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At least 793 records · Page 44Linked to original sources
PubMed1992

Amiodarone dosage in older patients with atrial fibrillation: an open, multi-centre study.

An open, multi-centre study was carried out to assess the effectiveness and tolerability of amiodarone at a lower dose than routinely used in the clinical and symptomatic treatment of older patients with atrial fibrillation who were resistant to other therapy or in whom other therapy was either poorly tolerated or contraindicated. Suitable patients for dose adjustment were selected from a dosing survey population of those aged 60 years or over who were currently receiving amiodarone at a dosage of 200 mg or more daily. Periodic 100 mg dose reductions were made at 6-weekly intervals until there were signs of exacerbation or recurrence of the arrhythmia or until a daily dose of 100 mg was reached. Evaluation of the results from 167 patients showed that 156 (94%) were stabilized on a final dose of 100 mg daily and the remaining 11 (6%) on 200 mg daily. The majority of these patients were either in sinus rhythm or atrial fibrillation with a ventricular rate less than 100 beats per min. Twenty-one patients reported 22 adverse events. The majority of adverse events were not considered serious by the investigators, while approximately half were considered as 'probably unrelated' to amiodarone treatment. Six deaths were recorded during the treatment period but none was linked to amiodarone or 'probably related' to dose reduction.

Aged↗
PubMed1982

Radiation safety for children.

In recent years there has been much public and professional concern about reducing patient exposure to radiation. This concern is especially appropriate for children because of their greater sensitivity to it. Exposure risks to children may be reduced by using radiography only when there is a specific clinical indication. Bitewing radiographs are indicated for detection of approximal caries in the child when the molar contacts are closed. The frequency of this examination should be determined on an individual basis. Other radiographs should be obtained only when there are clinical signs or symptoms suggesting disease. When a decision has been made to expose a patient to X-rays beam-restricting film holders, leaded aprons and thyroid collars should be employed. To minimize repeat radiographic examinations because of processing faults, the operator should use proper procedures coupled with an understanding of the film developing process. Further dose reduction may be anticipated with the advent of E-speed film, dental xeroradiography or rod-anode source radiography. Most importantly, dose reduction requires an awareness by the dentist and operator of its importance and the means available to accomplish it.

Child↗
PubMedDate not supplied

[Pharmacokinetics of etoposide short-term infusions within the scope of the GPOH therapy protocol].

Important interpatient variability of etoposide pharmacokinetics during continuous infusion has been reported and drug level targeting, therefore, been suggested. The current German therapeutic protocols are mainly based on short-term infusion. We determined pharmacokinetic parameters during short-term infusion in 18 children aged between 10/12 and 17 years on different therapeutic schedules in order to investigate interpatient variability. The dosages ranged from 66 to 200 mg/m2. In the subgroup of patients who received 150 mg/m2 (n = 10) the AUC was 106 +/- 15 micrograms.h/ml (range 82-139), clearance 24 +/- 3 ml/min/m2 (18-31), t1/2 3.5 +/- 0.4. To compare kinetic data of all 21 courses in 18 children, standard AUC was calculated (AUC/100 mg/m2). The AUC then was (68 +/- 17 micrograms.h/ml)/(100 mg/m2). Half-life was 3.3 +/- 0.7 h and total clearance 26 +/- 6 ml/min/m2, respectively. In 5 courses in children < 2 years (< 10 kg), pharmacokinetic parameters were within the normal range. In this group dosage was calculated per kg. Dose reduction of 31% (mean) resulted in 22% (mean) lower AUC's. In conclusion, interpatient variability of etoposide pharmacokinetics during short-term infusion is limited. Dose reduction in children < 2 years is not substantiated by our pharmacokinetic data.

Adolescent↗
PubMed1998

Combined cisplatin and gemcitabine for non-small cell lung cancer: influence of scheduling on toxicity and drug delivery.

The scheduling of cytotoxic chemotherapy has important bearing on the toxicity and ability to deliver chemotherapy at or close to full dose. We report new data on the influence of different schedules of cisplatin and gemcitabine on toxicity and drug delivery in phase II studies of non-small cell lung cancer. Patients in six phase II studies had standard entry criteria for advanced non-small cell lung cancer. Whereas gemcitabine was given on days 1, 8, and 15 of a 28-day cycle in all these studies, the scheduling of cisplatin varied and was given either on day 1, day 2, day 15 (in two studies), or days 1, 8, and 15 (in two studies). The protocol dose per infusion for gemcitabine was 1,000 mg/m2 (five studies) and 1,500 mg/m2 (one study); for cisplatin, it was 100 mg/m2 when given once per cycle and 30 mg/m2 when given on days 1, 8, and 15. Similar dose reduction schedules were implemented in the event of grade 3 or higher drug toxicity for all studies except for the day 1 cisplatin study, in which the dose was omitted for grade 2 thrombocytopenia. Nonhematologic toxicity was very low. Hematologic toxicity was moderate, and in patients who developed grade 3 or 4 toxicity, there was no hemorrhage from thrombocytopenia and neutropenic sepsis was rare. The incidence of grade 3 or 4 thrombocytopenia with the day 1, day 2, day 15 (two studies combined), and days 1, 8, and 15 (two studies combined) cisplatin regimens was 50%, 52%, 26%, and 38%. The incidence of grade 3 or 4 neutropenia with these four regimens was 51%, 37%, 56%, and 49%, respectively. Although the hematologic toxicity might appear relatively similar, it represents the toxicity at the administered rather than the intended (protocol) dose, because drug delivery was reduced or omitted in the event of grade 3 or 4 toxicity. Differences between the schedules are revealed by analysis of the actual dosages delivered. The median dosage of gemcitabine per scheduled infusion was statistically higher with the day 15 cisplatin regimens (combined) compared with any of the other regimens treating at 1,000 mg/m2 (P < .003, z-score). The dose with the day 1, day 2, day 15, and days 1, 8, and 15 cisplatin regimens was 664, 829, 889, and 774 mg/m2, respectively. Both the percentages of cycles in which gemcitabine infusions were given at full dose and in which there were no omissions of gemcitabine infusions (including infusions with dose reductions) were statistically higher in the day 15 cisplatin regimen than with any of the other regimens (P < .0001, chi-square test). The percentage of cycles containing full-dose gemcitabine with the day 1, day 2, day 15, and days 1, 8, and 15 cisplatin regimens was 24%, 44%, 75%, and 46%, respectively. The percentage of cycles in which there were no omissions of gemcitabine infusions for the four regimens above was 32%, 55%, 83%, and 72%, respectively. Apart from the once-weekly regimen (days 1, 8, and 15) in which the protocol gemcitabine dose was 1,250 mg/m2, the day 15 cisplatin schedule allowed for the highest median concentration of gemcitabine. More importantly, the day 15 cisplatin schedule provided the longest duration of gemcitabine exposure, which is particularly important for its activity as gemcitabine is a phase-specific agent. The day 15 cisplatin schedule is associated with the best dose intensity and the longest median duration of exposure to gemcitabine, and best meets the goal of administering both agents at full doses in combination.

Adult↗
PubMed2004

[Outcomes of treatment with gemcitabine for unresectable pancreatic cancer].

The efficacy and safety of gemcitabine were investigated in 16 patients with unresectable pancreatic cancer (Arm A), compared with 16 patients who received chemotherapy without gemcitabine (Arm B) and 44 patients who received best supportive care (Arm C). A gemcitabine 30 min i.v. infusion at a starting dose of 1,000 mg/m2 was administered once a week for 3 weeks with a 1 week rest. Dose reduction and cycle delay were applied because of toxicity in 62.5% of the cases in the first cycle and 31.3% in the second cycle. Hematological toxicity was observed in 81.3%, nausea/vomiting in 37.5% and fatigue in 18.8%. Clinical benefit response was observed in 25.0% in Arm A, as compared with the lower rate of 6.25% in Arm B. Response rates were comparable. The median time of outpatient treatment was 98.5 days in Arm A and 34.0 days in Arm B, respectively. The median survival time was 200 days in Arm A, 121 days in Arm B and 82.5 days in Arm C, respectively. In Arm A, the higher dose intensity showed a longer survival time. The results show that gemcitabine can be administered in outpatient clinics with dose reduction and cycle delay, and that higher dose intensity generates clinical benefit, survival advantage and prolonged outpatient treatment time.

Aged↗
PubMed1994

Low-dose radiography of scoliosis in children. A comparison of methods.

STUDY DESIGN: Records of 1,582 conventional and computed radiographic examinations performed to evaluate scoliosis were reviewed and compared to determine differences in total radiation burden. OBJECTIVE: This study evaluated the impact of computed radiographic imaging (CRI) on radiation exposure in children undergoing serial spinal radiographs for scoliosis assessment and compared exposure from CRI with that of low-dose film-screen combinations. SUMMARY OF BACKGROUND DATA: CRI permits diagnostic radiographic studies to be performed with a dose reduction of 80%-95% compared to conventional film-screen systems. High speed film-screen systems also permit a significantly lower exposure. Each approach has unique advantages and disadvantages. METHODS: Over 6 years, we performed 1,582 spinal examinations in children 4-14 years old using reduced dosage techniques with computed radiography. The images were obtained with Fuji FCR 101 and Philips PCR/SP systems. The adequacy of diagnostic image quality in the serial evaluation of scoliosis at different exposure levels was evaluated and compared with regular and film-screen systems with speeds ranging from 250 to 1,200. RESULTS: Diagnostic-quality images for evaluating scoliosis can be obtained with doses of 5% or less than required with conventional film-screen systems. Computed radiography provides image quality and dose reduction comparable to a 1,200-speed film-screen system. CONCLUSION: CRI gives satisfactory images at 5% reduction of the standard film-screen dose. Based on comparison with a 1,200 speed film-screen system, CRI provides equal or better image quality at a similar radiation dose. The cost of CRI is higher than for film-screen radiography, but wide latitude and the ability to tailor dose with requirements for image quality are significant advantages for CRI.

Adolescent↗
PubMed2005

Lower dose capecitabine has a more favorable therapeutic index in metastatic breast cancer: retrospective analysis of patients treated at M. D. Anderson Cancer Center and a review of capecitabine toxicity in the literature.

BACKGROUND: Capecitabine is active against anthracycline- and taxane-pretreated metastatic breast cancer. Post-marketing use of capecitabine at the FDA-approved dose (2500 mg/m2/day) leads to unacceptable toxicity in many patients. Dose reductions anecdotally improve tolerability without compromising efficacy. This retrospective analysis was designed to verify these anecdotal reports. PATIENTS AND METHODS: We retrospectively reviewed the records of 141 consecutive patients with metastatic breast cancer identified from pharmacy records as receiving capecitabine outside of a clinical trial between May 1998 and February 1999. Responses were defined as clinical improvement (ID), stabilization of disease (SD) for 6 weeks or longer, or progression (PD). Patients were grouped according to the starting dose level of capecitabine: A=2500+/-5% (dose range 2385-2560) mg/m2/day; B=2250+/-5% (range 2130-2350) mg/m2/day; C < or = 2000+5% (range 1000-2100) mg/m2/day. We also reviewed the safety profile of capecitabine at these doses and performed a safety review of capecitabine in phase II and III metastatic breast and colorectal cancer trials. RESULTS: Clinical data were available for 113 patients (105 for response, 106 for toxicity). The median age was 52.5 years and the mean number of prior metastatic chemotherapy regimens was 2 (range 0-7). The mean capecitabine starting dose was 2220 mg/m2/day and the median number of cycles administered was 4 (range 1-19). The mean tolerated dose was 2040 mg/m2/day (range 960-2670). Grade 3/4 toxic effects at dose levels A, B and C, respectively, included palmar-plantar erythrodysesthesia (33%, 63%, 20%), diarrhea (13%, 12%, 3%), stomatitis (8%, 0%, 3%), and nausea/vomiting (4%, 6%, 5%). Forty per cent of all patients required capecitabine dose reductions; fewer patients treated with 2000 mg/m2/day required dose modification (28%). Five per cent of the patients required discontinuation of capecitabine owing to toxicity. Patients started at the lowest doses of capecitabine did not have poorer response rates or shorter time to progression. CONCLUSIONS: This retrospective analysis supports a starting dose of 2000 mg/m2/day because of its superior therapeutic index; however, patients may still have toxic effects and individualization of dosing is necessary. A phase III, multicenter, randomized study to establish the safety and efficacy of different doses of capecitabine is urgently needed.

Adult↗
PubMed2005

Parenteral ketamine as an analgesic adjuvant for severe pain: development and retrospective audit of a protocol for a palliative care unit.

BACKGROUND: Ketamine is an effective analgesic agent for treating a variety of neuropathic and cancer pain syndromes. Recent studies indicate that ketamine may have a particular role in the management of patients with neuropathic and/or pain syndromes that are poorly responsive to opioids. OBJECTIVE: To develop, implement, and subsequently assess a protocol designed to maximize the analgesic effect of ketamine while minimizing its side effects. DESIGN: A retrospective chart audit of 16 patients who had used the ketamine protocol over a 12-month period. Criteria for assessing the effectiveness of ketamine were defined. RESULTS: Ketamine was an effective, well-tolerated analgesic adjuvant for 11 of 16 patients with previously uncontrolled pain. Pain scores were reduced by at least 4 of 10 in 15 of the 16 patients. Median opioid dose reduction on starting ketamine was 25%. CONCLUSION: The audit confirmed the safety and effectiveness of ketamine as an analgesic adjuvant for patients with severe pain. Baseline opioid dose reduction and prophylactic use of haloperidol or benzodiazepine were effective in minimizing psychotomimetic side effects.

Adult↗
PubMed2001

Cyclosporin A in the treatment of refractory immune thrombocytopenia purpura in children.

Patients with refractory autoimmune thrombocytopenia do not respond to standard therapy with high-dose corticosteroids, intravenous immunoglobulin, and splenectomy. We describe the cases of two patients with refractory autoimmune thrombocytopenia treated with oral cyclosporin A (CsA) to evaluate the efficacy of this alternative therapy. Blood pressure and hepatic and renal function were in the normal range before initiation of treatment. Induction therapy with pulses of high-dose methylprednisolone was used for 3 consecutive days to improve the initial immune suppression. Gradual dose reduction of CsA, according the platelet count, minimized the long-term adverse effects of CsA. Oral CsA with pulses of high-dose methylprednisolone induced remission of the thrombocytopenia. Gradual weaning of CsA over months, according the platelet count, produced no observable adverse effects of the CsA. Rapid dose reduction caused thrombocytopenia, which resolved with higher dosages of CsA. Our cases show the efficacy of CsA for refractory immune thrombocytopenia. This therapeutic option with oral CsA as an additional salvage option may avoid splenectomy and the adverse effects of long-term corticosteroids. Larger clinical investigations are necessary to establish the indications and therapeutic regimen for CsA in immune thrombocytopenia.

Adolescent↗
PubMed1994

Differential radiosensitising effect of the scid mutation among tissues, studied using high and low dose rates: implications for prognostic indicators in radiotherapy.

To assess whether radiation-sensitive or radiation-resistant individuals should in principle be predicted equally well using different cell types, the effect of the scid mutation on the radiosensitivity of colony-forming cells in different murine tissues was assessed using high and low dose-rates. At high dose-rate, the amount of radiosensitization due to the scid mutation was greater in epithelial cells of the intestine and the kidney than in haemopoietic and fibroblastoid cells in the bone marrow, when expressed as a dose reduction factor. However, this greater radiosensitization in intestine and kidney did not translate into bigger differences in SF2 (surviving fraction at 2 Gy) or SF3.5. This was because of the greater inherent radioresistance of the epithelial cells compared with the marrow cells, resulting in smaller changes in cell survival from a given dose. Reductions in cell survival due to the mutation increased with increasing dose as expected at high dose rate. The changes in SF2 and SF3.5 due to the scid mutation were not significantly increased by using low dose-rates, because of the tendency for the presence of some low dose-rate sparing in the scid cells as well as the marked amount observed in the wild-type cells. The implications for predictive testing in radiotherapy are that for genetic defects resulting in the same type of radiosensitization phenomenon shown here for scid cells, radiosensitive or radioresistant cell types may still give similar differentials in response due to the mutation when SF2 is used as an endpoint.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

UV endonuclease-mediated enhancement of UV survival in Micrococcus luteus: evidence revealed by deficiency in the Uvr homolog.

Unlike its phage T4 counterpart (also known as endonuclease V), Micrococcus luteus UV endonuclease (pyrimidine dimer DNA glycosylase/apurinic-apyrimidinic endonuclease) has suffered from lack of genetic evidence to implicate it in the promotion of UV survival of the cell, i.e., mutants with its deficiency are no more UV-sensitive than the wild type. On the assumption that the contribution of UV endonuclease is obscured by the presence of a homolog of Escherichia coli UvrABC endonuclease, which has recently been identified in this bacterium, survival studies were carried out in its absence. With 254-nm UV irradiation, which generates not only pyrimidine dimers but also 6-4 photoproducts as lethal lesions, a double mutant defective in both UV endonuclease and the Uvr homolog was shown to be more sensitive than a single mutant defective only in the latter, with a dose reduction factor of approximately 2 at the survival level of 37%. Furthermore, molecular photosensitization, which produces only pyrimidine dimers, revealed an even greater difference in sensitivity, the dose reduction factor being about 3.4. These results indicate that the contribution to cell survival of UV endonuclease, an enzyme specific for pyrimidine dimers, is manifest if the backup by the Uvr homolog is absent.

4-Nitroquinoline-1-oxide↗
PubMed2003

Lowering of furosemide dosage after clinical stabilization in patients with congestive heart failure.

OBJECTIVES: This study was performed to examine the safety of reducing the long-term doses of furosemide administered to patients with congestive heart failure (CHF) stabilized on a standard medical treatment. METHODS AND RESULTS: Twenty-nine patients with advanced CHF were treated with enalapril, digoxin, nitrates, and furosemide, as needed to alleviate their symptoms, and remained clinically stable for at least 3 months on those doses. Subsequently, the daily dose of furosemide was reduced to 1/3 of the previous dose, while the concomitant therapy was unchanged. All patients underwent a thorough clinical evaluation and right-heart catheterization before and 2 months after the furosemide dose reduction. After the treatment optimization the NYHA functional class decreased from 2.3 +/- 0.6 to 1.4 +/- 0.6 (p = 0.000), and the left ventricular ejection fraction increased from 22 +/- 10% to 32 +/- 13%, (p = 0.000). Clinical and haemodynamic evaluation before and after 2 months of treatment with lower furosemide doses showed that 24 of the 29 patients (83%) remained in a stable NYHA functional class and maintained a stable haemodynamic status. In the remaining 5 patients (17%), mean NYHA functional class increased from 1.8 +/- 0.4 to 2.4 +/- 0.6 (p = 0.07), accompanied by a significant increase of the right and left ventricular filling pressures from 4.2 +/- 2.7 to 9.0 +/- 3.0 mm Hg, p = 0.018 and from 8.6 +/- 3.0 to 19.8 +/- 3.6 mm Hg, p = 0.017, respectively. These 5 patients returned to a stable clinical status upon resumption of the prior doses of furosemide. CONCLUSIONS: Most patients with chronic CHF who were clinically stabilized on high doses of furosemide remained stable on a maintenance dose equal to one-third of the dose needed for their stabilization. Patients unable to tolerate the dose reduction regained their previous clinical status following the resumption of the prior diuretic doses.

Adult↗
PubMedDate not supplied

A preliminary report of neoadjuvant chemotherapy NSH-7 study in osteosarcoma: preoperative salvage chemotherapy based on clinical tumor response and the use of granulocyte colony-stimulating factor.

Eleven patients with high-grade osteosarcoma of an extremity were treated with neoadjuvant chemotherapy with NSH-7 protocol. NSH-7 is a refinement of the T-12 Rosen protocol. Preoperative chemotherapy is initiated with a doxorubicin (ADM) and high-dose methotrexate combination. If the primary tumor progresses after the first cycle, the preoperative chemotherapy is switched to a combination of cisplatin and ADM. Postoperative adjuvant chemotherapy was selected based on histological response of the primary tumor. In addition, recombinant human granulocyte colony-stimulating factor was used to prevent leukocytopenia and to increase the dose intensity of the chemotherapy. In 1 patient, preoperative chemotherapy was switched to salvage treatment. Of the 156 courses given, there were 10 delays and 4 dose reductions. Leukocytopenia accounted for only 1 delay. All 11 patients completed the chemotherapy and 5 patients were fully able to tolerate the protocol without delay or dose reduction. Nine patients remained alive and continuously free of disease at an average follow-up of 35 months. The rate of continuous disease-free survival at 3 years was 81%, which was significantly better than that of the T-12 study of our group. These observations suggest that the NSH-7 protocol is a safe and effective treatment regimen for osteosarcoma.

Adolescent↗
PubMed2006

Estimation of radiation exposure in low-dose multislice computed tomography of the heart and comparison with a calculation program.

The purpose of this study was to evaluate the achievable organ dose savings in low-dose multislice computed tomography (MSCT) of the heart using different tube voltages (80 kVp, 100 kVp, 120 kVp) and compare it with calculated values. A female Alderson-Rando phantom was equipped with thermoluminescent dosimeters (TLDs) in five different positions to assess the mean doses within representative organs (thyroid gland, thymus, oesophagus, pancreas, liver). Radiation exposure was performed on a 16-row MSCT scanner with six different routine scan protocols: a 120-kV and a 100-kV CT angiography (CTA) protocol with the same collimation, two 120-kV Ca-scoring (CS) protocols with different collimations and two 80-kV CS protocols with the same collimation as the 120-kV CS protocols. Each scan protocol was repeated five times. The measured dose values for the organs were compared with the values calculated by a commercially available computer program. Directly irradiated organs, such as the esophagus, received doses of 34.7 mSv (CTA 16x0.75 120 kVp), 21.9 mSv (CTA 16x0.75 100 kVp) and 4.96 mSv (CS score 12x1.5 80 kVp), the thyroid as an organ receiving only scattered radiation collected organ doses of 2.98 mSv (CTA 16x0.75 120 kVp), 1.97 mSv (CTA 16x0.75 100 kVp) and 0.58 mSv (CS score 12x1.5 80 kVp). The measured relative organ dose reductions from standard to low-kV protocols ranged from 30.9% to 55.9% and were statistically significant (P<0.05). The comparison with the calculated organ doses showed that the calculation program can predict the relative dose reduction of cardiac low photon-energy protocols precisely.

Coronary Angiography↗
PubMed2003

Clinical benefits of neoral C2 monitoring in the long-term management of renal transplant recipients.

BACKGROUND: Cyclosporine monitoring using the 2-hr postdose sample, C2, has been shown to have advantages in monitoring de novo renal transplant recipients. The purpose of this study was to assess cyclosporine exposure, using C2, in stable renal transplant patients previously monitored by C0 to determine the effect of dose reduction on patients with C2 more than 10% above target and the course of those with C2 at and more than 10% below target, whose dose was not modified. METHODS: One hundred and seventy-five patients, three or more months after transplantation, had C2 assessed. The relationship of C2 to C0 and of both to renal function was analyzed by linear regression. Blood pressure, serum creatinine level, and lipids were followed for a mean of 15+/-2.6 months. RESULTS: Eighty-five patients had values more than 10% above target, 42 were within 10% of target, and 48 were more than 10% below target. Cyclosporine dose was reduced in all patients above target. In this group, serum creatinine level was stable overall, but fell significantly in 46 (54%) of 85 from 153+/-55 to 132+/-49 microM. Blood pressure also fell in that group from 135/82 to 131/77. Serum creatinine level was stable in the remaining two groups of patients. CONCLUSIONS: These data suggest that dose reduction in many overexposed patients leads to improvements in renal function and blood pressure. Further study is required to confirm the long-term benefits of this strategy.

Adult↗
PubMed2001

Aciclovir selects for ganciclovir-cross-resistance of human cytomegalovirus in vitro that is only in part explained by known mutations in the UL97 protein.

Phenotypically, ganciclovir-resistant human cytomegalovirus strains could be selected by aciclovir as effectively as by ganciclovir in vitro. Three clinical human cytomegalovirus isolates with different sensitivities against ganciclovir, aciclovir, foscarnet, and cidofovir, but without any mutation in the viral UL97 protein known to confer ganciclovir resistance, were propagated each in duplicate in the presence of ganciclovir or aciclovir. After drug selection, all 12 strains were less susceptible to ganciclovir (increase of 50% focus reduction dose between 2.1- and 31.5-fold) but were still sensitive to foscarnet and cidofovir; 7/12 exhibited a ganciclovir-resistant phenotype with a 50% focus reduction dose >30 microM, and in 6 out of these typical mutations in the UL97 coding region could be found by genotyping. All four strains selected from one isolate carried the identical UL97 mutation at amino acid position 460 (methionine to valine). The decreased sensitivity to ganciclovir and aciclovir in the other strains could neither be attributed to known UL97 mutations nor to mutations in the viral polymerase (UL54), which have been reported to induce resistance.

Acyclovir↗
PubMed1994

Comparative and combined efficacy of doxazosin and enalapril in hypertensive patients.

Twenty patients with essential hypertension were randomised to a 7-week period of dose titration with doxazosin, 1-8mg/day or enalapril, 5-20mg/day. In a further 7-week period the dosage level reached with the initial drug was halved, and titration with the second agent was carried out. Blood pressure responses at the end of each treatment period were assessed by clinic measurements made 24 hours post-dose. In the first treatment period, enalapril (mean dose 19mg/day) reduced serum free ACE activity by 40% and had a greater effect than doxazosin (mean dose 5.2mg/day) on clinic supine blood pressure (systolic and diastolic). In the second period, the addition of enalapril to doxazosin was associated with a significant fall in clinic standing blood pressure (systolic and diastolic), despite the doxazosin dose reduction and consequent decrease in median plasma doxazosin concentration (from 10.6 to 5.2ng/ml). Alternatively, when doxazosin was added to enalapril, free ACE activity remained 40% decreased despite enalapril dose reduction, and blood pressure was not further affected. Plasma renin activity was increased by enalapril. No changes were observed in plasma aldosterone or lipid concentrations with either drug. The combination of doxazosin and enalapril was well tolerated and lowered blood pressure overall. Judged by clinic measurements 24 hours post-dose, most of the antihypertensive effect was attributable to the enalapril component. However, ambulatory blood pressure monitoring 0-12 hours post-dose in a subset of patients suggested a contribution of doxazosin earlier in the dose interval.

Acetylcholinesterase↗
PubMed2005

Rectal wall sparing by dosimetric effect of rectal balloon used during intensity-modulated radiation therapy (IMRT) for prostate cancer.

The use of an air-filled rectal balloon has been shown to decrease prostate motion during prostate radiotherapy. However, the perturbation of radiation dose near the air-tissue interfaces has raised clinical concerns of underdosing the prostate gland. The aim of this study was to investigate the dosimetric effects of an air-filled rectal balloon on the rectal wall/mucosa and prostate gland. Clinical rectal toxicity and dose-volume histogram (DVH) were also assessed to evaluate for any correlation. A film phantom was constructed to simulate the 4-cm diameter air cavity created by a rectal balloon. Kodak XV2 films were utilized to measure and compare dose distribution with and without air cavity. To study the effect in a typical clinical situation, the phantom was computed tomography (CT) scanned on a Siemens DR CT scanner for intensity-modulated radiation therapy (IMRT) treatment planning. A target object was drawn on the phantom CT images to simulate the treatment of prostate cancer. Because patients were treated in prone position, the air cavity was situated superiorly to the target. The treatment used a serial tomotherapy technique with the Multivane Intensity Modulating Collimator (MIMiC) in arc treatment mode. Rectal toxicity was assessed in 116 patients treated with IMRT to a mean dose of 76 Gy over 35 fractions (2.17-Gy fraction size). They were treated in the prone position, immobilized using a Vac-Loktrade mark bag and carrier-box system. Rectal balloon inflated with 100 cc of air was used for prostate gland immobilization during daily treatment. Rectal toxicity was assessed using modifications of the Radiation Therapy Oncology Group (RTOG) and late effects Normal Tissue Task Force (LENT) scales systems. DVH of the rectum was also evaluated. From film dosimetry, there was a dose reduction at the distal air-tissue interface as much as 60% compared with the same geometry without the air cavity for 15-MV photon beam and 2x2-cm field size. The dose beyond the interface recovered quickly and the dose reductions due to air cavity were 50%, 28%, 11%, and 1% at 2, 5, 10, and 15 mm, respectively, from the distal air-tissue interface. Evaluating the dose profiles of the more clinically relevant situation revealed the dose at air-tissue interface was approximately 15% lower in comparison to that without an air cavity. The dose built up rapidly so that at 1 and 2 mm, there was only an 8% and 5% differential, respectively. The dosimetric coverage at the depth of the posterior prostate wall was essentially equal with or without the air cavity. The median follow-up was 31.3 months. Rectal toxicity profile was very favorable: 81% (94/116) patients had no rectal complaint while 10.3% (12/116), 6.9% (8/116), and 1.7% (2/116) had grade 1, 2, and 3 toxicity, respectively. There was no grade 4 rectal toxicity. DVH analysis revealed that none of the patients had more than 25% of the rectum receiving 70 Gy or greater. Rectal balloon has rendered anterior rectal wall sparing by its dosimetric effects. In addition, it has reduced rectal volume, especially posterior and lateral rectal wall receiving high-dose radiation by rectal wall distension. Both factors may have contributed to decreased rectal toxicity achieved by IMRT despite dose escalation and higher than conventional fraction size. The findings have clinical significance for future very high-dose escalation trials whereby radiation proctitis is a major limiting factor.

Catheterization↗