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[Danger of sinoatrial block and the use of antiarrhythmic agents in myocardial infarcts].

Nine cases of major ventricular arrhythmia (tachycardia (VT), fibrillation (VF), torsades de pointe) are reported in patients with sequellae of myocardial infarction but without residual angina or cardiac failure. --Six of these disturbances of excitability occurred after a bradycardia due to sino atrial block (SAB) which favoured the breakthrough of abnormal automatic foci. This form of the bradycardia-tachycardia syndrome was demonstrated by endocavitary electrophysiological exploration.. These were the only cases of major ventricular arrhythmia observed in a series of 88 SABs. Reputedly benign, they illustrate the potential gravity of a conduction defect in patients with sequellae of myocardial infarction. --Three other cases of abnormal ventricular excitability complicating the administration of 1 mg/kg of Ajmaline to test for paroxysmal block after myocardial infarction. These were the only cases of VT observed in a series of 800 Ajmaline tests. The three patients have had no further episodes of VT after 1 year's follow-up. On the other hand, in 43 Ajmaline tests without VT in patients with myocardial infarction, 6 cases of VT and 1 lethal VF were later observed. This demonstrates the lack of significance of episodes of VT during Ajmaline tests, the depressant action of the drug on intracardiac conduction favouring the initiation of reentry. In conclusion, a history of myocardial infarction exposes the patient to the risk of major ventricular arrhythmias in SAB, the detection of which should indicate pacemaker therapy from the first symptoms. The use of an intravenous antiarrhythmic agent should be avoided as it may aggravate arrhythmias. However, the arrhythmia is of no prognostic significance.

Aged↗

Distributions of local oxygen saturation and its response to changes of mean arterial blood pressure in the cerebral cortex adjacent to arteriovenous malformations.

BACKGROUND AND PURPOSE: To test the hypothesis that neither "steal" as cortical ischemia caused by reduced perfusion pressure nor "breakthrough" on the grounds of loss of pressure autoregulation exist in brain tissue surrounding arteriovenous malformations (AVMs), we established patterns of cortical oxygen saturation (SO(2)) adjacent to AVMs and its behavior after alterations of mean arterial blood pressure. METHODS: With a microspectrophotometer, SO(2) was scanned in the cortex around AVMs of 44 patients before and after resection and in that of a non-AVM group (n=42) before transsylvian dissection. Autoregulation was evaluated by linear regression analysis after elevation of mean arterial blood pressure (5 microg/min IV noradrenaline). SO(2) values were calculated as medians, percentage of critical values (<25% SO(2)), and coefficients of variance (approximate heterogeneity of SO(2) distributions). All values are given as mean+/-SD. RESULTS: Forty patients with AVM had an uneventful postoperative course (group A). Four hyperemic complications ("breakthrough") occurred (group B). Autoregulation was tested intact in all groups at all times. Preoperative SO(2) distributions in groups A and C (non-AVMs) were identical. In group B, significantly (P<0.05) lower medians (group A, 52.9+/-16.3%; group B, 44.2+/-17.1%; group C, 51.9+/-11.5% SO(2)), more critical values (group A, 6.5+/-5.1%; group B, 14.7+/-11.1%; group C, 7.1+/-4.9%), and heterogeneous SO(2) distributions (group A, 20.2+/-12.7%; group B, 27.9+/-12.4%; group C, 26.8+/-10.9%) were seen. Increase of median values was significantly higher in group B (76.3+/-10.4% SO(2)) than in group A (65.9+/-13.4% SO(2)) after resection. CONCLUSIONS: Severely hypoxic areas are uncommon in the cortex adjacent to AVMs and occur predominantly in patients prone to hyperemic complications. Reduced perfusion pressure is compensated in most cases, and moderate hyperemia prevails after excision. Reperfusion into unprotected capillaries of severely hypoxic cortical areas results in "breakthrough," for which vasoparalysis appears not to be the underlying mechanism.

Adolescent↗

High-performance liquid chromatography of amino acids, peptides and proteins. CIX. Investigations on the relation between the ligand density of cibacron blue immobilized porous and non-porous sorbents and protein-binding capacities and association constants.

A porous silica of nominal 5 microns particle diameter and 30 nm pore size (Nucleosil 300-5) and a non-porous silica of nominal 1.5 microns particle diameter were activated with 3-mercaptopropyltriethoxysilane (MPTS), followed by the immobilization of the triazine dye, Cibacron Blue F3GA. Various biomimetic dye sorbents with graduated ligand densities between 1 mumol/m2 and 0.01 mumol/m2 were prepared. The capacities and the association constants associated with the binding of lysozyme to these sorbents were determined by frontal analysis experiments [J. Chromatogr., 476 (1989) 205-225]. Due to the ability of the Cibacron Blue F3GA-modified silicas to act as mixed mode coulombic and hydrophobic interaction sorbents and the highly charged nature of the surface structure of lysozyme (pl 11), two mobile phase conditions were examined. In one case a 0.1 M phosphate buffer, pH 7.8, was used as the equilibration and loading buffer, in the second case 1 M sodium chloride-0.1 M phosphate buffer, pH 7.8 was employed as the equilibration and loading buffer to monitor the influence of ionic interactions. The elution was performed in each case with a 2.5 M potassium thiocyanate solution. With the porous silica dye sorbents and 1 M NaCl present in the loading buffer, the highest capacity was achieved when Cibacron Blue F3GA was immobilised to the level of 0.1 mumol/m2. In the case of the non-porous silica dye sorbents, the maximum protein capacity was achieved when 0.5 mumol/m2 dye were immobilised onto the support. Evaluation of the frontal breakthrough curves confirmed that the kinetics of adsorption of lysozyme onto the non-porous sorbent were substantially faster than the adsorption of lysozyme onto the porous sorbent due to the absence of pore diffusion effects in case of the non-porous support. Furthermore, the adsorption of lysozyme on both sorbents was faster when no salt was added to the loading buffer, indicating that there is either conformational or reorientation effects operating during the specific binding of the protein to the dye ligand, or that the interaction is proceeding through the participation of a second class of binding sites. The magnitude of the association constants, Ka, for the lysozyme-Cibacron Blue F3GA systems were found to be dependent on the ligand density of the sorbent. With decreasing ligand density, the protein-ligand interaction became stronger, e.g. Ka values became larger. These results confirm earlier observations on the effect of ligand steric compression on the affinate-ligand association constant, e.g. the protein needs sufficient space to interact with the ligand in an optimum way.(ABSTRACT TRUNCATED AT 400 WORDS)

Amino Acids↗

Extended lamivudine therapy against hepatitis B virus infection in hematopoietic stem cell transplant recipients.

Lamivudine has demonstrated efficacy in the treatment and prevention of hepatitis B virus (HBV) reactivation after hematopoietic stem cell transplantation (HSCT). However, most of these studies involved short durations of prophylaxis, so there is significant concern regarding lamivudine resistance in these patients. Between March 1984 and November 2002, 71 HBV surface antigen-positive HSCT recipients, including a subgroup of 16 who received pretransplantation lamivudine therapy, which was continued into the posttransplantation period to prevent reactivation hepatitis, were enrolled onto our study. The efficacy of lamivudine therapy was first evaluated for the subgroup of 16 patients in terms of treatment response, lamivudine resistance, and viral recurrence after discontinuation by using virologic assays. Efficacy was then evaluated for all patients in terms of the hazards of lamivudine therapy for reactivation hepatitis after transplantation. During a median lamivudine therapy period of 73 weeks (range, 19-153 weeks), the initial response showed a median reduction of 2.54 log10 in serum HBV DNA (-0.28 to 6.72 range). Lamivudine-resistant mutations were detected in 10 (63%) of 16 patients during therapy, and 1 (12%) of 16 patients finally developed a viral breakthrough. At a median follow-up of 30 months after discontinuation, 3 (27%) of 11 cases had recurrence of HBV infection. Despite the emergence of the mutations, no deaths were due to HBV reactivation or severe cases of hepatitis. In the Cox proportion regression model regarding reactivation hepatitis after transplantation of all enrolled patients, lamivudine therapy was found to be the only favorable factor for the event, with a hazard ratio of 0.122 (95% confidence interval, 0.016-0.908; P = .040). In conclusion, extended lamivudine therapy is safe and effective for the prevention of HBV reactivation in an HSCT setting and significantly decreases reactivation hepatitis after transplantation.

Adult↗

Viral hepatitis B.

More than 400 million people worldwide are chronically infected by the hepatitis B virus. The virus is responsible for more than 300000 cases of liver cancer every year and for similar numbers of gastrointestinal haemorrhage and ascites. Major breakthroughs have been achieved in diagnosis and treatment of this virus. Hepatitis B vaccine reduces incidence of liver cancer. As with hepatitis C, advances have been made in molecular virology, especially for naturally occurring and treatment-induced mutant viruses. The clinical significance of low viral load and genotypes are also under investigation. Currently available monotherapies-interferon, lamivudine, and adefovir dipivoxil-very rarely eradicate the virus, but greatly reduce its replication, necroinflammatory histological activity, and progression of fibrosis. Lamivudine, and presumably other nucleoside analogues, can reverse cirrhosis of the liver.

Adenine↗

Viral hepatitis C.

More than 170 million people worldwide are chronically infected with the hepatitis C virus (HCV), which is responsible for more than 100000 cases of liver cancer per year, with similar numbers of digestive haemorrhage and ascites episodes. Major breakthroughs have been made in diagnosis and treatment, and advances in molecular biology mean that the replicative state of the virus can now be assessed. Genotype and serum viral load are useful predictors of response to treatment. The combination of pegylated interferon and ribavirin can eradicate the virus in more than 50% of patients. These antiviral treatments reduce liver fibrosis progression and can reverse cirrhosis. Unfortunately, even in developed countries, death due to hepatitis C is increasing because of inadequate detection and treatment.

Adult↗

Cerebral resuscitation after cardiac arrest: research initiatives and future directions.

At present, fewer than 10% of cardiopulmonary resuscitation (CPR) attempts prehospital or in hospitals outside special care units result in survival without brain damage. Minimizing response times and optimizing CPR performance would improve results. A breakthrough, however, can be expected to occur only when cerebral resuscitation research has achieved consistent conscious survival after normothermic cardiac arrest (no flow) times of not only five minutes but up to ten minutes. Most cerebral neurons and cardiac myocytes tolerate normothermic ischemic anoxia of up to 20 minutes. Particularly vulnerable neurons die, in part, because of the complex secondary post-reflow derangements in vital organs (the postresuscitation syndrome) which can be mitigated. Brain-orientation of CPR led to the cardiopulmonary-cerebral resuscitation (CPCR) system of basic, advanced, and prolonged life support. In large animal models with cardiac arrest of 10 to 15 minutes, external CPR, life support of at least three days, and outcome evaluation, the numbers of conscious survivors (although not with normal brain histology) have been increased with more effective reperfusion by open-chest CPR or emergency cardiopulmonary bypass, an early hypertensive bout, early post-arrest calcium entry blocker therapy, or mild cerebral hypothermia (34 C) immediately following cardiac arrest. More than ten drug treatments evaluated have not reproducibly mitigated brain damage in such animal models. Controlled clinical trials of novel CPCR treatments reveal feasibility and side effects but, in the absence of a breakthrough effect, may not discriminate between a treatment's ability to mitigate brain damage in selected cases and the absence of any treatment effect. More intensified, coordinated, multicenter cerebral resuscitation research is justified.

Animals↗

Contemporary approach to the male infertility evaluation.

Evaluation of infertile couples has revealed that male factor infertility contributes to the problem in up to 50% of cases. Evaluation of the male infertility patient may include endocrine studies, sophisticated semen testing, and select radiographic studies. Reversible and life-threatening causes of male infertility should be identified before proceeding directly to assisted reproductive technology. For cases with irreversible causes, a proper evaluation can identify patients who may be treated with the breakthrough method of intracytoplasmic sperm injection. Many men who were previously thought to be infertile may now initiate their own biologic pregnancies. This article emphasizes the essentials of the contemporary approach to evaluating the male factor in an infertile couple.

Diagnostic Imaging↗

Lumbar versus thoracic epidural buprenorphine for postoperative analgesia following coronary artery bypass graft surgery.

BACKGROUND: Thoracic epidural analgesia (TEA) is reported to provide effective analgesia following cardiac surgery. We compared the effect of buprenorphine (BN) through the lumbar and thoracic epidural routes for postoperative analgesia following coronary artery bypass graft surgery (CABG). METHODS: Forty patients with normal left ventricular ejection fraction scheduled for CABG were randomly divided into two groups, the TEA group (n = 19) and the lumbar epidural analgesia (LEA) group (n = 20). For postoperative pain relief they received epidural BN 0.15 mg at the first demand for pain relief following extubation. A top-up dose of BN 0.15 mg was administered in cases where visual analogue scale (VAS) score was > 3 at 1 h after first dose. Subsequent breakthrough pain was treated with 30 mg intramuscular ketorolac tromethamine (ketorolac). Pain assessed by VAS score on a 0-10 scale, respiratory rate, FEV1, FVC, mean arterial blood pressure, cardiac index, PaO2 and PaCO2 were measured at frequent intervals. Side effects of epidural opioids were noted. RESULTS: Both groups were comparable in demographic characteristics, had similar VAS scores from 1 to 24 h postoperatively, required similar amounts of intramuscular ketorolac for break-through pain and had comparable pulmonary functions and side effects. CONCLUSION: This study shows that BN by the lumbar epidural route for analgesia after CABG compares favourably with the same drug through the thoracic route in terms of quality of analgesia and incidence of side effects.

Adult↗

Cancer chemotherapy, biodiversity, public and private property: the case of the anti-cancer drug taxol.

The drug taxol has been hailed by many in the cancer community as a major breakthrough in the treatment of cancer. It has already been approved in use against ovarian and advanced breast cancer in many countries worldwide. Taxol has also promoted profound debates in the policy arena not, as one might expect, because of the characteristics or purposes of the drug itself, but because of other far-reaching effects. Taxol is a complex compound found in the bark of the Pacific yew tree, primarily in Oregon and Washington in the USA. The bark was first collected in 1962 and cytotoxicity demonstrated in 1964. Yet it was not until 1989 that the first results of clinical trials were reported. In the US taxol was then rushed through the Food and Drug Administration's regulatory procedures, approval being granted for use in refractory ovarian cancer in 1992. The controversies surrounding taxol surfaced in 1989 and grew substantially over the next few years. In this paper we examine two principal controversies concerning taxol, the first of which focused on apparent conflicts between the needs of environmental protection and those of cancer chemotherapy. Although the media portrayed this as a clash of interests between the environment and people with cancer, we argue that it was an attempt to increase lay participation in biomedical decision making and policy formulation. The second controversy was between health policy and the transfer of public scientific property to the corporate sector. The pharmaceutical company Bristol-Myers Squibb was given exclusive rights to provide taxol from Pacific yew trees under a Co-operative Research and Development Agreement signed in 1991. While this was seen to be in the US Government's (as well as the company's) interest, it provoked a public reaction questioning the terms and consequences of the transfer of publicly generated scientific knowledge to the private sector.

Antineoplastic Agents, Phytogenic↗

AIDS-CMV retinitis: Singapore's first cases.

Since April 1988, four cases of AIDS-CMV retinitis were diagnosed in Singapore. Two patients were given intravenous ganciclovir. Clinical response was good but recurrent episodes of breakthrough infection occurred in one patient despite maintenance therapy. Another patient was started on intravenous foscarnet. The fourth patient succumbed to systemic AIDs-related infection before therapy could be started. AIDS-CMV retinitis is a new disease entity in Singapore. With increasing number of AIDS patients, more cases can be expected in the near future. Early treatment and long term maintenance therapy is essential for preserving sight.

Acquired Immunodeficiency Syndrome↗

'The story of Abraham, Isaac and Jacob" or "am I my brother's keeper?".

Presented is a case report of a violent sexual assault where the DNA profile obtained from an item of evidence was compared to a suspect's profile. The profiles did not match, but the sharing of such a large number of alleles raised the suspicion that perhaps the real perpetrator was a blood relative of the suspect. The investigators requested a sample from the suspect's brother, and a match was defined. In an era of technological breakthroughs in the field of forensic DNA analysis, the importance of the scientist's attention to the evidence presented in each case is stressed.

Alleles↗

[A rare case of manifestation of reticulosarcoma by development of multiple cerebral hemorrhages].

Metastatic injury to the brain occurs very rarely in reticulosarcoma patients, presenting considerable difficulties for clinical diagnosis. Such an injury has not been reported in the neurological literature. The authors describe a case of the generalized form of reticulosarcoma with multiple metastases and secondary hemorrhages to the brain attended by blood breakthrough to the ventricular system. Difficulties are noted, occurring in differential diagnosis, and specific features of the clinical picture and pathomorphological alterations are described. In contrast to the primarily hemorrhagic manifestations in the brain, blastomatous proliferation in the visceral system (the gastrointestinal tract, lymph nodes) provoked appreciable necrotic lesions.

Adult↗

Breakthrough Scedosporium apiospermum (Pseudallescheria boydii) brain abscess during therapy for invasive pulmonary aspergillosis following high-risk allogeneic hematopoietic stem cell transplantation. Scedosporiasis and recent advances in antifungal therapy.

Systemic scedosporiasis due to the anamorph or asexual form Scedosporium apiospermum (Pseudallescheria boydii) has become an important cause of opportunistic mycosis, especially in patients undergoing high-risk hematopoietic stem cell transplantation. We report a case of rapidly progressive cerebellar hyalohyphomycosis due to Scedosporium apiospermum in an allogeneic marrow graft recipient receiving treatment for severe graft-versus-host disease. This fatal breakthrough intracranial abscess, due to amphotericin B-resistant (minimum inhibitory concentration > 16 micro g/ml) mold, developed during the course of systemic antifungal therapy given for multicentric pulmonary aspergillosis. Despite treatment with high-dose Abelcet (10 mg/kg daily), free amphotericin B was not detected in postmortem cerebellar tissue. A broad-spectrum triazole-based agent (voriconazole/UK-109, 496--Vfend), and a novel fungal cell wall inhibitor, an echinocandin/pneumocandin analog (caspofungin/MK-0991--Cancidas), which exhibit excellent in vitro activity against most clinical Pseudallescheria boydii-Scedosporium apiospermum isolates, have recently become available in the United States and may provide much needed treatment options for patients at risk.

Adult↗

Nocardiosis in cancer patients.

Nocardiosis (NOC) is an important cause of infection in immunocompromised patients. However, large series in patients with cancer have not been described. We review the records of patients with cancer and NOC who were evaluated at The University of Texas M. D. Anderson Cancer Center, Houston, Texas, between 1988 and 2001, and we describe the incidence, microbiologic and clinical characteristics, treatment, and outcome of NOC in this population. Forty-two patients with a total of 43 episodes of NOC were identified (incidence of 60 cases of NOC per 100,000 admissions). Twenty-seven patients (64%) had hematologic malignancies. In 13 patients, NOC complicated bone marrow transplantation. Neutropenia was observed in 4 (10%) of 40 episodes with information available, and lymphopenia in 20 (50%) of 40 episodes. Patients had received steroids for 25 episodes (58%) and had received chemotherapy for 10 episodes (23%) within 30 days before the onset of NOC. Nine episodes of breakthrough NOC were identified in 7 (23%) of the 40 patients with information available. Pulmonary NOC was seen in 30 (70%) of 43 cases; soft-tissue NOC in 7 (16%); central venous catheter-related nocardemia in 3 (7%); and disseminated NOC, central nervous system NOC, and a perinephric abscess each in 1 (2%). Twenty-three percent of patients with pulmonary NOC had an acute presentation. complex was the most common causative species (77%). Therapy for NOC was mainly concurrent trimethoprim/ sulfamethoxazole and either a tetracycline or a beta-lactam. The median duration of treatment was 113 days (range, 10-600 d). Nine (60%) of 15 patients with outcome data died from NOC. NOC, although infrequent, is an important cause of morbidity and mortality in patients with cancer. It has pleomorphic manifestations, and it can be seen as a breakthrough infection. The present study confirms that timely diagnosis, the site of NOC, the type of, the presence of comorbidities, and cytomegalovirus coinfection influence the outcome of patients with cancer and NOC.

Adult↗

Laparoscopic appendicectomy: review of 331 cases over 7 years, in a Saudi Arabian hospital.

BACKGROUND AND STUDY AIMS: Laparoscopic appendicectomy had been well established by Semm before the popular breakthrough of laparoscopic cholecystectomy. The aim of this study was to evaluate the role of laparoscopy in the diagnosis and treatment of acute appendicitis. PATIENTS AND METHODS: This is a retrospective study. Patients with signs and symptoms of suspected appendicitis necessitating surgery were selected for laparoscopic management between 1992 and 1999. RESULTS: A total of 331 patients were recruited into the study, 184 (56 %) male and 147 (44 %) female. The appendix was successfully removed laparoscopically in 98 % of the patients. The median operating time was 63.3 minutes, and 93 % of the appendices removed were histologically abnormal. Postoperative complications occurred in 19 patients (6 %), and included wound infection (1 %), enterocutaneous fistula, pelvic abscess, hemorrhage, urinary tract infection, respiratory tract infection, incisional herniae and pain at trocar sites. The mean hospital stay was 2.31 days (range 1 - 10 days). CONCLUSION: Laparoscopic appendicectomy is a safe procedure with low morbidity. It is advantageous in obese patients, patients with other pathology, and patients with an unusual position of the appendix, and it has a low infection rate.

Acute Disease↗