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PubMed2002

Failure of macrolide antibiotic treatment in patients with bacteremia due to erythromycin-resistant Streptococcus pneumoniae.

The rate of macrolide resistance among Streptococcus pneumoniae is increasing, but some investigators have questioned its clinical relevance. We conducted a matched case-control study of patients with bacteremic pneumococcal infection at 4 hospitals to determine whether development of breakthrough bacteremia during macrolide treatment was related to macrolide susceptibility of the pneumococcal isolate. Case patients (n=86) were patients who had pneumococcal bacteremia and an isolate that was either resistant or intermediately resistant to erythromycin. Controls (n=141) were patients matched for age, sex, location, and year that bacteremia developed who had an erythromycin-susceptible pneumococcus isolated. Excluding patients with meningitis, 18 (24%) of 76 case patients and none of 136 matched controls were taking a macrolide when blood was obtained for culture (P=.00000012). Moreover, 5 (24%) of 21 case patients with the low-level-resistant M phenotype and none of 40 controls were taking a macrolide (P=.00157). These data show that development of breakthrough bacteremia during macrolide or azalide therapy is more likely to occur among patients infected with an erythromycin-resistant pneumococcus, and they also indicate that in vitro macrolide resistance resulting from both the efflux and methylase mechanisms is clinically relevant.

Adolescent↗
PubMed1991

The idealisation of therapy: fantasy versus reality in clinical practice.

In this paper, object-relations theory is used to illuminate problems encountered in the psychotherapeutic management of severely disturbed psychiatric patients. The hazards of idealisation of the psychiatrist by the patient are reported in four case histories. Attention is drawn to the subsequent breakthrough of negative feelings where idealisation had been unrecognised or unwittingly encouraged. Some implications for the more successful management of the transference in patients such as these are discussed.

Adult↗
PubMed1993

Piperacillin/tazobactam/amikacin versus piperacillin/amikacin/teicoplanin in the empirical treatment of neutropenic patients.

A prospective randomized trial was performed to compare the efficacy of a regimen containing a glycopeptide versus one containing a beta-lactamase inhibitor in the treatment of febrile episodes in neutropenic patients. Fifty-eight patients received piperacillin/amikacin/teicoplanin (group 1) and 56 received piperacillin/amikacin/tazobactam (group 2). In the case of persistence of fever without microbiological documentation of the cause, teicoplanin was also given empirically in group 2 on day 4, and amphotericin B in both groups on day 6. In 114 evaluable febrile episodes, the rate of success without modification of therapy was 60% in patients on piperacillin/amikacin/teicoplanin and 41% in patients on piperacillin/amikacin/tazobactam (p < 0.03). Eleven of 34 patients in the latter group who failed to improve eventually responded upon addition of teicoplanin. Ten and nine patients in group 1 and group 2 respectively required the addition of amphotericin B for definite improvement. There were 14 episodes of gram-positive septicemia in each group: the response rate was 100% in group 1 and 43% in group 2. Three episodes of gram-negative breakthrough septicemia occurred in group 1 versus no cases in group 2 (p = 0.1). Three deaths occurred in each group. Piperacillin/amikacin/tazobactam may be as efficacious as piperacillin/amikacin/teicoplanin in the treatment of febrile neutropenic patients provided the regimen is modified (usually by addition of teicoplanin) in unresponsive cases.

Adolescent↗
PubMed1996

Acute phenytoin toxicity followed by seizure breakthrough from a ticlopidine-phenytoin interaction.

OBJECTIVE: To review a case of a drug-drug interaction between phenytoin sodium and ticlopidine hydrochloride that resulted in acute phenytoin toxicity and permanent memory loss. CASE REPORT: A 63-year-old man who was maintained with a stable dose of phenytoin for treatment of seizures began treatment with ticlopidine following percutaneous transluminal angioplasty and stent placement. Within 3 weeks of beginning treatment with ticlopidine, he experienced acute clinical toxic effects of phenytoin with a maximum measured phenytoin concentration of 162.4 micromol/L. Phenytoin concentration decreased to 36 micromol/L after discontinuing treatment with ticlopidine and reducing the phenytoin dose. Subsequently, the patient developed probable complex partial status epilepticus. CONCLUSIONS: Ticlopidine is a metabolic inhibitor of several drugs. Because of the potential for acute and permanent adverse effects from a drug-drug interaction, phenytoin concentrations should be carefully monitored when beginning or ending ticlopidine therapy.

Drug Interactions↗
PubMed2002

Breakthrough candidemia in patients with cancer differs from de novo candidemia in host factors and Candida species but not intensity.

OBJECTIVES: To evaluate the risk factors associated with breakthrough candidemia in patients with cancer and to compare them with those of de novo candidemia in this patient population. DESIGN: Retrospective case series of 120 episodes of candidemia, 90 de novo and 30 breakthrough candidemias. SETTING: University-affiliated, tertiary-care cancer center in Houston, Texas. PATIENTS: All patients with cancer who acquired candidemia between January 1993 and December 1998 were included if they had non-catheter-related candidemia and information about quantitative blood cultures. RESULTS: Although less frequent, breakthrough candidemia was seen more often in neutropenic patients with leukemia. The intensity of breakthrough candidemia was comparable to that of de novo candidemia. Most (70%) of the breakthrough candidemias were due to Candida glabrata or C. krusei. CONCLUSIONS: In breakthrough candidemia, the same risk factors seen in de novo candidemia were encountered, although more frequently. C. glabrata and C. krusei are the leading causes of breakthrough candidemia in patients with cancer.

Adolescent↗
PubMed1995

The use of intraarterial papaverine in the management of vasospasm complicating arteriovenous malformation resection. Report of two cases.

The authors report two cases of treatment by intraarterial papaverine of cerebral vasospasm complicating the resection of an arteriovenous malformation (AVM). Both cases had successful reversal of vasospasm documented on angiography. In the first case sustained neurological improvement occurred, resulting in a normal outcome by the time of discharge. In the second case, neurological deterioration occurred with the development of cerebral edema. This complication was thought to be due to normal perfusion pressure breakthrough, on the basis of angiographic arterial vasodilation and increased cerebral blood flow. These two cases illustrate an unusual complication of surgery for AVMs and demonstrate that vasospasm (along with intracranial hemorrhage, venous occlusion, and normal perfusion pressure breakthrough) should be considered in the differential diagnosis of delayed neurological deterioration following resection of these lesions. Although intraarterial papaverine may be successful in dilating spastic arteries, it may also result in pathologically high flows following AVM resection. However, this complication has not been seen in our experience of treating aneurysmal subarachnoid hemorrhage by this technique.

Adult↗
PubMed2002

Aerosolized pentamidine prophylaxis for Pneumocystis carinii pneumonia after allogeneic marrow transplantation.

Pneumocystis carinii pneumonia (PCP) poses a serious risk to allogeneic bone marrow transplant (BMT) patients, who are often intolerant of trimethoprim-sulfamethoxazole (TMP-SMX), the traditional first-line prophylactic agents. There are limited published data supporting the use of aerosolized pentamidine (AP) prophylaxis in the BMT population. We assessed the effectiveness of AP in BMT recipients by reviewing the experience at our center. We divided our review into four time periods from January 1990 to March 2000, during which approximately 700 BMTs were performed. The first period includes patients receiving AP treatments from January 1990 to July 1997 (baseline), the second from August 1997 to July 1998 (pre-outbreak), the third from August 1998 to October 1999 (outbreak), and the fourth from November 1999 to March 2000 (post-outbreak). At our center, TMP-SMX is the first-line agent for PCP prophylaxis, which is routinely continued for at least one year, or for the duration of enhanced immunosuppression. During the baseline period, 505 BMTs were performed and 192 patients (38%) received AP for part of their time at risk. Six patients (3%) experienced toxicities requiring discontinuation of AP. Three cases of PCP were diagnosed over 1114 patient-months of treatment in the baseline period. During the last 42 months of the baseline period, 2/154 patients receiving AP and 2 of an estimated 293 patients receiving exclusively oral prophylaxis developed breakthrough PCP (p = 0.61). During the outbreak period, 9 of 180 patients receiving AP developed PCP compared to none in the group receiving exclusively oral prophylaxis. Either changes in our AP protocol during the pre-outbreak period or pentamidine resistance may have led to this failure of prophylaxis. There were no further cases during the 5-month post-outbreak period. Our observed overall breakthrough rate was 12 cases out of 439 patients (2.7%). Our study shows that AP is an effective and well-tolerated second-line agent in preventing PCP post BMT and we recommend its continued use in this regard. However, it should be administered using a well-studied protocol, and only when TMP-SMX is not tolerated.

Administration, Inhalation↗
PubMed1995

Climacteric symptoms and control of the cycle in women aged 35 years or older taking an oral contraceptive with 0.150 mg desogestrel and 0.020 mg ethinylestradiol.

In a multicenter prospective trial, 58 healthy women aged between 35 and 49 years were studied for one year (639 cycles) while taking an oral contraceptive (OC) containing desogestrel 0.150 mg and ethinylestradiol (EE) 0.020 mg. Efficacy, control of the cycle, side effects, complaints, and climacteric symptoms were monitored after 3, 6, 9 and 12 cycles. No pregnancies occurred during the study period. Spotting gradually decreased from 29.3% in cycle 1 to 4.2% in cycle 12, while breakthrough bleeding (BTB) disappeared after cycle 7. One case of superficial thrombophlebitis and 3 cases of minor side effects were registered. With regard to the complaints, breast tenderness, headache, and depression gradually decreased during the study (basal vs. 12-month data: 50.9% vs. 31.2%, 48.3% vs. 18.7%, 39.6% vs. 20.8%, respectively), while nausea disappeared after three months. A significant treatment-dependent reduction of climacteric symptoms was obtained after cycle 3 and this tendency was maintained up to cycle 12. No changes were registered in body mass index (BMI) or blood pressure.

Adult↗
PubMed1994

The effect of kinetic positioning on lung function and pulmonary haemodynamics in posttraumatic ARDS: a clinical study.

In the treatment of adult respiratory distress syndrome (ARDS) no breakthrough has been achieved so far. In several cases of severe ARDS in multiply injured patients we have seen improvements of lung function by means of continuous body positioning. We therefore compared the effect of kinetic positioning (KIN) on lung function and haemodynamics in ARDS patients with conventional (CON) supine positioning. Pulmonary and systemic haemodynamics were determined on the basis of pulmonary artery catheter measurements. On a daily basis oxygenation ratio (PaO2/FiO2) and pulmonary shunt (Os/Ot. per cent) were calculated. Extravascular lung water (EVLW, ml/kg BW) was determined by the double indicator thermodilution technique. Twenty-two patients were included: KIN, N = 11, CON, N = 11. Mortality from ARDS in KIN patients was 18.2 per cent (N = 2): in CON patients it was 63.6 per cent (N = 7). The oxygenation ratio (PaO2/FiO2) increased significantly in KIN patients from 140 + 45 (day 0) to 237 + 40 (P < 0.05) (day 5); in CON patients no improvement was seen (143 + 48 (day 0). 133 + 44 (day 5); n.s. between groups at day 0: P < 0.05 between groups at day 5). Pulmonary shunt decreased significantly from 26.6 + 4 per cent (day 0) to 12.5 + 2 per cent (day 5) (P < 0.05) in KIN patients and was 36.6 + 6 per cent at day 0 and 31.4 + 2 per cent at day 5 in CON patients (P < 0.05 between groups at day 5).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1986

A review of the role of progestogens in hormonal replacement therapy: influence on bleeding patterns.

Most post-menopausal hormone replacement regimens lead to endometrial bleeding in some women. However, the response to any one regimen varies greatly from individual to individual. With most regimens, some women will experience amenorrhoea, some will experience scheduled withdrawal bleeding and some will experience unscheduled breakthrough bleeding. The proportions of women in each case will depend on the oestrogen and progestogen dosages, the regimen and route by which these are administered and their respective 'potencies'. With appropriate counseling, many women will tolerate continued menstrual bleeding after the menopause, but most would still prefer not to have it if given the option. Much additional research needs to be done to determine which hormonal regimens are the most effective, safe and acceptable for different groups of women.

Biomechanical Phenomena↗
PubMed2006

Differential effects of cervical vagosympathetic and mediastinal nerve activation on atrial arrhythmia formation in dogs.

To investigate the influence of the thoracic autonomic neuronal hierarchy on atrial arrhythmia formation, we compared the characteristics of atrial tachyarrhythmias induced by electrical stimulation of 1) the right vagosympathetic nerve complex at the cervical level and 2) the more caudal juxta-cardiac mediastinal nerves located on the anterior surface of the superior vena cava. Unipolar electrograms were recorded from 191 sites on the entire epicardial atrial surface and, in some experiments, from 63 right atrial endocardial sites. The sites of origin of initial beats at the onset of atrial tachyarrhythmias so induced were investigated analysing atrial activation maps. Neural effects on repolarization were determined by computing the integral surface subtended by unipolar recordings under basal conditions and at maximum neurally induced bradycardia, and calculating differences at each recording site. The mean area affected by nerve stimulation in all animals was significantly greater in response to vagosympathetic than mediastinal nerve stimulation. Atrial cycle length prolongation prior to tachyarrhythmia onset was more pronounced in response to vagosympathetic than mediastinal nerve stimulation. The earliest epicardial activations in early tachyarrhythmia beats were localized in the right atrial free wall and Bachmann bundle region in both cases, but with a higher incidence of double breakthroughs from septal sites of origin in response to vagosympathetic versus mediastinal nerve stimulation. Sites of early activation were associated with the areas of neurally induced repolarization changes. Thus, differential contributions are made to the electrophysiologic substrate of neurally induced atrial tachyarrhythmias depending on the pattern of engagement of neural elements within the autonomic neuronal hierarchy.

Animals↗
PubMed2006

Development and validation of a model of bio-barriers for remediation of Cr(VI) contaminated aquifers using laboratory column experiments.

Bench scale transport and biotransformation experiments and mathematical model simulations were carried out to study the effectiveness of bio-barriers for the containment of hexavalent chromium in contaminated confined aquifers. Experimental results showed that a 10cm thick bio-barrier with an initial biomass concentration of 0.205mg/g of soil was able to completely contain a Cr(VI) plume of 25mg/L concentration. It was also observed that pore water velocity and initial biomass concentration are the most significant parameters in the containment of Cr(VI). The mathematical model developed is based on one-dimensional advection-dispersion reaction equations for Cr(VI) and molasses in saturated, homogeneous porous medium. The transport of Cr(VI) and molasses is coupled with adsorption and Monod's inhibition kinetics for immobile bacteria. It was found that, in general, the model was able to simulate the experimental results satisfactorily. However, there was disparity between the numerically simulated and experimental breakthrough curves for Cr(VI) and molasses in cases where there was high clay content and high microbial activity. The mathematical model could contribute towards improved designs of future bio-barriers for the remediation of Cr(VI) contaminated aquifers.

Adsorption↗
PubMed2002

Electrogram polarity reversal as an additional indicator of breakthroughs from the left atrium to the pulmonary veins.

OBJECTIVES: We assessed the anatomical distribution and electrogram characteristics of breakthrough from the left atrium (LA) to the pulmonary veins (PVs). BACKGROUND: Localization of LA-PV breakthrough is an important technique for PV ablation in patients with atrial fibrillation (AF). METHODS: A total of 157 patients with paroxysmal AF underwent PV disconnection guided by mapping with a circumferential 10-electrode catheter. Radiofrequency (RF) current was delivered ostially at the site(s) of earliest activation (113 patients) or electrogram polarity reversal defined by opposite polarity across adjacent bipoles (44 patients). Breakthrough sites were proved by changes in pulmonary vein potential activation sequence occurring as a result of localized RF delivery and were classified into four segments around the ostium (top, bottom, anterior, posterior). Results of mapping and ablation were compared between the two groups. RESULTS: A total of 99% of 411 targeted PVs were successfully disconnected in both groups. Breakthroughs were most frequent at the bottom of superior PVs (85% prevalence) and the top of inferior PVs (75% prevalence). A wide activation front (>5 synchronous bipoles) indicating broad breakthrough was observed in 18% of PVs. Polarity reversal occurred with 88% sensitivity and 91% specificity at breakthrough sites. Polarity reversal was restricted to fewer bipoles (2.0 +/- 0.4 bipoles vs. 3.4 +/- 2.0 bipoles, p < 0.01) compared with earliest activation. Shorter RF application time was required to disconnect PVs with wide synchronous activation using polarity reversal compared with using conventional earliest activity (10.3 +/- 3.0 min vs. 12.3 +/- 3.4 min, p < 0.05). CONCLUSIONS: Bipolar electrogram polarity reversal allows more precise localization of breakthrough compared with the earliest activation, particularly in cases of wide synchronous PV activation.

Adult↗
PubMed1986

Left ventricular endocardial activation during right ventricular pacing: effect of underlying heart disease.

Endocardial catheter mapping of the left ventricle was performed in 40 patients during right ventricular pacing to determine the effect of underlying myocardial infarction on endocardial activation. Group I comprised 18 patients without infarction, Group II 12 patients with inferior infarction and Group III 10 patients with anteroseptal infarction. Thirty-nine of the 40 patients had only a single left ventricular breakthrough site located on the midseptum in 33 cases, apical septum in 4 cases and basal septum in 2 cases. The earliest left ventricular local activation time during right ventricular pacing was earlier in Group III (40 +/- 11 ms) than in Group I (55 +/- 17 ms) and Group II (60 +/- 15 ms) (p less than 0.01). Total endocardial activation time was significantly longer in Group III (118 +/- 30 ms) than in Group I (76 +/- 14 ms) and Group II (72 +/- 20 ms) (p less than 0.001). The latest left ventricular site of activation during right ventricular pacing was the inferoposterior base in 14 (77%) of the 18 Group I patients, and 10 (83%) of the 12 Group II patients. The latest site of activation in Group III patients was variable. It is concluded that: left ventricular endocardial activation patterns and conduction times are influenced by the site of previous infarction. Longer total endocardial activation in Group III suggests that specialized conducting tissue in the septal and anterior walls may play an important role in left ventricular activation during right ventricular pacing.(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiac Pacing, Artificial↗
PubMed2005

Predictors of pulmonary zygomycosis versus invasive pulmonary aspergillosis in patients with cancer.

BACKGROUND: Pulmonary zygomycosis (PZ), an emerging mycosis among patients with cancer, has a clinical manifestation similar to that of invasive pulmonary aspergillosis (IPA). Most cases of PZ in such patients develop as breakthrough infections if treatment with antifungal agents effective against Aspergillus species is administered. However, clinical criteria to differentiate PZ from IPA are lacking. METHODS: We retrospectively reviewed the clinical characteristics and computed tomography (CT) findings for 16 patients with cancer and PZ and for 29 contemporaneous patients with cancer and IPA at the time of infection onset (2002-2004). Patients with mixed infections were excluded. Parameters predictive of PZ by univariate analysis were included in a logistic regression model. RESULTS: Almost all patients with PZ (15 of 16) and IPA (28 of 29) had underlying hematological malignancies and typical risk factors for invasive mold infections. In logistic regression analysis of clinical characteristics, concomitant sinusitis (odds ratio [OR], 25.7; 95% confidence interval [CI], 1.47-448.15; P = .026) and voriconazole prophylaxis (OR, 7.76; 95% CI, 1.32-45.53; P = .023) were significantly associated with PZ. The presence of multiple (> or = 10) nodules (OR, 19.8; 95% CI, 1.94-202.29; P = .012) and pleural effusion (OR, 5.07; 95% CI, 1.06-24.23; P = .042) at the time that the patient underwent the initial CT were both independent predictors of PZ in the logistic regression analysis of radiological parameters. No difference occurred in the frequency of other CT findings suggestive of pulmonary mold infections (e.g., masses, cavities, halo sign, or air-crescent sign) between the 2 patient groups. CONCLUSIONS: PZ in immunocompromised patients with cancer could potentially be distinguished from IPA on the basis of clinical and radiological parameters; prospective validation is needed.

Adult↗
PubMed2004

The long-term outcome of the endoscopic subureteric implantation of polydimethylsiloxane for treating vesico-ureteric reflux in children: a retrospective analysis of the first 195 consecutive patients in two European centres.

OBJECTIVE: To determine the long-term efficacy of endoscopically implanting polydimethylsiloxane (PDS, Macroplastique, Uroplasty BV, Geleen, the Netherlands) for treating vesico-ureteric reflux (VUR) in children. PATIENTS AND METHODS: We retrospectively reviewed the records of 195 children treated with PDS over the past 10 years in two European centres (Netherlands and UK) and conducted follow-up investigations where deemed necessary. In the Dutch centre patients were treated according to a prospective approved study protocol. RESULTS: Of the 195 treated children, 155 had a successful outcome; in all, 311 refluxing renal units were treated, with an overall success rate of 82.3% in a mixed group of patients with unilateral or bilateral VUR and duplex systems. CONCLUSION: The long-term data from these two independent centres confirms the viability of PDS and the technique for treating VUR in children. We conclude that the material is safe and effective and can be used in VUR grades II-V. Treating patients with grade I VUR is recommended in those cases where there is no spontaneous resolution and 'breakthrough' infections.

Adolescent↗
PubMed1976

Drug stimulated biotransformation of hormonal steroid contraceptives: clinical implications.

On the basis of well documented biochemical and pharmacological data about the influence of drug mediated enzyme induction on the biotransformation of natural and synthetic sex steroids, practical consequences for hormonal steroid contraception are described and discussed. Clinical reports dealing with this problem are still sparse. The clinical symptoms of drug stimulated biotransformation of hormonal steroid contraceptives are characteristic. Spotting or breakthrough bleeding are observed and in the extreme case conception may occur despite the regular intake of the contraceptive. The appearance of these symptoms differs from one individual to another. With a strong enzyme inducer, bleeding disorders can be provoked artifically in 50 to 60% of the women receiving hormonal contraceptive treatment. The range of drugs which stimulate biotransformation of hormonal contraceptives with consequent loss of their biological effectiveness is not completely known. For practical purposes, it is recommended that bleeding disturbances under hormonal steroid contraception in a previously regular cycle be regarded as loss of reliability; they should be remedied and taken as a sign to search for uncontrolled drug taking.

Ampicillin↗
PubMed2001

[Clinical efficacy of lamivudine in the treatment of chronic hepatitis B].

OBJECTIVE: To study the clinical efficacy and safety of lamivudine in the treatment of chronic hepatitis B. METHODS: 72 patients with hepatitis B were randomly assigned into lamivudine (n = 54) and placebo groups (n = 18) for 12 weeks. Then, all the patients received lamivudine 100 mg daily until week 104. Clinical symptoms, liver function tests, serum HBV DNA and YMDD mutation were evaluated. RESULTS: HBV DNA response rate of lamivudine group was higher than that of placebo group after 12 weeks treatment (61% vs 6%, P < 0.01). ALT sustained normalization rate of lamivudine group was higher than that of placebo group (65% vs 11%, P < 0.05). At week 52 and week 104, HBV DNA response rate was 78% and 36% respectively, whereas the normalization rate of ALT was 39% and 33% respectively. Proportion of HBeAg/anti-HBe seroconversion was both 6.1% at week 52 and 104. Overall YMDD mutation rate was 13.7% at week 52 and 39.7% at week 104. The incidence of adverse effects was similar for lamivudine and placebo group at week 12. There was no severe drug-related adverse events during 104 weeks treatment. CONCLUSION: Lamivudine 100 mg daily could suppress HBV replication rapidly and be well tolerated. However, in some cases, YMDD mutation may lead to HBV DNA breakthrough.

Adolescent↗