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[Why is there a poor response to combined therapy with interferon alfa 2b and ribavirin in patients with chronic hepatitis C?].

BACKGROUND: Patients with chronic hepatitis C are now treated with a combination of interferon alpha (IFN) and ribavirin. Therapy was used in initial treatment, for those who were resistant to interferon and in relapsed patients. The aim of the study was to evaluate our results and to compare them with the already published data. METHODS AND RESULTS: 27 adult patients of the average age 46 years were cured from 1997 through 1999 for the histologically verified chronic hepatitis C with IFN-alpha 2 and ribavirin. 16 patients suffered from the chronic hepatitis with low, medium or high activity, 11 of them had cirrhosis. Serological testing was done using ELISA-3 test HCV RNA in serum was estimated by the polymerase chain reaction and serotype HCV was identified by the Murex kit. Treatment lasted 6 to 12 months. Incidences of side effects to both remedies, complications in therapy, therapeutical responses and possible failures of the combination therapy were analysed. In 20/27 patients the HCV serotype could be identified and always serotype 1 was found. Average score of histological activity was in patients with serious chronic active hepatitis and cirrhosis 10.1, in other patients 5.6. Sustained biochemical and virological response was found in 5 out of 27 patients (18.5%). Their average age was 39 years. 9 patients (33%) of average age 49 years had no biochemical and virological response. Sustained biochemical response without the accompanying virological response was found at the end of therapy in 10 patients (37%). After the end of therapy, 33% of patients had a relapse. The most frequently seen accompanying sign was the flu-like syndrome, in two female patients we found impairment of thyroid gland function, and in another two the breakthrough phenomenon. Treatment with ribavirin was in seven cases (26%) complicated with rather serious haemolytic anaemia and the dose had to be reduced. Toxic-allergic exanthema in 5 patients (18.5%) represented the second serious complication causing the termination of therapy. CONCLUSIONS: Sustained biochemical and virological response to the combination therapy was found only in patients with mild form of chronic hepatitis C. No such response was found in 8 patients with cirrhosis and in one female patients with medium activity of the chronic hepatitis. The age of patients with sustained response was significantly lower than in patients without the response (39 years versus 49 years). The most frequent serotype was HCV 1. The combination therapy was more frequently accompanied with clinically serious complications. To the adverse effects to the combination therapy belonged in our population the liver cirrhosis, age about 50 or more years, and the genotype HCV 1. It is also the answer to the question why the combination therapy of patients with chronic HCV infection has so poor results.

Adult↗

Drug utilization review on a tertiary palliative care unit.

Drugs are indispensable for the management of symptoms in palliative care patients, and account for a significant proportion of expenditures on a Tertiary Palliative Care Unit (TPCU). Drug expenditures for Edmonton's TPCU increased by 40% in 2002 compared to 2001. Fifty-five percent of the increase was attributable to injectable fentanyl, oral and injectable ondansetron, and total parenteral nutrition (TPN). As there was no increase in the unit cost of these drugs between 2001 and 2002, the increased expenditures reflected increased utilization. The hypothesis of this study was that the increased utilization of these drugs reflected appropriate prescribing. The objective was to compare the indications for prescribing these drugs in 2002 against evidence- and consensus-based criteria. Patients who received these drugs while admitted to the TPCU from January 1 to December 31, 2002 were identified through the pharmacy database. Evidence- and consensus-based criteria for drug utilization were developed. Prescribing indications were retrospectively compared against the criteria. Drug prescriptions were categorized as follows: (1) meeting criteria, (2) not meeting criteria, or (3) uncertain. The drugs under study were prescribed during 48 out of 234 admissions to the TPCU in 2002. Prescriptions for fentanyl met criteria in 26 of 29 cases. Indications were unsuccessful therapy with morphine, hydromorphone, and oxycodone (20), requirement for rapid titration from fentanyl patch (5), renal failure (2), and sublingual administration for breakthrough pain (1). Prescriptions for ondansetron met criteria in 19 of 21 cases. Indications were nausea refractory to metoclopramide and dexamethasone (13), and nausea related to radiotherapy or chemotherapy (6). Prescriptions for TPN met criteria for initiation in only one of five cases. However, in all cases, TPN had been started prior to admission. In cases where death was considered imminent, TPN was continued pending consultation with the patient and family regarding discontinuation. These data indicate that the increased prescribing of fentanyl and ondansetron on the TPCU satisfied evidence- and consensus-based criteria in most cases, apparently justifying the associated increase in drug expenditures. This type of analysis may be useful whenever increased drug utilization requires review. A cost effectiveness analysis would be the next step in evaluating the costs vs. the benefits. The issue of discontinuing TPN in palliative care patients requires further investigation.

Adult↗

Local recurrence of breast cancer after skin-sparing mastectomy following core needle biopsy: case reports and review of the literature.

The latest advances in diagnostic and therapeutic procedures for breast cancer have provided valuable technological breakthroughs. Yet the long-term consequences of these modern methods are still quite unclear. Such is the case for stereotactic or ultrasound-guided histologic needle biopsy and skin-sparing mastectomy. We report on three patients who presented with multicentric breast cancer diagnosed by stereotactic needle biopsy and treated by skin-sparing mastectomy. All three patients developed recurrence at the core needle entry site. Records of 58 patients with breast cancer who were treated by skin-sparing mastectomy followed by immediate reconstruction (with transverse rectus abdominis muscle [TRAM] flap or tissue expander) at the Breast Diseases Division of Buenos Aires British Hospital between December 1999 and December 2003 were reviewed retrospectively. Eleven of these patients were diagnosed by histologic needle biopsy. The mean follow-up was 28 months (range 5-60 months). Three (skin or subcutaneous) local recurrences at the needle entry site, diagnosed in a mean time of 23.6 months (16, 22, and 23 months), were reported. The three patients underwent complete resection with clear margins, radiation therapy to the "neobreast," and tamoxifen. All three patients are disease free with a mean postrecurrence follow-up of 24.3 months (30, 23, and 22 months). Based on the evidence of displacement of tumor cells and the potential nonresection of such tumor seeding at the time of skin-sparing mastectomy, as well as the poor probability of postoperative radiation therapy, we recommend surgical resection of the needle biopsy tract, including the dermal entry site, at the time of mastectomy.

Adult↗

Breakthrough candida Infection in a preterm infant with congenital cutaneous Candida albicans infection.

Amphotericin B is the primary antifungal agent used for candida sepsis in neonates. Breakthrough candidemia was not reported in neonates during either amphotericin B or liposomal amphotericin B (AmBisome) treatment. We describe a case of a premature infant with congenital cutaneous candida infection, who had two episodes of breakthrough infection, from Candida albicans and Candida parapsilosis, while he was treated with amphotericin B and AmBisome, respectively. We discuss the pathogenesis of breakthrough infections, and the relevance of antifungal resistance and sensitivities testing.

Amphotericin B↗

Continuous EEG monitoring and midazolam infusion for refractory nonconvulsive status epilepticus.

BACKGROUND: Although cIV-MDZ has emerged as a popular alternative to barbiturate therapy for refractory status epilepticus (RSE), experience with its use for this indication is limited. OBJECTIVE: - To evaluate the efficacy of continuous intravenous midazolam (cIV-MDZ) for attaining sustained seizure control in patients with RSE. METHODS: The authors reviewed 33 episodes of RSE treated with cIV-MDZ in their neurologic intensive care unit over 6 years. All patients were monitored with continuous EEG (cEEG). MDZ infusion rates were titrated to eliminate clinical and EEG seizure activity; cIV-MDZ was discontinued once patients were seizure-free for 24 hours. Acute treatment failures (seizures 1 to 6 hours after starting cIV-MDZ), breakthrough seizures (after 6 hours of therapy), post-treatment seizures (within 48 hours of discontinuing therapy), and ultimate treatment failure (frequent seizures that led to treatment with pentobarbital or propofol) were identified. RESULTS: All patients were in nonconvulsive SE at the time cIV-MDZ was started; the mean duration of SE before treatment was 3.9 days (range 0 to 17 days). In addition to benzodiazepines, 94% of patients had received at least two antiepileptic drugs (AED) before starting cIV-MDZ. The mean loading dose was 0.19 mg/kg, the mean maximal infusion rate was 0.22 mg/kg/h, and the mean duration of cIV-MDZ therapy was 4.2 days (range 1 to 14 days). Acute treatment failure occurred in 18% (6/33) of episodes, breakthrough seizures in 56% (18/32), post-treatment seizures in 68% (19/28), and ultimate treatment failure in 18% (6/33). Breakthrough seizures were clinically subtle or purely electrographic in 89% (16/18) of cases and were associated with an increased risk of developing post-treatment seizures (p = 0.01). CONCLUSIONS: Although most patients with RSE initially responded to cIV-MDZ, over half developed subsequent breakthrough seizures, which were predictive of post-treatment seizures and were often detectable only with cEEG. Titrating cIV-MDZ to burst suppression, more aggressive treatment with concurrent AED, or a longer period of initial treatment may reduce the high proportion of patients with RSE who relapse after cIV-MDZ is discontinued.

Adult↗

[Malaria in Hungary: origin, current state and principles of prevention].

Malaria was an endemic disease in Hungary for many centuries. A country-wide survey of the epidemiologic situation on malaria started in the year of 1927. That was done by the Department of Parasitology of the Royal State Institute of Hygiene (presently: Johan Béla National Center for Epidemiology). The notification of malaria was made compulsory in 1930. Free of charge laboratory examination of the blood of persons suffering from malaria or suspected of an infection have been carried out. Anti-malarial drugs were also distributed free of charge, together with appropriate medical advise given at the anti-malarial sanitary stations. Between 1933 and 1943, the actual number of malaria cases was estimated as high as 10-100,000 per year. The major breakthrough came in 1949 by the organized antimalarial campaign applying DDT for mosquito eradication. The drastic reduction of the vectors resulted in the rapid decline of malaria cases. Since 1956, there have not been reported any indigenous case in Hungary. In 1963, Hungary entered on the Official Register of the WHO to the areas where malaria eradication has been achieved. During the period of 1963-2001, 169 Hungarians acquired the malaria in abroad and 263 foreigners infected in abroad were registered in Hungary. More than half of the cases (230) were caused by Plasmodium falciparum. Further 178 cases were caused by Plasmodium vivax and 24 cases by other Plasmodium species. During that period, 7 fatal cases were reported (Plasmodium falciparum). The expansion of migration (both the increase of the number of foreigners travelling into Hungary and of Hungarians travelling abroad) favours to the appearance of imported cases. Attention is called of all the persons travelling to malaria endemic countries to the importance of malaria prevention by the International Vaccination Stations located in the National Center for Epidemiology and in the Public Health Institutes of 19 counties and of Budapest. The Johan Béla National Center for Epidemiology issued a protocol in 2001, the title of which is: "Antimalarial defence". This helps the information activity of the International Vaccination Stations. To prevent malaria infections, systemic mosquito eradication is organized and supervised by the Office of the Chief Medical Officer at the touristically important areas in the summer season.

History, 20th Century↗

[Autoimmunization induced by interferon alpha therapy in chronic hepatitis C].

We report the case of a 56 year-old woman with post-transfusion chronic hepatitis C who presented with a severe ALT flare up associated with a rapid progression of liver fibrosis during interferon alpha 2b therapy. Several hypotheses were considered to explain the etiology of this ALT flare: there was no viral super infection by other hepatotropic viruses, no toxic hepatitis, no metabolic disease, and no other specific liver diseases could be identified. HLA typing showed a specific profile A1 B8 DR3 (risk factor of auto-immunization during interferon alpha therapy) with antinuclear antibodies and anti smooth muscle antibodies. This case suggests that auto-immunization induced by interferon alpha should be investigated in case of ALT flare that is not followed by an HCV breakthrough.

Antiviral Agents↗

Pneumocystis carinii pneumonia presenting as an upper lobe cavity after aerosolized pentamidine prophylaxis in an HIV-infected patient.

We describe an atypical diagnostic feature of a breakthrough Pneumocystis carinii pneumonia (PCP) during primary prophylaxis with aerosolized pentamidine. Our case disclosed infiltrates restricted to the left upper lobe. After 2 weeks a solitary cavity developed. Diagnosis was easily established by bronchoalveolar lavage when performed in the affected segment bronchus. Cavitation clearly demonstrated localized infection, with tissue destruction as one main pathogenetic pattern of a breakthrough PCP during aerosolized pentamidine prophylaxis.

Adult↗

Dynamics of viscous penetration in percolation porous media.

We investigate the dynamics of viscous penetration in two-dimensional percolation networks at criticality for the case in which the ratio between the viscosities of displaced and injected fluids is very large. We report extensive numerical simulations that indicate that the scaling exponents for the breakthrough time distribution are the same as the previously reported values computed for the case of unit viscosity ratio. Our results are consistent with the possibility that viscous displacement through critical percolation networks constitutes a single universality class, independent of the viscosity ratio. We also find that the distributions of mass and breakthrough time of the invaded clusters have the same scaling form, but with different critical exponents.

Journal Article↗

Comparative study and evaluation of side effects of low-dose contraceptive pills administered by the oral and vaginal route.

This was a comparative study of side effects and acceptability of low-dose pills administered by the oral and vaginal rout. In an experimental clinical trial study, undesirable side effects of nausea, dysmenorrhea, breast tenderness, gastrointestinal disorders, vertigo, headache, and breakthrough bleeding (BTB) were studied. The participants of the case and the control groups were the same women. The side effects were compared in 143 women using contraceptive pill containing 150 microg levonorgestrel and 30 microg ethinyl estradiol by vaginal and oral route. The efficacy and acceptability were evaluated. The side effects among the patients who used the contraceptive pills orally were significantly higher than among those who used the vaginal route (p < 0.0001). BTB occurred more often with the oral route, but there was no significant difference between their incidences (p = 0.267). Most participants in this study expressed a high level of acceptability with the vaginal route. There was only one unwanted pregnancy, which occurred when the participant used the contraceptive pill vaginally, but used it incorrectly. Using the contraceptive pill administered by vaginal route is a safe method with fewer side effects and more acceptability when compared with the oral route.

Administration, Intravaginal↗

Terpyridine-based silica supports prepared by ring-opening metathesis polymerization for the selective extraction of noble metals.

The synthesis of a terpyridine-based sorbent for solid-phase extraction (SPE) of noble metal ions is described. For this purpose, 4'-(norborn-2-en-5-ylmethylenoxy)terpyridine was copolymerized with norborn-2-ene via Mo(N-2,6-i-Pr2-C6H3)(=CHCMe2Ph) (OC(CH3)(CF3)2)2-catalyzed ring-opening metathesis polymerization (ROMP) to give a poly(norbornene900(-b-4'-(norborn-2-en-5-ylmethylenoxy)terpyridine60) block-copolymer. This block-copolymer was used for the preparation of polymer-coated silica 60 (4.8 wt.% coating), which was investigated for its extraction capabilities for Cr(III), Mn(II), Re(II), Fe(III), Ru(III), Co(II), Rh(III), Ir(III), Ni(II), Pd(II), Pt(II), Cu(II), Ag(I), Au(III), Zn(II), Cd(II) and Hg(II), at different pH. Under competitive conditions and at pH < 0.6, the selectivity order was Pd approximately = Ag approximately = Au approximately = Pt > Re > Ir > Rh > Ru > Fe > Cr approximately = Mn approximately = Cd approximately = Zn. Enhanced selectivity was observed at pH = 3.5, the order was Au > Hg > Pd approximately = Ag > Rh > Pt > Ir approximately = Re > Cu > Co approximately = Zn approximately = Cd approximately = Ni > Cr > Mn. The maximum metal loading that was achieved under non-competitive conditions was > 6 mg/g for Au(III), Hg(II), Pd(II) and Ag(I). Even under competitive conditions, loadings of > 6 mg/g were realized for Au(III) and Hg(II). Quantitative recoveries > 97% were observed for all metals in case loading was stopped before reaching the point of breakthrough.

Magnetic Resonance Spectroscopy↗

Outbreak of varicella among vaccinated children--Michigan, 2003.

On November 18, 2003, the Oakland County Health Division alerted the Michigan Department of Community Health (MDCH) to a varicella (chicken pox) outbreak in a kindergarten-third grade elementary school. On December 11, MDCH and Oakland County public health epidemiologists, with the technical assistance of CDC, conducted a retrospective cohort study to describe the outbreak, determine varicella vaccine effectiveness (VE), and examine risk factors for breakthrough disease (i.e., varicella occurring >42 days after vaccination). This report summarizes the results of that study, which indicated that 1) transmission of varicella was sustained at the school for nearly 1 month despite high vaccination coverage, 2) vaccinated patients had substantially milder disease (<50 lesions), and 3) a period of > or =4 years since vaccination was a risk factor for breakthrough disease. These findings highlight the importance of case-based reporting of varicella and the exclusion of patients from school until all lesions crust or fade away. Information about recognizing vaccinated patients with mild cases should be disseminated to health-care providers, school administrators, and parents.

Chickenpox↗

[Epidemiological review of tuberculosis].

Current situation of tuberculosis (TB) problem of the world and of Japan is reviewed in terms of epidemiology and control strategy. Globally, TB has been increasing in the human history as ever. Even in the industrialized countries it is now in upsurge as one of the "re-emerging diseases". However, it is expected that with the wider and quick coverage of the new policy of treatment of cases using "DOTS strategy", we could attain the historical breakthrough of TB within couple of years. Japan is also faced with threats of TB with its new features to which the Japanese national control programme has not experienced enough. If we succeed in reorienting its programme well responding to the new TB problem, we will be able to achieve the goal of TB elimination by 2060, but maybe never earlier than that.

Humans↗

Adenosine restores atrio-venous conduction after apparently successful ostial isolation of the pulmonary veins.

AIMS: Pulmonary vein (PV) isolation is a curative treatment for patients with atrial fibrillation. The aim of this study was to evaluate prospectively the effects of adenosine administration on the PV activity and atrio-venous conduction after PV isolation. METHODS AND RESULTS: Twenty-nine patients (21 m; age: 55+/-8 years) were submitted to ostial PV isolation guided by basket catheter recordings. After successful isolation, the effects of a 12 mg intravenous bolus of adenosine were tested in 62 PVs. In 22/62 PVs (35%), left atrium (LA)-to-PV conduction was transiently (16.6+/-7.1 s, range: 3.8-27.9 s) or permanently (3 PVs) restored in response to adenosine administration. The prevalence of this phenomenon was 39% in left superior PVs, 43% in right superior PVs, and 22% in left inferior PVs (p=0.365). It occurred more frequently in the presence of dissociated PV activity (11/15 PVs, 73% vs. 11/47 PVs, 23%; p=0.002), whereas it was not influenced by the median duration of the radiofrequency current (RFC) delivery for each PV [19 (IQR: 12-26) min vs. 16 (IQR: 11-24) min: p=0.636]. A lengthening or shortening of the LA-PV conduction time was observed at LA-PV conduction appearance and disappearance in 36% and 55% of the cases, respectively. Further RFC applications (median: 5.5 min, IQR: 4-11 min) at the residual conduction breakthrough(s) indicated by the basket catheter recordings definitively eliminated adenosine-induced recovery of LA-PV conduction in all cases. Finally, when present, intrinsic PV discharge was invariably depressed by adenosine administration. CONCLUSIONS: Adenosine may transiently or permanently re-establish LA-PV conduction after apparently successful PV isolation. This phenomenon is abolished by additional RFC delivery. However, its possible influence on the clinical results of PV ablation must be evaluated by properly designed, randomized studies.

Adenosine↗

[Postoperative hemorrhage due to normal pressure hyperperfusion breakthrough after a trapping of VA-PICA dissecting aneurysm].

We described a case of cerebellar hemorrhage after trapping of a vertebral artery dissecting aneurysm. A forty-eight-year-old man had suffered from severe headache, vomiting and disturbance of consciousness. He was transferred to our hospital in an ambulance. Emergency CT scan showed subarachnoid hemorrhage in the posterior fossa predominantly, intraventricular hemorrhage and hydrocephalus change. Chest X-ray showed radiological evidence of pulmonary edema. The initial blood-gas determinations demonstrated a marked reduction in PaO2 and increased PaCO2. Five days after admission, the patient's condition was improving. Cerebral angiography was performed using the Seldinger method. It revealed a right vertebral artery dissecting aneurysm just distal to the posterior inferior cerebellar artery. We performed an operation to trap the VA dissecting aneurysm. Blood pressure was well controlled under 140 mmHg during the operation and he recovered from anesthesia completely. On the day after the operation, suddenly the patient's consciousness began to deteriorate. Emergency CT scan was performed and it showed SAH, cerebellar hemorrhage and diffuse swelling of the cerebellum on the same side as the operation. We suspected rebleeding of the aneurysm due to a clip's having slipped. Reoperation was performed, but the clip was not displaced and there were no definite bleeding vessels on the operative field. Consequently only external decompression and resection of the right cerebellum were performed. We discuss pathogenesis of the occurrence of hemorrhage in this particular case after trapping. We also review the relevant literature.

Aortic Dissection↗

Catamenial pneumothorax. Bilateral occurrence while on suppressive therapy.

A case of recurrent bilateral catamenial pneumothorax is presented with pathologic, cytologic, and radiologic documentation. Unlike previously reported cases where the pneumothorax is unilateral and the symptoms relieved while ovulation is suppressed with cyclic oral contraceptives, in the present case the pneumothorax occurred despite oral contraceptive therapy concurrent with anovulatory withdrawal or breakthrough bleeding.

Adult↗

Investigations on safety of hyperthermic intraoperative intraperitoneal chemotherapy (HIPEC) with Mitomycin C.

AIMS: Previous safety monitoring of hyperthermic intraoperative intraperitoneal chemotherapy (HIPEC) with Mitomycin C (MMC) did not demonstrate any detectable safety hazard to the personnel. Nevertheless, those results have been discussed controversially because of the methodological problems employed in the evaluation of potential exposure. We re-evaluated possible safety hazards of HIPEC by applying different monitoring strategies. METHODS: We monitored air samples in the operation room during HIPEC. In addition, we measured MMC in plasma of the surgeon with a newly developed analytical method. All samples were analysed by HPLC-UV at 360nm. The permeability of the gloves was tested using two in vitro techniques: diffusion cells and a glass cell chamber. In-use and worst-case exposure scenarios were imitated for in vitro experiments. RESULTS: The analysis of the air samples (n=3) could not detect any MMC. We found no drug above the limit of detection (1microg MMC/L) in the plasma samples of the surgeons (n=5). A breakthrough of latex glove material was detected in only one (worst-case exposure scenario) of 40 diffusion cell experiments. CONCLUSIONS: Established methods of safety monitoring could not reveal any detectable risk on in-use exposure conditions. The wearing of doubled latex gloves should prevent the surgeon from dermal exposure to MMC during HIPEC.

Air Pollutants, Occupational↗

The case against staged operative resection of cerebral arteriovenous malformations.

Three cases of large cerebral arteriovenous fistulae are presented in which surgical ablation was complicated by brain swelling from hyperperfusion breakthrough believed to be caused by acute intraoperative hypoperfusion superimposed on chronic preoperative hypoperfusion. On the basis of these cases, experimental data, and theoretical considerations, we seriously question the wisdom of using staged surgical resection of cerebral arteriovenous malformation to prevent complications related to alterations in cerebral hemodynamics. The reasons for this concern are: the repeated occurrence of acute-on-chronic hypoperfusion during staged resection; a lack of understanding of the time course for the correction of a disordered autoregulation; risk of hemorrhage between the initial and final resection; difficulty in assessing and substantiating flow reduction after subtotal resection; the rapidity of collateralization; the divergence of flow from large, readily accessible feeding arteries to deep penetrating vessels; and attenuation of the wall thickness in collateral vessels as a consequence of increased flow.

Adult↗