Richard A Perugini

University of Massachusetts Medical School, Worcester, MA, United States

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Publications (37)128.82 Total impact

  • Richard A Perugini, Samir Malkani
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    ABSTRACT: Roux-en-Y gastric bypass (RYGB) leads to remission of type 2 diabetes mellitus (T2DM) in a majority of patients. This is prompting investigation of RYGB, and other bariatric operations as interventional therapies for T2DM. The impact of RYGB is due to an increase in the release of gastrointestinal hormones in response to a meal [glucagon-like peptide, peptide YY, oxyntomodulin]. This effect involves the parasympathetic nervous system. These same hormones are responsible for an early increase in β-cell secretion of insulin, leading to early remission of T2DM following RYGB. Progressive weight loss leads to a later improvement in peripheral insulin sensitivity, which is required for later remissions, and is responsible for re-emergence of T2DM in individuals who regain weight in long-term follow-up. As the success of bariatric surgery has prompted the emergence of the concept that T2DM is reversible, we offer a theory to predict reversibility of diabetes after bariatric surgery that is based on baseline beta cell function. This review will improve the understanding of the physiology of bariatric surgery and its impact on T2DM, stimulate investigations into new avenues to treat T2DM, and allow better selection of nonobese individuals for interventional therapy of T2DM.
    Current opinion in endocrinology, diabetes, and obesity 04/2011; 18(2):119-28. · 3.77 Impact Factor
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    ABSTRACT: Obesity is a strong risk factor for resistance to insulin-mediated glucose disposal, a precursor of type 2 diabetes and other disorders. However, not all obese individuals are insulin resistant. We sought to identify the molecular pathways that might cause obesity-associated insulin resistance in humans by studying the morbidly obese who were insulin sensitive versus insulin resistant, thereby eliminating obesity as a variable. Combining gene expression profiling with computational approaches, we determined the global gene expression signatures of omental and subcutaneous adipose tissue samples obtained from similarly obese patients undergoing gastric bypass surgery. Gene sets related to chemokine activity and chemokine receptor binding were identified as most highly expressed in the omental tissue from insulin-resistant compared with insulin-sensitive subjects, independent of the body mass index. These upregulated genes included chemokines (C-C motif) ligand 2, 3, 4, and 18 and interleukin-8/(CC-X motif) ligand 8 and were not differentially expressed in the subcutaneous adipose tissues between the 2 groups of subjects. Insulin resistance, but not the body mass index, was associated with increased macrophage infiltration in the omental adipose tissue, as was adipocyte size, in these morbidly obese subjects. Our findings have demonstrated that inflammation of the omental adipose tissue is strongly associated with insulin resistance in human obesity even in subjects with similar body mass index values.
    Surgery for Obesity and Related Diseases 01/2011; 7(1):60-7. · 4.12 Impact Factor
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    ABSTRACT: Adipose tissue expands in response to excess caloric intake, but individuals prone to deposit visceral instead of subcutaneous adipose tissue have higher risk of metabolic disease. The role of angiogenesis in the expandability of human adipose tissue depots is unknown. The objective of this study was to measure angiogenesis in visceral and subcutaneous adipose tissue and to establish whether there is a relationship between obesity, metabolic status, and the angiogenic properties of these depots. Angiogenic capacity was determined by quantifying capillary branch formation from human adipose tissue explants embedded in Matrigel, and capillary density was assessed by immunohistochemistry. Subcutaneous adipose tissue had a greater angiogenic capacity than visceral tissue, even after normalization to its higher initial capillary density. Gene array analyses revealed significant differences in expression of angiogenic genes between depots, including an increased subcutaneous expression of angiopoietin-like protein 4, which is proangiogenic in an adipose tissue context. Subcutaneous capillary density and angiogenic capacity decreased with morbid obesity, and subcutaneous, but not visceral, adipose tissue angiogenic capacity correlated negatively with insulin sensitivity. These data imply that subcutaneous adipose tissue has a higher capacity to expand its capillary network than visceral tissue, but this capacity decreases with morbid obesity. The decrease correlates with insulin resistance, suggesting that impairment of subcutaneous adipose tissue angiogenesis may contribute to metabolic disease pathogenesis.
    Circulation 01/2011; 123(2):186-94. · 15.20 Impact Factor
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    ABSTRACT: Obesity is associated with a pathologic predominance of sympathetic over parasympathetic tone. With respect to the heart, this autonomic dysfunction presents as a decreased heart rate variability (HRV), which has been associated with increased cardiovascular morbidity. Gastric bypass (GB) reduces cardiovascular mortality, and, thus, could beneficially affect the HRV. We sought to identify the factors predictive of HRV in a severely obese population of undergoing GB at a university hospital in the United States. The data of all patients presenting for GB were included in a prospective database. The homeostatic model of assessment (HOMA) was used to calculate the insulin resistance and glucose disposition index. A 24-hour Holter monitor was used to assess the HRV. Measurements were repeated at 2 weeks and 6 months postoperatively. The correlations between variables were determined using linear mixed models. We studied 30 patients undergoing GB. All exhibited some degree of reduced HRV that improved postoperatively. The HOMA-insulin resistance inversely correlated with the HRV, and the HOMA-glucose disposition index directly correlated with the parameters of HRV in our longitudinal models. Weight, body mass index, excess body weight, gender, and age did not correlate with HRV. Improvements in HRV correlated with reductions in the average heart rate, underscoring a postoperative increase in relative vagal tone. HRV in the severely obese is better predicted by the degree of insulin resistance, than by the degree of obesity, age, or gender. GB led to an improvement in HRV, the magnitude of which correlated with the change in insulin resistance and glucose disposition index, but not with weight loss.
    Surgery for Obesity and Related Diseases 09/2009; 6(3):237-41. · 4.12 Impact Factor
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    ABSTRACT: The traditional therapy for perforated sigmoid diverticulitis with peritonitis is emergency colectomy usually with colostomy. We report laparoscopic exploration with peritoneal lavage as an alternative in seven patients who required emergency surgery for diverticulitis. Six patients presented with diffuse peritonitis and one with a failure of percutaneous therapy. All patients were explored laparoscopically and the peritoneal cavity was lavaged with saline in addition to receiving intravenous antibiotics. Patient demographics, clinical response, length of stay, and complications were recorded. Six patients had resolution of peritonitis resolved and patients were discharged from the hospital. One of these patients who developed a pelvic abscess required a percutaneous drainage postoperatively. This patient ultimately returned 3 months later with recurrent symptoms and underwent colectomy with primary anastomosis. One patient failed to improve initially and underwent colectomy with primary anastomosis on the same admission. Five patients subsequently had elective sigmoid resections, four laparoscopic and one open. Mean length of stay was 7.7 days. There was no mortality. We conclude that laparoscopic exploration and peritoneal lavage can be performed safely in patients with diffuse, purulent peritonitis. Using this approach, most patients with purulent peritonitis can avoid emergent laparotomy with the risk of colostomy, and the need for a second surgery.
    International Journal of Colorectal Disease 02/2009; 24(7):797-801. · 2.24 Impact Factor
  • Surgery for Obesity and Related Diseases 01/2009; 5(3):S16. · 4.12 Impact Factor
  • Journal of Surgical Research - J SURG RES. 01/2009; 151(2):239-239.
  • Surgery for Obesity and Related Diseases 01/2009; 5(3):S1. · 4.12 Impact Factor
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    ABSTRACT: The purpose of this study was to review the etiology and computed tomography (CT) findings of small-bowel obstruction (SBO) in patients who have undergone bariatric laparoscopic Roux-en-Y gastric bypass (LGBP) surgery. Prospectively entered data from a surgical database of 835 consecutive patients who underwent antecolic-antegastric LGBP for morbid obesity from June 1999 to April 2005 in a single institution were retrospectively reviewed. A total of 42 cases of bowel obstruction were observed in 41 patients. Surgical proof was available in 38 cases, and 4 cases had characteristic imaging features and/or clinical follow-up. Seventeen CT scans were reviewed to determine cause and level of obstruction, and this was correlated with surgical findings and clinical follow-up. Internal hernia was the most common (13 cases) and also the most frequently missed etiology of SBO on CT scans, with the diagnosis being made prospectively in only 2 of 6 cases, in which CT was done. Adhesions, ventral hernia, postoperative ileus, and jejunojejunal (JJ) anastomotic strictures, in that order, were the other commonly observed etiologies for SBO, with 11, 7, 5, and 4 cases, respectively. Some causes of SBO post-LGBP (JJ anastomotic stricture and postoperative ileus) developed relatively early, whereas others (internal hernia) tended to develop later or had a bimodal distribution (adhesions and ventral hernia). Fifteen (36%) of 42 cases had SBO at or near the level of jejunojejunostomy site; causes included internal hernia (5 cases), adhesions/kinking of small bowel (5 cases), JJ anastomotic stricture (4 cases), and JJ intussusception (1 case). The time interval between LGBP and development of SBO might provide a useful clinical clue to its etiology. The JJ level is an important location for SBO post-LGBP because of a variety of causes, and special attention must be paid to this site at imaging of post-LGBP patients.
    Journal of computer assisted tomography 01/2009; 33(3):369-75. · 1.38 Impact Factor
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    ABSTRACT: As the number of laparoscopic adjustable gastric bands (LAGBs) placed has increased, the number of patients requiring removal of the device has also increased. The data from our institution, a U.S. university medical center, were reviewed to determine the feasibility, patient characteristics, and early results of converting patients from LAGB to laparoscopic Roux-en-Y gastric bypass. A total of 350 patients underwent LAGB placement at our institution from 2001 to 2008. Of these, 26 required conversion to laparoscopic Roux-en-Y gastric bypass for the following reasons: slippage, poor weight loss, LAGB intolerance, esophageal dilation, infection, and gastric ischemia. All conversions were completed laparoscopically. The average operating time and length of stay was 160 minutes and 3 days, respectively. Three complications developed. The average interval to conversion was 29 months. The average follow-up after conversion was 18 months. The average percentage of excess body weight loss at conversion was 23%. At 12 months after conversion, the patients had achieved an average percentage of excess body weight loss of 56% from their pre-LAGB weight. The increasing popularity of the LAGB has led to a considerable number of revisions of the device. Our early experience has shown that converting patients from LAGB to laparoscopic Roux-en-Y gastric bypass is feasible and safe and can offer patients substantial additional weight loss.
    Surgery for Obesity and Related Diseases 12/2008; 5(4):439-43. · 4.12 Impact Factor
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    ABSTRACT: Storage of energy as triglyceride in large adipose-specific lipid droplets is a fundamental need in all mammals. Efficient sequestration of fat in adipocytes also prevents fatty acid overload in skeletal muscle and liver, which can impair insulin signaling. Here we report that the Cide domain-containing protein Cidea, previously thought to be a mitochondrial protein, colocalizes around lipid droplets with perilipin, a regulator of lipolysis. Cidea-GFP greatly enhances lipid droplet size when ectopically expressed in preadipocytes or COS cells. These results explain previous findings showing that depletion of Cidea with RNAi markedly elevates lipolysis in human adipocytes. Like perilipin, Cidea and the related lipid droplet protein Cidec/FSP27 are controlled by peroxisome proliferator-activated receptor gamma (PPARgamma). Treatment of lean or obese mice with the PPARgamma agonist rosiglitazone markedly up-regulates Cidea expression in white adipose tissue (WAT), increasing lipid deposition. Strikingly, in both omental and s.c. WAT from BMI-matched obese humans, expression of Cidea, Cidec/FSP27, and perilipin correlates positively with insulin sensitivity (HOMA-IR index). Thus, Cidea and other lipid droplet proteins define a novel, highly regulated pathway of triglyceride deposition in human WAT. The data support a model whereby failure of this pathway results in ectopic lipid accumulation, insulin resistance, and its associated comorbidities in humans.
    Proceedings of the National Academy of Sciences 07/2008; 105(22):7833-8. · 9.81 Impact Factor
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    ABSTRACT: Use of laparoscopy in penetrating trauma has been well established; however, its application in blunt trauma is evolving. The authors hypothesized that laparoscopy is safe and feasible as a diagnostic and therapeutic modality in both the patients with penetrating and blunt trauma. Trauma registry data and medical records of consecutive patients who underwent laparoscopy for abdominal trauma were reviewed. Over a 4-year period, 43 patients (18 blunt trauma / 25 penetrating trauma) underwent a diagnostic laparoscopy. Conversion to laparotomy occurred in 9 (50%) blunt trauma and 9 (36%) penetrating trauma patients. Diagnostic laparoscopy was negative in 33% of blunt trauma and 52% of penetrating trauma patients. Sensitivity/specificity of laparoscopy in patients with blunt and penetrating trauma was 92%/100% and 90%/100%, respectively. Overall, laparotomy was avoided in 25 (58%) patients. Use of laparoscopy in selected patients with blunt and penetrating abdominal trauma is safe, minimizes nontherapeutic laparotomies, and allows for minimal invasive management of selected intra-abdominal injuries.
    Surgical Innovation 04/2008; 15(1):26-31. · 1.54 Impact Factor
  • Journal of Surgical Research - J SURG RES. 01/2008; 144(2):305-305.
  • Richard A. Perugini, John Kelly, Donald Czerniach
    Surgery for Obesity and Related Diseases 01/2008; 4(3):290. · 4.12 Impact Factor
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    ABSTRACT: Obese individuals may have normal insulin-glucose homeostasis, insulin resistance, or diabetes mellitus. Whereas gastric bypass cures insulin resistance and diabetes mellitus, its effects on normal physiology have not been described. We studied insulin resistance and beta-cell function for patients undergoing gastric bypass. One hundred thirty-eight patients undergoing gastric bypass had fasting insulin and glucose levels drawn on days 0, 12, 40, 180, and 365. Thirty-one (22%) patients with diabetes mellitus were excluded from this analysis. Homeostatic model of assessment was used to estimate insulin resistance, insulin sensitivity, and beta-cell function. Based on this model, patients were categorized as high insulin resistance if their insulin resistance was >2.3. Body mass index did not correlate with insulin resistance. Forty-seven (34%) patients were categorized as high insulin resistance. Correction of insulin resistance for this group occurred by 12 days postoperatively. Sixty (43%) patients were categorized as low insulin resistance. They demonstrated an increase of beta-cell function by 12 days postoperatively, which returned to baseline by 6 months. At 1 year postoperatively, the low insulin resistance group had significantly higher beta-cell function per degree of insulin sensitivity. Adipose mass alone cannot explain insulin resistance. Severely obese individuals can be categorized by degree of insulin resistance, and the effect of gastric bypass depends upon this preoperative physiology.
    Journal of Gastrointestinal Surgery 10/2007; 11(9):1083-90. · 2.36 Impact Factor
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    ABSTRACT: Cultured adipocyte cell lines are a model system widely used to study adipose function, but they exhibit significant physiological differences compared with primary cells from adipose tissue. Here we report short interfering RNA-based methodology to selectively attenuate gene expression in mouse and human primary adipose tissues as a means of rapidly validating findings made in cultured adipocyte cell lines. The method is exemplified by depletion of the PTEN phosphatase in white adipose tissue (WAT) from mouse and humans, which increases Akt phosphorylation as expected. This technology is also shown to silence genes in mouse brown adipose tissue. Previous work revealed upregulation of the mitochondrial protein UCP1 in adipose cells from mice lacking the gene for the transcriptional corepressor RIP140, whereas in cultured adipocytes, loss of RIP140 has a little effect on UCP1 expression. Application of our method to deplete RIP140 in primary mouse WAT elicited markedly increased oxygen consumption and expression of UCP1 that exactly mimics the phenotype observed in RIP140-null mice. This ex-vivo method of gene silencing should be useful in rapid validation studies as well as in addressing the depot- and species-specific functions of genes in adipose biology.
    The Journal of Lipid Research 03/2007; 48(2):465-71. · 4.39 Impact Factor
  • Surgery for Obesity and Related Diseases 01/2007; 3(3):285. · 4.12 Impact Factor
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    ABSTRACT: Weight loss after bariatric surgery varies and depends on many factors, such as time elapsed since surgery, baseline weight, and co-morbidities. We analyzed weight data from 494 patients who underwent laparoscopic Roux-en-Y gastric bypass (RYGBP) by one surgeon at an academic institution between June 1999 and December 2004. Linear regression was used to identify factors in predicting % excess weight loss (%EWL) at 1 year. Mean patient age at time of surgery was 44 +/- 9.6 (SD), and the majority were female (83.8%). The baseline prevalence of co-morbidities included 24% for diabetes, 42% for hypertension, and 15% for hypercholesterolemia. Baseline BMI was 51.5 +/- 8.5 kg/m(2). Mean length of hospital stay was 3.8 +/- 4.6 days. Mortality rate was 0.6%. Follow-up weight data were available for 90% of patients at 6 months after RYGBP, 90% at 1 year, and 51% at 2 years. Mean %EWL at 1 year was 65 +/- 15.2%. The success rate (> or = 50 %EWL) at 1 year was 85%. Younger age and lower baseline weight predicted greater weight loss. Males lost more weight than females. Diabetes was associated with a lower %EWL. Depression did not significantly predict %EWL. The study demonstrated a 65 %EWL and 85% success rate at 1 year in our bariatric surgery program. Our finding that most pre-surgery co-morbidities and depression did not predict weight loss may have implications for pre-surgery screening.
    Obesity Surgery 09/2006; 16(9):1227-31. · 3.10 Impact Factor
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    ABSTRACT: Exaggerated activation of peritoneal immunity after major abdominal surgery activates peritoneal macrophages (PMs), which may lead to a relative local immunosuppression. Although laparoscopy (L) is known to elicit a smaller attenuation of peritoneal host defenses, compared with open (O) surgery, effects of the hand-assisted (HA) approach have not been investigated to date. Eighteen pigs underwent a transabdominal nephrectomy via O, HA, or L approach. PMs were harvested at 4, 12, and 24 hours through an intraperitoneal drain and stimulated in vitro with lipopolysaccharide. The production of interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-alpha) by the purified macrophage cultures was measured with the use of a standard enzyme-linked immunosorbent assay technique. Statistical comparison was performed by using analysis of variance and Student t test. In vitro lipopolysaccharide-induced IL-6 and TNF-alpha production by PMs increased over the 24-hour period in all 3 groups. Stimulated PMs harvested at 12 and 24 hours postoperatively secreted higher levels of IL-6 in the O group, compared with both the HA group (P = .02, P = .01) and L group (P = .04, P = .001). PMs harvested at 4, 12 and 24 hours postoperatively also produced more TNF-alpha in O group, compared with both the HA group (P = .03, P = .03, and P = .01) and L group (P = .01, P = .05 and P = .03). There was no significant difference between H and L groups in production of either cytokine. Abdominal surgery attenuates peritoneal host defenses regardless of the surgical approach employed. However, for the first time, we demonstrated that the HA approach, similar to laparoscopy, is superior to open surgery in the degree of PM activation. Overall, in addition to clinical benefits of minimal access, HA surgery may confer an immunologic advantage over laparotomy.
    Surgery 02/2006; 139(1):39-45. · 3.37 Impact Factor
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    ABSTRACT: Hand-assisted laparoscopic surgery (HALS) devices may be well suited to splenectomy in cases of splenomegaly. All cases of HALS for splenectomy between 1997 and 2001 were reviewed. Patient characteristics, operative details, and morbidity and mortality were analyzed. HALS for splenectomy was performed in 54 patients. A total of 39 patients with massive splenomegaly (MS) (>600 g) were identified. The average weight of the MS group was 1285 +/- 505 g. There was one (3%) conversion. Operative time was 159 +/- 65 min, estimated blood loss was 257 +/- 240 ml, and length of hospital stay was 5.4 +/- 2.9 days. Morbidity was limited to 13 patients (24%), and there were two postoperative mortalities (5.1%). HALS for splenectomy in the setting of splenomegaly is feasible and safe. For the surgeon considering a laparoscopic approach in the setting of splenomegaly, a hand-assisted technique is ideally suited for removal of the enlarged spleen.
    Surgical Endoscopy 09/2004; 18(9):1340-3. · 3.43 Impact Factor

Publication Stats

912 Citations
128.82 Total Impact Points

Institutions

  • 1999–2011
    • University of Massachusetts Medical School
      • • Program in Molecular Medicine
      • • Department of Surgery
      • • Division of Preventive and Behavioral Medicine
      Worcester, MA, United States
  • 2007–2009
    • University of Massachusetts Amherst
      Amherst Center, Massachusetts, United States