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Carbamazepine toxicity induced by concurrent erythromycin therapy.

We describe a 41-year-old woman receiving carbamazepine for epilepsy, in whom concurrent erythromycin stearate administration led to carbamazepine toxicity, including inappropriate antidiuretic hormone syndrome. We review the literature on erythromycin-carbamazepine interaction and discuss the mechanism for such interaction.

Adult↗

Mycotic aortic aneurysms. A reappraisal.

Mycotic aneurysms are uncommon but not rare lesions with potential for catastrophic hemorrhage or sepsis. They have been ascribed to bacterial endocarditis and, when present in the aorta, were termed "inevitably fatal" as recently as 1967. A 15-year review of the English-language literature on mycotic aneurysms showed that arterial trauma, concurrent sepsis, and depressed host immunity have become the cardinal "risk factors" in the development of these lesions. Conventional treatment of mycotic aortic aneurysms usually includes aortic ligation, aneurysmal excision, and extra-anatomic bypass grafting. Nevertheless, four of our patients with well-localized mycotic aortic aneurysms survived three to 54 months (mean, 40 months) after aortic excision and in situ prosthetic graft restoration of aortic continuity. This experience suggests that mycotic aortic aneurysms can be successfully treated, frequently by in situ grafting, if diagnosis and treatment are timely and aggressive.

Adult↗

Fine-needle aspiration of abdominal fat pad for amyloid detection: a clinically useful test?

Fine-needle aspiration of abdominal fat pad (FNAFP) is commonly employed for the diagnosis of systemic amyloidosis, a disease with highly variable clinical manifestations, often presenting difficult patient management problems. We evaluated the role of FNAFP particularly in reference to its clinical usefulness. Pathology reports and clinical histories of 91 consecutive cases of FNAFP with Congo red (CR) staining at The Johns Hopkins Hospital (1999-2000) were reviewed. Major emphases were assessment of the clinical utility of the test, correlation with concurrent or subsequent biopsies, and treatment strategies. The primary indications for FNAFP were monoclonal gammopathy (34%), cardiomyopathy (22%), renal insufficiency (20%), neuropathy (8%), plasma cell dyscrasia (6%), and other conditions (10%). Of the 91 patients who underwent FNAFP, the results were as follows; 20 cases (22%) positive; 62 cases (68%) negative; eight cases (9%) insufficient for diagnosis; and one case (1%) equivocal. Of the 20 positive cases, follow-up biopsies were performed on 11 cases, of which six were positive and five were negative for amyloid by CR. Of the 62 negative cases, follow-up biopsies were performed on 19 cases, 14 of which were negative and five positive for amyloid by CR. A follow-up biopsy on the single equivocal case was positive for amyloid by CR. Twenty-one patients positive for amyloid, based on initial or follow-up biopsies, were managed symptomatically without any specific treatment for amyloidosis. One patient, who was specifically treated for amyloidosis by melphalan and dexamethasone, died 1 wk after therapy. Three patients with multiple myeloma and amyloidosis underwent chemotherapy. We conclude that primary clinical indications for FNAFP for amyloidosis are highly variable. An FNAFP result is often not considered clinically conclusive and is followed by further invasive procedures to detect amyloid (55% of our positive and 31% of our negative FNAFP cases were rebiopsied). The estimated sensitivity and specificity of FNAFP were 75% and 92%, respectively. Overall, the reliance on the results of FNAFP depended on the degree of clinical suspicion of the treating physician. Although in the majority of cases diagnosis of amyloidosis did not alter the treatment strategies, a conclusive positive result helped in ruling out other underlying conditions as the cause of patients' symptoms.

Abdomen↗

Diagnosis, etiology, and therapy of fibromyalgia.

Fibromyalgia is characterized by diffuse pain, multiple tender points, fatigue, and sleep disturbance. Its frequent concurrence with rheumatic diseases modifies the clinical picture of the "primary" disease. This article reviews new information about the etiopathogenesis and treatment of this syndrome.

Algorithms↗

The Role of Hormonal Therapy in Breast Cancer.

This review reassesses the role of hormonal therapy in breast cancer specifically the sequential or concurrent use of endocrine therapy and the combined use of chemotherapy with endocrine therapy. In advanced disease the sequential use of hormone therapies is generally recommended rather than the combined use of various hormonal agents, though combination hormonal therapy offers advantages in certain subsets of patients. The efficacy of combined chemo-endocrine therapy is questionable. Chemotherapy with estrogenic recruitment is an attractive but still experimental concept. However, in an adjuvant setting there is evidence that combined chemo-endocrine therapy causes a significant increase in disease-free and/or overall survival, particularly in postmenopausal patients with estrogen receptor(ER)-positive tumors. While hormonal treatment strategies have clearly benefitted from randomized studies, data regarding optimal endocrine therapy are still insufficient.

Journal Article↗

Acute lung injury: an indicator of serious systemic illness.

The history of the acute respiratory distress syndrome (ARDS) parallels that of critical care. Descriptive and colorful names for the condition such as "shock lung," "post perfusion lung," and "traumatic wet lung" clearly communicate the reality that the pulmonary tissue is involved in a pathologic process. It is not difficult to speculate that the focus on the lung originated from the dramatic chest radiographs and gas exchange abnormalities frequently observed in association with the syndrome. However, a named condition does not necessarily dictate the therapeutic approach to it, and a review of some pertinent studies suggests the condition is in fact systemic in nature. Concurrent with this recognition, the need for markers of severity of illness has become more important. Rather than a process needing primarily pulmonary approaches to management, it now seems that ARDS is the result of systemic events with noticeable pulmonary manifestations, which may suffice as a clinical marker for severity of systemic inflammation. Because the pathophysiology has been described elsewhere, this article will focus on the clinical trials that are shaping our perception and management of the syndrome.

Enteral Nutrition↗

Primary radical external beam radiotherapy of rectal adenocarcinoma: long term outcome of 271 patients.

BACKGROUND AND PURPOSE: To assess local control, survival and toxicity following primary radical external beam radiotherapy of rectal adenocarcinoma treated between 1978 and 1997, and to compare practices and outcomes between the two decades of study. PATIENTS AND METHODS: A retrospective review of 271 patients who underwent primary radical external beam radiotherapy, without prior or concurrent chemotherapy, was conducted. All patients received radiation doses of at least 40 Gy. Most patients (82%) were followed until death. RESULTS: Tumor fixation was the only significant prognostic factor for complete response by multivariate analysis. Complete response rates for mobile, partially fixed and fixed tumors were 49, 22 and 9%, respectively. For patients with mobile, partially fixed and fixed tumors, overall 5 year survival was 48, 26 and 6%, respectively, and cancer specific 5 year survival was 59, 33 and 9%, respectively. On multivariate analysis, tumor fixation and CEA higher than 8.7 microg/L at presentation were associated with significantly shortened survival. Outcomes did not change significantly during the two decades of the study. RTOG grade 3 or higher acute (1.8%) and late (1.5%) toxicity occurred only in the first decade of study. CONCLUSIONS: Radical external beam radiotherapy is a reasonable treatment option for rectal carcinoma for patients who are not surgical candidates or refuse surgery. However in patients with fixed tumors in this study, the outcome is poor and treatment should be considered palliative. Severe radiation toxicity is infrequent with current schedules and techniques of radiotherapy.

Adenocarcinoma↗

Successful repair of myocardial free wall rupture after thrombolytic therapy for acute infarction.

BACKGROUND: Controversy exists regarding the timing of thrombolytic administration and rupture rate. METHODS: Hospital records at St. Luke's-Roosevelt Hospital of the 4 study patients were reviewed and compared with those of 41 patients from a group of 537 patients concurrently admitted with a diagnosis of myocardial infarction (MI). RESULTS: Four patients experienced ventricular free wall rupture after having a MI between November 17, 1993, and July 28, 1995. All received tissue plasminogen activator. In 1 patient, pericardial effusion associated with a pseudoaneurysm was discovered in the operating room. The 3 others developed clinical pericardial tamponade before surgery. All 4 patients survived and left the hospital on postoperative days 10, 11, 11, and 82, respectively. During this same time period, 537 patients were admitted with MI, 41 of whom died; the study's 4 patients were compared with these 41. CONCLUSIONS: These data demonstrate that rupture of the ventricular free wall can occur early after thrombolytic therapy and may have a subacute course. Prompt diagnosis and surgery offer excellent chances of surviving this fatal condition.

Aged↗

[Fast-track multimodal rehabilitation programs in laparoscopic colorectal surgery].

For the last two decades, general and digestive surgeons have attempted to improve the postoperative course of surgical patients. Classical perioperative treatment can be described as a period of preoperative dehydration caused by fasting and intensive colon preparation followed by fluid overload generally due to excessively prolonged serum therapy. There is also perioperative surgical stress, the trauma of surgery itself, and a long period of drainage and nasogastric tubes. The patient is thus literally confined to bed and mobilization is, at the very least, difficult. Moreover, the use of opiates delays intestinal peristalsis and consequently oral nutrition. All together, these factors prolong the length of hospital stay and hamper recovery. All these perioperative treatment modalities have been questioned by Kehlet, resulting in a set of new, more realistic and evidence-based modalities, currently known as the fast-track program. The aim of this program is to decrease perioperative stress, reduce organ involvement produced by surgical trauma and hasten the patient's general recovery. Major advantages of this program consist not only of shorter length of hospital stay but also of a concurrent improvement in patients' quality of life and a reduction in mortality. The present review article analyzes all these modalities, with special emphasis on laparoscopic colorectal surgery. This approach is presented as one of the elements of the fast-track program.

Anesthesia, Conduction↗

Adherence intervention research: what have we learned and what do we do next?

Although there is general agreement from studies demonstrating that adherence to inhaled corticosteroid therapy is often inadequate to establish consistent control, relatively little concurrence exists in reports of interventions to correct the problem. Half of the studies reviewed found that the experimental intervention did not change adherence, and behavior change reported by patients was often not accompanied by changes in treatment success. Studies used a variety of methods that differed in quality with findings that were often contradictory. Key limitations in many studies included reliance on inadequate adherence measures, inclusion of convenience samples of well-motivated patients, and assessments of intervention outcomes artificially boosted by attrition of least adherent participants. Research is encouraged into innovative interventions that are brief, easily implemented, and can be tailored to individual patients and diverse clinical settings. Of particular importance is inclusion of hard-to-reach patients, including urban and rural poor and the use of valid measures of adherence at intervals sufficient to establish enduring benefit.

Administration, Inhalation↗

Spiral CT of the abdomen: increased diagnostic potential.

Over the last 10 years, spiral CT has become the optimal method of performing all CT within the abdomen and pelvis. Not only has the technique improved the quality of individual examinations, it has also opened up many new diagnostic possibilities which are currently being evaluated and compared with the concurrent advances in ultrasound and MRI. These new diagnostic possibilities are discussed in this review article. So too are the economic advantages of the shorter data-acquisition times which also make the examination much better tolerated by the patient.

Acute Disease↗

Thrombolytics in infectious endocarditis associated myocardial infarction.

The use of thrombolytics in the management of acute myocardial infarction in eligible patients is the accepted standard of practice. We present the case of an embolic myocardial infarction in the setting of acute infectious endocarditis, treated with thrombolytics, resulting in a massive intracerebral hemorrhage and the patient's death. Historical and current literature has shown a consistent and significant incidence of concurrent intracerebral mycotic aneurysms in the setting of infectious endocarditis. Despite this, a literature review of contraindications to the use of thrombolytics rarely recognizes endocarditis as a contraindication. It is imperative that the etiology for myocardial infarction be identified; if contraindications to thrombolytic treatment exist, alternative therapeutic interventions must be pursued. This case highlights the importance of the correct etiologic diagnosis of myocardial ischemia, and increases the awareness of the significant risks of intracerebral hemorrhage associated with the use of thrombolytics in the setting of endocarditis.

Contraindications↗

Using the ISMP Medication Safety Self-Assessment to improve medication use processes.

BACKGROUND: The 194-item Institute for Safe Medication Practices (ISMP) Medication Safety Self-Assessment for hospitals is being used by a 21-hospital collaborative as a framework for understanding, evaluating, and systematically implementing medication use system safety improvements. METHODS: The results of the self-assessment were used to prioritize and organize the review of medication use processes, in which each self-assessment-defined "representative characteristic" is reviewed in detail, and "best implementation practices" for the characteristic are established. The collaborative concurrently identifies educational needs and develops tools to assist organizations in implementing improvements. RESULTS: By December 2002 participating organizations had implemented a wide variety of medication safety improvements. Collaborative member scores for the self-assessment increased approximately 20% during the initial assessment when the self-assessment was repeated by members in the second quarter of 2002. SUMMARY: Participant progress in improving medication safety practices is supportive of collaborative methods and the value of completing the ISMP self-assessment, expanding on the knowledge gained, developing effective implementation tools, and systematically applying lessons learned.

Benchmarking↗

Impact of obesity in intima media thickness of carotid arteries.

OBJECTIVE: To explore differences in intima media thickness (IMT) of the carotid arteries induced by differences in BMI. RESEARCH METHODS AND PROCEDURES: Data from 3173 consecutive subjects, who were referred to our Hypertension Center from 1998 to 2004, were reviewed. Criteria for patients to be considered for further analysis included no past or concurrent antihypertensive medication, no concurrent medication with the potential to raise blood pressure (BP) (e.g., prednisone), and no clinical signs or laboratory evidence of secondary causes of hypertension. Our population was divided into four groups according to NIH criteria for obesity: underweight, normal weight, overweight, and obese. BMI, mean IMT of internal carotid arteries, and 24-hour BP values were available for all subjects. Five hundred thirty six subjects of the four groups, matched for age, gender, and mean 24-hour BP values, were included in the analysis. RESULTS: Mean IMT of internal carotid arteries was increased with increasing BMI. Mean IMT was significantly higher in obese subjects compared with normal-weight (p < 0.01) and underweight (p < 0.001) subjects. Mean IMT was significantly higher in overweight subjects compared with normal-weight ones (p < 0.05). Furthermore, multivariate regression analysis in obese subjects revealed that fasting serum glucose was independently associated with IMT. DISCUSSION: Obesity may be an important factor for carotid atherosclerosis, and at least some of the effects of obesity are independent of the BP levels. Fasting serum glucose levels in obese subjects may play an important role in carotid atherosclerosis.

Adult↗

Novel modalities for appraising individual and coordinate pulsatile hormone secretion: the paradigm of luteinizing hormone and testosterone release in the aging male.

To quantify aging- and disease-associated alterations in the integrative and interactive components of a pulsatile neuroendocrine axis, novel biomathematical strategies are required. Here, I illustrate as an investigative paradigm otherwise subtle aging-dependent disturbances of the gonadotropin-releasing-hormone (GnRH)-luteinizing hormone (LH)-testosterone feedback axis in men, in whom strong age-related contrasts become evident via any of four strategies applied alone or in combination: (1) intensified blood sampling schedules to capture the temporal structure of episodic hormone (LH and testosterone) secretion; (2) deconvolution analysis as a technique to quantify underlying pituitary and gonadal hormone secretory rates from the observed plasma hormone concentration profiles; (3) approximate entropy as a scale- and model-independent measure of the serial regularity or orderliness of the hormone release process over time; and (4) cross-approximate entropy (cross-ApEn) to quantify joint asynchrony between two concurrent pulse trains without confounding by variable lag. These new methodologies are introduced and reviewed briefly, a stochastic differential equation feedback construct alluded to, and the resultant insights into distinct alterations of the aging male gonadotropic axis highlighted. In summary, the new experimental strategies of intensified venous sampling, multiparameter deconvolution analysis, approximate entropy, and cross-approximate entropy unveil new mechanisms underlying dynamic neuroendocrine-axis activity, as exemplified by aging-associated disruption of the human male reproductive axis.

Aging↗

Magnesium sulfate administered via continuous intravenous infusion in pediatric patients with refractory wheezing.

PURPOSE: To evaluate the dosing and safety of intravenous magnesium sulfate administered via continuous infusion for refractory wheezing. MATERIALS AND METHODS: All patients admitted to the pediatric intensive care unit (PICU) between January 1998 and March 2001 who were prescribed magnesium sulfate via continuous infusion were identified via retrospective chart review. The patient's medical history, demographic data, vital signs, magnesium dosing history, and concurrent medications were recorded. RESULTS: Forty PICU patients represent our study population. The mean age was 82.6 +/- 64.6 mo; 18 patients were boys.The mean magnesium loading dose (mg/kg) was 29.6 +/- 13.2 with a mean infusion dose (mg/kg/h) of 18.4 +/- 6.5 with a significant difference in dosing noted between patients weighing less than 30 kg and those with a higher weight. The mean magnesium loading dose (mg/kg) in the less than 30 kg group was 35.3 +/- 12.7 compared with 21.9 +/- 9.9 in the higher weight group (P <.05). Mean infusion doses (mg/kg/h) were 21.6 +/- 6 and 14.6 +/- 4.2, respectively (P <.05). There was no significant difference between the mean concentrations (mg/dL) reported between the 2 groups (less than 30 kg group = 3.9 +/- 0.6; higher weight group = 3.6 +/- 0.5). All patients received nebulized albuterol, ipratropium, and intravenous methylprednisolone before magnesium therapy. Aminophylline and ketamine were prescribed to 28 and 4 patients, respectively. No cardiovascular adverse effects were noted during magnesium therapy. CONCLUSIONS: For the treatment of refractory wheezing, intravenous magnesium sulfate administered via continuous infusion represents a safe mode of drug delivery.

Adolescent↗

Malignancy is increased in ANCA-associated vasculitis.

OBJECTIVE: In the light of previous reports of an association between malignancy and renal vasculitis, we aimed to investigate the association of malignancy in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis, either Wegener's granulomatosis (WG) or microscopic polyangiitis (MPA), and compare it with the general population and disease control groups comprising patients with systemic lupus erythematosus (SLE) or Henoch-Schonlein purpura (HSP). METHODS: A retrospective review of 200 consecutive patients with WG or MPA was performed. Malignancies preceding or concurrent with vasculitis were recorded and the incidence of malignancy was compared with those in a population of 129 patients with HSP, 333 patients with SLE and a normal population in the West Midlands of the UK. RESULTS: Twenty patients had a diagnosis of malignancy, 14 had MPA and six had WG. Patients with ANCA-associated vasculitis had an increased risk of malignancy compared with HSP patients, of whom six patients had malignancy (relative risk 0.85, confidence interval 0.69-1.05; P = 0.034), or SLE patients, of whom five patients had malignancy (relative risk 0.31, 95% confidence interval 0.14-0.7; P<0.0001). The rate of malignancy compared with an age-matched control group was increased in patients with ANCA-associated vasculitis and HSP (ANCA-associated vasculitis, relative risk 6.02, 95% confidence interval 3.72-9.74; HSP, relative risk 5.25, 95% confidence interval 2.4-11.5). The presence of ANCA was not predictive of malignancy. CONCLUSION: In conclusion, patients with ANCA-associated vasculitis have an increased risk of preceding or concurrent malignancy.

Adult↗