bluuebunny/crossref_metadata_2025 huggingface dataset:
Cefpodoxime Proxetil: A New, Broad-Spectrum, Oral Cephalosporin
Authors: Chocas Elaine C. , Paap Christopher M. , Godley Paul J.
Published: January 2017

OBJECTIVE:

To discuss the chemistry, pharmacokinetics, spectrum of activity, clinical trials, adverse effects, drug interactions, and dosage guidelines of cefpodoxime proxetil.

DATA SOURCES:

Literature was identified through a MEDLINE search from 1988 to the present and from review of bibliographies in that literature.

STUDY SELECTION:

Data were limited to comparative trials published in the English literature. Although many studies were conducted in Japan, the results often were available only in Japanese or partly in English. As these studies could not be completely evaluated, they are not included in this review.

DATA SYNTHESIS:

Cefpodoxime exhibits good activity against many gram-positive and gram-negative organisms. In clinical trials, cefpodoxime was similar in both clinical and bacteriologic efficacy to amoxicillin, cefaclor, amoxicillin/clavulanate, and penicillin in the treatment of respiratory and urinary tract infections. It also appeared effective in the treatment of skin and soft tissue infections, although no comparative trials have been performed. Cefpodoxime is well tolerated by children and is effective in the treatment of otitis media and pharyngitis. It has a similar adverse effect profile to that of other penicillins and cephalosporins, with gastrointestinal effects being most common.

CONCLUSIONS:

Cefpodoxime demonstrates good in vitro activity against pathogens frequently associated with respiratory tract, urinary tract, and skin and tissue infections. It has not demonstrated greater efficacy than the other antibiotics to which it has been compared. The available published clinical trials are fraught with methodologic, statistical, and evaluative flaws. Thus, further trials comparing cefpodoxime with established treatments, as well as the newer cephalosporins, are needed before its place in therapy can be established.
Bioequivalence of Two Methotrexate Formulations in Psoriatic and Cancer Patients
Authors: Teresi Mary E. , Riggs Charles E. , Webster Paul M. , Adams Michael J. , Noonan Patrick K. , O'Donnell John P.
Published: January 2017

OBJECTIVE:

To compare the bioequivalence of a generic methotrexate (MTX) tablet (Mylan) with that of a brand-name (Lederle) product.

DESIGN:

A single-dose, randomized, crossover study.

SETTING:

Clinical Research Center (CRC) at a university hospital.

PATIENTS:

Men and women who had a diagnosis of malignancy or psoriasis who were at least 21 years old.

METHODOLOGY:

Two overnight study periods were scheduled at the CRC at least one week, but not more than two weeks apart. Each period consisted of a 10-hour fast prior to and 4 hours following oral MTX 15 mg administered as six 2.5-mg tablets. Blood samples were collected over 48 hours. Plasma MTX concentrations were determined using an HPLC assay. Area under the curve from zero to infinity (AUC0-∞) was calculated by the log-trapezoidal method.

RESULTS:

Twenty-two patients (21 psoriasis, 1 colon cancer) aged 23–61 years completed both study periods. Mean values for peak concentration, time to peak concentration, and AUC0-∞ were 0.80 μmol/L, 1.2 hours, and 3.0 μmol•h/L, respectively, for Mylan's MTX tablets and 0.81 μmol/L, 1.4 hours, 3.0 μmol•h/L, respectively, for Lederle's MTX. Normalization for weight or body surface area did not affect interpatient variability. Relative bioavailability of generic MTX was 99.2 percent Rate and extent of absorption were not significantly different and the confidence intervals were within the range of 80–120 percent required by the Food and Drug Administration.

CONCLUSIONS:

Mylan's MTX tablet is bioequivalent to Lederle's product.
Phenytoin Concentration Elevation Subsequent to Ranitidine Administration
Authors: Tse C.S. Ted , Akinwande Kayode I. , Biallowons Klaus
Published: January 2017

OBJECTIVE:

To report elevated phenytoin (PHT) plasma concentrations in a patient receiving ranitidine.

CASE SUMMARY:

A patient treated with PUT and ranitidine experienced elevated PHT plasma concentrations that persisted several days after PHT was discontinued. The PHT plasma concentration declined rapidly after withdrawal of ranitidine.

DISCUSSION:

This is an unusual case report of elevated PHT plasma concentrations associated with concurrent ranitidine use. Ranitidine has been reported to interfere with the hepatic metabolism of other drugs. The proposed mechanism of this interaction is similar to that of other histamine2-receptor antagonists—by binding to cytochrome P-450 hepatic mixed-function oxidase. We postulate that a small subset of patients may be susceptible to this effect of ranitidine.

CONCLUSIONS:

This case was complicated by several variables that may have affected the changes observed in total PHT concentrations. However, an interaction between ranitidine and PHT should be considered, especially in a subpopulation of patients that are more susceptible to this effect. Patients using ranitidine and phenytoin concurrently should be routinely monitored.
Acute Pancreatitis Associated with the Use of Lisinopril
Authors: Maliekal James , Drake Clayton F.
Published: January 2017

OBJECTIVE:

To report a case of acute pancreatitis associated with lisinopril use.

CASE SUMMARY:

A 67-year-old man with no past history of pancreatitis or its associated risk factors developed acute pancreatitis after taking lisinopril for two years. To date, the use of angiotensin-converting enzyme (ACE) inhibitors and development of pancreatitis has been described in the literature with captopril, enalapril maleate, and one case temporally related to lisinopril use.

CONCLUSIONS:

The use of ACE inhibitors as first-line agents in controlling hypertension and congestive heart failure has increased. In addition to monitoring for efficacy and commonly reported adverse effects, clinicians need to be aware that acute pancreatitis may occur with all ACE inhibitors.
Salmeterol: A Novel, Long-Acting Beta2-Agonist
Authors: Meyer Joette M. , Wenzel Christine L. , Kradjan Wayne A.
Published: January 2017

OBJECTIVE:

The clinical pharmacology, pharmacokinetics, clinical efficacy, and adverse effects of the long-acting beta2-agonist salmeterol are reviewed.

DATA SOURCES:

A MEDLINE search was performed to identify English-language publications pertaining to salmeterol.

STUDY SELECTION:

Open and controlled trials were reviewed in assessing clinical efficacy. Only the results of controlled, randomized trials were considered in the effectiveness evaluation.

DATA EXTRACTION:

The primary measures of effectiveness in the clinical trials were bronchodilator activity and reduction of hyperresponsiveness that may reflect antiinflammatory activity. Bronchodilator activity was measured as changes in pulmonary function; reduction of hyperresponsiveness was evaluated using respiratory challenge with methacholine, histamine, allergen, or cold air. Secondary measures included symptom scores, need for rescue doses, and patient preference.

DATA SYNTHESIS:

Salmeterol is a selective, beta2-agonist that has been studied in the treatment of exercise-induced, nocturnal, and allergen-induced asthma. Salmeterol interacts with the traditional beta-receptor in a similar manner as other beta-agonists, and it exhibits potent in vitro antiinflammatory effects as an inhibitor of inflammatory mediator release. Less evidence exists for its in vivo antiinflammatory activity. Salmeterol demonstrates prolonged receptor occupancy, which is thought to contribute to its long duration of action. The recommended dose is 50 μg via metered-dose inhaler or dry-powdered inhalation. In the published clinical trials, salmeterol was more effective than albuterol in treating asthma, including exercise and allergen-induced asthma. Salmeterol's major advantage over other inhaled beta-agonists is its long duration of action (12 hours), making it an excellent choice for treatment of nocturnal asthma. A potential disadvantage is delayed onset of action. Tachyphylaxis to salmeterol's bronchodilator effects has not been shown, but tolerance to its protective effects against methacholine-induced bronchoconstriction has occurred. Adverse effects reported have been mild and have included headache, tremor, and palpitations.

CONCLUSIONS:

Salmeterol is an effective beta2-agonist in the treatment of asthma. However, several issues require further investigation regarding its long-term effects on disease control, significance of antiinflammatory activity, and role as a rescue medication.
Pharmacotherapy of Disseminated Histoplasmosis in Patients with AIDS
Authors: Goodwin S. Diane , Fletcher Courtney V. , Drew Richard H.
Published: January 2017

OBJECTIVE:

To review the pharmacotherapy of disseminated histoplasmosis (DH) in patients with AIDS. The article provides an overview of the pathophysiology, epidemiology, clinical presentation and diagnosis of this disease. Clinical trials reporting intervention with antifungal therapy are reviewed, with an emphasis on efficacy and toxicity of these agents.

DATA SOURCES:

A MEDLINE search from 1976 to the present was performed to identify pertinent biomedical literature, including reviews.

STUDY SELECTION:

All available reviews and clinical trials in AIDS patients were evaluated, as were all available case series and interventional clinical trials.

DATA SYNTHESIS:

DH in patients with HIV infection is an AIDS-defining opportunistic infection caused by Histoplasma capsulatum. It is most frequently observed in HIV-infected patients living in or traveling to endemic regions. The clinical presentation most often includes fever and weight loss, but may be complicated by comorbid illness such as other opportunistic infections. Diagnosis is best established by histologic examination of peripheral blood smear or bone marrow aspirate, or isolation of the organism in cultures of blood, bone marrow, and respiratory secretions. Serologic examinations may provide supportive diagnostic information. Detection of histoplasma polysaccharide antigen (HPA) in serum or urine may prove to be a promising approach for the rapid diagnosis and therapeutic monitoring of DH in AIDS patients. In contrast to immunocompetent hosts, high relapse rates are reported after therapy in AIDS patients. Therefore, initial (induction) therapy is routinely followed by long-term (maintenance) therapy to prevent relapse. Issues regarding the selection, dosage, and duration of therapy, as well as prophylaxis of patients at highest risk, still need to be addressed by controlled clinical trials.

CONCLUSIONS:

Amphotericin B is presently the drug of choice for induction therapy. Maintenance therapy with either amphotericin B or an oral azole antifungal agent active against H. capsulatum is necessary to prevent relapse. Itraconazole, a triazole antifungal agent, may provide effective alternative therapy for both induction and maintenance treatment of DH.
Newer Insights into Cisplatin Nephrotoxicity
Authors: Hartshorn Edward A. , Anand Ajay J. , Bashey Baquar
Published: January 2017

OBJECTIVE:

To review recent advances in the understanding of the mechanisms of cisplatin nephrotoxicity. Factors affecting this toxicity and agents that may protect against it are discussed.

DATA SOURCES:

A MEDLINE search was used to identify pertinent literature including reviews. A manual search of bibliographies was performed to include all articles on the subject.

STUDY SELECTION:

All available data relating to the mechanisms, modifying factors, and management of cisplatin nephrotoxicity were assessed.

DATA EXTRACTION:

As limited human data are available, all animal studies were included. Articles with hypotheses or suggestions not backed by scientific data were excluded from review.

DATA SYNTHESIS:

Cisplatin is one of the most effective agents available for treating a variety of solid tumors. Nephrotoxicity is the dose-limiting factor for the use of this drug. Mechanisms for renal toxicity range from definitive histologic changes found in the proximal convoluted tubules to physiologic and biochemical alterations involving a decrease in mitochondrial respiratory function, enzymatic activity in the respiratory chain and glutathione peroxidase, and effects on cellular calcium homeostasis. Important factors related to nephrotoxicity include age, renal irradiation, and concurrent alcohol intake. Agents that appear promising in attenuating the nephrotoxic effects of cisplatin include loading with NaCl solution and/or mannitol, sodium thiosulfate, WR 2721, glutathione, probenecid, and many other compounds under active investigation.

CONCLUSIONS:

Cisplatin is a nephrotoxic drug; however, agents that may make cisplatin therapy more safe and rewarding will be available in the near future.
Therapeutic Monitoring and Pharmacist Intervention in a Hansen's Disease Clinic
Authors: Robinson J. Daniel , Piscitelli Stephen C. , Occhipinti Donna J. , Danziger Larry H. , Hill Carlotta , West Dennis P. , Fischer James H.
Published: January 2017

OBJECTIVE:

To describe the role of the clinical pharmacist in a Hansen's disease (HD, leprosy) clinic and to describe the development, validation, and operation of a dapsone compliance monitoring program.

RATIONALE:

HD remains a major, worldwide healthcare problem. Dapsone is the drug of choice for treatment of HD; however, high rates of noncompliance with this agent have been reported by many treatment centers. The assessment of compliance in HD patients is important to help distinguish between treatment failure secondary to noncompliance or to the development of resistance.

SETTING:

In the US, the Chicago Regional Hansen's Disease Center at the University of Illinois at Chicago is one of ten centers that provide comprehensive care to patients diagnosed with this condition. This article reviews the clinical pharmacy services and dapsone compliance program in the clinic encompassing the years 1983–93.

RESULTS:

The clinical pharmacist provides a variety of clinical services in the clinic as well as coordinating the clinical research program. A pharmacist-generated dapsone compliance program led to improvement in compliance rates and clinical outcome. This improvement in compliance has been sustained over an extended period of time.

CONCLUSIONS:

The clinical pharmacy services performed in the HD clinic provide a model for pharmacy involvement in other chronic disease states. The dapsone compliance program has been successful in improving patient care and obtaining reimbursement for clinical pharmacy services.
Amphotericin B Infusion-Related Toxicity: Comparison of Two- and Four-Hour Infusions
Authors: Nicholl Tessa A , Nimmo Cindy Reesor , Shepherd John D , Phillips Peter , Jewesson Peter J
Published: January 2017

Objective:

To investigate the influence of infusion duration on infusion-related adverse effects (IRAEs) associated with prophylactic or treatment regimens of amphotericin B in patients with leukemia/bone marrow transplant (BMT).

Design:

Randomized, double-blind, 2-arm, complete crossover, prospective clinical trial.

Setting:

A university-affiliated tertiary care teaching hospital.

Participants:

The study population consisted of 25 consecutive patients with leukemia/BMT who received 162 prophylactic regimen infusions and 169 treatment regimen infusions of amphotericin B via a central line. Prior to each infusion all patients received a parenteral IRAE prophylaxis regimen of diphenhydramine 25 mg and hydrocortisone 25 mg. No test doses or incremental amphotericin B doses were administered. Patients were monitored closely for IRAEs, which were documented by using a standardized data collection form.

Main Outcome Measures:

The incidence and nature of IRAEs during a 6-hour monitoring period following the initiation of each infusion was measured. Patients served as their own controls. IRAEs were compared according to infusion duration and therapeutic indication.

Results:

Three hundred and thirty-one 2- and 4-hour amphotericin B infusions were administered. We found no difference between 2- and 4-hour infusions in the incidence and severity of IRAEs, including overall events (29% of 166 2-hour infusions vs. 25% of 165 4-hour infusions), chill scores (8% of 166 2-hour infusions vs. 7% of 165 4-hour infusions; highest score 7 vs. 6), nausea and vomiting (7% vs. 12%; highest score 4 in both groups), fever (3% vs. 2%), highest temperature increase (2.4 vs. 1.6 °C), systolic hypotension (6% vs. 2%), greatest decrease from baseline (40 vs. 62 mm Hg), diastolic hypotension (5% vs. 3%), and greatest decrease (30 vs. 28 mm Hg) (p > 0.05). Overall, IRAEs were less common in prophylactic treatment regimens (35 events [22%] in 162 infusions) than in treatment regimens (55 events [32%] in 169 infusions) (p < 0.05).

Conclusions:

This study demonstrates that patients with leukemia/BMT without myocardial or renal dysfunction who receive hydrocortisone and diphenhydramine as premedications can tolerate 2-hour central line infusions of prophylactic or treatment regimens of amphotericin B as well as 4-hour infusions.
Acute Myocardial Infarction Treatments in 58 Italian Hospitals: A Drug Utilization Survey
Authors: Venturini Francesca , Romero Marilena , Tognoni Gianni
Published: January 2017

Objectives:

To provide an updated and comprehensive profile of therapeutic practice in the management of acute myocardial infarction (AMI) in a sample of Italian hospitals, and to test the possible role of a network of hospital pharmacists in providing drug utilization data.

Design:

Prospective drug utilization survey. Participating pharmacists collected information on patients consecutively admitted to the hospital with a suspected AMI. The form reproduced those adopted in the Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto miocardico trials.

Setting:

Fifty-eight general hospitals in Italy belonging to the National Health Service, 6 of which are teaching hospitals. Thirty-four hospitals recruited patients from a coronary care unit, 10 from intensive monitoring beds in cardiology wards, and 14 from an intensive care unit.

Participants:

The study population consisted of patients consecutively admitted with a suspected AMI from May 31 through July 5, 1993.

Main Outcome Measures:

The management of AMI in terms of the use of drugs and nonpharmacologic treatments is described.

Results:

Of the 676 patients recruited for the study, 47.8% received thrombolytic therapy; alteplase was the preferred agent (55.4% of treated patients). The use of thrombolytic therapy varied significantly according to different demographic and clinical parameters such as age, sex, delay from the onset of symptoms to admission, and Killip scale class. During the first day of hospitalization 63.9% of patients received aspirin, 83.3% received nitrates, 24.8% received beta-blockers, and 77.1% received heparin therapy.

Conclusions:

Thrombolytic therapy was prescribed in a higher percentage of patients than is reported in the US, but lower than that reported in large trials. That a low percentage of patients who experienced a long delay between the onset of symptoms and admission as well as elderly patients received thrombolytic therapy reflects the lower expectations of clinicians for these subgroups of patients. A low proportion of patients received aspirin therapy. This study showed that in Italy an institutional network of hospital pharmacists could be interested observers of therapeutic practice, but further training is needed before high-quality data can be collected.
Vigabatrin-Associated Reversible Acute Psychosis in a Child
Authors: Martínez Andrés Cánovas , Ordovás Baines Juan Pablo , Marqués Marian Beltrán , Aparisi Amelia Escrivá , Cordón Fructuoso Delgado
Published: January 2017

Objective:

To describe a child with vigabatrin-associated reversible acute psychosis and review the literature reports on this adverse effect.

Case Summary:

A 7-year-old boy with intractable epilepsy developed acute psychosis 3 days after initiating a rapid vigabatrin dosage escalation. All symptoms resolved within 48 hours after vigabatrin therapy was withdrawn. Two months later, reinitiation of vigabatrin therapy using a slower dosage escalation was well-tolerated by the patient, and he currently is being treated with vigabatrin successfully.

Discussion:

Although vigabatrin-associated psychosis is rare, a few cases have been reported in predisposed adult patients, especially in the early stages of treatment. The mechanism of this reaction remains unclear and its incidence is unknown. To our knowledge, there has been no previous report of this adverse effect in children.

Conclusions:

Caution must be taken in children with predisposing factors at the beginning of vigabatrin therapy.
Rifabutin-Associated Uveitis
Authors: Tseng Alice L , Walmsley Sharon L
Published: January 2017

Objective:

To review rifabutin-associated uveitis and discuss the mechanism and potential role of drug interactions with clarithromycin and fluconazole in contributing to this adverse event.

Data Sources:

A MEDLINE search (1991 through September 1994) of English-language literature using the main MeSH headings “rifabutin” and “uveitis” and the subheadings “adverse effects” and “chemically induced.” Relevant articles also were selected from references of identified articles. Abstracts from recent medical conferences of infectious diseases, pharmacology, and HIV were screened for additional data.

Study Selection and Data Extraction:

All articles and abstracts reporting uveitis potentially related to rifabutin were considered for inclusion. Fifty-four cases were identified. Pertinent information from the case reports, as judged by the authors, was selected and synthesized for discussion.

Data Synthesis:

Rifabutin is being prescribed increasingly for the treatment and prophylaxis of Mycobacterium avium complex (MAC) infection in the HIV-infected population. Uveitis was initially thought to be a rare, dose-limited complication of rifabutin therapy. In an early dose-ranging tolerance study, uveitis was associated with daily doses of 1200 mg or more. Because this toxicity appeared to be dose-related, lower dosages (300–600 mg/d) of rifabutin were selected for study in subsequent clinical trials. More recent reports noting the association of uveitis with these lower dosages of rifabutin have raised concerns about the prevalence of this adverse event. In the 54 identified cases, patients presented with symptoms of unilateral or bilateral uveitis from 2 weeks to more than 7 months following initiation of rifabutin therapy. In all reported cases, patients were receiving concurrent therapy with clarithromycin and/or fluconazole, both of which have inhibitory effects on rifabutin metabolism. In most cases, uveitis resolved within 1–2 months following discontinuation of rifabutin with or without administration of topical corticosteroids.

Conclusions:

Rifabutin is prescribed frequently for the prophylaxis and treatment of MAC infection, especially in patients with HIV. Uveitis is a rare, dose-related toxicity of this therapy. The risk of rifabutin-associated uveitis may be increased in patients receiving concurrent therapy with clarithromycin or fluconazole because of drug interactions. Patients receiving therapy with combinations of any of these agents should be warned about signs and symptoms of uveitis and be monitored closely for the development of rifabutin toxicity. If uveitis develops, rifabutin therapy should be discontinued promptly.
Symptomatic Syndrome of Inappropriate Antidiuretic Hormone Secretion Associated with Azithromycin
Authors: Cadle Richard M , Darouiche Rabih O , Ashton Carol M
Published: January 2017

OBJECTIVE:

To report a case of symptomatic syndrome of inappropriate antidiuretic hormone (SIADH) secretion associated with azithromycin and review the literature related to this adverse drug reaction.

DATA SOURCES:

Review articles identified by a computerized (MEDLINE) (1966–April 1996) and manual ( Index Medicus) search.

DATA SYNTHESIS:

Azithromycin is a well-tolerated broad-spectrum macrolide antibiotic. We report a symptomatic case of SIADH secretion associated with azithromycin. The patient received two doses of azithromycin before the development of sudden mental status changes associated with severe hyponatremia. All other potential causes were ruled out. No previous reports exist in the literature.

CONCLUSIONS:

Azithromycin may be associated with symptomatic SIADH secretion. Awareness and attention are required if patients develop mental status changes or hyponatremia while receiving azithromycin so that appropriate diagnostic and therapeutic actions can be implemented.
Use of Estrogen Therapy in a Patient with Gastrointestinal Bleeding Secondary to arteriovenous malformations
Authors: Siple Jolene F , Joseph Carol L , Pagel Keith J , Leigh Sharon
Published: January 2017

OBJECTIVE:

To describe a patient with gastrointestinal (GI) bleeding caused by arteriovenous malformations (AVMs) that was treated with estrogen therapy.

CASE SUMMARY:

A 70-year-old white man was diagnosed with multiple AVMs in the cecum, duodenum, and stomach. Pharmacologic management included the use of ferrous sulfate; however, the patient continued to have recurrent bleeding that required multiple transfusions and endoscopic cauterization. Therapy was initiated with ethinyl estradiol 0.05 mg po qd; no further transfusions have been required for 10 months.

DISCUSSION:

It is estimated that AVMs of the GI tract account for 1–8% of upper GI bleeding episodes and up to 6% of lower GI bleeding episodes. Hormonal agents have been reported to decrease bleeding in patients with both hereditary and acquired AVMs.

CONCLUSIONS:

The role of estrogen therapy in treating AVMs of the GI tract is unclear and supported by only one clinical study.
Baclofen Toxicity in Patients with Severely Impaired Renal Function
Authors: Chen Kuo-Su , Bullard Michael J , Chien Yu-Yi , Lee Sheng-Yuan
Published: January 2017

OBJECTIVE:

To report the toxic effects of baclofen in patients with severely impaired renal function.

DATA SOURCES:

From 1991 to 1995, nine patients with severely impaired renal function (2 not receiving dialysis, 1 undergoing continuous ambulatory peritoneal dialysis [CAPD], and 6 receiving maintenance hemodialysis), who exhibited clinical toxicity after baclofen therapy at our hospital were included for analysis. Another seven cases from the literature obtained by computerized (MEDLINE) and manual ( Index Medicus) search methods published between 1980 and 1995 were also reviewed.

INTERVENTION:

Among our nine patients, the six undergoing chronic hemodialysis and one not undergoing dialysis received early (<48 h) hemodialysis after toxic symptoms developed. The patient undergoing CAPD received late hemodialysis (>72 h), and the other patient who had not undergone dialysis received only supportive care.

RESULTS:

A review of these 16 cases revealed that most patients received only small doses and very short-term baclofen therapy. Altered consciousness was the major presenting feature. Severe acute complications, such as seizures and respiratory depression, were relatively uncommon among patients with severely impaired renal function. However, abdominal pain, which has previously rarely been reported, was noted in five of our nine patients. Most patients showed clinical improvement after hemodialysis. An analysis of these nine patients revealed that those who received early hemodialysis had a shorter recovery time than the patient who received only supportive care (2.71 ± 0.42, respectively, vs. 9 d; p < 0.01). A lag of several hours between the end of the hemodialysis session and an improvement in the level of consciousness was noted.

DISCUSSION:

As most patients with severely impaired renal function developed toxic symptoms soon after initiating a low-dose baclofen regimen, the accumulated dosage was small and severe complications were less common. Abdominal pain may have occurred as a result of the γ-aminobutyric acid—mediated cholinergic effect exerted by baclofen. The delay in conscious recovery after hemodialysis may be due to a delay in the clearance of baclofen from the central nervous system.

CONCLUSIONS:

Patients with severely impaired renal function generally develop baclofen intoxication soon after the initiation of low-dose therapy. Thus, the administration of baclofen, regardless of the dosage, in these patients is not appropriate. Abdominal pain, in addition to altered consciousness, is a common presenting feature in patients with renal failure who have baclofen intoxication. Hemodialysis is effective in alleviating the clinical symptoms and shortening the recovery time for such patients.
Agranulocytosis Induced by Vancomycin or Ticarcillin/Clavulanate
Authors: Mandl Delbert L , Garrison Mark W , Palpant Samuel D
Published: January 2017

OBJECTIVE:

To reacquaint clinicians with a reportedly rare adverse event of agranulocytosis occurring after long-term administration of vancomycin and ticarcillin/clavulanate, with a subsequent review of other reported cases in the literature.

CASE SUMMARY:

A 45-year-old white woman with spina bifida developed agranulocytosis (2.7 × 103/mm3 white blood cells with only 3% polymorphonuclear leukocytes and no reported eosinophils or basophils) after long-term administration of vancomycin and ticarcillin/clavulanate for decubitus ulcers and chronic osteomyelitis. Consequently, the cell counts rebounded rapidly on discontinuation of both medications and returned to normal within 1 week.

DISCUSSION:

The incidence of vancomycin-associated neutropenia is presumably rare, but the increased use of vancomycin may disclose a more frequent occurrence. It is suggested that the mechanism for the reaction is immunologically mediated, yet this remains unclear. Although it is difficult to determine the causative agent in this case, vancomycin was most suspect clinically. Ticarcillin/clavulanate is less likely because our patient has since been readmitted and treated with oxacillin, imipenem/cilastatin, and amoxicillin/clavulanate without affecting the white blood cell count. In that regard, it could be reasoned that an immunologic reaction to ticarcillin would have resulted in a similar outcome with other penicillins.

CONCLUSIONS:

This case serves as a reminder to clinicians that patients receiving long-term treatment with vancomycin should have their white blood cell count monitored at least weekly.
Recombinant Human Tumor Necrosis Factor Receptor (P75) Fc Fusion Protein (Tnfr: Fc) in Rheumatoid Arthritis
Authors: Murray Kim M , Dahl Stephen L
Published: January 2017

BACKGROUND:

Tumor necrosis factor (TNF) is the dominant mediator of the cytokine cascade that causes inflammation and joint destruction in rheumatoid arthritis. A new class of agents under investigation, the biologic TNF inhibitors, inhibits the activity of TNF. Recombinant human TNF receptor p75 Fc fusion protein (TNFR: Fc; Enbrel) blocks the activity of the cytokine TNF. The preclinical, Phase I, and Phase II data of TNFR: Fc in rheumatoid arthritis are reviewed in this article.

METHODS:

All available data on TNFR: Fc in rheumatoid arthritis were reviewed. These data included published literature and data on file at the manufacturer.

RESULTS:

TNFR: Fc has been effective in many models of inflammation, including animal models of rheumatoid arthritis and in clinical rheumatoid arthritis trials. Conclusions from a study with TNFR “knockout” mice (genetically altered mice incapable of producing TNFR proteins) demonstrated that p75 TNFR is a natural antagonist of TNF-mediated inflammation. A placebo-controlled, dose-escalation, Phase I trial evaluated the safety and efficacy of TNFR: Fc in patients with rheumatoid arthritis. There were no serious adverse effects reported. A Phase II, randomized, double-blind, placebo-controlled trial evaluated 180 patients with active rheumatoid arthritis whose previous therapy had failed. A dose-response relationship was observed in the number of tender and swollen joints; patients who received the highest dose (16 mg/m2) of TNFR: Fc had the greatest improvement. Treatment was generally well tolerated. TNFR: Fc is nonimmunogenic; no antibodies to TNFR: Fc have been detected thus far in human studies.

CONCLUSIONS:

Preliminary data indicate that TNFR: Fc is an excellent candidate for future long-term studies in the treatment of rheumatoid arthritis.
Prehospital-Initiated Thrombolysis
Authors: Spinler Sarah A , Mikhail Peter A
Published: January 2017

OBJECTIVE:

To evaluate the feasibility, safety, and efficacy of prehospital-initiated thrombolysis in decreasing the mortality rate due to acute myocardial infarction.

DATA SOURCES:

English-language clinical studies, abstracts, and review articles identified from MEDLINE searches and bibliographies of identified articles. Epidemiologic data were extracted from the Internet.

STUDY SELECTION:

Eight randomized clinical trials and two metaanalyses that compared prehospital-initiated thrombolysis with in-hospital-initiated thrombolysis.

DATA EXTRACTION:

Pertinent studies were selected and the data were synthesized into a review format.

DATA SYNTHESIS:

Early reperfusion of an infarct-related coronary artery is associated with lower mortality rates. Most of the delay in initiating treatment is caused by patient delay rather than transport delay or hospital delay. In addition, more than 30% of eligible patients do not receive thrombolytic therapy. Prehospital initiation of thrombolysis has been evaluated as a means of decreasing hospital delay and increasing the number of eligible patients receiving thrombolysis. Clinical trials document that prehospital-initiated thrombolysis is feasible and safe, and saves time. Of the eight randomized trials, three demonstrated a decrease in either cardiac or total mortality with prehospital thrombolysis. All studies were limited by relatively small sample sizes. Two published metaanalyses suggest a 16-17% reduction in mortality with prehospital thrombolysis. In the US, prehospital thrombolysis is not routinely recommended due to medical issues related to diagnostic accuracy and monitoring, legal concerns, and economic implications. Additional strategies, such as community-wide education and prehospital diagnostic electrocardiograms (ECGs), are being studied.

CONCLUSIONS:

In clinical trials, prehospital-initiated thrombolytic therapy was shown to be safe and probably more effective than in-hospital administration of thrombolytic therapy, but this has not proven feasible in the US at this time. Despite time-savings by decreasing treatment delay with prehospital-initiated thrombolysis, patient delay still persists and accounts for the majority of delay. Future investigations will center on increasing the number of patients treated with thrombolytic agents through patient education, in-patient and out-patient programs that rapidly identify eligible patients, as well as prehospital diagnostic ECGs.
The Effects of Rotation on Radiographic Evaluation of the Tibiofibular Syndesmosis
Authors: Pneumaticos Spiros G. , Noble Philip C. , Chatziioannou Sofia N. , Trevino Saul G.
Published: January 2017

Radiographs of 12 normal cadaveric lower extremities were prepared with each extremity in seven increments of axial rotation, ranging from 5° of external rotation to 25° of internal rotation. The tibiofibular clear space, the tibiofibular overlap, the width of the tibia and fibula, and the medial clear space were measured on each film.

The width of the tibiofibular clear space (syndesmosis A) averaged 3.9±0.9 mm (range, 2 to 5.5 mm), but did not change significantly with rotation. Its size was independent of the size of tibia and fibula. All other measurements changed dramatically with rotation.

In our specimens, a true mortise view of the ankle joint was obtained by internally rotating the extremity an average of 13.6±0.7° (range, 12.0° to 17.0°).

Based on our results the width of the tibiofibular clear space on the anterior-posterior view is the most reliable parameter for detecting widening of the syndesmosis on plain radiographs. However, due to its variability among different individuals, comparison views of the contralateral extremity are warranted for confirmation of clinical suspicion of syndesmosis disruption.
The Orthopaedic Research Institute-Ankle Strength Testing System: Inter-Rater and Intra-Rater Reliability Testing
Authors: Paoloni Justin A. , Appleyard Richard C. , Murrell George A.
Published: January 2017

Achilles tendinosis is a degenerative overuse tendinopathy involving the primary ankle plantarflexors, namely the soleus and gastrocnemius muscles forming the tendo Achilles. The Orthopaedic Research Institute-Ankle Strength Testing System (ORI-ASTS) was designed to record objective measurements of force generated with a resisted ankle plantarflexion test. Testing normal subjects (n=6) was used to establish the reliability of the ORI-ASTS for measuring ankle plantarflexion force. Testing patients with Achilles tendonitis (n=5) over time and comparing Achilles tendon analogue pain scores to ankle plantarflexion force measurements was used to assess the validity of the ORI-ASTS for monitoring progression of Achilles tendinopathy.

Inter-rater reliability of the ORI-ASTS with normal subjects was excellent, with single measure intraclass correlation coefficients (ICC) for right mean peak force of 0.92, left mean peak force of 0.96, right mean total force of 0.89, left mean total force of 0.91. The ORI-ASTS also had excellent intra-rater reliability for normal subjects with the following single measure ICC scores: right mean force 0.96, left mean force 0.92, right mean total force 0.97, left mean total force 0.92. The relative technical errors of measurement were calculated from these results, and ranged from 1.0% to 2.7%.

Testing patients with Achilles tendinosis (n=5), and comparing analogue activity pain scores to ORI-ASTS testing demonstrated a strong negative relationship between the two parameters (Spearman Rho −0.87 to −1.0, Kendall tau b −0.82 to −1.0). The relationship was statistically significant at the p=0.01 level for two of the five patients.

The ORI-ASTS shows excellent reliability for testing ankle plantarflexor force, and appears valid for objectively assessing and monitoring patients with Achilles tendinosis.
The Relationship of the Anterior Drawer Sign to the Shape of the Tibial Plafond in Chronic Lateral Instability of the Ankle
Authors: Kanbe Katsuaki , Hasegawa Atsushi , Nakajima Yasushi , Takagishi Kenji
Published: January 2017

To determine what factors correlate with values for tested anterior drawer (AD) sign, we investigated stress radiographs in 71 patients with severe chronic lateral instability of the ankle as well as 320 normal controls. We found no correlation between AD and talar tilt (TT), but measurement of the anterior tip ratio (ATR) (ATR=tanA × 100) demonstrated a link of ATR with AD (r=0.74, p<0.001). The posterior tip ratio (PTR) (PTR=tanP × 100) was not correlated with AD (r=0.34, p=0.16). The ankle mortise angle (AMA) (the anterior opening of the lateral ankle mortise) was also not correlated with AD (r=0.27, p=0.23).

Investigation of 320 normal ankles revealed a mean ATR of 9.1%±1.4%. The ATR in patients was 7.6%±1.7%, significantly lower than in the control patients. The values in female patients with chronic lateral instabilities were significantly less than the values in the females in the control group. But values for male patients were not different from the control group. Thus the anterior tip of the lateral tibial plafond, as it affects the ATR, may influence instability in anterior drawer function, especially in female patients with chronic lateral ligamentous instability of the ankle.
Proprioception of the Ankle: A Comparison Between Female Teenaged Gymnasts and Controls
Authors: Aydin Taner , Yildiz Yavuz , Yildiz Cemil , Atesalp Sabri , Kalyon Tung Alp
Published: January 2017

Proprioceptive mechanisms appear to play a role in stabilizing the joints and may serve as a means for interplay between static stabilizers and dynamic muscular restraints. The purpose of our study was to investigate whether or not gymnastic training has any effect on the balance and on proprioception in an ankle, as seen in gymnasts and in nongymnasts. We evaluated the proprioceptive ability of the ankle using four different tests (a one-leg-standing test, a single-limb-hopping test, an active angle-reproduction test, and a passive angle-reproduction test). Proprioception of the ankle was measured in 40 subjects who were assigned to two experimental groups. Group 1 (n: 20) were healthy control subjects, and group 2 (n: 20) were teenaged female gymnasts.

The sense of position of a joint was actively measured using a Cybex NORMTM isokinetic dynamometer and measured passively with a proprioception-testing device. A Mann-Whitney U test was used to compare mean values of the gymnasts to the controls. Results revealed statistically significant differences (p<0.05) between two groups. We found no statistically significant differences between the dominant and nondominant ankle in volunteers or in gymnasts, in all tests. The results of this study suggest that gymnastic training has a positive influence on sense of position of the ankle joint and on balance, in addition to increasing muscle tone.
Management of the Neuromuscular Foot Deformities with the Llizarov Method
Authors: Kucukkaya Metin , Kabukcuoglu Yavuz , Kuzgun Unal
Published: January 2017

Nine feet of eight patients with neurologic foot deformities caused from poliomyelitis, Charcot-Marie-Tooth disease, and traumatic nerve injury were treated with V-osteotomy and the llizarov method. A painless and plantigrade foot was obtained in all but one patient. A residual deformity occurred in this case because of the soft-tissue problems during the correction period. No major complication had been encountered by the latest follow-up at a mean of 42 months. The results of the current study indicate that the V-osteotomy and the llizarov method, while technically difficult, is an effective method for correcting neurologic foot deformities and obtaining a stable, plantigrade, painless foot, especially when complicated with other lower leg problems (i.e., leg length discrepancy, joint contractures).
A Comparison of Two Analytical Techniques for Detecting Differences in Regional Vertical Impulses Due to Plantar Fasciitis
Authors: Wearing Scott C. , Smeathers James E. , Urry Stephen R.
Published: January 2017

The vertical impulse distribution beneath the foot has been shown to be a useful objective method for evaluating gait and the efficacy of treatment programs. However, recent studies employing similar methods, but different analytical techniques, have reached divergent conclusions regarding the effect of plantar fasciitis on hindfoot, midfoot and forefoot impulses. The aim of the current study was to determine whether the impulse distribution beneath the hind-foot, midfoot and forefoot in subjects with, and without, plantar fasciitis was dependent on the analytic technique employed. A pressure platform was used to collect impulse estimates from 16 subjects with plantar fasciitis, and 16 control subjects, while walking at their preferred speed. The findings indicate that an impulse calculation incorporating the position of the center of pressure is more effective in detecting alterations in gait than the conventional method of estimating the impulse distribution beneath the foot. This study also demonstrates that subjects with plantar fasciitis possess modified gait patterns that are primarily manifest by a reduced hindfoot and an increased midfoot impulse, as defined by the pathway of the center of pressure.
An Unusual Case of Bilaterally Symmetrical Neuropathic Osteoarthropathy of the Midfoot as a Result of Lyme Disease-Induced Peripheral Neuropathy: A Case Report
Authors: Adams Heiko B. , Blasko Gregory A. , DiDomenico Lawrence A.
Published: January 2017

The first known report of a patient with Lyme Disease-induced peripheral neuropathy resulting in bilaterally symmetrical “Charcot” changes of the midfoot is reported. An extensive review of the literature failed to produce any known cases of neuropathic osteoarthropathy that would be linked directly or indirectly with Lyme Disease-Induced peripheral neuropathy. The relationship between Lyme Disease, the secondary neurologic manifestations caused by the infection, and neuropathic osteoarthropathy are discussed.
Microscopic Metallic Wear and Tissue Response in Failed Titanium Hallux Metatarsophalangeal Implants: Two Cases
Authors: Ghalambor Navid , Cho David R. , Goldring Steven R. , Nihal Aneel , Trepman Elly
Published: January 2017

The membranes present at the implant-bone interface were retrieved from two patients with titanium single stem hallux implants that had failed. Both patients had pain and valgus deformity of the hallux, and radiographs showed a radiolucent shadow around the implant stem, with thinning of the dorsal cortex of the proximal phalanx in one patient. After removal of the implants, arthrodesis of the first metatarsophalangeal (MP) joint was performed. Histologic analysis of the membrane tissue at the implant-bone interface showed a synovial-like appearance. There was a fibrous tissue stroma adjacent to the bone surface, with multiple regions of scalloping covered by mononuclear cells. Fine metallic debris was seen throughout the fibrous tissue. Multinucleated foreign body giant cells were sparsely observed associated with fine particulate metallic wear debris similar to observations from failed total hip arthroplasties. The histologic appearance is evidence that foreign-body granulomatous infiltration associated with metallic wear debris may be a causative factor of peri-implant osteolysis leading to aseptic loosening and failure of titanium single stem hallux implants.
Arthrodesis of the Ankle for Non-Inflammatory Conditions—Healing and Reliability of Outcome Measurements
Authors: Anderson Thomas , Montgomery Fredrik , Besjakov Jack , Verdier Hans , Carlsson Åke
Published: January 2017

This is a retrospective study of 30 consecutive primary ankle arthrodeses in 29 patients with osteoarthrosis, operated on in our hospital between 1984 and 1994. Two different techniques were utilized: internal fixation with screws or external fixation using Charnley or Hoffman frames. Only 25 ankles in 24 patients were available for clinical examination. They were examined by two independent surgeons on an average of 51 months after surgery (13 to 187 months). Two radiologists separately examined the radiographs that were available — in this case, 29 ankles, without knowledge of clinical data, and 26/29 (89%) were unanimously considered as fused. This is comparable with what is reported in other series. Unanimity among all four observers regarding healing of the arthrodesis occurred in 20/25 ankles (80%).

We consider that both a radiological and a clinical evaluation is important for a fair judgement of fusion. We found high consistency among the observers with respect to the clinical scores. However, the consistency was somewhat better for the Mazur than for the Kofoed system.
Incidence of DVT following Surgery of the Foot and Ankle
Authors: Solis Gregory , Saxby Terence
Published: January 2017

A prospective study was undertaken to establish the incidence of deep vein thrombosis (DVT) in patients who had undergone surgery of the foot and ankle. All consecutive patients who underwent foot and ankle surgery in the senior author's practice had duplex ultrasound performed of the bilateral calves at the first postoperative visit. Of 201 patients, deep calf clots were found in seven patients (3.5%), but none of these showed progression on follow-up ultrasound or extension proximal to the calf. By the authors' criteria, none of the studied patients required treatment. The authors feel that the rate and progression of DVT after foot and ankle surgery is low and does not require routine prophylaxis. Factors associated with risk of DVT formation were postoperative immobilization, hindfoot surgery, tourniquet time and advancing age.