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PubMed1998

MR and CT findings in a case of hibernoma of the thigh extending into the pelvis.

Review of the literature shows no report of hibernoma of the thigh extending into the pelvis. Herein we report a case of hibernoma which appeared on CT and MR as a well-defined pelvic mass with contrast enhancement extending through the obturator foramen into the thigh. Fat was demonstrated by CT, whereas MR, using multiplanar sections, better analyzes the extension of the mass. This case demonstrates that hibernoma as liposarcoma can extend through the obturator foramen. However, no definite diagnosis could be made by CT or MR and the tumor must be considered as a "potential" malignant liposarcoma.

Adipose Tissue↗

PubMed1999

Extended fronto-lateral laryngectomy with simultaneous reconstruction by means of a mucochondral nasal septum flap.

As treatment for laryngeal cancers the extended fronto-lateral laryngectomy allows tumor to be removed that involves the glottis with the vestibule of the larynx. Since 1979 we have performed 417 extended fronto-lateral laryngectomies with simultaneous reconstruction of the anterior part of the larynx using a mucoperichondral flap from the anterior septum. This operation was indicated for stage T1b cancer (175 cases), stage T2 tumor (231 tumors) and T3 extended operations with epiglottectomy (11 cases). For the total number of 417 patients operated on, 19 cases during the 5-year period of following had local recurrences that required total laryngectomy. In 11 cases, metastases to the cervical lymph nodes required surgical neck dissection. In the remaining 387 cases, a normal air passage and a large laryngeal lumen were found. In 15 cases graft rotation into the larynx made respiration and phonation difficult but without dyspnea occurring. Follow-up to a maximum of 18 years showed that the oncological and functional results after this surgical procedures are encouraging.

Aged↗

PubMed2006

Temporally extended gene expression of the ADP-Glc pyrophosphorylase large subunit (AgpL1) leads to increased enzyme activity in developing tomato fruit.

Tomato plants (Solanum lycopersicum) harboring the allele for the AGPase large subunit (AgpL1) derived from the wild species Solanum habrochaites (AgpL1 ( H )) are characterized by higher AGPase activity and increased starch content in the immature fruit, as well as higher soluble solids in the mature fruit following the breakdown of the transient starch, as compared to fruits from plants harboring the cultivated tomato allele (AgpL1 ( E )). Comparisons of AGPase subunit gene expression and protein levels during fruit development indicate that the increase in AGPase activity correlates with a prolonged expression of the AgpL1 gene in the AgpL1 ( H ) high starch line, leading to an extended presence of the L1 protein. The S1 (small subunit) protein also remained for an extended period of fruit development in the AgpL1 ( H ) fruit, linked to the presence of the L1 protein. There were no discernible differences between the kinetic characteristics of the partially purified AGPase-L1(E) and AGPase-L1(H) enzymes. The results indicate that the increased activity of AGPase in the AgpL1 ( H ) tomatoes is due to the extended expression of the regulatory L1 and to the subsequent stability of the heterotetramer in the presence of the L1 protein, implying a role for the large subunit not only in the allosteric control of AGPase activity but also in the stability of the AGPase L1-S1 heterotetramer. The introgression line of S. lycopersicum containing the wild species AgpL1 ( H ) allele is a novel example of transgressive heterosis in which the hybrid multimeric enzyme shows higher activity due to a modulated temporal expression of one of the subunits.

Alleles↗

PubMed2006

Thoracoscopic and laparoscopic oesophagectomy improves the quality of extended lymphadenectomy.

BACKGROUND: Oesophagectomy with extended lymphadenectomy carries considerable morbidity due to parietal trauma. It is also technically extremely demanding because the difficult access even through a large thoracotomy requires the use of long instruments to reach the deepest recess in the chest cavity. Since the first thoracoscopic oesophagectomy reported by Cuschieri et al. [1] in 1992, different minimally invasive approaches have been proposed [2-12]. The aim of this video is to show the accurate and relative ease of an entirely thoracoscopic and laparoscopic oesophagectomy with an extended lymph node dissection of mediastinum in prone position (thoracoscopically) and celiac trunk (laparoscopically). METHODS: Oesophagectomy by thoracoscopy, laparoscopy and cervicotomy was proposed in a 63-year-old man with a lower third oesophageal cancer. General anaesthesia was performed with a double-lumen endotracheal tube and the patient was placed in prone position. Surgeons were positioned at the right side of the patient. Only three trocars were needed. A 10 mm 30-degree angled scope was inserted in the 7th intercostal space on the posterior axillary line and the remaining two 5 mm trocars were inserted in the 5th and 9th intercostal spaces on the posterior axillary line. Prone position allows an excellent visibility of the operative field even in an only partially deflated lung. In order to achieve a good exposure, transitory pneumothorax with CO2 (14 mmHg) was performed. The mediastinal pleura overlying the oesophagus was incised and the arch of azygos vein was isolated, ligated and divided. The oesophagus was circumferentially mobilized from the thoracic inlet down to oesophageal hiatus. Para oesophageal and subcarinal lymph nodes were dissected so as to remain in block with the surgical specimen. A 28 F chest tube was inserted in the 8th intercostal space on the anterior axillary line. In the second stage the patient was placed in supine position and pneumoperitoneum was established. Five trocars were placed along an ideal semicircular line, with the concavity facing the subcostal margin and a 30-degree angled laparoscope was used. The lesser omentum was widely opened up the right pillar of the hiatus. Mobilization of the greater curvature of the stomach was performed preserving the right gastroepiploic artery. A wide Kocher maneuver was performed. Celiac lymphadenectomy started with skeletonization of the hepatic artery until the root of left gastric artery was reached. This artery and the left gastric vein were dissected, clipped and sectioned. All fatty tissue and lymph nodes along hepatic artery, left gastric artery and celiac trunk were resected in block with the surgical specimen. Multiple applications of a linear endoscopic stapler were used to create the gastric tube. Finally the distal oesophagus was dissected, until the thoracoscopic dissection field was joined. In the third stage a left lateral cervicotomy was performed and the cervical oesophagus was dissected down to the thoracoscopic dissection plane. Oesophagus and stomach were delivered through the cervical incision and an oesophagogastric anastomosis was created by a linear stapler technique. Cervical and abdominal drainages were installed. RESULTS: The total operative time was 271 minutes (thoracoscopy: 106 minutes, laparoscopy 120 minutes and cervicotomy 45 minutes) and blood loss was about 100 ml. Histological examination demonstrated a squamous cell carcinoma. Both margins of resection were free of tumour and 29 lymph nodes were retrieved. The final stage was IIA (pT3N0Mx). CONCLUSIONS: Thoracoscopic and laparoscopic oesophagectomy with extended lymphadenectomy is technically feasible and safe. Thoracoscopic oesophagectomy in prone position improves the quality of dissection because: The oesophagus and aorto-pulmonary window are reached under excellent visibility, despite a partially deflated lung, which because of gravity will always remain out of harm's way. For the same reason small to moderate bleeding will not obscure the operative field. Dissection with the long endoscopic instruments is more accurate due to the support provided by the entrance site at the parietal level and the ergonomic position of surgeon. This article contains a supplementary video.

Blood Loss, Surgical↗

PubMed2001

Definitive treatment of extended Hirschsprung's disease or total colonic form.

BACKGROUND: Between December 1990 and March 1999, five laparoscopic Duhamel pull-through procedures for extended or total aganglionosis were performed in our department, one of which had a rectosigmoid form with a short bowel and a colonic resection due to a volvulus. METHODS: The aim of this study was to show that even when the extended form of Hirschprung's disease or anatomic difficulties such as a short bowel and anterior colonic resection are encountered, the laparoscopic approach is possible and total colectomy is feasible. The procedure has been described previously. We used one camera port and three working ports. The sigmoid, transverse, and right colon up to the last ileal cove were mobilized laparoscopically. A standard posterior ileo-anal anastomosis was performed, and an endo-GIA stapler was used for the anterior anastomosis. RESULTS: A total of five patients underwent laparoscopic surgery for Hirschprung's disease. There were three total colonic forms, one rectosigmoid form with a short bowel and colon resection attributed to a volvulus, and one transverse variant that required a Deloyers' maneuver for the pull-through. Three of the infants required total parenteral nutrition (TPN) for an average of 49 days (range, 28-60) from diversion until the time of the definitive procedure. Only one patient did not receive TPN. Postoperatively, there were two complications-one wound infection and one hectic fever. The clinical results were good, with no soiling or stool incontinence and no constipation. CONCLUSION: The laparoscopic procedure for total aganglionosis or the extended form of Hirschprung's disease is safe, feasible, and reproducible.

Feasibility Studies↗

PubMed1997

Lobectomy with extended lymph node dissection by video-assisted thoracic surgery for lung cancer.

BACKGROUND: Between September 1992 and September 1996, we performed 88 VATS (video-assisted thoracic surgery) lobectomies and two VATS pneumonectomies. METHODS: The indications for surgery were 68 cases of lung cancer, nine cases of bronchiectasis, six cases of tuberculosis, and seven cases of benign lesions. Of the 68 cases of lung cancer, 36 were treated by VATS lobectomy with extended lymph node dissection for clinical stage I lung cancer, making full use of recently developed devices for thoracoscopic surgery, such as roticulating endoscissors, miniretractors, endoclips, and harmonic scalpels. RESULTS: Twenty-four lymph nodes were resected on average (range, 10 to 51) by VATS. This number was comparable to lymph nodes resected in open thoracotomy during the same period. Among the 36 patients who underwent extended lymph node dissection, 20 showed no lymph node metastasis postoperatively (stage I), while 16 had N1 or N2 cancer. All patients with stage I cancer have survived 4 to 36 months (median: 17 months) with no signs of recurrence. CONCLUSIONS: This survival of stage I lung cancer after VATS is comparable to that of open thoracotomy. We thus believe that VATS lobectomy with extended lymph node dissection can be an alternative to standard posterolateral thoracotomy for stage I lung cancer.

Adenocarcinoma↗

PubMed2005

A poly(propylene glycol-co-fumaric acid) based bone graft extender for lumbar spinal fusion: in vivo assessment in a rabbit model.

STUDY DESIGN: An animal model of posterolateral intertransverse process lumbar spinal fusion compared fusion rates amongst autologous bone (group 1), a porous, bioabsorbable, scaffold based on the biopolymer, poly(propylene glycol-co-fumaric acid) (PPF) (group 2), and a combination of autograft and the bioabsorbable scaffold (group 3). OBJECTIVES: To evaluate the feasibility of augmenting spinal fusion with an osteoconductive and bioabsorbable scaffold as an alternative or as an adjunct, i.e., an extender, to autograft. SUMMARY OF BACKGROUND DATA: There is little preclinical data on applications of bioabsorable bone graft extenders in spinal fusion. METHODS: New Zealand White rabbits underwent single-level lumbar posterolateral intertransverse process fusion. Animals were treated with one of three materials: autologous bone (group 1), a bioabsorable material based on PPF (group 2), and the PPF biopolymer scaffold with autologous bone graft (group 3). Animals were evaluated at 6 weeks, and fusion was evaluated by manual palpation, and radiographic, histologic, and histomorphometric analyses. RESULTS: Radiographic and manual palpation showed evidence of fusion in all three groups. Histomorphometric measurement of bone ingrowth showed the highest quantity of new bone in group 3 (91%), followed by group 1 (72%) and group 2 (53%). CONCLUSIONS: Results of this study suggested that osteoconductive bioabsorbable scaffolds prepared from PPF might be used as an autograft extender when applied as an adjunct to spinal fusion.

Animals↗

PubMed2002

Follow-up of extended pterional orbital decompression in severe Graves' ophthalmopathy.

BACKGROUND: Compressive optic neuropathy (CON) with visual loss is, apart from corneal exposure and disfigurating proptosis, the most serious clinical sign encountered in Graves' ophthalmopathy. However, numerous different approaches and operative techniques have been proposed for orbital decompression, with varying results and side effects. The purpose of the present study was to analyze peri-operative data and long-term results in patients with severe thyroid-related orbitopathy, treated by extended pterional orbital decompression, comparing its effectiveness to other procedures. METHOD: An extended pterional orbital decompression was performed in 42 consecutive patients (59 orbits) with severe thyroid-associated ophthalmopathy after failure of medical and radiation therapy during an 11-year period. Pre- and postoperative examination included visual acuity, Hertel exophthalmometry, ocular motility, visual fields (Goldmann perimetry) and notification of complications. Long-term evaluation was carried out on average at 11 months postoperatively (range 5-26 months). FINDINGS: Visual acuity improved rapidly from a preoperative average of 0.53 +/- 0.33 (range, 0-1) to 0.77 +/- 0.31 (range, 0-1) postoperatively (p<0.001). Worsening was not seen. An average reduction of proptosis of 3.79 +/- 2.32 mm (range, 0.5-8 mm) was achieved with a mean preoperative Hertel measurement of 24.7 +/- 3.93 mm (range, 15-33 mm) (p<0.001). Double vision and restriction of eye motility was present in 76.3% of patients preoperatively and improved in 63% of patients (p<0.001). No new onsets of not already pre-existing double vision was seen. Complications included two cases of permanent palsy of the frontal branch of the facial nerve. INTERPRETATION: The extended pterional orbital decompression improved vision and decreased proptosis and restriction of extra-ocular movements in patients with severe sight-threatening and disfiguring cases of Graves' orbitopathy and is still an effective and low-risk alternative to other non-neurosurgical operative techniques. Especially new developing postdecompression strabismus can be successfully avoided.

Adult↗

PubMed2004

Comparative efficacy of once-a-day extended-release methylphenidate, two-times-daily immediate-release methylphenidate, and placebo in a laboratory school setting.

BACKGROUND: Given the dosing limitations of methylphenidate short-acting preparations in treating ADHD, galenics with longer release of the substance were developed mainly to avoid drug intake during school hours. OBJECTIVES: This investigation was conducted to assess the efficacy and the duration of action of a new extended-release formulation of methylphenidate (Medikinet retard) as a once-daily treatment for children with attention-deficit hyperactivity disorder (ADHD). METHOD: This was a randomized, double-blind, crossover multicentre study with three treatment conditions: once-daily extended-release methylphenidate, twice-daily immediate-release methylphenidate and placebo given to 79 children (8-14 years old) with ADHD. Daily assessments in an analogue classroom setting included blind ratings of attention and deportment and a performance measure (math test) obtained 5 times over an 8-hour period. Secondary measures included an ADHD rating scale, based on DSMIV/ ICD-10 separately rated for the morning and the afternoon. RESULTS: Both active treatment conditions displayed significant time course effects and were superior to placebo in improving all efficacy measures. Once a day extended-release methylphenidate was not different from the same dose of twice daily immediate-release methylphenidate. CONCLUSIONS: These data provide support for the benefit of this novel, once-daily methylphenidate preparation in the treatment of ADHD. The longer duration of action of Medikinet Retard has the potential to simplify psychostimulant treatment, thus reducing dose diversion and eliminating the need for in-school administration.

Adolescent↗

PubMed2006

Novel endovascular treatment of blunt thoracic aortic trauma with a self-expanding stent lined with aortic extender cuffs.

We report the successful treatment of blunt thoracic aortic trauma with a self-expanding stent lined with commercially available aortic extender cuffs. A 24 x 70 mm Wallstent was positioned distal to the left subclavian artery via a left femoral approach. The stent was then lined with three overlapping Gore Excluder aortic extender cuffs. Intravascular ultrasound was performed pre- and post-deployment. The aortic pseudoaneurysm was successfully excluded. The self-expanding stent facilitated placement of the extender cuffs and improved the contact between the multiple cuffs. This technique could still have utility in emergency settings when approved thoracic endografts are available for this indication.

Aneurysm, False↗

PubMed2007

Cost-effectiveness of extended prophylaxis with fondaparinux compared with low molecular weight heparin against venous thromboembolism in patients undergoing hip fracture surgery.

A model was developed to estimate costs and clinical effectiveness of fondaparinux compared with enoxaparin after hip fracture surgery in Sweden. Outcomes and costs of venous thromboembolism (VTE)-related care from a health care perspective were incorporated, with symptomatic deep-vein thrombosis and pulmonary embolism, recurrent VTE, post-thrombotic syndrome, major haemorrhage and all-cause death being included. Event probabilities were derived from fondaparinux clinical trial data and published data. VTE-related resource use and associated costs as well as costs of prophylaxis were based on local Swedish data. Extended prophylaxis with fondaparinux could avoid an additional 28 symptomatic VTE per 1,000 patients compared with extended prophylaxis with enoxaparin in hip fracture surgery patients. Although the prophylaxis costs were higher in the fondaparinux group, these were offset by the lower costs associated with treating fewer VTE, which thus indicates that extended fondaparinux prophylaxis is the dominant alternative when compared with enoxaparin in hip fracture surgery.

Aged↗

PubMed2005

The cognitive cost of extending an evolutionary mind into the environment.

Clark and Chalmers (1998) have argued that mental states can be extended outside an organism's skin. In response to some worries about the availability, reliability and portability of such extended resources, Clark (2005) offers a set of rough criteria that non-biological objects must fulfil to legitimately ground mental states. One such criterion is that the information retrieved from these non-biological sources be (more or less) automatically endorsed. But Sterelny (2003, 2005) has persuasively argued that the extended sphere is epistemologically opaque: a domain of contested truth and deliberate deception. As such, retrieving information from this domain requires the deployment of social guards for the information to remain reliable. But deploying such guards would seem to endanger endorsability by increasing cognitive load. Here I demonstrate that deploying social guards does not increase cognitive load if the guards are implemented in a highly distributed connectionist economy or off-loaded to the external environment.

Animals↗

PubMed2006

Cost-effectiveness of letrozole in the extended adjuvant treatment of women with early breast cancer.

Adjuvant tamoxifen therapy for 5 years reduces recurrence in hormone receptor positive, post-menopausal women with early breast cancer, but offers no advantage when prolonged to another 5 years, during which the risk of recurrence remains high. Treating patients, who remain disease-free after 5 years of tamoxifen, with letrozole significantly reduces recurrence, regardless of nodal status. This study evaluated the life-time cost-utility of extended adjuvant letrozole therapy in 62-year-old patients from a third-party payer perspective. A Markov model incorporated locoregional, contralateral, and metastatic recurrences. The comparator was placebo. Event rates were based on published trials. Utility values were taken from a clinical trial and published literature. Costs were obtained from published literature, provincial payment schedules, cancer agencies, and drug plans formularies. Resource use reflected Canadian treatment patterns. Robustness of the model was tested using deterministic and probabilistic sensitivity analyses. Extended adjuvant letrozole therapy of a cohort consisting of 50% node-negative and 50% node-positive patients prolonged their lives on average by 0.466 years or 0.267 quality-adjusted life years (QALYs) at an additional cost of Can$8,031 per patient, yielding an incremental cost-utility ratio (ICUR) of $34,058 per QALY. Letrozole was more cost-effective in node-positive than in node-negative patients (Can$26,553 vs Can$46,049 per QALY). Results were robust to variations in age, healthcare costs, and utilities. The degree of confidence that the cost per QALY would be below Can$50,000 reached 100% for node-positive and 77% for node-negative patients. Extended adjuvant letrozole is cost-effective in both node-negative and node-positive patients having ICURs below Can$50,000/QALY.

Antineoplastic Agents↗

PubMed2005

GENEHUNTER versus SimWalk2 in the context of an extended kindred and a qualitative trait locus.

GENEHUNTER and SimWalk2 are among the most commonly used software for parametric multipoint linkage analysis. In the context of extended kindred analysis, GENEHUNTER has a limitation in terms of the number of individuals it can handle. One solution is to manually split the kindred into smaller pedigrees. SimWalk2 can handle a much larger number of individuals. However, its major drawback is the time it takes to process the data when compared to GENEHUNTER. Aside from the limitations of each program, when studying extended kindreds researchers are typically confronted with missing data. In this work we used simulated genotype data based on the structure of a real extended pedigree in order to compare the results obtained through GENEHUNTER and SimWalk2, evaluate the effect of discarding individuals and splitting the kindred on the logarithm of odds (lod) score, and to assess how missing data affect the performance of each program. Our results show that (1) for pedigrees of a moderate size, GENEHUNTER and SimWalk2 produce nearly the same results; (2) when using GENEHUNTER, either splitting the kindred into smaller sub-pedigrees or discarding individuals has an adverse effect when compared to the results obtained when using SimWalk2 with the whole pedigree; and (3) the performance of both programs is qualitatively similar in the missing data scenario. These conclusions are based on the sample distributions of the lod score values and of the estimates of the recombination fraction.

Computer Simulation↗

PubMed2005

Advances in surgical management of malignancies of the cranial base: the extended transbasal approach.

The extended transbasal approach combines a bifrontal craniotomy with an orbital nasal and potentially a sphenoethmoidal osteotomy to provide excellent access to malignancies of the anterior, middle and posterior skull base. The approach enables the en bloc resection of tumors within the frontal lobes, orbits, paranasal sinuses and sphenoclival corridors without brain retraction and may obviate the need for transfacial access. We present our 7-year experience during which 29 patients underwent surgery with the extended transbasal exposure. In 25 patients the extended transbasal approach was used alone; in the remaining four it was combined with additional approaches. With exception of two patients, all lesions were removed en bloc. Reconstruction was accomplished with the use of pericranium and in some instances a temporalis muscle pedicle or a gracilis microvascular free flap. There were no mortalities associated with this approach. Seven patients experienced infections, four patients experienced cerebral spinal fluid (CSF) leakage, two patients who had received adjuvant radiation experienced scalp necrosis, three patients experienced pneumocephalus, and 29 patients experienced cranial neuropathies, the majority of which were loss of olfaction. The average follow-up for our patients was 34 months with a range of 2--62 months.

Adenoma↗

PubMed1990

Extended clinical safety profile of lovastatin.

Lovastatin has been available for prescription use in the United States for about 20 months (as of June 1989). Over 1 million patients have received the prescription drug, and approximately 14,000 patients have participated in clinical trials. It is estimated that 500,000 patients have received lovastatin continuously for at least 1 year. This report reviews the extended safety experience from all clinical trials and prescription use. At least 645 patients have received lovastatin for more than 3 years. There are new data from a recently completed 1 year, placebo-controlled trial in 8,245 patients (Expanded Clinical Evaluation of Lovastatin study) and 20 months of health professionals' reports on spontaneous adverse events associated with large prescription usage. Data from recent large clinical trials suggest that the risk of myopathy and asymptomatic sustained liver transaminase elevations is less than reported in prior studies. The early clinical trials enrolled very high risk patients receiving lovastatin at a usual dose of 80 mg/day and often receiving concomitant hypolipidemic agents including gemfibrozil and niacin. After more than 42 months' long-term clinical trial experience, data have not established adverse effects from lovastatin on the human lens. Possible new types of rare drug-related adverse events observed with large prescription use include hypersensitivity reactions such as arthralgia, thrombocytopenia, symptomatic hepatitis and interaction with warfarin. No new, unique adverse-event profile has emerged with extended clinical use, including use in a few patients who have received therapy for more than 5 years. The lovastatin extended safety profile is that of a generally well-tolerated drug.

Cataract↗

PubMed1993

Once-daily, extended-release gemfibrozil in patients with dyslipidemia. The Lopid SR Work Group I.

This randomized, parallel-group, multicenter clinical trial compared a newly developed, once-daily, extended-release formulation of gemfibrozil (Lopid SR) and gemfibrozil twice daily (Lopid) in terms of lipid-regulating effects and toxicity. Patients were men and women with elevations of low-density lipoprotein cholesterol and low levels of high-density lipoprotein cholesterol. The trial consisted of a 1-week screening period, an 8-week diet baseline period (Step One Diet), and a 24-week double-blind treatment period (extended-release gemfibrozil 1,200 mg once daily vs gemfibrozil 600 mg twice daily). At the end of the trial, the 2 treatment groups showed comparable improvements in all primary lipid factors: mean percent changes in triglyceride, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol were -32, +10 and -10% for extended release (n = 325) and -36, +11 and -10% for twice daily (n = 330). The 90% confidence interval for the relative difference between the treatment means fell within the equivalence bounds of +/- 35% for all 3 factors, demonstrating equivalence of efficacy. Adverse events were reported at low rates and were similarly distributed in frequency and intensity between treatment groups; they were preponderantly mild or moderate, and gastrointestinal effects were the most frequent. The once-daily formulation of gemfibrozil may afford better control of dyslipidemia through improved compliance by patients who have this asymptomatic disease.

Adolescent↗

PubMed1992

Clinical experience with a once-daily, extended-release formulation of diltiazem in the treatment of hypertension.

Although calcium channel blockers were only recently approved for antihypertensive therapy, 10 years of data have demonstrated their beneficial effects. Among the available calcium channel blockers, diltiazem hydrochloride appears to have a highly favorable side-effect profile. A new, extended-release formulation of diltiazem has been developed for the treatment of essential hypertension. The safety and efficacy of various once-daily doses of this new formulation were assessed in two multicenter studies. The first study was a dose-ranging trial of 275 patients with mild-to-moderate hypertension. Patients were randomly assigned to once-daily diltiazem (120, 240, 360, or 480 mg) or placebo for a 4-week, double-blind treatment period. A patient subgroup underwent ambulatory blood pressure monitoring (ABPM) twice. Once-daily diltiazem (dose range, 240-480 mg) significantly lowered trough systolic and diastolic blood pressure in a clearly dose-related fashion. ABPM results demonstrated consistent decreases in systolic and diastolic blood pressure throughout the 24-hour dosing interval. Dosages greater than or equal to 240 mg/day provided trough drug blood levels within the therapeutic range (i.e., greater than or equal to 40 ng/mL). The second study was a forced-escalation trail of 115 patients with mild-to-moderate hypertension. Patients were randomized to treatment with either placebo or escalating dosages of diltiazem (180 mg/day for 2 weeks, 360 mg/day for 2 weeks, and then 540 mg/day for 2 weeks). Statistically significant (p less than 0.01) reductions in supine systolic and diastolic blood pressure were observed with the 360 mg/day and 540 mg/day dosages. Dose escalations resulted in incremental blood pressure reductions and an increase in the percentage of responders. There was a significant correlation between diltiazem peak and trough plasma concentrations and antihypertensive effects in both studies, supporting the 24-hour efficacy of this extended-release formulation. Diltiazem administered once daily was found to be safe and well tolerated by the patients in these studies; adverse events were generally mild, with an incidence similar to placebo. Results indicate that this new extended-release formulation of diltiazem, administered once daily in doses greater than 120 mg, effectively lowers systolic and diastolic blood pressure in patients with mild-to-moderate essential hypertension.

Adolescent↗