Open label, prospective, randomized controlled trial of an endoscopic duodenal-jejunal bypass sleeve versus low calorie diet for pre-operative weight loss in bariatric surgery.

BACKGROUND: The duodenal-jejunal bypass sleeve (DJBS) has been shown to achieve a completely endoscopic duodenal exclusion without the need for stapling. This report is the first randomized controlled trial for weight loss. METHODS: In a 12-week, prospective, randomized study, subjects received either a low fat diet and the DJBS or a low fat diet control (no device). Twenty-five patients were implanted with the device and 14 received the control. The groups were demographically similar. Both groups received counseling at baseline only, which consisted of a low calorie diet, and exercise/behavior modification advice. No additional counseling occurred in either group. Measurements included starting and monthly body weight and serum blood tests. The device group also had a plain abdominal film post implant, a monthly KUB and a 4-week post explant EGD. RESULTS: Twenty device (80%) subjects maintained the DJBS without a significant adverse event for the 12-week duration. At 12 weeks, the mean excess weight loss was 22% and 5% for the device and control groups, respectively (p < 0.001). Five subjects (20%) were endoscopically explanted early secondary to upper GI (UGI) bleeding (n = 3), anchor migration (n = 1) and sleeve obstruction (n = 1). The UGI bleeding occurred at a mean of 13.8 days post implant. EGD was performed in each of these cases with no distinct bleeding source identified. No blood transfusion was required. The migration occurred on day 47 and manifested as abdominal pain. The subject with the sleeve obstruction presented with abdominal pain and vomiting on day 30. Eight subjects (40%) underwent the 4 week post explant EGD at which time mild degrees of residual duodenal inflammation was noted. CONCLUSION: The DJBS achieves noninvasive duodenal exclusion and short term weight loss efficacy. Longer term randomized controlled sham trials for weight loss and treatment of T2DM are underway.

Acute technical feasibility of an endoscopic duodenal-jejunal bypass sleeve in a porcine model: a potentially novel treatment for obesity and type 2 diabetes.

BACKGROUND: The concept of endoluminal therapy for various disease states has gained significant attention. This report describes the authors' initial animal experience with a novel endoscopic duodenal-jejunal bypass sleeve (DJBS) in a porcine model. The DJBS consists of an implant delivered endoscopically, anchored in the proximal duodenum, and extended into the jejunum. This device aims to mimic the intestinal bypass effects of Roux-en-y gastric bypass without the need for stapling or anastomosis and may offer novel therapeutic benefit for patients with obesity, type 2 diabetes, or both. METHODS: Five DJBS devices were delivered in five domestic, female Yorkshire pigs. The devices were delivered and retrieved the same day and left in situ for less than 1 h. The animals were kept alive for 4 days after explantation for evaluation of their general health after the procedure. After they were killed, gastric, duodenal, and jejunal tissues were examined and harvested for histologic assessment of any acute device or procedure-related effects. RESULTS: Delivery of the implant took an average of 18 min (range, 10-38 min) and required an average fluoroscopy time of 8.1 min (range, 3.8-16.6 min). Retrievals were performed in an average of 7.4 min (range, 5-9 min) using fluoroscopy for an average of 2.3 min (range, 1.3-4.5 min). Followed for 4 days after explantation, the animals were normal and healthy. There were no pathologic findings in the explanted tissue. CONCLUSIONS: The DJBS can be safely deployed and retrieved endoscopically. Future long-term survival studies are warranted to help define the role of promising technology.

Chronic in-vivo experience with an endoscopically delivered and retrieved duodenal-jejunal bypass sleeve in a porcine model.

BACKGROUND: The role of duodenal bypass as an underlying mechanism of action in gastric bypass surgery has received considerable attention. We report the initial feasibility study of a totally endoscopically delivered and retrieved duodenal-jejunal bypass sleeve in a chronic porcine model. METHODS: The implant consists of a 60-cm fluoropolymer sleeve that is endoscopically deployed via a coaxial catheter system into the jejunum and fixed in the proximal duodenum with a Nitinol anchor. The system creates a proximal biliopancreatic diversion. Six female Yorkshire pigs were endoscopically implanted; all survived. Four animals (group 1) were slated to survive 90 days, two animals (group 2) for 120 days, and three animals (group 3) underwent sham endoscopy and were survived 120 days. Animals were fed standard dry pig chow 0.5 kg three times daily. Data points included daily general health, weekly weight, serum blood tests (complete blood count, amylase, lipase, liver function tests), and monthly evaluation of anchor/sleeve position/patency by fluoroscopy and endoscopy. Following the in-vivo period, the devices were endoscopically removed and the animals were sacrificed. Duodenal and jejunal tissue samples were assessed histologically. RESULTS: All six test animals were implanted and explanted without significant adverse events. In group 1, the first animal had no device-related issues. The second animal had a pivoted anchor requiring repositioning at day 63. That animal had no further difficulties. The third animal had an incidental partial rotation of the anchor noted at the 90 day explantation. The fourth animal was incidentally implanted with a crossover of the anchor struts, which was endoscopically corrected on day 14. However, on day 20 the animal had persistent vomiting, and the device was explanted. Both group 2 animals survived 120 days. One animal had a partially rotated anchor but was asymptomatic. The average weight gain between test and sham groups was 0.23 kg/day and 0.42 kg/day, respectively (p = 0.01). CONCLUSIONS: A totally endoscopic and reversible bypass of the duodenum and proximal jejunum has been achieved for 90-120 days. Initial experience suggests patency of the sleeve and acceptable tissue response. Reduced weight gain in the test animals suggests device efficacy. Further investigation is warranted.

Outcome of laparoscopic splenectomy based on hematologic indication.

BACKGROUND: Laparoscopic splenectomy is the procedure of choice for elective splenectomy at the Cleveland Clinic Foundation. Although the literature clearly documents the technical feasibility and safety of laparoscopic splenectomy, little data exists concerning the results of this procedure based on the hematologic indication for splenectomy. We sought to examine the clinical experience with laparoscopic splenectomy in a single institution, with particular attention to morbidity and clinical outcomes based on hematologic disease process. METHODS: This study retrospectively reviewed a consecutive series of laparoscopic splenectomies performed for nontraumatic, splenic pathology at the Cleveland Clinic Foundation from August 1995 to January 2001. Patient demographics, operative indications, morbidity, mortality, and clinical outcome were evaluated. Hematologic diagnostic groups were compared using Fisher's exact tests and Wilcoxon rank-sum tests. RESULTS: A total of 147 laparoscopic splenectomies were performed. Seven patients (5%) required conversion to open splenectomy. Indications for splenectomy included idiopathic thrombocytopenic purpura (ITP) in 65 patients, hematologic malignancy in 43 patients, autoimmune hemolytic anemia (AIHA) in 9 patients, thrombotic thrombocytopenic purpura (TTP) in 9 patients, splenomegaly in 5 patients, splenic cyst in 4 patients, splenic abscess in 3 patients, hereditary spherocytosis in 2 patients, splenic artery aneurysm in 2 patients, Felty's syndrome in 1 patient, myelofibrosis in 1 patient, and other in 3 patients. Accessory spleens were identified in 20 patients (14%). Postoperative complications occurred in 23 (16%) patients. Patients with ITP had significantly shorter operation times (134 vs 163 min; p = 0.001), decreased estimated blood loss (126 vs 307 ml; p = 0.001), decreased length of hospital stay (2.8 vs 4.6 days; p < 0.001), and less chance of conversion (0 vs 7; p = 0.02) than patients with any other diagnosis. A mean follow-up period of 20 +/- 14 months showed an 85% rate of remission for ITP, 89% for TTP, and 89% for AIHA. Patients with malignant disease had significantly larger spleens (822 vs 313 g; p < 0.001), more estimated blood loss (380 vs 168 ml; p = 0.04), and longer operative times (170 vs 142 min; p = 0.009), as compared patients treated for benign disease. However, the length of hospital stay (4.3 vs 3.6 days; p = 0.06) and complication rates (19% vs 14%; p = 0.08) were not significantly different between the two groups. CONCLUSIONS: When performed for ITP, laparoscopic splenectomy resulted in shorter operations, minimal blood loss, earlier discharge, no conversions, and excellent remission rates, as compared with other hematologic indications. Despite larger spleens, more blood loss, and longer operations in patients with hematologic malignancies, morbidity and length of hospital stay still were similar to those associated with benign indications for laparoscopic splenectomy. In conclusion, laparoscopic splenectomy is safe and efficacious for a multitude of benign and malignant hematologic indications, and our data compares favorably to those for open series.

Planned totally extraperitoneal laparoscopic Spigelian hernia repair.

A Spigelian hernia is a congenital defect in the tranversus aponeurosis fascia. Traditionally, an open anterior hernioplasty was used to repair these defects. Recently, laparoscopic approaches have been described. This report describes the first application of the totally extraperitoneal laparoscopic approach to a planned repair of a Spigelian hernia. The patient was a 62-year-old white female with a reducible left lower quadrant anterior abdominal wall bulge consistent with a Spigelian hernia. At the time of surgery, we exposed the posterior rectus fascia and modified our extraperitoneal inguinal hernia technique by passing the balloon dissector in a more lateral orientation. This created a unilateral preperitoneal space with adequate room for dissection and mesh fixation. The Spigelian defect was easily identified. Its preperitoneal fat contents were reduced, and a 5-mm laparoscopic tacking device was used to secure a piece of prolene mesh. The patient was discharged home with no complications. Placement of the mesh in the preperitoneal space avoids direct interaction of the mesh prosthesis and the intraperitoneal viscera. In conclusion, we find that a laparoscopic totally extraperitoneal approach is technically feasible and advantageous when a Spigelian hernia is diagnosed preoperatively.

Laparoscopic lateral L4-L5 disc exposure.

BACKGROUND: The anterior laparoscopic approach requires precarious dissection around the iliac vessels to expose the L4-L5 level. Furthermore, a retroperitoneal endoscopic approach to the L4-L5 level requires a technically demanding dissection to access the L5-S1 disc space. A unique lateral laparoscopic approach to the L4-L5 disc space allows concurrent access to the L5-S1 space while avoiding major dissection around the iliac vessels. This article describes this novel lateral approach and reviews the initial clinical outcomes. METHODS: Between January 1999 and April 2000, five patients underwent laparoscopic lateral L4-L5 disc exposure at the Cleveland Clinic Foundation. All charts were reviewed retrospectively. Mean values +/- standard deviation were determined for patient demographics and operative characteristics. A standard five-port laparoscopic technique was used. The sigmoid colon was retracted medially with an endoloop. The retroperitoneum was entered and the ureter and left iliac artery were retracted medially, whereas the psoas was retracted laterally. Fluoroscopy delineated the L4-L5 disc space allowing discectomy and cage insertion. Postoperatively, subjective patient satisfaction was obtained and radiologic evidence of fusion was assessed. RESULTS: All five patients were males, with a mean age of 47.4 +/- 7 years and a body mass index of 30 +/- 6 kg/m2. Four patients had an L4-L5 and L5-S1 fusion and one patient had an L4-L5 and L3-L4 fusion. Mean operative time was 349 +/- 32 min, with a mean blood loss of 210 +/- 74 cc. There were no intraoperative complications and no conversions, and postoperatively all patients were started on a clear liquid diet on postoperative day 1. The mean length of stay was 3.4 +/- 0.9 days. Patients returned to work in a mean of 12 +/- 7 weeks. All patients had evidence of fusion on their radiologic follow-up. Four patients were pain free, whereas one patient required intermittent narcotics at 1-year follow-up. CONCLUSIONS: For multilevel fusions including the L4-L5 disc space, the lateral laparoscopic exposure is a safe and efficacious procedure allowing simultaneous access to multiple disc spaces while avoiding the sympathetic chain, ureter, and major vascular structures. The lateral approach affords excellent exposure for accurate deployment of the appropriate orthopedic hardware.

Cost-effectiveness of ambulatory laparoscopic cholecystectomy.

The merits of laparoscopic cholecystectomy include faster recovery, less postoperative pain, earlier return to work, and decreased cost. However, there are few economic data comparing laparoscopic cholecystectomy in an ambulatory versus overnight stay setting. In a 12-month period, 74 consecutive cholecystectomies were performed laparoscopically by one surgeon. The ambulatory group consisted of 36 patients who were discharged from the hospital the same day after a mean recovery time of 5 hours (range, 2.25-10.33). Of the remaining 38 patients, 19 were admitted after surgery on 23-hour observation status, and 19 were inpatients. The average hospital cost was significantly less in the ambulatory group than in the observation group, with an 11% mean reduction in cost per patient (P = 0.0061). No patient in either group was readmitted to the hospital within 30 days of surgery. Laparoscopic cholecystectomy can be performed safely in an outpatient setting. The cost savings of ambulatory care versus observation are clearly shown in this study.

Predictors of operative outcome in patients with human immunodeficiency virus infection and acquired immunodeficiency syndrome.

BACKGROUND: Plasma viral load has recently been associated with clinical outcome in patients with human immunodeficiency virus (HIV) infection and acquired immunodeficiency syndrome (AIDS). We hypothetized that, in addition to CD4 lymphocytes, plasma HIV-1 RNA counts are predictive of postoperative outcome. METHODS: HIV-infected and AIDS patients admitted to a major teaching hospital requiring invasive or surgical procedures were retrospectively analyzed for postoperative outcome. Preoperative and postoperative immune cell counts including plasma HIV-1 RNA counts were recorded. Chi-square analysis, Fisher's exact test, and multivariate regression were performed with statistical significance P

Ten-year experience with Mersilene-reinforced sternal wound closure.

BACKGROUND: We were interested in reviewing our experience with Mersilene-reinforced sternal wound closure to evaluate its overall morbidity and its impact on patient management. METHODS: We reviewed our experience with 1,039 patients undergoing median sternotomy with Mersilene-reinforced sternal wound closure over the past 10 years. Major wound complications, which were categorized into two groups, required in-hospital management and operative intervention. Group 1 had a sternal dehiscence alone. Group II had a major sternal infection or mediastinitis. RESULTS: The incidence of wound morbidity was 2.4% (n = 25). There were 6 (0.58%) sternal dehiscences (Group I) and 19 (1.8%) sternal wound infections (Group II). Patients taken to the operating room for repair of their sternal dehiscence or sternal infection were noted to have two completely intact sternal halves. CONCLUSIONS: While wound related morbidity with Mersilene tape closure is equivalent to the historical results of conventional wire closure, dehiscence occurs in a more controlled fashion with less bony destruction. The reduction in tissue damage associated with sternal wound dehiscence and sternal infection after Mersilene-reinforced sternal wound closure makes treatment of these potentially devastating complications easier and more efficient.

Use of three-dimensional microscopy with multiple oblique illumination in evaluating cytopathology preparations.

OBJECTIVE: To analyze whether the use of multiple oblique illumination (MOI), in contrast to axial illumination (AI), improves imagery in bright field microscopy. Specimens containing thick cell clusters, such as cervical Pap smears, are often misread because of out-of-focus cell clusters. We hypothesized that visualization of these specimens with MOI would enhance this information as compared with AI. STUDY DESIGN: Micrometer images and Pap smears were analyzed in focus, and 8 and 40 microns out of focus by MOI and AI. All fields were captured to a remote computer, histograms were constructed, and mean light intensity was calculated. Mathematical formulation was used to define the histogram distribution of the micrometer images. Statistical analysis was performed using one-way ANOVA and Newman-Keuls test. RESULTS: K(focus) was improved (P < .01) and at 20 and 40 microns out of focus, mean light intensities were greater (P < .003, P < .05, respectively) with MOI as compared to AI. CONCLUSION: MOI improves out-of-focus information by increasing light penetration through the specimen and enhancing contrast and resolution.

Efficacy of jejunogram after jejunostomy insertion.

The era of managed care has spawned a national debate over the allocation of health care resources. We hypothesized that routine postjejunostomy jejunogram rarely provides additional clinical information or changes patient management and, therefore, is unwarranted. We retrospectively reviewed the charts of 128 consecutive patients undergoing feeding jejunostomy tube insertion between January 1995 and December 1996. All patients had postinsertion jejunograms. Eighty-five (66%) of the jejunograms were performed after operative insertion of the jejunostomy, and 43 (33%) were performed after percutaneous reinsertion of a previously placed jejunostomy. Data extracted from the charts include age, sex, indication for jejunogram, length of time prior jejunostomy was in place at time of reinsertion, and results of jejunogram. There were no patients (0%) with misplaced jejunostomy or extravasation of dye, as noted on jejunogram. There were no management changes implemented as a result of jejunogram readings (P < <0.05). The use of routine jejunogram after operative insertion or reinsertion of a prior jejunostomy that has become dislodged or occluded does not alter patient management, incurs unnecessary costs, and, therefore, is unwarranted.

The value of routine posttracheostomy chest radiography.

OBJECTIVE: This study proposes to evaluate the efficacy of routine posttracheostomy chest radiography. DESIGN: A retrospective chart review provided the framework of this study. SETTING: The study took place at a university teaching hospital-level one trauma center. PATIENTS: The study included 293 patients undergoing elective tracheostomy between 1989 and 1993. MEASUREMENTS AND RESULTS: Data extracted from the charts included indication for tracheostomy, immediate preoperative and postoperative chest radiograph reports, management changes made secondarily to radiographic findings, including chest tube placement, institution of chest physiotherapy, and need for tracheal tube reposition. Complications were defined as findings not noted on the preoperative radiographs; these were pneumothorax, tube malposition, atelectasis, or clinical information resulting in management changes. All patients received postoperative chest radiographs in the trauma ICU. Statistical analysis of our data was carried out using the chi2 test. Patients with chest tubes in place at the time of surgery were the only group who were excluded so as not to confuse whether pneumothorax developed postoperatively. Of the initial 293 patients, 25 patients were excluded on the basis of having a chest tube. The remaining 268 charts were analyzed; 220 (82%) patients underwent tracheostomy for ventilator-dependent respiratory failure, 31 (12%) due to multiple facial fractures, 6 (2.1%) secondary to penetrating neck wounds, and 11 (4%) as a result of refractory vocal cord edema. One (0.3%) patient was found to have a postoperative 10% apical pneumothorax. Eight (2.4%) patients were found to have postoperative subsegmental atelectasis. There were no significant (p>0.05) management changes implemented as a result of these findings. No new infiltrates, effusions, or malpositioned tubes were noted. Deletion of routine posttracheostomy radiographs would save $52.39 per patient (cost) or $15,350 for 293 patients and $35,453 in total patient charges. CONCLUSIONS: Abnormalities revealed by routine chest radiography after tracheostomy did not appear to alter patient management frequently enough to warrant the costs. A randomized, prospective study should be performed to analyze the safety of abandoning this practice.

Effect of advance directives on the management of elderly critically ill patients.

OBJECTIVE: To evaluate the effects of advance directives on the management of elderly, critically ill patients. DESIGN: Retrospective chart review. SETTING: Teaching hospital medical/surgical, noncardiac intensive care unit (ICU). PATIENTS: The medical records of 401 patients, > or =65 yrs of age, admitted to the ICU between 1992 and 1995 were reviewed. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Advance directive statements included refusal of cardiopulmonary resuscitation (CPR), nutrition, intravenous medications, antibiotics, mechanical ventilation, and blood products. Nineteen (5%) patients had advance directives (study group). These patients were compared with 28 case-matched (age, Acute Physiology and Chronic Health Evaluation II score, and diagnosis) critically ill patients without advance directives (control group). We compared the following data: cost per day; number of surgical procedures; number of radiographic studies; number of central venous and pulmonary artery catheter insertions; number of complete blood counts, electrolytes, and cultures sent for laboratory testing; number of days in the ICU/hospital; and mortality rates. Statistical analysis was performed using the Student's t-test for independent means and the chi-square equation. For all observed parameters, quantitative and dichotomous differences between study and control groups were not statistically significant. Two patients received CPR, despite advance directive statements refusing this treatment. CONCLUSIONS: Few critically ill seniors have advance directives. As assessed by objectively documented information, the level of care delivered to elderly ICU patients is not affected by the presence or absence of advance directive statements. Medical personnel need to be aware of whether or not patients have advance directive statements, as unauthorized CPR was administered to 11% of the patients who died with advance directives.

A comparison of laparoscopic and open appendectomy.

BACKGROUND AND OBJECTIVES: To compare laparoscopic appendectomy with traditional open appendectomy. METHODS: Seventy-one patients requiring operative intervention for suspected acute appendicitis were prospectively compared. Thirty-seven patients underwent laparoscopic appendectomy, and 34 had open appendectomy through a right lower quadrant incision. Length of surgery, postoperative morbidity and length of postoperative stay (LOS) were recorded. Both groups were similar with regard to age, gender, height, weight, fever, leukocytosis, and incidence of normal vs. gangrenous or perforated appendix. RESULTS: Mean LOS was significantly shorter for patients with acute suppurative appendicitis who underwent laparoscopic appendectomy (2.5 days vs. 4.0 days, p < 0.01). Mean LOS was no different when patients classified as having gangrenous or perforated appendicitis were included in the analysis (3.7 days vs. 4.1 days, P = 0.11). The laparoscopy group had significantly longer surgery times (72 min vs. 58 min, p < 0.001). There was no significant difference in the incidence of postoperative morbidity. CONCLUSIONS: Laparoscopic appendectomy reduces LOS as compared with the traditional open technique in patients with acute suppurative appendicitis. The longer operative time for the laparoscopic approach in our study is likely related to the learning curve associated with the procedure and did not increase morbidity.

Interactions between outcomes and tumor response to preoperative cisplatin-sensitized radiotherapy in advanced head and neck cancer. Southern New Jersey Head and Neck Cancer Treatment Group.

BACKGROUND: Whether or not tumor response to chemotherapy-sensitized radiation therapy (CTRT) for head and neck cancer leads to an improved outcome is unknown. METHODS: Forty patients who received preoperative cisplatin plus simultaneous radiotherapy for operable stage III and IV head and neck cancer were reviewed retrospectively regarding clinical demographics, staging, and survival status. RESULTS: Twenty-one (57%) patients had a histologic complete response (HCR) and 16 (43%) had a partial (PR) (9) or clinical complete (7) response (CCR). Tumor response of N1 versus N2-3 nodal disease showed 6 (75%) HCR and 4 (25%). Five-year disease-free survival overall was 82% for HCR versus 38% for PR/CCR (P <0.05). Disease-specific 5-year survival was 100% for HCR versus 27% for PR/CCR (P <0.002). CONCLUSIONS: Histologic complete response to CTRT for head and neck cancer is associated with increased survival and encouraging disease-free status. Response to CTRT is inversely proportional to lymphatic tumor load.

Rat renal allograft tolerance is associated with local TGF-beta and absence of IL-2r expression within chimeric immunocytic foci.

Tolerance was induced in Lewis (LEW) rat renal allograft recipients of Brown Norway kidneys by multiple pretransplant donor-blood transfusions and prior limited cyclosporine A. Rat renal allograft tolerance was associated with the induction of systemic donor T cells (10%), an early phase of nonspecific suppressor-cell generation, followed by maturation of systemic antigen-specific suppressor cells, and renal cellular infiltrates that develop long-term in situ in the kidney graft model. It was hypothesized that these infiltrates represent chimeric immunocytic foci that are locally regulated via a TGF-beta-dependent mechanism. Both immunohistochemical staining and digital image analysis for cellular and extracellular TGF-beta, IL-2 receptor (CD25), and the BN Class I-MHC marker (OX-27) were performed. Control rejecting (REJ) kidneys did not demonstrate any differences with respect to levels of infiltrating immunocyte area vs long-term surviving (TOL) kidneys (3.9% vs 4.5%, P = .303). Immunostaining with the BN Class I MHC marker (OX-27) demonstrated high levels of chimerism within immunocyte foci of the tolerant grafts (OX-27 BN+immunocytes 49.0% +/- 5.1%). In situ cellular IL-2 receptor (CD25) expression was demonstrated in REJ kidney infiltrates but not within TOL immunocytic infiltrating foci, when measured as percent of total lymphocytes (REJ = 5.0% vs TOL = 0.4%, P = .031). Conversely, TGF-beta expression was significantly higher in immunocytes of TOL kidneys when measured as the number of DAB chromogen-staining pixels per total immunocyte area (TOL = .076 vs REJ = .047, P = .003). In conclusion, these results suggested that stable mixed immune chimerism (SMIC) plays an important role in DST-CyA-induced tolerance in situ. SMIC-induced tolerance may involve a local TGF-beta-dependent mechanism that is associated with in situ TGF-beta (+) and IL-2r (-) immunocytes.

Nimodipine enhances new learning after hippocampal damage.

Rats were trained to lever press and then were given either bilateral lesions of the hippocampus or control operations. Half of the rats in each group received oral nimodipine, a calcium entry blocker, while the remaining rats received vehicle, over a 14-day period that began the evening of surgery. The rats were studied on a DRL 20-s schedule of reinforcement (differential reinforcement of low rates of responding) that required them to withhold a response for at least 20 s after their last lever press in order to earn a reward. Rats with lesions that did not receive the drug performed poorly on the DRL 20-s schedule. In contrast, rats sustaining the same hippocampal lesions but given the drug showed scores that were virtually equivalent to those of the sham-operated control animals. Similar trends were observed when the rats were then tested on a DRL 40-s schedule of reinforcement. These findings suggest that nimodipine may attenuate the effects of acute, focal brain lesions on new learning of even difficult behavioral and cognitive tasks.