Managing nocturnal breakthrough pain.
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Analgesia, Patient-Controlled↗
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Factors associated with relapse during maintenance treatment of affective disorders.
Five case studies were selected from a group of 22 patients with affective illness who have been followed during carbamazepine prophylaxis in an NIMH naturalistic prospective followup study. They highlight several factors which may be associated with relapse during maintenance treatment: (1) noncompliance; (2) breakthrough episodes with dose reduction; (3) illness exacerbation during psychosocial stress; and (4) progressive emergence of the illness or tolerance to therapeutic effects of psychotropic medications. Attention to these factors may lead to new and better management, as illustrated in case 5. The utility of a life charting approach is emphasized in delineating past and present course of illness, considering the relevance of cycling pattern and past treatment efficacy in selection of present pharmacological interventions, and helping to formulate a multifactorial concept of the interplay of biological and psychosocial factors in the evolution or exacerbation of mood disorders. Clinical recommendations and new areas of study are offered for a more comprehensive approach to maintenance treatment of affective disorders.
Adult↗
Modulation of blood flow following excision of a high-flow cerebral arteriovenous malformation. Case report.
The authors present a case in which a large high-flow arteriovenous malformation was totally excised. The success of the operation was in part attributed to the prevention of hyperperfusion breakthrough phenomena by the use of Selverstone clamps on the cervical carotid artery. Monitoring of cortical blood flow during surgery was found to be helpful.
Cerebral Angiography↗
Cancer therapy and the randomized clinical trial. Good medicine?
True improvements in the treatment of cancer--by the introduction of new drugs or novel drug combinations, new therapeutic modalities, or technologic improvements of old modalities--result in higher response rates and prolonged survival when compared with existing therapies. When a new treatment convincingly meets the test of improving survival rates or, at worst, improving patients' quality of life, it becomes the accepted standard of care if its side effects are acceptable and its cost is not prohibitive. Improved therapeutic results can be demonstrated only by clinical trials with an adequate numbers of patients, appropriate control subjects, and a sufficient duration of follow-up. Therapeutic breakthroughs are revolutionary advances in treatment, usually rapidly and dramatically obvious in comparison with historic controls; demonstration of benefit in these cases does not usually require randomized trials. Much more common, however, are new therapies that represent modest, incremental advances over existing treatment and that usually require randomized comparison trials to demonstrate convincingly statistically significant improvement. A randomized clinical trial should test an important hypothesis. It must be carefully designed to ensure that both groups of patients are comparable in terms of various prognostic variables and to minimize subtle sources of bias. An honest belief that both arms of the trial are a priori equal must be maintained. Meeting these criteria, the randomized clinical trial offers to the individual cancer patient treatment that should be at least equal to the best available nonexperimental therapy. This equates with Good Medicine.
Cost-Benefit Analysis↗
Prospective study on fungemia in children with cancer: analysis of 35 cases and comparison with 130 fungemias in adults.
The aim of this prospective study on fungemia in children with cancer compared with adults with cancer appearing during the last 10 years in a pediatric hospital and in national cancer institutions was to investigate risk factors, etiology, therapy, complications and outcome. Univariate analysis showed significant differences in 35 children with cancer and fungemia in comparison with 130 cases of fungemias in adults with cancer. It was found that (1) therapy with corticosteroids (40 vs 18.5%, P<0.03), (2) breakthrough fungemia during ketoconazole prophylaxis (20 vs 7.7%, P<0.025), and (3) meningitis as a complication of fungemia (11.4 vs 0.8%, P< 0.001) occurred more frequently in the pediatric subgroup with fungemia. Candida albicans was more common as the causative agent of fungemia among adults (58.5 vs 37.1, P<0.02) than in children. However, mortality was similar in children with cancer and in adults with cancer and fungemia (31.4 vs 23.1%, NS). Comparison of risk factors revealed no differences between adults and children with cancer and fungemia except in etiology, breakthrough fungemia during prophylaxis with ketoconazole, prior therapy with corticosteroids and meningitis as a complication. The outcome was also similar in pediatric and adult cancer patients with fungal bloodstream infection.
Adolescent↗
Failure of malaria chemoprophylaxis with a proguanil-chloroquine combination in Papua New Guinea.
Proguanil 200 mg daily and chloroquine base 300 mg weekly were used as prophylaxis for 120 British Army soldiers from Hong Kong on a seven-week jungle exercise in the highly malarious Sepik district of Papua New Guinea. Compliance was rigidly enforced. Four men developed falciparum malaria whilst in Papua New Guinea and one within a few days of returning to Hong Kong. After stopping chloroquine four weeks after returning to Hong Kong 11 cases of mixed vivax and falciparum malaria and three cases of falciparum alone occurred within a 16-week period. This proguanil-chloroquine combination allows an unacceptably high level of breakthrough malaria and cannot be recommended for visitors to the highly malarious areas of Papua New Guinea.
Chloroquine↗
Localization of septal pacing sites in the dog heart by epicardial mapping.
To examine whether different septal pacing sites could be distinguished by their epicardial activation patterns, six to eight stimulating electrodes were placed throughout the septum in seven open chest dogs. Unipolar electrograms were obtained from 52 epicardial electrodes during pacing from each stimulating electrode and isochronous epicardial maps were constructed. The location of each stimulating electrode was found by dissection, and its distance from the overlying epicardium was measured. To allow comparison among epicardial maps, the septum was conceptually subdivided into nine regions to which stimulating electrodes were assigned. Epicardial activation patterns from the same region were similar and these patterns allowed the region containing a stimulating electrode to be identified in many cases. Three other variables were found to have additional localizing value. There were: 1) the time from the stimulus to epicardial breakthrough, 2) the duration of epicardial activation, and 3) the area of epicardium activated in the first 5 ms after epicardial breakthrough. For those stimulating electrodes that could not be localized by their epicardial activation patterns, the distance of the stimulating electrode beneath the epicardium was well fit from these three variables by multiple regression (correlation coefficient [r] = 0.97). Thus, using all the previous factors, localization of septal pacing sites was possible in the noninfarcted dog heart by epicardial mapping.
Animals↗
Discovery, innovation and the cyclical nature of the pharmaceutical business.
Unlike many recent articles, which paint the future of the pharmaceutical industry in gloomy colours, this article provides an optimistic outlook. It explores the foundations on which the pharmaceutical industry has based its outstanding successes. Case studies of important drug classes underpin the arguments made and provide the basis for the authors' argument that recent technological breakthroughs and the unravelling of the human genome will provide a new wave of high quality targets (substrate) on which the industry can build. The article suggests that in a conducive environment that understands the benefits that pharmaceuticals provide to healthcare, those players who can base their innovation on a sufficient scale and from a large capital base will reshape the industry.
Drug Design↗
Hydrophobic interaction chromatography of proteins. II. Binding capacity, recovery and mass transfer properties.
Hydrophobic interaction chromatography media suited for large scale separations were compared regarding dynamic binding capacity, recovery and mass transfer properties. In all cases, pore diffusion was the rate limiting step. Reduced heights equivalent to a theoretical plate for bovine serum albumin derived from breakthrough curves at reduced velocities between 60 and 1500 ranged from 10 to 700. Pore diffusion coefficients were derived from pulse response experiments for the model proteins alpha-lactalbumin, lysozyme, beta-lactoglobulin, bovine serum albumin and immunoglobulin G. Diffusivity of lysozyme did not follow the trend of decreasing diffusivity with increasing molecular mass, as observed for the rest of the proteins. In general, mass transfer coefficients were smaller compared to ion-exchange chromatography. Dynamic binding capacities for the model protein bovine serum albumin varied within a broad range. However, sorbents based on polymethacrylate showed a lower dynamic capacity than media based on Sepharose. Some sorbents could be clustered regarding binding capacity affected by salt. These sorbents exhibited a disproportional increase of binding capacity with increasing ammonium sulfate concentration. Recovery of proteins above 75% could be observed for all sorbents. Several sorbents showed a recovery close to 100%.
Chromatography, Liquid↗
Current approaches to the molecular and physiological basis of cystic fibrosis.
Cystic fibrosis (CF) is the most common disease caused by a single gene abnormality within the caucasian population. Its severity of expression in homozygotes varies widely, and the disease involves multiple organ systems. During the past few years, major advances in CF research have been made. These advances have occurred primarily in the fields of physiology and molecular genetics. As a result of these advances, it is now generally accepted that the basic defect in CF is the inability of an epithelial chloride channel to respond to adrenergic stimulation in affected organs. The recent major breakthrough in CF research is the localization of the CF gene and identification of the mutation responsible for the majority of cases of CF. In this article, the evidence which has led to this conclusion, as well as possible mechanisms by which a mutation in a single codon can produce the CF defects are reviewed. Finally, new approaches to the characterization of the CF gene by complementation of the defect in immortal cell lines displaying the transport phenotype associated with CF are discussed.
Blood Proteins↗
Breakthrough time of a respirator cartridge for carbon tetrachloride vapor flow of workers' respiratory patterns.
Breakthrough times of a commercially-available respirator cartridge packed with a small amount of activated carbon were determined by three different flow patterns: workers' respiratory patterns, conventional steady-state flows, and three standard patterns consisting of rectangle, sine, and triangle waves. A mechanical breathing simulator was used to reproduce the three standard wave patterns as well as the workers' respiratory patterns, which had been recorded from three workers of a paint manufacturing plant wearing a gas mask equipped with a respirator cartridge. The breakthrough test was carried out with 300 ppm carbon tetrachloride vapor at average flow rates of the respiratory and standard patterns equivalent to the steady-state flow rates. The breakthrough times determined by the workers' respiratory patterns were found to be shorter than those by a steady-state flow of the equivalent flow rate, and to be as short as those by sine and triangle wave patterns. It was considered that shorter breakthrough times in the workers' respiratory patterns could be attributed to a faster maximum inspiratory flow rate than that in the case of steady-state flow. The present results suggest that the passing time of CCl4 molecules through the thin activated carbon layer of respirator cartridge may be too short to attain an adsorption equilibrium.
Adolescent↗
Cancer therapy and the randomized clinical trial: good medicine?
True improvements in the treatment of cancer--by the introduction of new drugs or novel drug combinations, new therapeutic modalities, or technologic improvements of old modalities--result in higher response rates and prolonged survival when compared with existing therapies. When a new treatment convincingly meets the test of improving survival rates or, at worst, improving patients' quality of life, it becomes the accepted standard of care if its side effects are acceptable and its cost is not prohibitive. Improved therapeutic results can be demonstrated only by clinical trials with an adequate numbers of patients, appropriate control subjects, and a sufficient duration of follow-up. Therapeutic breakthroughs are revolutionary advances in treatment, usually rapidly and dramatically obvious in comparison with historic controls; demonstration of benefit in these cases does not usually require randomized trials. Much more common, however, are new therapies that represent modest, incremental advances over existing treatment and that usually require randomized comparison trials to demonstrate convincingly statistically significant improvement. A randomized clinical trial should test an important hypothesis. It must be carefully designed to ensure that both groups of patients are comparable in terms of various prognostic variables and to minimize subtle sources of bias. An honest belief that both arms of the trial are a priori equal must be maintained. Meeting these criteria, the randomized clinical trial offers to the individual cancer patient treatment that should be at least equal to the best available nonexperimental therapy. This equates with Good Medicine.
Clinical Trials, Phase I as Topic↗
Pill method failures.
This is a study over a four year period from November 1981 to December 1985 documenting 163 cases of pill method failures in reliable pill takers. In over one third of these cases (36%) there were no predisposing factors. Significant factors which were associated with failure were diarrhoea and/or vomiting in 35%, and breakthrough bleeding on the combined pill in 21%. While there is controversy in the literature about the role of antibiotics in causing pill failure, this study found 23% of failures associated with antibiotic use. Two failures occurred on anticonvulsant medication. Recommendations are made for improved instructions to patients.
Abortion, Induced↗
[Treatment of erectile dysfunction using intracavernous pharmacotherapy].
Intracavernous injection of vasodilators has been the greatest diagnostic and therapeutical breakthrough in erectile dysfunction (E.D.). After 15 years experience, these vasodilators have demonstrated efficacy rates over 85%. This suggests that most cases of E.D. are the result of and inability of the smooth muscle to relax. This paper presents an overview of the diagnostic and therapeutic use of intracavernous vasodilating drugs. It includes an extensive review of the literature and our personal series with regard to efficacy, indications, contraindications and side-effects of these compounds. Alprostadil i.c. injection (PGE1) is an effective (> 70%) and safe treatment, and its use has been accompanied by an increased quality of life of patients, with very few side effects. Currently, PGE1 is a first choice drug in the treatment of impotence. When no response is seen, or pain develops after PGE1 administration, a number of vasoactive compounds associations can be used instead (phentolamine + PGE1, papaverine + phentolamine, and papaverine + phentolamine + PGE1). The phentolamine + VIP association has shown encouraging results. Prior to prescribe IC treatment with vasoactive drugs it is necessary to conduct a basic diagnostic study, and advise the patient. If treatment is finally accepted, the performance of adequate training and detailed medical follow-up is crucial.
Contraindications↗
An effective way to manage breakthrough pain.
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Analgesics, Opioid↗
[Ventricular pseudoaneurysm. Clinical and echocardiographic evolution].
The case of a patient with cardiac rupture following a myocardial infarction is presented. The rupture led to the formation of a ventricular pseudoaneurysm that was occupied by a thrombus that sealed the breakthrough point. The patient has survived without surgical treatment during the last 5 years.
Echocardiography, Transesophageal↗
Cefotaxime-ciprofloxacin combination therapy for nontyphoid Salmonella bacteremia and paravertebral abscess after failure of monotherapy.
Therapeutic failure of monotherapy with either a third-generation cephalosporin or a fluoroquinolone against nontyphoid salmonellae has been observed in clinical practice. Combination therapy with both agents is recommended in the literature for treating life-threatening infections. However, we know of no published case reports that indicate a therapeutic advantage of this combination therapy for nontyphoid salmonellae infections. We describe a 60-year-old man who had breakthrough bacteremia with vertebral osteomyelitis and paravertebral abscess caused by Salmonella enterica serotype Choleraesuis. This was not controlled with sequential monotherapy but was eventually cured with cefotaxime-ciprofloxacin combination therapy. The Etest showed that the strain was susceptible to cefotaxime and ciprofloxacin, but resistant to nalidixic acid. Cefotaxime and ciprofloxacin in combination may be considered as an option for difficult-to-treat salmonellosis.
Abscess↗
Selection of a hepatitis B virus strain resistant to adefovir in a liver transplantation patient.
BACKGROUND/AIMS: In contrast to lamivudine, adefovir dipivoxil (ADV) therapy is associated with delayed and infrequent selection of drug resistant hepatitis B virus (HBV). METHODS: A 52 year-old man was treated with lamivudine for an HBV recurrence on his liver graft. A viral breakthrough was observed and the patient received ADV. Serum HBV DNA decreased rapidly and lamivudine was discontinued while ADV monotherapy was maintained. Serum HBV DNA levels remained suppressed until a second breakthrough was observed. Lamivudine was then reintroduced together with ADV, and serum HBV DNA became undetectable by polymerase chain reaction. RESULTS: Sequence analyses of the HBV polymerase gene revealed a sequential selection of lamivudine resistance mutations L180M+M204V, followed by a reversion to wild-type, and subsequently the selection of a novel adefovir resistance mutation N236T. Phenotypic analyses in cell culture assays demonstrated that the HBV isolates at the time of ADV breakthrough had reduced susceptibility to ADV. This mutant remained sensitive to lamivudine, entecavir and emtricitabine in vitro. CONCLUSIONS: We describe the first case of sequential selection of lamivudine and adefovir resistant strains of HBV in a liver transplantation patient. The selection of the N236T polymerase mutant was associated with resistance to ADV but remained sensitive to lamivudine in vitro and in vivo.
Adenine↗