SEARCH · PubMed Health

Results for “Targeted dosing”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 397 records · Page 22Linked to original sources

PubMed2002

The role of intensity-modulated radiotherapy in the treatment of parotid tumors.

PURPOSE: To compare intensity-modulated radiotherapy (IMRT) treatment plans with three-dimensional conformal radiotherapy (3D-CRT) plans to investigate the suitability of IMRT for the treatment of tumors of the parotid gland. METHODS AND MATERIALS: One 3D-CRT treatment plan and 10 IMRT treatment plans with differing beam arrangements were produced for each of nine patient data sets. The plans were compared using regret analysis, dose conformity, dose to organs at risk, and uncomplicated tumor control probability (UTCP). RESULTS: The target dose was comparable in the 3D-CRT and IMRT plans, although improvements were seen when seven and nine IMRT fields were used. IMRT reduced the mean dose to the contralateral parotid gland and the maximum doses to the brain and the spinal cord, but increased the ipsilateral lens dose in some cases. Each IMRT arrangement produced a higher UTCP than the 3D-CRT plans; the largest absolute difference was 9.6%. CONCLUSIONS: IMRT is a suitable means for treating cancer of the parotid, and a five-field class solution is proposed. It produced substantial sparing of organs at risk and higher UTCPs than 3D-CRT and should enable dose escalation.

Humans↗

PubMed2000

Novel cancer therapies: more efficacy, less toxicity and improved organ preservation.

Novel approaches to the treatment of cancer include techniques such as gene therapy, antiangiogenic therapy, monoclonal antibodies either alone or linked with radioactive isotopes or cytotoxins, cancer immunotherapy and vaccines, oligonucleotides and antisense technologies as well as anticancer drugs targeting single metabolic processes, enzymes or oncoproteins. However, substantial improvements are also being made in more conventional cancer treatment modalities. These comprise radiotherapy given concomitantly with chemotherapy, which appears to improve treatment results in a number of common types of human cancer. Other important advances include conformal and intensity-modulated radiation therapy, which may allow for higher target doses with little or no increase in toxicity. Stereotactic radiation therapy for extracranial targets is also being developed, as well as biologically targeted radiation therapy, in which targeting is based on metabolic pathways or carrier molecules, such as boronated compounds in boron neutron capture therapy or monoclonal antibodies in radioimmunotherapy. Sentinel node biopsy and neoadjuvant chemotherapy for breast cancer represent advances in surgery and cancer chemotherapy, which may also allow for a greater chance for organ and tissue preservation without a loss in treatment efficacy.

Breast Neoplasms↗

PubMed2001

Elimination of early rehospitalization in a randomized, controlled trial of multidisciplinary care in a high-risk, elderly heart failure population: the potential contributions of specialist care, clinical stability and optimal angiotensin-converting enzyme inhibitor dose at discharge.

BACKGROUND: Despite a growing body of data demonstrating the benefits of multidisciplinary care in heart failure, persistently high rates of readmission, especially within the first month of discharge, continue to be documented. AIMS: As part of an ongoing randomized study on the value of multidisciplinary care in a high risk (NYHA Class IV), elderly (mean age 69 years) heart failure population, we examined the effects of this intervention on previously high (20%) 1-month readmission rates. METHODS: Unlike previous studies of this approach, both multidisciplinary (MC) and routine care (RC) populations were cared for by the cardiology service, complied with adherence to clinical stability criteria prior to discharge (100% of patients) and received at least target dose angiotensin-converting enzyme (ACE) inhibition with perindopril prior to discharge (94% of indicated patients). We analysed death and unplanned readmission for heart failure at 1 month. RESULTS: This early report from the first 70 patients (67% male, 71% systolic dysfunction with a mean ejection fraction of 31.0+/-6.7%) enrolled in this study demonstrates elimination of 1-month hospital readmission in both RC and MC groups. This unexpected result represents a dramatic improvement both for this patient cohort (20% 30-day readmission rate prior to enrollment reduced to 0% following the index admission in both care groups) and in comparison with available data. CONCLUSIONS: Critical contributors to this improvement appear to be specialist cardiology care, adherence to clinical stability criteria prior to discharge and routine use of target or high-dose ACE inhibitor therapy prior to discharge. Widespread application of this approach may have a dramatic improvement in morbidity of CHF while limiting the escalating costs of this condition.

Aged↗

PubMed1993

Clinical evaluation of tumor targeting with a high-affinity, anticarcinoembryonic-antigen-specific, murine monoclonal antibody, MN-14.

BACKGROUND: The authors previously reported that an anticarcinoembryonic antigen antibody against a carcinoembryonic antigen (CEA)-specific epitope is preferred for clinical investigations. They developed a second generation, CEA-specific murine monoclonal antibody (MoAb), MN-14 (IMMU-14), that has a tenfold higher affinity. This report summarizes the initial clinical experience with the new MoAb. METHODS: MN-14 immunoglobulin G (IgG) (0.5-6.0 mg) was labeled with radioactive iodine (I131) (5-80 mCi) and injected into 22 patients with cancer. External scintigraphy was used to determine targeting in patients with low and highly elevated plasma CEA. Quantitative external scintigraphy methods were used to determine organ and tumor clearance rates and absorbed radiation doses. Targeting data were correlated with several factors, including MoAb protein dose, plasma CEA, and relative tumor burden. RESULTS: Despite more than 80% complexation with plasma CEA of more than 500 ng/ml, all known tumor sites were disclosed by external scintigraphy. The overall sensitivity of tumor targeting on a lesion basis was 89%. The residence time in the blood was predicted by body weight (P = 0.05) and the log of plasma CEA (P = 0.043). The absorbed dose to the red marrow and total body could be predicted by the body weight of the patient, but no other factor contributed significantly to the clearance rate or absorbed dose to the organs. Individual tumors received an average dose of 9.3 +/- 6.4 cGy/mCi. The absorbed dose to the tumors was negatively correlated to the weight of the tumor, and the percent uptake in the tumor was positively correlated to the estimated total tumor burden. Patients injected with approximately 5 mg of MN-14 IgG were more likely to have anti-mouse antibodies (HAMA) develop than were patients who were injected with less MoAb. CONCLUSIONS: These results suggest that MN-14 targets tumors effectively, even in the presence of elevated circulating CEA. Additional studies are necessary to determine if an advantage for the higher affinity MN-14 MoAb, compared with the lower affinity NP-4 MoAb, can be appreciated clinically.

Adult↗

PubMed2002

Five years' experience of combination therapy: peritoneal dialysis with hemodialysis.

The fundamental objective of dialysis is to maintain the dose of solute clearance and ultrafiltration (UF). When peritoneal dialysis (PD) patients cannot maintain the target dose of clearance [weekly Kt/V > 2.0, weekly creatinine clearance (CCr) > 60 L/1.73 m2], the dialysis dose needs to be increased. But the means of increasing the dose only by PD are limited, especially for patients with UF failure (UFF). Combination therapy--PD with hemodialysis (PD + HD)--is the simplest way to solve the problem. The purpose of PD + HD therapy is to support solute clearance and UF when PD alone cannot meet the necessary targets. Acute and transient dialysis cases should be excluded. The general prescription for PD + HD should be 5-6 days of PD weekly and 1 session of HD weekly. For determine the adequacy of PD + HD, we adopted the equivalent renal clearance (EKR), transforming the PD weekly Kt/V and then evaluating total clearance from both modalities. Of our 238 dialysis patients, 31 (13%) use combined therapy. Except for 1 patient that transferred from long-term HD, all of patients had been on PD for more than 60 months, and were experiencing uremic symptoms after decline of residual renal function. In 12 cases, the problem was lack of solute clearance; in 5 cases, it was UFF. High permeability was involved in 5 cases: 4 after long-term PD and 1 from the start of PD. Poor self-management occurred in 9 cases. Contributing factors included hernia, diaphragmatic intercourse, and severe heart failure with strict fluid control. Among the 31 patients, 8 used HD twice weekly. After combination therapy was started, the dialysis dose increased and body fluids became controllable. As a result, uremic symptoms improved and the patients' quality of life increased.

Humans↗

PubMed2005

Topiramate monotherapy in epilepsy and migraine prevention.

OBJECTIVES: The purposes of this review were to assess the efficacy of topiramate as monotherapy for epilepsy and migraine prevention, describe how it should be used, and give clinical advice on how to manage the practical aspects of dosing, titration, and possible adverse events in these 2 indications. METHODS: We searched the PubMed and BIOSIS databases using the key words topiramate, epilepsy, and migraine from the year 1987 onward, and subsequently focused the search on larger controlled trial studies of topiramate as monotherapy. RESULTS: Studies have evaluated the use of topiramate as monotherapy in the treatment of partial-onset and generalized seizures and in the prevention of migraine. In a randomized study, 75% of epilepsy patients treated with 400 mg/d topiramate remained seizure free at 1 year. Patients in the same study treated with a lower dose of topiramate (50 mg/d) also experienced notable seizure reductions, with 59% of patients free of seizures at 1 year. A comparison trial of topiramate (100 or 200 mg/d), valproate, and carbamazepine found that topiramate was associated with a similar time to first posttreatment seizure as the other 2 agents (P = NS). Trials of topiramate monotherapy in migraine prevention found that 100 mg/d was associated with a > or =50% reduction in monthly migraine frequency in 49% to 54% of patients. The migraine prevention trials typically used a starting dose of 25 mg/d, with weekly increases of 25 mg and an initial monotherapy target dose of 100 mg/d. The most common adverse events associated with topiramate are paresthesia, weight loss, and other centrally mediated symptoms, many of which may be ameliorated by proper titration and dosing and by good communication between physician and patient. CONCLUSIONS: Data from controlled trials suggest that 100 mg/d topiramate as monotherapy is effective in the treatment of partial-onset and generalized seizures and in the prevention of migraine.

Anticonvulsants↗

PubMed2004

Phase II study of carboplatin and weekly paclitaxel combination chemotherapy in advanced non-small cell lung cancer: a Kansai Clinical Oncology Group study.

The objective of this phase II study was to evaluate the efficacy and toxicity of carboplatin and weekly paclitaxel combination chemotherapy in previously untreated, advanced non-small cell lung cancer (NSCLC). Patients received paclitaxel at a dose of 70 mg/m(2) on days 1, 8, 15, and carboplatin with the target dose of area under the curve (AUC) of 6 on day 1 every 28 days. Forty-six patients were enrolled. A median of four cycles (range, 1-13) were administered. Complete response was observed in one patient (2.2%) and partial response in 23 patients (50%), yielding an overall intent-to-treat response rate of 52.2% (95% confidence interval, 37.8-66.6%). The median survival time was 395 days and 1-year survival rate was 51.4%. Toxicities were mild. Twelve patients (26%) had grade 3 and three patients (7%) had grade 4 neutropenia. Grade 3 thrombocytopenia was seen in four patients (8%). Massive hematoemesis due to duodenal ulcer was observed in one patient, but no other patients experienced grade 3 or more non-hematological toxicities. There was no treatment-related death. Carboplatin and weekly paclitaxel combination chemotherapy is an efficacious and feasible regimen in patients with advanced NSCLC, and this treatment will be a reasonable alternative to the conventional triweekly regimen of paclitaxel and carboplatin.

Adult↗

PubMed2000

Prostate brachytherapy in patients with prostate volumes >/= 50 cm(3): dosimetic analysis of implant quality.

OBJECTIVES: Permanent implantation with (125)I in patients with localized prostate cancer who have prostate volumes >/= 50 cm(3) is often technically difficult owing to pubic arch interference. The objective of this study was to describe dosimetry outcomes in a group of patients who were implanted using the real-time ultrasound-guided technique who had prostate volumes >/= 50 cm(3). MATERIALS AND METHODS: A total of 331 patients received an (125)I prostate seed implant from January 1, 1995, to June 1, 1999, of whom 66 (20%) had prostate volumes >/= 50 cm(3) at the time of the procedure. The real-time seed implant method was used in all patients and consisted of intraoperative planning and real-time seed placement using a combination of axial and sagittal ultrasound imaging. Pubic arch interference was managed using an extended lithotomy position or by angling the tip of the ultrasound probe in an anterior direction. No preimplant pubic arch CT scan study was performed and no patients were excluded from treatment because of prostate size. Implant quality was assessed using CT-based dosimetry performed 1 month postimplant. Dose-volume histograms for the prostate, bladder, rectum, and urethra volumes were generated. The target dose for these implants was 160 Gy and an adequate implant was defined as the dose delivered to 90% of the prostate (D90) >/= 140 Gy. The dose delivered to 95% of the prostate (D95) and doses to 30% of the rectal (DRECT30) and urethral (DURE30) volumes were also calculated. RESULTS: Prostate volumes in the 66 patients ranged from 50 to 93 cm(3) (median 57, mean 61 cm(3)). Total activity implanted was 27.8-89.1 mCi (median 57 mCi), with a range in activity per seed of 0.36-0.56 mCi (median 0.4 mCi). The prostate D90s and D95s ranged from 13,245 to 22,637 cGy (median 18,750) and 11,856 to 20,853 cGy (median 16,725), respectively. Only one patient (1.5%) had a D90 < 140 Gy. The DURE30 values ranged from 15,014 to 27,800 cGy (median 20,410) and the DRECT30 values were 3137-9910 cGy (median 5515). CONCLUSION: Implantation of the large prostate can be accomplished using the real-time method. A total of 98.5% of the patients receive a high-quality implant. In addition, these implants should not put patients at increased risk for significant urinary and bowel complications because urethral and rectal doses can be kept at acceptable levels.

Brachytherapy↗

PubMed2001

Efficacy of levetiracetam: a review of three pivotal clinical trials.

Levetiracetam is a novel antiepileptic drug (AED) with favorable pharmacologic characteristics and demonstrated activity in improving seizure control. Three multicenter double-blind, placebo-controlled studies were conducted in 904 patients with refractory partial-onset seizures. Patients were required to have a minimum of two or four seizures per week (depending on the study) and were maintained on a stable regimen of one or two AEDs at baseline that was continued during the study period. Patients ranged in age from 14 to 70 years, with a mean age of approximately 37 years. After an 8- to 12-week baseline period, patients were randomized and had doses titrated upward every 2 weeks over a period of 4 weeks to a target dose of 1,000, 2,000, or 3,000 mg/day of levetiracetam or placebo. Treatment was continued for a 12- to 14-week evaluation phase followed by an optional open-label treatment phase. The treatment period consisted of the dose titration period combined with the evaluation period. The median percentage reduction in seizure frequency (over placebo) was calculated for each of the levetiracetam treatment groups over the entire treatment period. For all levetiracetam dose groups, in all studies, reduction in seizure frequency over placebo was statistically significant (p < or = 0.001). Median percentage reductions were 26.1% and 17.1% in the 1,000-mg/day groups (study 1 and study 2, respectively), 21.4% in the 2,000-mg/day group (study 2), and 30.1% and 23.0% in the 3,000-mg/day groups (study 1 and study 3, respectively). The percentage of patients achieving a > or = 50% reduction from baseline in seizure frequency compared with the treatment period was 37.1% and 20.8% in the 1,000-mg/day groups (study 1 and study 2, respectively), 35.2% in the 2,000-mg/day group (study 2), and 39.6% and 39.4% in the 3,000-mg/day groups (study 1 and study 3, respectively). These responder rates were significantly higher than those for placebo (p < 0.001 for all comparisons). Levetiracetam was generally well tolerated in all studies. Results from these three pivotal studies demonstrate that levetiracetam, as adjunctive therapy, is a safe and effective treatment for refractory partial-onset seizures in adults.

Adolescent↗

PubMed1991

Interstitial IR-192 implants of the oral cavity: the planning and construction of volume implants.

The success of radioactive implant therapy for head and neck carcinomas depends critically on careful planning and execution of the implant procedure. In this paper we discuss our experience with oral tongue and floor of mouth implants, and some innovations introduced to facilitate these procedures. Implants were carried out using standard angiocatheters modified with magnetic caps at the open end and terminated with Teflon spacers and lead shot at the closed end. The importance of accurate source placement and careful determination of the target dose rate is discussed with numerical examples. Differential hot-loading of sources is clearly indicated in cases of extension of the lesion to the dorsal or lateral tongue surface. For dorsal surface extension the use of Teflon spacers at the closed ends of the catheters helps to ensure adequate coverage of the target volume with the higher dose region enclosing the demonstrable tumor. All 10 patients implanted with this technique are controlled without recurrence at a median follow-up of 38 months. The two complications observed appeared to be associated with excessive hot-loading of edge plane sources.

Brachytherapy↗

PubMed1994

Intra-operative radiation therapy for malignant brain tumors: rationale, method, and treatment results of cerebral glioblastomas.

In radiation therapy for malignant brain tumours, the dose of radiation that can be safely delivered to a tumour is limited by the radiation tolerance of the adjacent normal brain tissue. Among various radiation modalities to produce local tumour eradication without unacceptable complications, we chose a large, single irradiation dose during the operation (intra-operative radiation therapy, IORT). In contrast to X-ray or Cobalt-60 gamma ray irradiation, IORT with a high-energy electron beam delivered by the Shimadzu 20 MeV betatron provides acceptable dose homogeneity with rapid fall-off of the radiation dose beyond the treatment volume. Thus, IORT has the advantage of precise demarcation of the target volume, minimum damage to surrounding normal tissues, and a high absorbed target dose (15-25 Gy in 5-10 min). On the basis of our experience with 170 patients treated by IORT, we established the treatment indications and method in patients with malignant brain tumours. IORT with a dose of 15-25 Gy was delivered to widely resected tumours followed by external radiation therapy. No acute or subacute complications were observed. Treatment results of 30 patients with glioblastoma treated by IORT (mean 18.3 Gy) combined with external radiation therapy (mean 58.5 Gy) resulted in a median survival of 119 weeks and a 2-year survival rate of 61%.

Adolescent↗

PubMed1988

An external beam treatment technique for retinoblastoma.

The main difficulty in the irradiation of retinoblastoma has been to deliver a high uniform dose to the entire retinal surface and spare the lens. Conventional techniques are inadequate to deliver an acceptable dose distribution especially for cases when there are both anterior and posterior lesions. We have developed a procedure to deliver a high dose anteriorly at the ora serrata for a compromise of about 30-35% of the target dose to the lens. The technique consists of 3 pairs of non-coplanar arcs using a 4 MV accelerator. This technique may offer a higher probability of tumor control and cure when gross tumor is present at the ora serrata when compared to the conventional techniques using lateral techniques.

Eye Neoplasms↗

PubMedDate not supplied

What is the optimal angiotensin-converting enzyme inhibitor dose in heart failure?

Doses of angiotensin-converting enzyme (ACE) inhibitors used in the landmark heart failure trials that demonstrated survival benefit are rarely reached in routine practice. The authors review the current literature regarding optimal dosing of ACE inhibitors in heart failure with specific focus on neurohormonal, functional capacity, and clinical outcomes. Neurohormonal studies have shown that lower ACE inhibitor dosing may provide inadequate suppression of the renin-angiotensin-aldosterone system. Higher doses of ACE inhibitors have resulted in greater increments in exercise and functional capacity. Clinically, patients on high-dose ACE inhibitor therapy had significant reductions in all-cause mortality or hospitalization, cardiovascular hospitalizations, and heart failure-specific hospitalizations. There is, however, conflicting evidence, and so continued uncertainty exists regarding optimal dosing. Despite underutilization of ACE inhibitors, there is insufficient evidence to support lower doses. Likewise, limited data exist for doses higher than those used in the landmark trials. Clinicians should therefore attempt to reach target doses in heart failure whenever possible.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed1999

An optimized strategy for choosing the number of platelet concentrates to pool.

CONTEXT: The number of platelet concentrates (PCs) pooled per dose varies widely. The number should be based on quality control statistics. OBJECTIVE: To determine the optimal number of PCs per pool that will achieve a target dose. DESIGN: The population statistics of PC cell counts were obtained from routine quality control records. A target value of 3.00x10(11) cells was chosen. A theoretical model to predict the probability of achieving this target cell count was developed. MAIN OUTCOME MEASURES: The calculated probability was tested in a Monte Carlo simulation. RESULTS: The mean of a sequential series of 100 PC counts (obtained from routine quality control records) was 9.08x10(10), and the standard deviation was 2.70x10(10). Platelet loss during pooling was measured at 8.3%, so that the pooling of 3.27x10(11) cells is required to deliver a dose of 3.00x10(11) cells. The pooling of 4 PCs from this data set predicts an average pool cell count of 3.63+/-2.30x10(11). Using standard tables for normal distribution, the probability of achieving a minimal pool dose of 3.00x10(11) cells is estimated to be greater than 0.76. Similarly, the probability of achieving the target value by pooling 5 PCs is greater than 0.99. In a Monte Carlo simulation selecting 4 PCs, 76.5% of the trials were successful, and for 5 PCs, 99.5% were successful (estimated P values of .77 and .99, respectively). CONCLUSION: Five PCs per pool are necessary and sufficient to achieve the chosen target value given the cell count characteristics of our PC supply.

Humans↗

PubMed2001

The benefit of implementing a heart failure disease management program.

BACKGROUND: To handle the increasing complexity of congestive heart failure (CHF) care, several new models for the care of patients with CHF have been developed to replace traditional strategies. We undertook this study to evaluate the potential benefit of implementing a CHF disease management program at a tertiary care center, particularly in terms of beta-blocker use and cost to the health care system. METHODS: After reviewing the literature regarding therapies and management strategies for patients with CHF, we developed the Duke Heart Failure Program. All enrolled patients had 1 of the following: recent CHF hospitalization, ejection fraction less than 20%, or symptoms consistent with New York Heart Association class III or IV. We compared preenrollment and postenrollment medication use and resource utilization. RESULTS: We enrolled 117 patients from July 1998 to April 1999. Mean enrollment time was 4.7 months. beta-Blocker use and dose significantly increased (52% vs 76% for beta-blocker, P<.01; 6% vs 13% of target dose, P<.01). The hospitalization rate decreased (1.5 vs 0 hospitalizations per patient-year, P<.01), while the number of clinic visits increased (4.3 vs 9.8 clinic visits per patient-year, P<.01). The Duke University Health System saved a median of $8571 per patient-year. CONCLUSIONS: Implementing a CHF disease management program was associated with improved CHF medication dosing and with decreased hospitalization for patients with CHF. A CHF disease management program is an effective method for a health care system to care for patients with CHF.

Adrenergic beta-Antagonists↗

PubMed2003

A 6-month randomized, placebo-controlled, dose-ranging trial of topiramate for weight loss in obesity.

OBJECTIVE: To evaluate the efficacy and safety of topiramate (TPM) for weight loss in healthy obese subjects. RESEARCH METHODS AND PROCEDURES: A randomized, double-blind, placebo-controlled, dose-ranging trial was conducted. Three hundred eighty-five subjects, 18 and 75 years of age, were randomized to receive either placebo or TPM at 64, 96, 192, or 384 mg daily. Dosing began at 16 mg once daily. In week 2, the dose was increased to 16 mg twice daily. Thereafter, the dose was raised every week by 32 mg/d (16 mg twice daily) until subjects reached their target dose. Twenty-four weeks after beginning treatment, all subjects were tapered off treatment by a dose reduction of 50% per week. All participants received the same lifestyle program. RESULTS: Mean percent weight loss from baseline to week 24 was -2.6% in placebo-treated patients vs. -5.0%, -4.8%, -6.3%, and -6.3% in the 64, 96, 192, and 384 mg/d TPM groups, respectively. Greater percentages of TPM-treated patients lost at least 5% or 10% of body weight compared with placebo. The most frequent adverse events were related to the central or peripheral nervous system, including paresthesia, somnolence, and difficulty with memory, concentration, and attention. Most events were dose-related, occurred early in treatment, and usually resolved spontaneously; only 21% receiving TPM withdrew due to adverse events compared with 11% on placebo. DISCUSSION: TPM produced significantly greater weight loss than placebo at all doses.

Adolescent↗

PubMed1993

Lack of effect of nitrates on exercise tolerance in patients with mild to moderate heart failure caused by coronary disease already treated with captopril.

OBJECTIVE: To test the hypothesis that the addition of nitrates improves exercise tolerance in patients with heart failure caused by coronary artery disease already treated with an angiotensin converting enzyme inhibitor and diuretics. DESIGN: Randomised, double blind, placebo controlled, 16 week treatment periods. SETTING: Outpatient clinic at a university hospital. PATIENTS: 54 patients with previous myocardial infarction, symptoms of mild to moderate heart failure, left ventricular ejection fraction below 40%, no exercise-induced angina or electrocardiographic signs of ischaemia. Four patients in the nitrate group (n = 24) and one patient of the placebo group (n = 25) were withdrawn from the study. INTERVENTION: After the patients had been on constant doses of captopril and diuretics for at least 2 weeks, they were randomised to receive a target dose of 40 mg isosorbide dinitrate twice daily or placebo in addition to the continuation of captopril and diuretics. MEASUREMENTS: Bicycle exercise tests with measurement of gas exchange were carried out before randomisation and after 1, 6, 12, and 16 weeks of the double blind treatment. The change in peak oxygen uptake from control to week 16 was prospectively defined as the main outcome measure. RESULTS: The increase in peak oxygen uptake from before randomisation tended to be greater in the placebo group (before randomisation 17.4 (3.4) ml/min/kg) than in the nitrate group (before randomisation 17.1 (3.5) ml/min/kg) after 12 weeks (mean increase 1.1 (2.7) v 0.0 (2.7) ml/min/kg, p < 0.12) and 16 weeks (1.7 (3.0) v 0.3 (2.6) ml/min/kg, p < 0.14) of treatment. CONCLUSION: The addition of nitrates to a baseline treatment consisting of captopril and diuretics did not improve exercise tolerance.

Adult↗

PubMed1997

Guidelines for optimizing growth hormone replacement therapy in adults.

To minimize the rate of side-effects, a retrospective analysis of 28 studies of GH replacement therapy in adults indicates that the maintenance dose should usually not exceed 1.0 IU/m2/day (about 1.5-2.0 IU/day) in GHD patients 40-60 years old, or 1.5 IU/m2/day (about 2.5-3.0 IU/day) in GHD patients 20-40 years old. GHD women may tolerate, and in fact may need, higher replacement doses, though this issue requires further investigation. GH treatment should be started at a low dose, i.e. about 1.0 IU/day, and increased gradually, by about 0.5 IU per month, until the target dose is reached. In the absence of side-effects, the GH dose may be either too low, adequate, or too high. Measurement of GH-dependent serum markers provides the most promising approach to detect both GH depletion and excess, with serum IGF-I concentration the current method of choice. Clinical awareness of symptoms of GH excess remains important, however, particularly in patients with IGF-I levels in the high normal range.

Adult↗