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Resistance trends in gram-negative bacteria: surveillance results from two Mexican hospitals gastritis zimt purchase nexium 40mg with amex, 2005-2010 gastritis diet coffee best nexium 40 mg. Phenotypic detection and occurrence of extended-spectrum beta-lactamases in clinical isolates of Klebsiella pneumoniae and Escherichia coli at a tertiary hospital in Trinidad & Tobago gastritis je buy 20mg nexium amex. Community acquired urinary tract infection and susceptibility profile of Escherichia coli to the main antimicrobial agents gastritis diet discount nexium 20mg without a prescription. In vitro resistance to cephalosporins in women with bacterial urinary tract infections. Uropathogens and their susceptibility patterns in children at Princess Rhmah Hospital, Jordan. Incidence, aetiology and resistance of late-onset neonatal sepsis: a five-year prospective study. Etiology and antibiotic susceptibility patterns of community- and hospital-acquired urinary tract infections in a general hospital in Kuwait. Escherichia coli isolated from urinary tract infections of Lebanese patients between 2000 and 2009: Epidemiology and profiles of resistance. A reflection on bacterial resistance to antimicrobial agents at a major tertiary care center in Lebanon over a decade. Characterization of extended- spectrum ß-lactamase-producing Escherichia coli and Klebsiella pneumoniae isolates from the community in Morocco. Detection of AmpC beta lactamase in clinical isolates of Escheria coli among children. An audit for microbiological surveillance and antimicrobial susceptibility in the intensive care unit. Evaluation of resistance to fuoroquinolones in clinical isolates of Escheria coli. Extended spectrum beta lactamases in urinary gram negative bacilli and their susceptibility pattern. Prevalence of antimicrobial resistance and integrons in Escherichia coli from Punjab, Pakistan. Multiple drug resistance patterns in various phylogenetic groups of uropathogenic E. Epidemiology of bacteraemia in Hamad general hospital, Qatar: a one year hospital-based study. Prevalence and antimicrobial susceptibility of extended spectrum beta-lactamase-producing Escherichia coli and Klebsiella pneumoniae in a tertiary care hospital. Clinical and laboratory profles of urinary tract infections caused by extended- spectrum beta-lactamase-producing Escherichia coli in a tertiary care center in central Saudi Arabia. Antimicrobial susceptibility pattern of bacterial pathogens causing urinary tract infections in a Saudi Arabian hospital. Prevalence of antimicrobial resistance among gram-negative isolates in an adult intensive care unit at a tertiary care center in Saudi Arabia. Antibiotic sensitivity pattern of common community-acquired uropathogens in children in a Saudi tertiary care hospital. Antimicrobial-resistant bacteria in a general intensive care unit in Saudi Arabia. Antibiotic resistance pattern and empirical therapy for urinary tract infections in children. Increased multidrug resistant Escherichia coli from hospitals in Khartoum state, Sudan. Resistance trends and risk factors of extended spectrum ß-lactamases in Escherichia coli infections in Aleppo, Syria. Resistance patterns of bacterial isolates to antimicrobials from 3 hospitals in the United Arab Emirates. Prevalence and antimicrobial susceptibility pattern of extended-spectrum beta-lactamase-producing Enterobacteriaceae in the United Arab Emirates. Antibiotic resistance of coliform bacteria from community-acquired urinary tract infections in the Zenica-Doboj Canton, Bosnia and Herzegovina. Epidemiology and susceptibility to antimicrobials in community, hospital and long-term care facility bacteremia in northern Israel: a 6 year surveillance. Epidemiology of bacteremia episodes in a single center: increase in Gram-negative isolates, antibiotics resistance, and patient age. Community-acquired complicated intra-abdominal infections in children hospitalized during 1995-2004 at a paediatric surgery department. Study of extended-spectrum (beta)-lactamase-producing bacteria from urinary tract infections in Bangladesh. Study of antimicrobial susceptibility of clinically signifcant microorganisms isolated from selected areas of Dhaka, Bangladesh. Antibiotic susceptibility patterns of uropathogens isolated from pediatric patients in a selected hospital of Bangladesh. A survey on antimicrobial sensitivity pattern of diferent antibiotics on clinical isolates of Escherichia coli collected from Dhaka city, Bangladesh. A ten year analysis of multi-drug resistant blood stream infections caused by Escherichia coli & Klebsiella pneumoniae in a tertiary care hospital. Symptomatic and asymptomatic urinary tract infection by Escherichia coli among pregnant women attending out patient clinic of obstetrics and gynecology. Extended-spectrum beta-lactamase-producing Escherichia coli and Klebsiella pneumoniae in diabetic foot infections. Prevalence of extended-spectrum beta-lactamases among Escherichia coli and Klebsiella pneumoniae isolates in a tertiary care hospital. Prevalence of extended spectrum beta lactamase and AmpC beta lactamase producers among Escherichia coli isolates in a tertiary care hospital in Jaipur. Antimicrobial susceptibility profles of aerobic and facultative Gram-negative bacilli isolated from patients with intra-abdominal infections in the Asia-Pacifc region according to currently established susceptibility interpretive criteria. Antibiotic susceptibility of intra-abdominal infection isolates from Indian hospitals during 2008. The eect of age on the bacteria isolated and the antibiotic-sensitivity pattern in infections among cancer patients. Antibiotic resistance pattern among common bacterial uropathogens with a special reference to ciprofloxacin resistant Escherichia coli. Study of antimicrobial susceptibility pattern of Escherichia coli isolated from clinical specimens in a Teaching Hospital, Pondicherry. High prevalence of extended-spectrum (beta)-lactamase-producing pathogens: Results of a surveillance study in two hospitals in Ujjain, India. Increasing burden of hospital acquired infections: Resistance to cephalosporin antibiotics among klebsiella and Escherichia coli. Prevalence of bacteriuria in Jeyaseharan hospital of South India and their antibiogram. Changing trends of in vitro antimicrobial resistance patterns in blood isolates in a tertiary care hospital over a period of 4 years. Antibacterial resistance and trend of urinary tract pathogens to commonly used antibiotics in Kashmir Valley. Trends in antimicrobial susceptibility of gram-negative bacteria isolated from blood in Jakarta from 2002 to 2008. Surveillance and correlation of antibiotic prescription and resistance of Gram-negative bacteria in Singaporean hospitals. Aetiology of community-acquired urinary tract infection and antimicrobial susceptibility patterns of uropathogens isolated. A survey of bacterial isolates cultured from apparently healthy individuals in South Western Nigeria. Prevalence and susceptibility patterns of urine isolates of escherichia coli to various fuoroquinolones in South-South Nigeria. Bacteriuria and antimicrobial susceptibility of e coli isolated from urine of asymptomatic university students in Kef, Nigeria. Increasing resistance to quinolones: A four-year prospective study of urinary tract infection pathogens.

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The diference in proportions comparing infants having favourable response gastritis symptoms dizziness generic 20mg nexium with amex, and the safety of the two regimens was gentamicin every 12 hours with those having it every 24 hours compared gastritis and diarrhea buy nexium 20mg with mastercard, besides according any symptoms due to side efects gastritis diet order nexium 40mg visa. A starting gentamicin dosage A favourable response was observed in 89% of Indian children interval of 12 hours in infants of any gestational age diet by gastritis cheap nexium 40mg online, or a treated with once-daily dosing of gentamicin and 76% of children starting dosage interval of 24 hours for infants of less than treated with multiple-daily dose of gentamicin. A 100% of 30 weeks gestational age, leads to most having toxic trough children in the once-daily dosing group and 87% of children in serum gentamicin levels. In infants of 30 weeks gestational age the multiple-daily dosing group had favourable gentamicin peak. Infants were stratifed according to gestational age (group 1, ≤ 34 Peak and trough serum gentamicin concentrations in gestational age) and (group 2, > 35 gestational age). Infants in neonates and infants the study arm received 5 mg/kg intravenously every 36 hours, the peak and trough gentamicin concentrations were whereas infants in the control arm received traditional dosage. Elevated serum this paediatric cohort receiving once-daily dose of 7 mg/kg gentamicin trough were reduced by 66% in group 1 (P-value = gentamicin, nephrotoxicity was uncommon and reversible, but 0. Therapeutic gentamicin dosage of 5 mg/kg every 36 hours to infants of drug monitoring using a monogram neither predicted nor all gestational ages is safe and results in serum gentamicin prevented toxicity, which was only observed in those with risk concentrations in goal therapeutic ranges. Infants were treated with 4 mg/kg gentamicin intravenously Once-daily versus twice-daily gentamicin dosage in infants once-daily [12]. In infants with gestational age between 32 Hagen and Oymar [16] evaluated once-daily or twice-daily and 36 weeks, 14 of 65 (22%) had trough gentamicin serum gentamicin dosage in infants with a gestational age ≥ 34 concentration > 2 µg/ml. In both groups, levels Among term neonates, only 2 out of 50 (4%) had the trough of gentamicin were obtained before and after the third dose. A dose of 4 mg/kg gentamicin once-daily the twice-daily regimen compared to the once-daily regimen produces serum gentamicin levels outside the therapeutic (P-value < 0. The trough gentamicin level was > 2 range in two-ffths of infants between 32+6 and 36+6 weeks of µg/ml in 16 infants who were treated with twice-daily regimen gestation. A single dose of 4 mg/kg once-daily is appropriate compared to 2 infants treated with once-daily regimen (P-value for term neonates and probably excessive for 32-36 gestational < 0. In infants with suspected sepsis, gentamicin 4 mg/kg once-daily provided higher peak In a previous study, 22% of infants who received a once-daily and lower trough gentamicin levels compared to administering gentamicin dosage of 5 mg/kg per day had unacceptably high gentamicin 2. The twice-dose and the once- toxicity) serum gentamicin concentrations were collected daily dose group had mean steady-state gentamicin peak on day 3 of therapy. Gentamicin once-daily therapeutic range, two infants with too high trough level (> 2 at 4 mg/kg/dose in infants at ≥ 34 gestational age achieved µg/ml) and one with subtherapeutic level (4 µg/ml). This regimen is convenient and does patient in the once-daily regimen had undesirable trough level not increase renal toxicity or ototoxicity. All infants in the twice-daily and in once- daily dosage groups showed improvement in clinical outcome. This regimen produces peak concentration that may have for each infant to achieve goal peak and trough gentamicin greater clinical efcacy and trough concentration with less concentrations. Age was the primary factor in determining the children aged 1 month to 13 years (median age was 7 months). Children received 5 mg/kg gentamicin once-daily and 6 A total of 79 children aged 1 month to 16 years (median mg/kg gentamicin divided 8 hourly (thrice-daily). Twenty- similar age without previous gentamicin treatment were six children received 4. Serum through gentamicin concentrations were and vestibulotoxic efects in newborns than it does in older signifcantly lower in the once-daily regimen. These results show a similar outcome in children concentration determined 30 min before (trough value) and receiving 4. Thirty-seven of these children, aged 9 to 17 years, had two or more audiograms; of these, 9 children Risk of hearing loos in infants and children exposed to developed objective evidence of hearing loss; in 2 children the gentamicin impairment was severe and permanent. If there is an increased burden hearing loss of 20 dB was found in 2 (3%) children. Brainstem auditory evoked potential recording was used to Hearing loss rates preterm infants run at 2-15%, compared to screen presymptomatically the hearing of 200 infants, with 0. The infants were divided into 2 groups according to risk of referral on the distortion product otoacoustic emission duration of antibiotic treatment; group 1 (179 infants) received assessments and/or automated auditory brainstem response antibiotic agents for ≤ 7 days. More than 80% of 82 infants received recordings, only 8 of these brain-damage infants (4. Distortion product otoacoustic emission referrals (6 with peripheral and 2 with central dysfunction) later were signifcantly greater for infants receiving > 2 days of manifested abnormal recordings. All were treated for 10 to 30 days; brainstem auditory evocated infants were exposed to higher levels of ambient sound that potential recordings were abnormal in 7 infants (33. In this group, referrals were generated by distortion product otoacoustic infants so treated usually had underlying disease or severe emission assessment than with auditory brainstem response infection all of which were clinically signifcant indicators of screens, with signifcantly more distortion product otoacoustic high risk for auditory pathway dysfunction. The auditory pathway was studied product otoacoustic emission assessments to existing neonatal on the third day of life by analyzing brainstem auditory evoked intensive cure unity hearing screening protocols could better potentials elicited by a click stimulus presented at the infants identify infants at-risk for ototoxicity. The total cumulated dose group, indicating impairment of the central component of the of gentamicin administered did not difer between the study auditory pathway. The been treated with gentamicin were examined to ascertain impact of gentamicin on sensorineural hearing loss can be whether gentamicin induces hearing loss [27]. Objective minimized with treatments of short duration, monitoring of thresholds to clicks were obtained using auditory nerve and gentamicin blood levels and dose adjustment. Serum gentamicin before and after gentamicin treatment were at therapeutic concentrations. A total of 220 infants were enrolled; 110 infants who ears, with the exception of two with demonstrable middle had received gentamicin and 110 infants had not received ear efusion. Gentamicin group were further concentrations does not cause hearing loss in infants. Fifty infants who had received gentamicin for 5 days or less, and 60 infants Cooper et al. Auditory brain gentamicin concentrations are associated with hearing loss response was performed 3 months later for failed cases to indicated by otoacoustic emission screen failure in critically confrm the hearing impairment. Extended intravenously to achieve the peak serum concentration of 7-10 interval dosing of gentamicin therapy in infants does not µg/ml and a target trough serum concentration < 2 µg/ml. Multivariate analysis of non-very- trough and peak levels of gentamicin on the values of serum low-birth-weight infants determined that 1-µg/ml increase creatinine, urine albumin/urine creatinine, fractional excretion in gentamicin peak is associated with an increase risk of of sodium and potassium, and urine calcium/urine creatinine otoacoustic emission screen failure (P-value = 0. Infants in 61 preterm infants treated with gentamicin for suspected weighing > 1,500 gram at birth and whose peak exceeded 10 infection on the third gentamicin dose and 48-72 hours after the µg/ml are at an increased risk for otoacoustic screen failure. Trough and peak levels of Maintaining serum gentamicin peak concentration at, or below gentamicin were positively correlated with serum creatinine, 10 µg/ml, may minimize hearing impairment. One hundred and twenty-fve (49%) children urine creatinine, fractional excretion of sodium and urine were exposed to gentamicin during 0-2 months of life, and 130 calcium/urine creatinine values recorded during treatment (51%) children were not treated with gentamicin (controls) were statistically signifcantly diferent from sub-therapeutic, [29]. The outcome measure was hearing loss, which was therapeutic, and high peak gentamicin levels. Children found to have a serum peal level-dependent microalbuminuric, in the gentamicin exposed group were not at increased risk for natriuric and calciuric efect in preterm infants. Children with history of ear suggest that when the monitoring of serum gentamicin is not of discharge and children with family history of deafness were possible, the monitoring of urine albumin/urine creatinine, the more at risk for having hearing loss. Serum and 3-hours urine electrolytes were fve infants afected by sensorineural hearing loss, leading to measured before and immediately after gentamicin infusion an incidence of sensorineural hearing loos was 1. Therapeutic doses of gentamicin result in urinary loss antibiotics (gentamicin with penicillin) for 6. These electrolyte changes infants) were included (nine randomized controlled trials and may be of clinical importance, especially for sick preterm two prospective cohort studies). Thirteen infants, 8 term and 5 preterm were treated for Nephrotoxicity could not be assessed due to variation in case between 3 and 7 days with gentamicin and ampicillin or defnitions used. Estimates of the number of infants potentially cloxacillin because suspected bacterial infection [34]. Urinary afected by gentamicin toxicity were not undertaken due to alanine aminopeptidase, urinary β-2-microglobulin, serum insufcient data. Given wider scale-up of outpatient-based and urea, and β-2-microglobulin were measured during and after lower-level treatment of possible serious bacterial infection, the end of treatment to detect signs of renal toxicity. Levels improved data are essential to better assess the risk from of urinary aminopeptidase increased in 12 infants, indicating neonatal gentamicin treatment without assessment of blood damage to cells of the proximal tubuli. Serum levels of urea and β-2- A Bartter-like syndrome is a toxic manifestation of gentamicin microglobulin did not indicate any drug-associated depression which includes nephrotoxic syndrome. Hypocalcaemia, Ten infants were treated with gentamicin and 10 infants not- hypomagnesaemia, alkalosis, and hypokalemia were the main treated served as controls. After discontinuation of rate and the fractional excretion of β-2-microglobulin in gentamicin, recovery of the tubular functions and resolution urine were used as indicators of renal dysfunction [35]. The fractional excretion of of 7 bacteria are reported in table 2, by Sader, et al.

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More frequent assessment could be considered once metastatic disease is identified and/or in response to intercurrent patient symptoms chronic antral gastritis definition 20mg nexium overnight delivery, and less frequent imaging performed once a pattern of stability is identified gastritis celiac generic nexium 20mg line. Although serum thyroglobulin levels should be measured as biomarkers of the disease extent diabetic gastritis diet order nexium 20 mg line, patients should not be identified as having progressive disease and requiring more aggressive therapy solely on the basis of rising levels of thyroglobulin; accelerating increases in thyroglobulin levels should gastritis diet buy 40 mg nexium amex, however, lead to consideration of more frequent and comprehensive imaging in efforts to identify previously occult structural correlates. These local treatment modalities should be considered prior to initiation of systemic treatment when the individual distant metastases are symptomatic or at high risk of local complications. They may also be helpful in case of progression in a single lesion in patients with otherwise controlled disease during systemic 241 Page 242 of 411 242 treatment. In these patients, benefits can be achieved in preventing local complications, in improving symptoms such as pain, in delaying the initiation of systemic treatments, and even in improving survival. These techniques can be a less aggressive alternative to surgery, and may be indicated in cases of lung metastases associated with insufficient respiratory reserve, poor patient clinical status, or after multiple previous surgical resections, local recurrence at the site of previous surgery or refusal of additional surgery. In selected patients, they may be an alternative to surgery as first-line treatment, and they may induce local tumor control with a similar efficacy to surgical resection. Of interest, long- term benefits in terms of disease control have been reported in patients with a single or few metastases and in whom the disease is slowly progressive. The main principle of these techniques is to selectively treat the lesion, to be minimally invasive, to be well tolerated with relatively few side effects. The indications and the feasibility of each technique depend on the location and the size of the lesion to be treated. Experience with metastases from thyroid cancer is scarce, and most available data have been obtained in patients with metastases from non-thyroid cancers. It has been used in several trials to treat brain, liver, lung and bone metastases. It is usually well tolerated, and brain necrosis that occurred in less than 10% of cases is usually limited and had no clinical consequences. The patient outcome depends mostly on the progression rate of extra cerebral lesions (1015). Data on lung and liver metastases are available only in retrospective studies on low numbers of patients and with a median follow-up of less than 1 year in most cases and in one prospective study (1016). This study included patients with many different primary tumors, including 10% of the patients having thyroid cancer. They showed a local control rate ranging from 63% to 98% in lung lesions, from 57% to 100% in liver lesions with a cumulative dose delivered ranging from 20-75 Gy in 5-15 fractions. The local tumor control seems to be long lasting with complete response ranging form 70 to 90 % at 2-3 years. Furthermore, rare (<3%) grade 3-4 toxicities (pneumonitis, pleural effusion, intestinal complications) were reported (1017). These toxicities are much less common that those associated with percutaneous treatment modalities. Concerning bone lesions, radiotherapy plays an important role because it can complement surgery in case of incomplete resection or be used alone for pain relief or palliation. Spinal myelopathy or vertebral fractures are the most important side effects, especially in case of large volume lesions. Percutaneous thermal ablation is aimed to destroy tumor foci by increasing (radiofrequency ablation) or decreasing (cryoablation) temperatures sufficiently to induce irreversible cellular damages. A multicenter prospective trial on 183 lung metastases from cancer other than colorectal showed a complete response rate of 88 % at 1 year and an overall survival of 92% and 64% at 1 year and at 2 years, respectively (1022). Cases of delayed recurrence have also been reported, and long-term follow up is needed. Furthermore, repeated treatments can be performed on the same lesion and multiple lesions can be treated in the same patient. The association of cryoablation and cementoplasty seems promising in purely lytic bone metastases from thyroid cancer. Published experience using thermal ablation and stereotactic radiation in thyroid cancer patients is limited, and recommendations are currently based on more robust evidence in other solid tumors. Randomized prospective studies comparing the efficacy and tolerability of these different techniques are lacking, and their choice in clinical practice is based on local experience, lesion location as well as patient status and preference. Surgical resection and stereotactic external beam radiotherapy are the mainstays of therapy (933;1029;1030). Stereotactic radiation therapy is preferred to whole brain irradiation because life expectancy in patients with brain metastases may be prolonged, and stereotactic irradiation induces less short and long-term toxic damages to the brain toxicity compared with whole brain irradiation (fatigue, headache, cognitive decline, and behavioral changes), and it may be effective even in patients with multiple brain lesions. Clinicians considering referral of patients for trials should review available treatment options and eligibility criteria, preferably through discussions with trial center personnel and review of trial materials at the website 246 Page 247 of 411 247 A broad variety of such trials may exist at any given time, which can generally be identified through online databases such as There is limited evidence that enrollment into clinical trials is associated with lower overall cancer-specific mortality for patients with common cancers, even within contexts in which approved and “standard of care therapies already exist (1031). The reasons for this association are unclear, but there is no evidence to suggest that trial participation is deleterious to patient outcomes, and it may be beneficial. Participation in a clinical trial should be considered in any situation wherein there exists no effective or proven standard of care, or when a standard of care is being compared with a promising new or investigational therapy. Adjuvant therapy trials may be appropriate for patients at high risk for disease recurrence following primary treatment who wish to pursue aggressive therapy. However, given the indolent nature of metastatic disease in most patients, therapeutic clinical trial participation should not be considered for patients with stable, asymptomatic metastatic disease unless agents with significant likelihood of complete remission, prolongation of survival, or biologic impact such as redifferentiation that could sensitize to definitive therapy are available (see section [C37]). Benefit has been demonstrated in the form of improved progression free survival (delay in time to disease progression or death) in three randomized, double-blinded, placebo-controlled, clinical trials (vandetanib (1033); sorafenib (1013); lenvatinib (1034). Benefit has also been demonstrated in the form of induced durable tumor regression (1035-1037). However, randomized clinical trial data are not yet available to address many additional critical questions, including effects of systemic therapies of various types on: i) survival and ii) quality of life – and also to address critical issues of optimal patient selection/inclusion/exclusion criteria for therapyand duration of treatment. Consequently, therapeutic decisions are presently based upon the convergence of “expert opinion and patient preference/philosophy, thus emphasizing the critical need to address the above questions definitively through clinical trials. In the absence of definitive data related to improved overall survival and/or quality of life to inform As a guide, evidence-based recommendations with expert consensus have been recently published (953). Although more “novel approaches have attracted attention recently, it is important to optimally apply fundamental approaches. Also important is the consideration of alternatives to the use of systemic therapy – such as the application of surgery or other localized approaches (including radiation therapy or thermal ablation approaches). It is also critically important to assure that the disease prompting therapy represents metastatic thyroid cancer. In particular, because pulmonary nodules attributable to benign causes are common, the presence of pulmonary nodules does not in and of itself justify the application of systemic therapy. Thus, in cases of diagnostic uncertainty where the result would have definitive therapeutic implications, biopsy is required, especially when thyroglobulin levels are low/unhelpful (such as in the presence of anti-thyroglobulin antibodies). Conversely, stable, asymptomatic pulmonary nodules of a few millimeters in size likely do not justify invasive assessment or systemic therapy. The introduction of systemic therapy requires that both the clinician and the patient agree that clinical benefits are expected to exceed risks for that individual patient. The problem in this determination, however, is that it is often very difficult to precisely define such risks and benefits – as risks and benefits vary greatly depending upon patient context, and as they are often poorly articulated in the literature. It is also critical to weigh not just risks of death and injury – but also risks of systemic therapies on quality of life, especially as viewed by a particular patient considering treatment. Hence, the decision is not based solely on benefits and risks of therapy, but also on patient value judgments. Issues of risks and benefits are reviewed in this context in conjunction with each therapeutic modality below. Finally, it is important that the involved care team (physicians, physician assistants, nurse practitioners, nurses) be experienced in the use and management of toxicities associated with these therapies. Appropriate informed consent should be obtained and documented in the medical record prior to initiation of any therapy, regardless of whether the patient is being treated in the context of a clinical trial. Kinase inhibitors, however, are associated with numerous adverse effects including diarrhea, fatigue, induced hypertension (requiring initiation of antihypertensive therapy in about half of all 251 Page 252 of 411 252 previously normotensive individuals), hepatotoxicity, skin changes, nausea, increased levothyroxine dosage requirement, changes in taste and weight loss. These potential side effects have high probability of negatively impacting quality of life and/or necessitating dosage reductions in nearly two-thirds of treated many patients, and treatment discontinuation in up to 20% of patients.

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These results suggested that formation of the cysteine conjugate is a quantitatively important meta- bolic pathway in humans gastritis diet cheap 40mg nexium otc, especially in persons with high hexachlorobenzene body burdens diet of gastritis patient generic nexium 20mg with amex. Moreover gastritis zdravlje discount nexium 40 mg without prescription, pentachlorobenzenethiol is a urinary marker of the internal dose of hexachlorobenzene and of glutathione-mediated metabolism (To-Figueras et al gastritis symptoms loose stools order nexium 20mg overnight delivery. In rats fed hexachlorobenzene for 4 weeks, subsequent food deprivation appeared to enhance the toxic response (liver hypertrophy), implying decreased mobilization of hexachlorobenzene residues into fat and resulting in greater accumulation of hexachlorobenzene in plasma, liver, brain and adrenal glands (Villeneuve et al. In rhesus monkeys (Macaca mullata) given hexachlorobenzene at a dose of 8, 32, 64 or 128 mg/kg bw per day by gavage for 60 days, body fat and bone marrow had the highest concentrations, followed by adrenal glands, liver, kidney, brain, ovaries, muscle and serum. The serum concentrations did not appear to correspond to the dose (Knauf & Hobson, 1979). After administration of a single intravenous injection of hexachlorobenzene to male beagles, the chemical was initially found primarily in the lung (2 h) but after 8 h was found primarily in the fat. Excretion in these dogs occurred essentially through the bile and faeces, urinary excretion being of less importance (Sundlof et al. Absorption of hexachlorobenzene applied dermally to male Fischer 344 rats increased from 1% to 9. In adult female Sprague-Dawley rats dosed with 50 mg/kg bw hexachlorobenzene by gavage, the chemical was found to concentrate primarily in the fat and also in endocrine glands with large lipid components, such as the follicular fluid of the ovary and thyroid. The concentrations of residues of hexachlorobenzene in nine rats given 50 mg/kg bw per day were significantly (p < 0. The concentrations of residues of hexachlorobenzene in the ovary were greater than those in the thymus, liver or lung (Foster et al. Hexachlorobenzene was found in the milk of cows given the compound (Fries & Marrow, 1976) and in the organs of 18-day-old offspring of rat dams fed a diet containing hexachlorobenzene (Mendoza et al. Toxicokinetics demonstrated that hexachlorobenzene is transferred across the placenta and into breast milk in rodents (Courtney & Andrews, 1985; Courtney et al. A similar 6-day study of pregnant hamsters and guinea-pigs showed that the hamster fetuses had fivefold greater concentrations of hexachlorobenzene than the guinea-pig fetuses (Courtney et al. The distribution in infants showed concentration in fat, bone marrow and adrenal glands (Bailey et al. When pregnant Sprague- Dawley rats were given a diet containing hexachlorobenzene during gestation and lactation (35 nmol/100 g diet [100 μg/kg diet]), about 0. A large proportion of the hexachlorobenzene body burden was lost during lactation, and the concentration in the stomach contents of suckling pups was highest on day 2 after birth (Nakashima et al. The major urinary metabolites were pentachlorophenol, tetra- chlorohydroquinone and pentachlorothiophenol. The other urinary metabolites were tetrachlorobenzene, pentachlorobenzene, 2,4,5- and 2,4,6-trichlorophenols and 2,3,4,6- and 2,3,5-6-tetrachlorophenols; 2,3,4-trichlorophenol and other tetrachloro- phenols were present in traces amounts. After 110 μg/day [14C]hexachlorobenzene were given orally to Macaca mulatta monkeys for 11–15 months, 50% of the radiolabel found in the urine was associated with pentachlorophenol and 25% with pentachlorobenzene, the remaining being asso- ciated with unidentified metabolites and unchanged hexachlorobenzene. Examination of 1 g of liver tissue from adult female Wistar rats given 178 μmol/kg bw [50. The authors hypothesized that the sulfur in the latter two compounds was derived from glutathione (Koss et al. Male and female Fischer 344 rats were dosed every other day for 103 days with 50 μmol/kg bw [14. Urine was collected periodically and analysed for pentachlorophenol, 2,3,5,6-tetrachlorobenzene-1,4-diol and penta- chlorothiophenol. The combined urinary excretion of these metabolites was greater in females than males, especially during the first 10 weeks. Pentachlorothiophenol was present at particularly high concentrations in the urine of females. The male:female ratios for pentachlorophenol and pentachlorothiophenol in bile were identical to those Figure 1. Excretion of metabolites by both males and females was stimulated by pretreatment with diethylstilbestrol. No sex differences in metabolism were observed in immature rats (Rizzardini & Smith, 1982). A study of the metabolism of hexachlorobenzene in isolated hepatocytes from male and female Fischer 344 adult rats showed that sex differences in metabolism did not explain the differences in porphyria development. The significant metabolites were pentachlorophenol, pentachlorothiophenol and tetrachloro-1,4-benzenedithiol. Likewise, covalent binding of [14C]hexachlorobenzene to protein after incubation with hepatocytes could not account for the sex-dependent porphyrogenic activity (Stewart & Smith, 1987). Sexually immature male and female Wistar rats given hexachlorobenzene showed initially no differences in the excretion of N-acetyl-S-(pentachlorophenyl)cysteine, but 5–8 days after weaning, the urinary concentrations of the sulfur derivative began to increase in females, until a 10-fold difference between the sexes was established. Studies in vitro and analysis of tissues after administration of pentachloronitrobenzene in vivo showed that conjugation with glutathione and hydrolysis of the conjugates to yield free pentachlorothiophenol did not differ between males and females. These findings tend to reinforce the view that an active renal secretory mechanism, probably induced by estrogens during sexual maturation, is responsible for the highly efficient excretion of sulfur derivatives of hexachlorobenzene and pentachloronitrobenzene by female rats (To-Figueras et al. The metabolism of [14C]hexachlorobenzene was studied in microsomes derived from 12-week-old male Wistar rats. In addition, a considerable amount of covalent binding of radiolabel to protein was found: 11 pmol covalent binding per 4 mg microsomal protein in an incubation mixture containing 25 μmol/L hexachlorobenzene. In order to establish the potential role of reductive dechlorination in the covalent binding, the anaerobic metabolism of hexachlorobenzene was investigated. Incubation at low oxygen concentrations indicated a relationship between covalent binding and micro- somal oxidation of hexachlorobenzene. The finding of conversion-dependent covalent binding indicated that less than 10% of the covalent binding occurs during conversion of hexachlorobenzene to pentachlorophenol, and the remainder is produced during conversion of pentachlorophenol to tetrachlorohydroquinone, which is in redox equi- librium with the corresponding semiquinone and quinone (chloranil). These results indicate the involvement of chloranil or the semiquinone radical in covalent binding during microsomal hexachlorobenzene metabolism (van Ommen et al. In rats given diets containing either hexachlorobenzene or its metabolite penta- chlorobenzene for 13 weeks, both compounds were oxidized to pentachlorophenol and tetrachlorohydroquinone, which were the only two common metabolites excreted in urine. Male and female Sprague-Dawley rats were given five consecutive doses of 1 g/kg bw hexachlorobenzene by gavage over 2 days. The cumulative dose produced porphyria in female but not male rats after a delay of 6 weeks. The hepatic glutathione concentration showed a diurnal cycle in both male and female rats, which was more pronounced in males; the minimum concentration was observed 12 h after dosing. The glutathione concentration in hexachlorobenzene-treated male rats was significantly lower than that in controls at 6, 18 and 24 h, whereas no significant difference was observed in hexachlorobenzene- treated female rats. Biliary excretion of a metabolite originating from glutathione conjugation of hexachlorobenzene was higher in male than in female rats. These results suggested that hepatic glutathione conjugation of hexachlorobenzene is more important in male than in female rats, which may be related to the lower incidence of liver porphyria observed in hexachlorobenzene-treated male than female rats (DAmour & Charbonneau, 1992). The estimated intake of hexachlorobenzene was 50–200 mg/day over a relatively long period before the disease became apparent (Peters et al. The majority of the patients were children, mostly boys, aged 4–14 years (Cam & Nigogosyan, 1963). The exposure to hexachlorobenzene led to the development of bullae on sun-exposed areas, hyper- pigmentation, hypertrichosis and porphyrinuria. Children under the age of 4 rarely developed porphyria, but in breastfed infants a condition known as pink sore was reported, with a mortality rate greater than 95% (Cam, 1960; Peters, 1976). Samples of breast milk from the mothers of these infants were shown to contain hexachlorobenzene (Peters et al. Follow- up studies of 32 of the patients have shown that abnormal porphyrin metabolism and active symptomatology persisted 20 years after ingestion of hexachlorobenzene (Peters et al. After exposure beginning in childhood, small stature, small hands and painless arthritis were present. Of particular note, enlarged thyroids were present in 25% of men and 60% of women in comparison with 5% of unexposed persons from this region of Turkey. Two persons died of liver failure; one was a 27-year-old man and the other a 54-year-old woman during treatment for tuberculosis (Cripps et al. In another follow-up of 252 persons with a history of porphyria after the Turkish incident 20–30 years earlier, similar findings were reported.

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