal detachment. Two patients (3.4%) developed ARN in the initially unaffected eye. Current treatment trends vary widely, including single agents or combinations of oral, intravenous, and intravitreal agents. Differing strategies did not affect outcomes. The final visual acuity in ARN was generally poor. Retinal detachment was common and could neither be predicted nor prevented. Development of ARN in the unaffected fellow eye occurred rarely. Long-term oral antiviral treatment strategies varied with unclear relative efficacy. Proprietary or commercial disclosure may be found after the references.

Unexplained Graft Dysfunction after Heart Transplantation—Role of Novel Molecular Expression Test Score and QTc-Interval: A Case Report

In the current era of immunosuppressive medications there is increased observed incidence of graft dysfunction in the absence of known histological criteria of rejection after heart transplantation. A noninvasive molecular expression diagnostic test was developed and validated to rule out histological acute cellular rejection. In this paper we present for the first time, longitudinal pattern of changes in this novel diagnostic test score along with QTc-interval in a patient who was admitted with unexplained graft dysfunction. Patient presented with graft failure with negative findings on all known criteria of rejection including acute cellular rejection, antibody mediated rejection and cardiac allograft vasculopathy. The molecular expression test score showed gradual increase and QTc-interval showed gradual prolongation with the gradual decline in graft function. This paper exemplifies that in patients presenting with unexplained graft dysfunction, GEP test score and QTc-interval correlate with the changes in the graft function.

New York Heart Association functional class predicts exercise parameters in the current era

The New York Heart Association (NYHA) functional class is a subjective estimate of a patient's functional ability based on symptoms that do not always correlate with the objective estimate of functional capacity, peak oxygen consumption (peak V(O2)). In addition, relationships between these 2 measurements have not been examined in the current medical era when patients are using beta-blockers, aldosterone antagonists, and cardiac resynchronization therapy (CRT). Using baseline data from the HF-ACTION (Heart Failure and A Controlled Trial Investigating Outcomes of Exercise TraiNing) study, we examined this relationship. One thousand seven hundred fifty-eight patients underwent a symptom-limited metabolic stress test and stopped exercise due to dyspnea or fatigue. The relationship between NYHA functional class and peak V(O2) was examined. In addition, the effects of beta-blockers, aldosterone antagonists, and CRT therapy on these relationships were compared. The NYHA II patients have a significantly higher peak Vo(2) (16.1 +/- 4.6 vs 13.0 +/- 4.2 mL/kg per minute), a lower ventilation (Ve)/V(CO2) slope (32.8 +/- 7.7 vs 36.8 +/- 10.4), and a longer duration of exercise (11.0 +/- 3.9 vs 8.0 +/- 3.4 minutes) than NYHA III/IV patients. Within each functional class, there was no difference in any of the exercise parameters between patients on or off of beta-blockers, aldosterone antagonists, or CRT therapy. Finally, with increasing age, a significant difference in peak Vo(2), Ve/V(CO2) slope, and exercise time was found. For patients being treated with current medical therapy, there still is a difference in true functional capacity between NYHA functional class II and III/IV patients. However, within each NYHA functional class, the presence or absence or contemporary heart failure therapies does not alter exercise parameters.

TCT-249: Long-Term Results of Percutaneous Coronary Intervention of Chronic Total Occlusion in the Optimal Medical Therapy Era:

TCT-249: Long-Term Results of Percutaneous Coronary Intervention of Chronic Total Occlusion in the Optimal Medical Therapy Era:

Tumour Necrosis Factor-α Antagonists in the Management of Rheumatoid Arthritis in the Elderly

Rheumatoid arthritis (RA) is a chronic inflammatory disease that frequently affects people aged >or=65 years, causing significant impairment with pain and functional disability. Elderly RA patients have specific problems, including co-morbid diseases, numerous concomitant medications, greater number of damaged joints as a result of longer disease duration and often a more severe disease presentation in elderly-onset RA. These factors, together with an age-related decline in the immune defence mechanisms, make elderly patients more vulnerable. The new era of biologic medications has made intensive treatment of RA patients possible. Anti-tumour necrosis factor-alpha (anti-TNFalpha) agents can cause a dramatic improvement in disease activity and functional capacity, making complete remission of RA a possible target. TNFalpha has been shown to play an important role in both the healthy aging process and age-related diseases such as RA. Targeting this cytokine in elderly patients is therefore reasonable. However, it is not clear whether treatment effects can be reached to the same extent in both elderly and younger patients and whether anti-TNFalpha treatment specifically increases the risk of certain adverse events in elderly RA patients. This review discusses the currently available evidence relating to the efficacy and safety of anti-TNFalpha medication in RA patients aged >or=65 years treated in clinical trials and observational studies. Despite a slightly less robust effect in elderly patients, anti-TNFalpha treatment has a similar long-term efficacy in patients aged >or=65 years and patients aged <65 years. The majority of the study results showed that anti-TNFalpha treatment does not elevate the risk of infections beyond the risk found in age-matched controls. When a moderate increase in risk was found, this occurred equally in elderly and younger patients. Furthermore, whereas anti-TNFalpha agents were found to be relatively safe in the treatment of elderly RA patients, treatment with corticosteroids significantly elevated the risk of serious infections. Corticosteroids are frequently used in elderly patients, but the evidence suggests that preference should increasingly be given to anti-TNFalpha agents, for which the expected benefits will mostly outweigh the modestly increased risks of associated adverse events.

The Dawn of Anxiolytics: Frank M. Berger, 1913–2008

Back to table of contents Previous article Next article Images in PsychiatryFull AccessThe Dawn of Anxiolytics: Frank M. Berger, 1913–2008Richard Balon M.D.Richard Balon M.D.Search for more papers by this authorPublished Online:1 Dec 2008https://doi.org/10.1176/appi.ajp.2008.08040552AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail The discovery that ushered in the era of tranquilizers and other anxiety medications was Frank Berger’s discovery of meprobamate. Frank Berger, M.D. , was a microbiologist of Czech origin working in the United Kingdom during World War II. Shortly after Florey and colleagues purified penicillin, Berger was looking for a substance that would preserve penicillin by inhibiting penicillinase-producing bacteria. One of these substances, mephenesin (Myanesin) met this criterion. While performing toxicity studies, Berger noted that large doses of mephenesin produced tranquilization in laboratory animals. He published his findings in 1946 in the British Journal of Pharmacology(1) . Shortly after this discovery, Berger moved to the United States and worked at Carter Products (later Carter-Wallace), a small pharmaceutical company. There he continued working with mephenesin, investigating why it was metabolized rapidly. He and his co-workers found that mephenesin’s rapid deactivation by oxidation of its terminal hydroxy groups was best blocked by carbamates. They synthesized a few hundred carbamates. Meprobamate (2) seemed to be “the best one.” Several clinical trials with meprobamate were conducted, one by Berger himself. To convince hesitant executives about meprobamate’s properties, Berger produced a short documentary showing the drug’s effect on rhesus monkeys. The brand name “Miltown,” after a small village near New Brunswick, N.J., was selected (meprobamate was also later distributed as “Equanil”). Meprobamate became extremely popular during the 1950s and opened the market to other “tranquilizing” drugs (e.g., chlordiazepoxide). Meprobamate relieved anxiety, relaxed muscles, and induced mild euphoria and “inner peace.” Some even suggested that it should be added to drinking water so the masses would be less anxious. Thus, it is interesting that the Associated Press reported in March 2008 that traces of meprobamate were found in water supplies of Los Angeles and several other places. Only a few years after its introduction, it became obvious that meprobamate could be habit forming, its sudden withdrawal could be dangerous, and overdose could be lethal. Its use decreased, especially after the arrival of benzodiazepines, but it never totally faded away. Generic meprobamate is still available. Frank Berger continued his research and development of carbamates (e.g., the pain reliever carisoprodol) and later returned to bacteriology and immunology. Berger is an example of an alert observer and astute researcher from the golden era of serendipity in psychopharmacology research, along with R. Kuhn, J. Delay, P. Deniker, and others. Recently, Donald Klein (3) reminded us of “a seismic shift in psychiatry between 1950 and 1970,” the Age of Serendipitous Psychopharmacology Discoveries. During those times, lithium, chlorpromazine, iproniazid, meprobamate, chlordiazepoxide, haloperidol, and other psychotropic drugs were “discovered” mostly because of “chance observations of unexpected clinical benefits or as inadvertent outcomes of blind pharmaceutical searches” (3) . Address correspondence and reprint requests to Dr. Balon, UPC-Jefferson, 2751 East Jefferson #200, Detroit, MI 48207; [email protected] (e-mail). Photograph used by permission of Christine Berger. Image accepted May 2008 (doi: 10.1176/appi.ajp.2008.08040552). The author thanks Thomas Ban, M.D., for providing information about Frank Berger.

Purple urine bag syndrome in nursing homes: Ten elderly case reports and a literature review

Purple urine bag syndrome (PUBS) is a rare occurrence, in which the patient has a purple-colored urine bag following urinary catheterization for hours to days. Most of authors believe it is a mixture of indigo (blue) and indirubin (red) that becomes purple. Previous study showed that PUBS occurred predominantly in chronically catheterized, constipated women. We collected 10 elderly patients with PUBS in two nursing homes. The first two cases were identified by chart review in 1987 and 2003, and then later eight cases (42.1%) were collected among 19 urinary catheterized elderly in the period between January 2007 and June 2007. In the present report, PUBS probably can occur in any patients with the right elements, namely urinary tract infection (UTI) with bacteria possessing these enzymes, diet with enough tryptophan, and being catheterized. Associations with bed-bound state, Alzheimer's, or dementia from other causes are reflections of the state of such patients who are at higher risk for UTI, and hence PUBS occurred. Although we presented PUBS as a harmless problem, prevention and control of the nosocomial catheter-associated UTIs (CAUTIs) has become very important in the new patient-centered medical era. Thus, we should decrease the duration of catheterization, improve catheter care, and deploy technological advances designed for prevention, especially in the elderly cared for in nursing homes.

Remembering Alexander Brunschwig, MD (1901–1969)

To capsulize Alexander Brunschwig is impossible. But it is my honor to try. This is the photo he gave me when I was at Memorial 44 years ago (Fig. 1). Fasten your seatbelts for a 30 minute sprint through the science, the legend, and some stories of this giant. And also a little about the medical era that nurtured him. It is a remarkable coincidence that my father was also born in 1901...and almost surreal that his birth date is today, March 8th. So today I publicly and privately honor two giants; two great mentors in my life, Dr. Brunschwig and my father. Happy Birthday, Dad! Alexander Brunschwig was born in El Paso, of immigrant parents from the Alsace Lorraine area. They gave him little in the way of material things but gifted him with a superb intellect (Table 1). He graduated from medical school with honors, and as a student, received a National Institutes of Health grant and made several significant contributions. As a resident in pathology, his interest in oncology became focused. This was subsequently intensified by the early death of his greatly admired father from pancreatic cancer. Subsequently, his work at the University of Chicago focused primarily on the surgical management of cancer. This is reflected in most of his contributions in scientific publications. He authored 4 books, 40 book chapters, and 420 papers. However, his research interests and publications reflected diverse areas of inquiry and scientific scholarship (Table 2). He was honored by many foreign governments and medical societies (Table 3). He was also a Founding Member of the American Board of Surgery and he fought his entire career for formal training and certification of surgical oncology in all disciplines. His first book, The Roentgen-Ray Diagnosis of Diseases of the Bones and Joints, was a co-authorship [1]. His contributions focused on bone and soft tissue injuries secondary to radiation