Clinical course of pain in acute osteoporotic vertebral compression fractures.

PURPOSE: The authors prospectively determined the natural course of pain in patients with conservatively treated acute osteoporotic vertebral compression fractures (VCF). In addition, the type of conservative therapy that these patients received was assessed. MATERIALS AND METHODS: Patients older than 50 years, referred for spine radiography for acute back pain, were asked to complete a baseline clinical questionnaire. Patients with an acute VCF were followed up at 6 and 23 months with a questionnaire that included a Visual Analog Score (VAS) and type of pain medication and other conservative treatment. Significant pain relief was defined as a decrease in VAS of 50% or more. RESULTS: Forty-nine patients (mean age, 78 years; range, 51-95) with acute VCF were followed up for almost 2 years. Significant pain relief was noted in 22 of 35 patients (63%) at 6 months and in 25 of 36 (69%) at 23 months. In patients with persisting pain at 23 months (mean VAS 6.4), some decrease in VAS was apparent at 6 months but not in the 6-23 months interval. No predictors for significant pain relief could be identified. Patients with significant pain relief used less pain medication and had less physical therapy. CONCLUSIONS: In most patients with an acute VCF, pain decreases significantly with conservative therapy, predominantly in the first 6 months. However, almost 2 years after an acute VCF, a third of patients still had severe pain necessitating pain medication and physical therapy in the majority. No predictors for transition from acute to chronic pain could be identified.

Percutaneous vertebroplasty is not a risk factor for new osteoporotic compression fractures: results from VERTOS II.

BACKGROUND AND PURPOSE: PV is increasingly used as treatment for osteoporotic VCFs. However, controversy exists as to whether PV increases the risk for new VCFs during follow-up. The purpose of our research was to assess the incidence of new VCFs in patients with acute VCFs randomized to PV and conservative therapy. MATERIALS AND METHODS: VERTOS II is a prospective multicenter randomized controlled trial comparing PV with conservative therapy in 202 patients. Incidence, distribution, and timing of new VCFs during follow-up were assessed from spine radiographs. In addition, further height loss during follow-up of treated VCFs was measured. RESULTS: After a mean follow-up of 11.4 months (median, 12.0; range, 1-24 months), 18 new VCFs occurred in 15 of 91 patients after PV and 30 new VCFs in 21 of 85 patients after conservative therapy. This difference was not significant (P = .44). There was no higher fracture risk for adjacent-versus-distant vertebrae. Mean time to new VCF was 16.2 months after PV and 17.8 months after conservative treatment (logrank, P = .45). The baseline number of VCFs was the only risk factor for occurrence (OR, 1.43; 95% CI, 1.05-1.95) and number (P = .01) of new VCFs. After conservative therapy, further height loss of treated vertebrae occurred more frequently (35 of 85 versus 11 of 91 patients, P < .001) and was more severe (P < .001) than after PV. CONCLUSIONS: Incidence of new VCFs was not different after PV compared with conservative therapy after a mean of 11.4 months' follow-up. The only risk factor for new VCFs was the number of VCFs at baseline. PV contributed to preservation of stature by decreasing both the incidence and severity of further height loss in treated vertebrae.

VERTOS II: percutaneous vertebroplasty versus conservative therapy in patients with painful osteoporotic vertebral compression fractures; rationale, objectives and design of a multicenter randomized controlled trial.

BACKGROUND: The standard care in patients with a painful osteoporotic vertebral compression fracture (VCF) is conservative therapy. Percutaneous vertebroplasty (PV), a minimally invasive technique, is gaining popularity as a new treatment option. Many prospective and retrospective studies have reported on the effectiveness and safety of PV, but no large randomized controlled trial (RCT) has been published. OBJECTIVE: To estimate cost-effectiveness of PV compared to conservative therapy in terms of: pain reduction, quality of life, complications, secondary fractures and mortality. MATERIALS AND METHODS: The VERTOS II study is designed as a prospective, multicenter RCT. Patients with a painful VCF with bone edema on MR imaging, local back pain for 6 weeks or less, osteopenia and aged 50 years or older, after obtaining informed consent are included and randomized for PV or conservative therapy. In total 200 patients will be enrolled. Follow-up is at regular intervals during a 1-year period with standard questionnaires, addressing: clinical symptoms, pain medication, Visual Analogue Scale (VAS) score, quality of life and cost-effectiveness. Secondary fractures, necessary additional therapies and complications are recorded. CONCLUSION: The VERTOS II study is the first methodologically sound RCT designed to assess the cost-effectiveness of PV compared to conservative therapy in patients with an acute osteoporotic VCF. TRIAL REGISTRATION: http://www.clinicaltrials.gov, NCT00232466.

Percutaneous vertebroplasty compared with optimal pain medication treatment: short-term clinical outcome of patients with subacute or chronic painful osteoporotic vertebral compression fractures. The VERTOS study.

PURPOSE: To prospectively assess the short-term clinical outcome of patients with subacute or chronic painful osteoporotic vertebral compression fractures (VCF) treated with percutaneous vertebroplasty (PV) compared with optimal pain medication (OPM). METHODS: Randomization of patients in 2 groups: treatment by PV or OPM. After 2 weeks, patients from the OPM arm could change therapy to PV. Patients were evaluated 1 day and 2 weeks after treatment. Visual analog score (VAS) for pain and analgesic use were assessed before, and 1 day and 2 weeks after start of treatment. Quality of Life Questionnaire of the European Foundation for Osteoporosis (QUALEFFO) and Roland-Morris Disability (RMD) questionnaire scores were assessed before and 2 weeks after start of treatment. Follow-up scores in patients requesting PV treatment after 2 weeks OPM treatment were compared with scores during their OPM period. RESULTS: Eighteen patients treated with PV compared with 16 patients treated with OPM had significantly better VAS and used less analgesics 1 day after treatment. Two weeks after treatment, the mean VAS was less but not significantly different in patients treated with OPM, whereas these patients used significantly less analgesics and had better QUALEFFO and RMD scores. Scores in the PV arm were influenced by occurrence of new VCF in 2 patients. After 2 weeks OPM, 14 patients requested PV treatment. All scores, 1 day and 2 weeks after PV, were significantly better compared with scores during conservative treatment. CONCLUSION: Pain relief and improvement of mobility, function, and stature after PV is immediate and significantly better in the short term compared with OPM treatment.

Pain response in the first trimester after percutaneous vertebroplasty in patients with osteoporotic vertebral compression fractures with or without bone marrow edema.

BACKGROUND AND PURPOSE: Presence of bone marrow edema (BME) in osteoporotic vertebral compression fractures (VCF) detected by MR imaging as selection criterion for percutaneous vertebroplasty (PV) is speculative. To clarify significance of BME in VCF, we assessed pain response after PV in patients with VCF with full BME versus patients with VCF with absent BME. METHODS: From a cohort of patients with painful VCF selected for PV, pain response in 14 patients with absent BME in VCF was prospectively compared with pain response in 31 patients with full BME in VCF. Pain was evaluated before PV and at 1 and 3 months after PV with visual analog scores and analgesics used. Back pain in general and at treated vertebral levels was assessed. RESULTS: Pain decrease after PV at treated levels was observed in 10 (71%) patients with absent BME in VCF at both follow-up periods and in 29 (94%) patients with full BME 1 month after PV and 30 (97%) at 3 months after PV. Differences between the groups were significant (P = .04 at 1 month; P = .01 at 3 months). Pain response was not affected by other patient or imaging characteristics. General back pain after PV was comparable in both groups after PV (P = .08 at 1 month; P = .4 at 3 months). CONCLUSION: Pain decrease after PV in patients with VCF is more frequently observed when full BME is present. Because 71% of patients with VCF with absent BME responded favorably on pain, PV should not be withheld based on absence of BME alone.

Bone marrow edema in osteoporotic vertebral compression fractures after percutaneous vertebroplasty and relation with clinical outcome.

BACKGROUND AND PURPOSE: Little is known about the evolution of bone marrow edema (BME) in osteoporotic vertebral compression fractures (VCF) after percutaneous vertebroplasty (PV) or about its relation with relief of pain. In this study, we prospectively assessed changes in BME with MR imaging at 3, 6, and 12 months after PV and related changes in BME with pain evolution and analgesic use over time. METHODS: BME percentage was assessed in 64 patients after PV of 89 VCF with serial MR imaging follow-up at 3, 6, and 12 months. Pain was assessed before PV and at every follow-up interval by visual analog scale for pain and type of analgesic used. Relation between changes in BME and pain evolution was assessed in a subgroup of 31 patients with a single treated VCF and neither new VCF at follow-up nor pain at another untreated level. RESULTS: BME gradually decreased over time. At 1 year after PV, 29% of treated VCF still demonstrated BME. Once BME disappeared, it did not return. Pain relief was most striking the first 3 months after PV and remained constant thereafter. There was no relation between relief of pain and extent, presence, or absence of BME after PV. CONCLUSION: A gradual decrease of BME in osteoporotic VCF treated with PV is apparent during 12 months of MR imaging follow-up. Decrease of BME is unrelated to relief of pain.

Comparison of two once-daily regimens with a regimen consisting of nelfinavir, didanosine, and stavudine in antiretroviral therapy-naïve adults: 48-week results from the Antiretroviral Regimen Evaluation Study (ARES).

BACKGROUND: To improve the dosing frequency and pill burden of antiretroviral therapy, we compared two once-daily dosed regimens to a twice-daily dosed regimen. METHOD: HIV-1-infected, antiretroviral drug-naïve adults were randomized to either twice-daily nelfinavir and stavudine and once-daily didanosine (regimen A) or simplified once-daily dosed antiretroviral regimens consisting of nevirapine, didanosine, and lamivudine (regimen B) or saquinavir, ritonavir, didanosine, and lamivudine (regimen C). RESULTS: At 48 weeks of therapy, the proportion of patients with a blood plasma HIV-1 RNA concentration (pVL) <50 copies/mL by intention-to treat analysis was 42.3%, 50.0%, and 56.5% for regimens A (n = 26), B (n = 22), and C (n = 23), respectively. The time to a pVL <50 copies/mL for the first time was significantly shorter in regimen C, and there was significantly more progression to CDC events in regimen B. These differences are possibly due to differences in baseline characteristics. Adverse events were lowest for regimen C; more signs associated with mitochondrial toxicity occurred in regimen A. Increase in CD4 count was comparable between arms. CONCLUSION: No statistically significant difference in efficacy was found between the two investigated once-daily dosed treatment regimens (B and C) and the reference (A). Regimen C possibly had a better virological response and less toxicity than regimens A and B.

[Percutaneous vertebroplasty in the treatment of osteoporotic vertebral compression fractures: first short term results]. / Percutane vertebroplastiek bij osteoporotische wervelinzakkingsfracturen: eerste kortetermijnresultaten.

OBJECTIVE: To describe the technique of percutaneous vertebroplasty and the short-term results in patients with symptomatic, osteoporotic vertebral compression fractures. DESIGN: Prospective follow-up study. METHOD: In a pilot-study to evaluate the short-term safety and effectiveness of percutaneous vertebroplasty, 18 consecutive patients with a total of 33 osteoporotic thoracic or lumbar vertebral compression fractures were treated from October 2001 to June 2002 with a follow-up of 3-6 months. The indication for treatment was a symptomatic, therapy-resistant osteoporotic vertebral compression fracture. Percutaneous vertebroplasty was performed under radiographic control, after previous intraossal venography, using bone cement mixed with barium sulphate. Post-procedural follow-up consisted of radiological evaluation with conventional thoracolumbar X-rays and MRI scans, and interviews of the patients. RESULTS: Percutaneous vertebroplasty was technically successful in 31 of 33 vertebral fractures (94%), and in 16 of 18 patients (89%). One patient with extreme venous contrast leakage could not be treated. Sixteen patients had less or no pain after treatment. One patient retained thoracolumbar back pain after inadequate cementations and refused further treatment. None of the patients reported aggravation of symptoms following the procedure. Contrast leakage was absent in 18 vertebrae. In 8 vertebrae there was contrast leakage to paravertebral veins. In three of these cases the leakage was so severe that embolisation was performed, with success in one case. In 13 vertebrae, cement leakage to intervertebral and paravertebral spaces and pedicular cement spurs were seen, without clinical consequences. Immediately after the procedure and during follow-up there were no clinically relevant complications. CONCLUSION: Percutaneous vertebroplasty was a technically feasible treatment in these patients with symptomatic, therapy-resistant, osteoporotic vertebral fractures. The first short-term results were comparable with results in the literature. A prospective randomised intervention study will be needed to compare percutaneous vertebroplasty with optimal conservative treatment.

Intravenous pamidronate compared with oral alendronate for the treatment of postmenopausal osteoporosis.

There are several options for the treatment of osteoporosis in postmenopausal women. One of the options is treatment with bisphosphonates, which are very potent inhibitors of osteoclast-mediated bone resorption in vitro and in vivo. The most potent bisphosphonates have a nitrogen side chain and can be given orally or intravenously (i.v.). In the present study we evaluated retrospectively the effect of intravenously administered pamidronate (60 mg monthly) in comparison with oral alendronate with regard to bone mineral density (BMD) and vertebral fractures. A total of 117 consecutive women aged 46 to 78 years were seen in the outpatient clinic because of postmenopausal osteoporosis. Three-year follow-up data were available for a total of 45 patients treated with pamidronate i.v. and 40 patients on alendronate for at least three years. In the pamidronate group mean T score of lumbar spine BMD increased from -3.49 +/- 0.72 to -2.81 +/- 0.74 SDs after three years of treatment (p < 0.001). In the 40 patients treated with alendronate we observed an increase in the T score from -2.95 +/- 0.67 to -2.33 +/- 0.74 SDs (p < 0.001) during the same observation period. X-rays of the lumbar and thoracic spine were analysed from 25 patients in each group who had been treated for at least three years. At baseline nine patients (36%) in the pamidronate group had one or more vertebral fractures compared with seven patients (28%) in the alendronate group. After three years of treatment no new fractures were observed, while only three women in the pamidronate group and two in the alendronate group showed a deterioration of one or more pre-existing vertebral fractures (p = ns between groups). This retrospective analysis demonstrates that monthly intravenous administration of pamidronate is at least as good as alendronate taken orally in the treatment of women with postmenopausal osteoporosis, with regard to improvement of bone mineral density of the lumbar spine. We conclude that it is a good alternative for the more widely used oral bisphosphonates as it is effective, well-tolerated and easy to administer.

Management of common bile duct stones: selective endoscopic retrograde cholangiography and endoscopic sphincterotomy: short- and long-term results.

BACKGROUND: Common bile duct stones are still a frequent problem. Although new diagnostic and therapeutic techniques are continually being development, they remain poorly defined. Therefore, we decided to evaluate our standard method of diagnosing and treating common bile duct stones. The aim of the study was to determine the short- and long-term results of this method. METHODS: Between 1985 and 1995, 552 consecutive patients (200 men and 352 women; median age, 69 years) underwent endoscopic retrograde cholangiography (ERC) because of suspected common bile duct stones. If stones were detected, they were treated endoscopically, if possible. The results and complications of this policy were recorded. Patients were followed 1-13 years after undergoing ERC and endoscopic sphincterotomy (ES). Long-term results and complications during this period were also recorded. RESULTS: ERC was attempted in 552 patients and succeeded in 510 patients (92%): ES was attempted in 315 patients and failed in five (98%). Duct clearance was done in 271 patients; in 26 of these patients, symptoms disappeared spontaneously. Ten patients underwent common bile duct exploration. Complications occurred in 46 patients (8.3%). Mortality was 0.4%, hemorrhage occurred in 3.6%, pancreatitis in 1.4%, sepsis and cholangitis also in 1.4%, and the lithotripter basket became impacted in four patients (0.8%), necessitating to common bile duct exploration. During follow-up, 45 patients (8%) returned, 35 with recurrent stones, five with cholangitis, two with stenosis of the papilla of Vater, and one with biliary pancreatitis. In 35 cases, complications were treated endoscopically, common bile duct exploration was performed in five cases, and symptoms disappeared spontaneously in five cases. CONCLUSIONS: ERC is a safe and reliable way of diagnosing common bile duct stones, and ES is a very efficient way of treating them. Morbidity and mortality are low, and the long-term results are very good.

Randomized trial comparing saquinavir soft gelatin capsules versus indinavir as part of triple therapy (CHEESE study).

OBJECTIVE: To compare efficacy and tolerability of saquinavir soft gelatin capsule (SQV-SGC) formulation and indinavir, both given as part of a triple drug regimen containing zidovudine and lamivudine, in HIV-1-infected individuals. DESIGN: Randomized, open label, multicentre study. PATIENTS: A total of 70 patients who were antiretroviral-naive and who had a CD4 cell count < 500 x 10(6)/I and/or > 10000 HIV RNA copies/ml plasma and/or HIV-related symptoms. Subjects were assigned randomly to zidovudine 200 mg three times per day plus lamivudine 150 mg twice per day plus either SQV-SGC 1200 mg three times per day (SQV-SGC group) or indinavir 800 mg three times per day (indinavir group). Data are presented for all patients up to week 24. RESULTS: Mean baseline CD4 cell counts (+/- SE) were 301+/-29 x 10(6) cells/l and 310 +/-43 x 10(6) cells/l in the SQV-SGC and indinavir groups, respectively. The log10 median baseline HIV RNA load was 5.00 copies/ml in the SQV-SGC group and 4.98 copies/ml in the indinavir group. No difference in antiretroviral effect between the treatment arms could be demonstrated. Intention-to-treat analysis (last observation carried forward [LOCF]) at week 24 revealed that RNA levels decreased to < 50 copies/ml in 74.3% of patients in the SQV-SGC group and in 71.4% of the patients in the indinavir group (P = 0.78). In the on-treatment analysis the proportion of patients < 50 copies/ml at week 24 was 88.0% in the SQV-SGC group and 84.6% in the indinavir group (P = 0.725). Intriguingly, the mean increase of CD4 cells in the first 24 weeks was 162+/-20 x 10(6) cells/l in the SQV-SGC group and 89+/-21 x 10(6) cells/l in the indinavir group (P = 0.01), but preliminary data indicate that this difference in CD4 cell count gain may disappear after 24 weeks of treatment. Both regimens were generally well tolerated. CONCLUSION: During the first 24 weeks of the study, we found no difference in antiviral potency between the indinavir group and the SQV-SGC group. A significantly higher CD4 response in the SQV-SGC group was observed.

Incidence of discontinuation of highly active antiretroviral combination therapy (HAART) and its determinants.

OBJECTIVE: To determine the incidence and determinants for discontinuation of initial highly active antiretroviral therapy (HAART). DESIGN: In this retrospective follow-up study from hospital files and pharmacy dispensing data, a standard dataset was collected including patient characteristics, therapy characteristics, and HIV-monitoring parameters (e.g., CD4+ lymphocyte counts, viral load determinations). Kaplan-Meier estimates of the cumulative probability of discontinuation of initial HAART were calculated. Cox proportional hazard analysis was used to identify determinants for discontinuation of initial HAART. PATIENTS: All patients starting HAART (n = 99) during June 1996 to February 1997 at our regional AIDS center. MAIN OUTCOME MEASURES: Incidence and determinants for discontinuation of HAART. RESULTS: During the mean follow-up of 450+/-10 days, 27 patients switched initial HAART, 3 patients stopped any antiretroviral therapy. Reasons for switching were increasing viral load (18x), insufficient decrease of viral load (3x), and adverse events (6x). Nonnaivete for antiretroviral therapy and a lower CD4+ lymphocyte count at start were identified as determinants for discontinuation of initial HAART. CONCLUSIONS: The overall incidence density for discontinuation of initial HAART was 25 per 100 patients/year. The main reason for switching was an increasing viral load. CD4+ lymphocyte counts at start and nonnaivete for antiretroviral therapy were identified as determinants for discontinuation.

Three monthly intravenous injections of ibandronate in the treatment of postmenopausal osteoporosis.

PURPOSE: Oral treatment of osteoporosis with bisphosphonates relies on compliance, the absorption being low and suppressed by simultaneous food intake. Intravenous (IV) treatment with an aminobisphosphonate, pamidronate (once every 3 months) was effective, but required infusions. Ibandronate, a new very potent aminobisphosphonate, can be administered safely as an IV bolus injection, and therefore offers an interesting alternative suitable for outpatient treatment. PATIENTS AND METHODS: To test the efficacy of this bolus IV treatment in postmenopausal osteoporosis in randomized partly double-blind, placebo controlled study, 125 postmenopausal women (mean age, 64 years) with osteoporosis (bone mineral density [BMD] < -2.5 SD T score) received a placebo or ibandronate (0.25, 0.5, 1, or 2 mg) every 3 months. All patients received 1 g calcium/day. BMD, in g/cm2, was measured by dual-energy x-ray absorptiometry at all standard sites. RESULTS: Lumbar spine BMD (L2 to L4) did not change (0.85%) in the placebo group, but increased by 2.4%, 3.5%, 3.7%, and 5.2% at 12 months for dose-ranging groups (no significant differences among ibandronate groups). The increase was statistically significantly different from placebo for the 0.5 mg (P < 0.006), 1 mg (P < 0.004), and 2 mg (P < 0.001) group, whereas with 0.25 mg no significant differences occured. After 1 year there were no significant changes in BMD compared with placebo at the femoral neck, Ward's triangle, and distal forearm. Total hip and trochanter BMD increased significantly, by 1.8% and 2.9% for total hip and by 2.7% and 4.2% for trochanter in the 1 and 2 mg group, respectively. Urinary excretion of C-telopeptide and N-telopeptide decreased after 1 month in all ibandronate groups, with a clear dose dependency. Three months after the first injection of 2 mg ibandronate there was still a significant reduction in these markers of bone resorption. Osteocalcin decreased progressively and dose dependently over time. There was a correlation between the decrease in C-telopeptide measured after 1 month and the increase in lumbar spine BMD after 1 year (n = 115, r = -0.26, P < 0.012). Ibandronate therapy proved to be safe. There was no significant difference in the overall number of adverse events in the ibandronate groups compared with the placebo group. Considering specific adverse events, no dose dependency and difference to placebo could be observed apart from acute reactions that occurred in 7% of the patients. CONCLUSION: Treatment of postmenopausal osteoporosis by interval IV bolus injections of the bisphosphonate ibandronate was safe and effective in increasing BMD through a dose-dependent inhibition of bone resorption. The high potency of ibandronate allows 3-month interval bolus IV injections as a new therapeutic approach with optimal compliance.

Effect of alfacalcidol on natural course of renal bone disease in mild to moderate renal failure.

OBJECTIVE: To determine whether alfacalcidol--used in management of overt renal bone disease--may safely prevent renal bone disease when used earlier in course of renal failure. DESIGN: Double blind, prospective, randomised, placebo controlled study. SETTING: 17 nephrology centres from Belgium, France, the Netherlands, and the United Kingdom. SUBJECTS: 176 patients aged 18-81 with mild to moderate chronic renal failure (creatinine clearance 15-50 ml/min) and with no clinical, biochemical, or radiographic evidence of bone disease. INTERVENTIONS: Alfacalcidol 0.25 micrograms (titrated according to serum calcium concentration) or placebo given for two years. MAIN OUTCOME MEASURES: Quantitative histology of bone to assess efficacy of treatment and renal function to assess safety. RESULTS: 132 patients had histological evidence of bone disease at start of study. Biochemical, radiographic, and histological indices of bone metabolism were similar for the 89 patients given alfacalcidol and the 87 controls given placebo. After treatment, mean serum alkaline phosphatase activity and intact parathyroid hormone concentration had increased by 13% and 126% respectively in controls but had not changed in patients given alfacalcidol (P < 0.001). Hypercalcaemic episodes occurred in 10 patients given alfacalcidol (but responded to decreases in drug dose) and in three controls. Histological indices of bone turnover significantly improved in patients given alfacalcidol and significantly deteriorated in controls: among patients with abnormal bone histology before treatment, bone disease resolved in 23 (42%) of those given alfacalcidol compared with two (4%) of the controls (P < 0.001). There was no difference in rate of progression of renal failure between the two groups. CONCLUSION: Early administration of alfacalcidol can safely and beneficially alter the natural course of renal bone disease in patients with mild to moderate renal failure.

Safety of the coadministration of carvedilol and nifedipine sustained-release in the treatment of essential hypertension.

A single-center, randomized, double-blind study in 14 hypertensive patients was conducted to investigate the acute and short-term safety of the addition of carvedilol to pre-existent nifedipine sustained-release (SR) therapy as well as on the addition of nifedipine SR to pre-existent carvedilol therapy when treatment with the initial monotherapy did not adequately control blood pressure. Mean supine blood pressure at study entry was 171/106 mm Hg. Acute reductions in blood pressure were greater with combination treatment than with either monotherapy. Dosing with 25 mg carvedilol once daily or 20 mg nifedipine SR twice daily resulted in mean peak reductions in supine blood pressure of 21/11 and 20/16 mm Hg, respectively, after 1 week of treatment with each respective monotherapy. With combination treatment, mean peak reductions (after dosing on days 1, 3, and 10) ranged from 26 to 40 mm Hg in supine systolic blood pressure and from 14 to 23 mm Hg in supine diastolic blood pressure. Acute changes in mean standing systolic and diastolic pressures were comparable to those in the supine position. Combination treatment resulted in an additive acute antihypertensive response without synergistic potentiation. Neither monotherapy nor the coadministration of the two agents in the doses used resulted in a significant antihypertensive response at the time of trough plasma levels of study medication, perhaps due to the short-term nature of the trial which did not allow the full antihypertensive effect of either agent to be realized. Before dosing with study medication, heart rates were minimally changed from study entry levels with either monotherapy or combination treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

A testicular tumour in the left adnex. The persistent mullerian duct syndrome with testicular malignancy.

Cryptorchidism is known to increase the incidence of testicular malignant tumours. In this report a patient is described with the Mullerian duct syndrome in connection with a cryptorchistic malignant testicular tumour.

Percutaneous endoscopic gastrostomy as a standard procedure in head and neck surgery.

Adequate nutritional support is essential in patients with head and neck cancer, especially if extended oropharyngeal surgery is indicated. Enteral nutrition is an effective and safe alternative to parenteral nutrition, but the use of nasogastric tubes has several disadvantages in these patients. We describe our experience with percutaneous endoscopic gastrostomy as a standard procedure prior to surgical resection in patients with head and neck cancer.

[A testis tumor in the left adnexi]. / Een testistumor in het linker adnex.

Cryptorchidism increases the incidence of malignant testicular tumours. The case is described of a normally functioning male patient with a tumour in an undescended testis, in whom a special type of intersexuality was found: the persistent müllerian duct syndrome, one of the types of male pseudohermaphroditism, in which no disturbances of virilisation occur and which is often associated with cryptorchidism and other developmental anomalies.