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PubMed2005

Galactomannan and computed tomography-based preemptive antifungal therapy in neutropenic patients at high risk for invasive fungal infection: a prospective feasibility study.

BACKGROUND: Empirical antifungal therapy is the standard treatment for persistent or relapsing antibiotic-resistant neutropenic fever. However, overtreatment resulting in increased toxicity and treatment-related cost is a major shortcoming of such therapy. We assessed the feasibility of a "preemptive" approach based on the incorporation of sensitive, noninvasive diagnostic tests for consecutive high-risk neutropenic patients who had received fluconazole prophylaxis while avoiding empirical therapy. METHODS: A total of 136 treatment episodes for persons who were at risk of acquiring invasive fungal infection (IFI) were screened for the presence of galactomannan with an enzyme immunoassay. A diagnostic evaluation, which included thoracic computed tomography scanning (HRCT) and bronchoscopy with lavage, was performed on the basis of well-defined clinical, radiological, and microbiological criteria. Only seropositive patients and patients with a positive microbiological test result plus supportive radiological findings received liposomal amphotericin B. RESULTS: Neutropenic fever developed in 117 episodes, of which at least 41 episodes (35%) satisfied existing criteria for empirical antifungal therapy. However, our protocol-driven preemptive approach reduced the rate of antifungal use for these episodes from 35% to 7.7% (a 78% reduction) and led to the early initiation of antifungal therapy in 10 episodes (7.3%) that were clinically not suspected of being IFI. No undetected cases of invasive aspergillosis were identified; 1 case of zygomycosis was missed. Breakthrough candidemia was diagnosed by conventional culture techniques and was treated successfully. With use of a preemptive approach, the 12-week survival rate for patients with IFI was 63.6% (it was 63.1% for those with invasive aspergillosis). CONCLUSION: Preemptive therapy based on enzyme immunoassay and HRCT reduced the exposure to expensive and potentially toxic drugs and offered effective antifungal control, but it failed to detect non-Aspergillus IFI.

Adolescent↗

PubMed1990

Evidence for an epidermal growth factor-stimulated protein kinase cascade in Swiss 3T3 cells. Activation of serine peptide kinase activity by myelin basic protein kinases in vitro.

Two intermediary kinases in a protein serine/threonine kinase cascade that is triggered in the response of Swiss 3T3 cells to epidermal growth factor (EGF) have been identified. Several separable EGF-stimulated serine/threonine kinase activities were characterized in the preceding paper (Ahn, N. G., Weiel, J. E., Chan, C. P., and Krebs, E.G. (1990) J. Biol. Chem. 265, 11487-11494). These were preincubated in various combinations in the presence of MgATP with chromatographic fractions from unstimulated cell extracts. Activation of the rate of phosphorylation of a synthetic peptide, Arg-Arg-Leu-Ser-Ser-Leu-Arg-Ala, was observed on preincubation of the breakthrough fraction from unstimulated cell extracts with either of two distinct EGF-stimulated kinase activities, each of which phosphorylated myelin basic protein. Kinetic analysis and fractionation by sizing gel chromatography demonstrated that two myelin basic protein kinase activities (of approximately 30 and approximately 50 kDa) represented the activating components in the mixtures whereas the unstimulated cell extract breakthrough gave rise in each case to the activated Arg-Arg-Leu-Ser-Ser-Leu-Arg-Ala peptide kinase activity of approximately 110 kDa. Inasmuch as the in vitro activation reactions required magnesium plus ATP and were reversed by protein phosphatase treatment, an activation mechanism involving phosphoryl transfer is suggested.

Amino Acid Sequence↗

PubMed1977

Respiratory distress syndrome: progress in prenatal prediction and prevention.

The concept of idiopathic respiratory distress syndrome (RDS) as a disease of multiple etiology has shifted during the past decade to that of a developmental biochemical dysfunctional state which has a distinct pattern of clinical expression. Knowledge of the biosynthetic processes of physiologic lung maturation together with the now available perinatal technology have made possible laboratory analysis and quantification of surface active phospholipids, and also correlation of their concentrations with the subsequent respiratory status. Whereas prediction of the syndrome now appears well established, such is not the case with prevention although significant breakthroughs have undoubtedly occurred. It is hoped that development of simple and safe modalities of preventive intervention will follow soon in the wake of these pioneering major accomplishments.

Amniotic Fluid↗

PubMed1997

New strategies for old problems: tardive dyskinesia (TD). Review and report on severe TD cases treated with clozapine, with 12, 8 and 5 years of video follow-up.

Tardive dyskinesia (TD) is the most feared and troublesome extrapyramidal side-effect of prolonged neuroleptic (NL) treatment. We present a review of TD. Its pathophysiology remains elusive, although extrapyramidal symptoms (EPS) increase the liability for TD. Nowadays, therefore, avoidance of all EPS remains the best preventive strategy, as it is not possible to predict which liable patients will develop TD, or of what type or severity. TD frequently includes dystonic features, and is more disabling when these dystonias are present. Clozapine (CLZ) has been reported to be effective in suppressing nearly 60% of TD syndromes, specially those with dystonic features. Based on the few reports in the literature on CLZ and TD by the early 1980s, we started to videotape the first severe TD patient treated with CLZ in 1984. We present the first three case reports of severe TD, with prominent disabling dystonic features, treated with CLZ and videotaped since pretreatment and then periodically for 12, 8 and 5 years of follow-up, respectively. The patients' current diagnosis, gender and age are: Case 1, DSM-IV Schizophrenia Residual Type, male, 39 years; Case 2, DSM-IV Polysubstance Related Disorder, Borderline Personality Disorder, female, 28 years; Case 3, DSM-IV Schizoaffective Disorder, male, 40 years. Two of them presented with a recurrence of TD because of CLZ interruption within the first 2 months of treatment, with no further breakthrough to date. The first two cases have complete remission of TD; the third case is still improving after 5 years of CLZ treatment, with only minor dystonic features persisting that constitute no impairment for work or daily routines at present. All patients, independent of their psychiatric primary diagnosis, have shown significant and progressive improvement in both motor and psychosocial aspects. None of them has been rehospitalized. Long-term treatment and follow-up is required to avoid TD recurrence and to assure full assessment of treatment effectiveness. Ideally, periodic video recording with standardized examination is advisable for long-term follow-up and outcome assessment. At present, CLZ could be regarded as the drug of choice for patients with TD, specially for those with disabling and or dystonic features and who require ongoing NL therapy. The use of novel antipsychotic agents for TD treatment and prevention, with their low EPS liability, is promising, but has yet to be tested.

Adult↗

PubMed2005

Integrated care for patients with a stroke in the Netherlands: results and experiences from a national Breakthrough Collaborative Improvement project.

PURPOSE: This article considers the question if measurable improvements are achieved in the quality of care in stroke services by using a Breakthrough collaborative quality improvement model. CONTEXT OF CASE: Despite the availability of explicit criteria, evidence based guidelines, national protocols and examples of best practices; stroke care in the Netherlands did not improve substantially yet. For that reason a national collaborative started in 2002 to improve integrated stroke care in 23 self selected stroke services. DATA SOURCES: Characteristics of sites, teams, aims and changes were assessed by using a questionnaire and monthly self-reports of teams. Progress in achieving significant quality improvement has been assessed on a five point Likert scale (IHI score). CASE DESCRIPTION: The stroke services (n=23) formed multidisciplinary teams, which worked together in a collaborative based on the IHI Breakthrough Series Model. Teams received instruction in quality improvement, reviewed self reported performance data, identified bottlenecks and improvement goals, and implemented "potentially better practices" based on criteria from the Edisse study, evidence based guidelines, own ideas and expert opinion. CONCLUSION AND DISCUSSION: Quality of care has been improved in most participating stroke services. Eighty-seven percent of the teams have improved their care significantly on at least one topic. About 34% of the teams have achieved significant improvement on all aims within the time frame of the project. The project has contributed to the further development and spread of integrated stroke care in the Netherlands.

Journal Article↗

PubMed2004

Effect of long-term lamivudine in chronic hepatitis B virus-infected children.

OBJECTIVE: To evaluate, retrospectively, biochemical, serological and histological responses in chronic hepatitis B (CHB)-infected children who received combination therapy and continued with prolonged treatment with lamivudine (3TC). PATIENTS AND METHODS: CHB infection was defined as the presence of hepatitis B surface antigen (HBsAg), hepatitis Be antigen (HBeAg) and hepatitis B virus (HBV) DNA in serum screened at 3-month intervals for at least 1 year, serum alanine aminotransferase (ALT) levels >1.5 times the normal limit and CHB with histological activity index (HAI) >5 by liver biopsy. A total of 99 children with CHB infection were treated with IFN-alpha (three times a week, 5 MU/m2) and 3TC (4 mg/kg/d) orally for 6 months. End of therapy response (CR) was defined as ALT normalization, HBV-DNA clearance and e seroconversion. Partial responders (PR) were defined as patients who had ALT normalization and HBV-DNA clearance, but who had not had e seroconversion. Forty-five children with PR at the end of the sixth month continued to receive 3TC alone thereafter. Breakthrough infection was determined as re-emergence of HBV DNA in serum after its clearance. The response rate, side effects and the breakthrough infection rate were examined on prolonged 3TC treatment. Liver biopsy was held in 29 patients at median 32 (14-66) months of 3TC; pre- and post-treatment liver histology was compared. RESULTS: Pre- and post-treatment evaluation was carried out in 45 children [mean age: 11+/-4.2 years, 31 males (69%), 14 females (31%)] with PR at the end of the sixth month of combination therapy. The initial mean ALT values and HAI scores were 75.6+/-60 IU/l and 8+/-3.3, respectively. 3TC was continued for median 33 (14-66) months and CR was achieved in 15.6% (7/45) and 5.6% (2/36) at the end of first and second year, and 0% (none) at the end of third and fourth year, respectively. Breakthrough incidence was detected in six (13.3%) cases at 12 months and increased to 69.4% (n=25) and 82.4% (n=14) at the end of the second and third years, respectively. Patients with breakthrough continued to receive 3TC. Seroconversion and CR of the mutant virus was achieved in one patient (2.9%) at month 46 of treatment with 3TC. Liver biopsy was held in 29 cases at median 32 (14-66) months of 3TC. Pre- and post-treatment mean HAI scores were 8+/-3.3 and 3.9+/-2.1, respectively (P=0.000). Mean necrosing scores were not different at the beginning and end of therapy (P=1.0). Inflammation, bridging and fibrosis scores decreased to 0.8+/-0.6, 1.3+/-1.2 and 0.6+/-0.8, respectively (P=0.000, P=0.002, P=0.000). CONCLUSION: The long-term 3TC usage in children with PR does not induce complete response and is associated with high breakthrough incidence. However, histological improvement is achieved and/or sustained even in children with HBV DNA breakthrough.

Adolescent↗

PubMed2001

Breakthrough candidaemias during empirical therapy with fluconazole in non-cancer and non-HIV adults caused by in vitro-susceptible Candida spp.: report of 33 cases.

The objective of this study was to assess risk factors and the outcome of breakthrough fungaemias (BFs) occurring during fluconazole (FLU) therapy in non-cancer and non-HIV individuals. Thirty-three fungaemias occurring during therapy with FLU among a total of 310 fungaemias observed within a 10-y national survey were analysed. The agar disk diffusion method was used for antifungal susceptibility testing and the Vitek system for species identification. Univariate and multivariate analysis was performed to determine risk factors for BF. All BFs were due to species known to be susceptible to FLU: Candida albicans (25/33), C. parapsilosis (6/33) and C. guillermondii (2/33). The mean number of positive blood cultures per episode was 2.4. The MIC of Candida spp. to FLU was 0.5-8 mg/ml (all strains were susceptible in vitro). Neonatal age (< 4 weeks), very low birth weight, prior surgery, central venous catheter placement, artificial ventilation, total parenteral nutrition and C. parapsilosis were significantly related to BF in univariate analysis, but only central venous catheter placement was significantly related in multivariate analysis. However, the outcome of BFs and non-BFs was similar. All BFs occurred in non-HIV patients who were not previously treated with azoles, and were caused by in vitro FLU-susceptible species (C. albicans and C. tropicalis). Thus factors other than in vitro susceptibility play a role in BFs.

Adult↗

PubMed1989

[Experiences with DHPG (ganciclovir)--treatment of cytomegalovirus retinitis in AIDS].

Nine patients with unilateral cytomegalovirus (CMV) retinitis were treated with intravenous infusions of the new virustatic drug DHPG (Ganciclovir). The induction dose was 10 mg/kg body weight per day (2-5 weeks). In six cases, a maintenance dose was given thereafter of 5 mg/kg body weight per day. After the induction dose, five patients had visual improvement and satisfactory cicatrization. In one patient, PVR (proliferative vitreous reaction) developed with total tractional retinal detachment. More ocular complications were seen while on longterm therapy: relapses during discontinuation because of leukopenia (three times in two patients), breakthrough (= relapse during maintenance therapy) (one case), serous retinal detachment (one case), and optic atrophy (two cases). The complications caused blindness in two further patients. Only one patient has tolerated maintenance therapy for 22 weeks without having any complications. One patient wanted to have therapy suspended and has remained free of relapse for 28 weeks while on cytostatic therapy. The eyes of two deceased patients were examined histopathologically, immunhistochemically, and ultrastructurally and the findings compared with those of an untreated case. Given at an early stage and without discontinuation, DHPG is an effective means of preventing or delaying blindness caused by cytomegalovirus retinitis in AIDS patients. The directives for an optimal dosage are subject to further prospective randomized clinical studies.

Acquired Immunodeficiency Syndrome↗

PubMed1996

Intraosseous ganglion cyst associated with neuropathy.

We present a case of expansile intraosseous ganglion of the fibular head with cortical breakthrough, which has not been previously reported. Also associated with this case, and not previously reported, is peroneal nerve compression, causing foot drop caused by the large expansile nature of the lesion.

Aged↗

PubMed1993

[Effect of continuous change in axial position in treatment of post-traumatic lung failure (ARDS). A clinical study].

In the treatment of posttraumatic adult respiratory distress syndrome (ARDS) so far no breakthrough has been achieved. In several cases of severe ARDS 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 hemodynamics in ARDS patients to conventional (KON) supine positioning. 22 ARDS patients with multiple trauma treated by supportive continuous body positioning (KIN) (KCI-Mediscus) and without continuous positioning (KON) were investigated daily. Pulmonary and systemic hemodynamics were determined on the basis of pulmonary artery catheter measurements. Oxygenation ratio (PaO2/FiO2) and pulmonary shunt (Qs/Qt,%) were calculated. Extravascular lung water (EVLW, ml/kg body weight) was determined by double indicator thermodilution technique. Total injury severity by injury severity score (ISS) was 29.6 +/- 6 points (KIN) and 31.6 +/- 5 points (KON). The oxygenation ratio (PaO2/FiO2) increased significantly from 140 +/- 45 (day 0) to 237 +/- 40 (p < 0.05) [day 5] (KIN), in KON patients no improvement (143 +/- 48 [day 0], 133 +/- 44 [ay 5]) was seen (p < 0.05 between groups). There were no significant changes of systemic hemodynamics between the groups or compared to day 0. Pulmonary shunt decreased significantly from 26.6 +/- 4% (day 0) to 12.5 +/- 2% (day 5) (p < 0.05) in KIN patients and was 36.6 +/- 6% at day 0 and 31.4 +/- 2% at day 5 in KON patients (p < 0.05 between groups). EVLW was 11.1 +/- 2 ml/kg body weight at day 0 and 9.4 +/- 1 ml/kg body weight at day 5 (KIN)-EVLW was 12.9 +/- 2 ml/kg body weight at day 0 and 17.4 +/- 3 ml/kg body weight at day 5 (KON) (not significant). We found no hemodynamic side effects from continuous body positioning. In ARDS-patients submitted to body positioning oxygenation and pulmonary shunt improved significantly and were significantly better compared to those with conventional supine positioning. Continuous body positioning appears to represent a promising supportive treatment regimen in posttraumatic ARDS.

Adolescent↗

PubMed1998

Role of anti-interferon antibodies in breakthrough occurrence during alpha 2a and 2b therapy in patients with chronic hepatitis C.

BACKGROUND/AIMS: Alpha interferon induces aminotransferase normalization in about 50% of patients with chronic viral hepatitis C. However, some patients who initially respond experience a relapse during the treatment period (breakthrough phenomenon). The aim of this study was to evaluate the prevalence of breakthrough and its relationship with the emergence of neutralizing anti-interferon antibodies. METHODS: We studied 172 patients with histologically proven chronic hepatitis C, treated with interferon alpha 2a or 2b 3 mega units three times a week for 6 months. For each patient, HCV RNA level (polymerase chain reaction and bDNA) and anti-interferon antibodies dosage were determined during therapy. RESULTS: Among 84 patients with initial response, 13 (15.5%) experienced breakthrough. The kinetics of alanine aminotransferase and HCV RNA levels were strongly correlated, suggesting that breakthrough is not due to a random alanine aminotransferase fluctuation during treatment, but to the reappearance of viral replication. Neutralizing anti-interferon antibodies emergence was observed in 38.5% in patients with breakthrough, as compared to 9.0% and 2.8% of non-responder and complete-responder patients, respectively (p<0.0005). By multivariate analysis, the only factor predictive of breakthrough was the emergence of neutralizing anti-interferon antibodies 3 months after the onset of therapy. CONCLUSION: Our results suggest that the emergence of neutralizing anti-interferon antibodies during treatment may explain breakthrough in about one third of cases. Other causes may also be responsible for this phenomenon and they remain to be determined.

Adult↗

PubMed2000

Bacteremia due to Stenotrophomonas maltophilia in patients with hematologic malignancies.

Predisposing factors, clinical characteristics, and antimicrobial treatment of 37 hematology patients with Stenotrophomonas maltophilia bacteremia who were seen at the department of hematology of the University La Sapienza (Rome) from 1987 to 1996 were evaluated. The results were compared with a control group of patients with Pseudomonas aeruginosa bacteremia. Profound neutropenia was more prolonged in the S. maltophilia group (P=.025), severe cellulitis occurred only in S. maltophilia-infected patients (11 [30%]; P=.0002), and the bacteremia presented as breakthrough infection in 56% of the cases due to S. maltophilia (vs. only 24% of those due to P. aeruginosa; P=.002). Acute mortality rates associated with S. maltophilia and P. aeruginosa bacteremia were 24% and 21%, respectively. In both groups, profound neutropenia and hypotension at the onset of bacteremia, duration of profound neutropenia during bacteremia, severity-of-illness score > or =4, and inappropriate antibacterial treatment were factors significantly associated with death. Most S. maltophilia isolates were resistant to aminoglycosides, beta-lactams, and ciprofloxacin. Cotrimoxazole and ticarcillin-clavulanic acid showed borderline activity. Prompt administration of in vitro-active antibiotics may improve the prognosis of S. maltophilia bacteremia, especially for immunocompromised patients, and novel drug combinations are needed for the treatment of severe infections.

Adolescent↗

PubMed2002

Observational study of vaccine efficacy 14 years after trial of hepatitis B vaccination in Gambian children.

OBJECTIVE: To determine the duration of protection from hepatitis B vaccine given in infancy and early childhood. DESIGN: Cross sectional serological study of hepatitis B virus infection in children of various ages 14 years after the start of a trial of vaccination regimens. SETTING: Two villages in the Gambia. PARTICIPANTS: Children and adolescents given hepatitis B vaccine in infancy or early childhood: 232 were aged 1-5 years, 225 aged 5-9 years, 220 aged 10-14 years, and 175 aged 15-19 years. MAIN OUTCOME MEASURES: Vaccine efficacy against infection and against chronic infection in the different age groups. RESULTS: Vaccine efficacy against chronic carriage of hepatitis B virus was 94% (95% confidence interval 89% to 97%), which did not vary significantly between the age groups. Efficacy against infection was 80% (76% to 84%). This was significantly lower in the oldest age group (65%, 56 to 73). Of the uninfected participants in this age group, 36% had no detectable hepatitis B virus surface antibody. Time since vaccination and a low peak antibody response were the most powerful risk factors for breakthrough infection (P<0.001 in each case). Low peak antibody response was also a risk factor for chronic carriage (odds ratio 95, 19 to 466). CONCLUSIONS: Children vaccinated in infancy are at increased risk of hepatitis B virus infection in the late teens. The risk of chronic carriage after sexual exposure needs further assessment to determine if booster vaccines are necessary.

Adolescent↗

PubMedDate not supplied

When an executive defects.

The news that one of the company's senior managers is leaving comes as a complete surprise to Paul Simmonds, CEO of Kinsington Textiles, Inc. Ned Carpenter, KTI's vice president of operations for three years, writes in his resignation letter than he is leaving for a better opportunity. Simmonds soon learns that Carpenter's new job is at Daltex, one of KTI's main rivals in the intensely competitive carpet industry. Hiring Carpenter had helped Simmonds establish his reputation as a topnotch manager. Carpenter came to KTI with lots of ideas and put his enthusiasm to good use. Three years into a five-year change program, Carpenter had turned KTI's operations from one of the worst in the industry to one of the best. He also had helped develop and plan the upcoming launch of a new fiber coating--KTI's first breakthrough in years. In this fictitious case study, Simmonds, along with the company's counsel and vice president of human resources, must figure out how much and what sort of damage control they need. What are they going to tell the company's employees and the media? Should they immediately replace Carpenter with John Brady, the second-in-command of operations? What if Carpenter is taking KTI employees--and strategic information--with him to Daltex? Should Simmonds ask all his managers to sign noncompete agreements-something Carpenter was never asked to do? Should KTI sue Carpenter? Five experts offer advice about communicating with KTI's employees, the media, and Carpenter himself, and about protecting the company's confidential information.

Administrative Personnel↗

PubMed2002

[Successful treatment of gastric cancer accompanied by multiple liver metastases with TS-1 followed by curative gastrectomy affiliation].

Despite the improvement in the operative results for patients with gastric cancer, the prognosis of those with liver metastasis remains dismal. Multimodal therapy has attracted considerable attention as a breakthrough in the strategy for treating cases of highly advanced gastric cancer. We report the case of a 62-year-old female with gastric cancer accompanied by multiple liver metastases successfully treated by TS-1, a novel oral fluoropyrimidine derivative. One treatment course consisted of 4 weeks of TS-1 administration (100 mg daily) followed by a 2-week break. After 3 courses of treatment, an abdominal CT scan showed no evidence of liver metastases and gastroscopy revealed that the primary gastric lesion was reduced. Grade 1 toxicity (nausea and diarrhea) was seen but 6 days rest improved the condition. Distal gastrectomy was subsequently performed without any finding of residual tumor. TS-1 may have a promising role in neoadjuvant chemotherapy for gastric cancer.

Administration, Oral↗

PubMed1992

The big picture. Total quality management and continuous quality improvement.

The pressure to improve the quality of clinical and customer service outcomes continues to escalate. In most cases, sustained improvement (either incremental or breakthrough) is a direct result of improving service delivery and work processes. The challenge, for managers, is to design work processes that predictably lead to satisfying and cost-effective results. Total quality management (TQM) and continuous quality improvement (CQI) may seem like "this year's fads," but they are form, not fashion. TQM and CQI processes generate a customer-responsive environment in which employees can contribute to achieving the organization's mission, vision, and strategic objectives.

Humans↗

PubMed1990

Pharmacokinetic drug interactions with oral contraceptives.

Oral contraceptive steroids are used by an estimated 60 to 70 million women world-wide. Over the past 20 years there have been both case reports and clinical studies on the topic of drug interactions with these agents. Some of the interactions are of definite therapeutic relevance, whereas others can be discounted as being of no clinical significance. Pharmacological interactions between oral contraceptive steroids and other compounds may be of 2 kinds: (a) drugs may impair the efficacy of oral contraceptive steroids, leading to breakthrough bleeding and pregnancy (in a few cases, the activity of the contraceptive is enhanced); (b) oral contraceptive steroids may interfere with the metabolism of other drugs. A number of anticonvulsants (phenobarbital, phenytoin, carbamazepine) are enzyme-inducing agents and thereby increase the clearance of the oral contraceptive steroids. Valproic acid has no enzyme-inducing properties, and thus women on this anticonvulsant can rely on their low dose oral contraceptive steroids for contraceptive protection. Researchers are now beginning to unravel the molecular basis of this interaction, with evidence of specific forms of cytochrome P450 (P450IIC and IIIA gene families) being induced by phenobarbital. Rifampicin, the antituberculous drug, also induces a cytochrome P450 which is a product of the P450IIIA gene subfamily. This isozyme is one of the major forms involved in 2-hydroxylation of ethinylestradiol. Broad spectrum antibiotics have been implicated in causing pill failure; case reports document the interaction, and general practitioners are convinced that it is real. The problem remains that there is still no firm clinical pharmacokinetic evidence which indicates that blood concentrations of oral contraceptive steroids are altered by antibiotics. However, perhaps this should not be a surprise, given that the incidence of the interaction may be very low. It is suggested that an individual at risk will have a low bioavailability of ethinylestradiol, a large enterohepatic recirculation and gut flora particularly susceptible to the antibiotic being used. Two drugs, ascorbic acid (vitamin C) and paracetamol (acetaminophen), give rise to increased blood concentrations of ethinylestradiol due to competition for sulphation. The interactions could have some significance to women on oral contraceptive steroids who regularly take high doses of either drug. Although on theoretical grounds adsorbents (e.g. magnesium trisilicate, aLuminium hydroxide, activated charcoal and kaolin) could be expected to interfere with oral contraceptive efficacy, there is no firm evidence that this is the case. Similarly, there is no evidence that smoking alters the pharmacokinetics of oral contraceptive steroids. These agents are now well documented as being able to alter the pharmacokinetics of other concomitantly administered drugs.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1995

A new breakthrough in treatment of visceral leishmaniasis in children.

Fifty cases of visceral leishmaniasis were admitted in Children's Hospital, Islamabad. Common clinical features were fever (100%), splenomegaly (100%), hepatomegaly (100%), anaemia (96%), abdominal distension (40%), bronchopneumonia (26%) and bleeding diathesis (22%). Hb was below 7.0 G/dl in 80%, white cell count below 4 x 10(9)/cmm in 88% and platelet count below 100 x 10(9)/c4mm in 86%. All the patients showed leishmania donovani bodies in the marrow smears. Fourteen patients were treated with aminosidine (15 mg/kg), intramuscularly daily for 4 weeks. All responded dramatically and none of them went into relapse in a year's follow-up. No side-effects were observed. Aminosidine can therefore, be recommended as a treatment of choice for visceral leishmaniasis in children.

Anemia↗