Expected and Unexpected Consequences of the Affordable Care Act: The Impact on Patients and Surgeons-Pro and Con Arguments.

The Patient Protection and Affordable Care Act (PPACA), called the Affordable Care Act (ACA) or "ObamaCare" for short, was enacted in 2010. The Public Policy and Advocacy Committee of the Society for Surgery of the Alimentary Tract (SSAT) hosted a debate with an expert panel to discuss the ACA and its impact on surgical care after the first year of patient enrollment. The purpose of this debate was to focus on the impact of ACA on the public and surgeons. At the core of the ACA are insurance industry reforms and expanded coverage, with a goal of improved clinical outcomes and reduced costs of care. We have observed supportive and opposing views on ACA. Nonetheless, we will witness major shifts in health care delivery as well as restructuring of our relationship with payers, institutions, and patients. With the rapidly changing health care landscape, surgeons will become key members of health systems and will likely need to lead transition from solo-practice to integrated care systems. The full effects of the ACA remain unrealized, but its implementation has begun to change the map of the American health care system and will surely impact the practice of surgery. Herein, we provide a synopsis of the "pro" and "con" arguments for the expected and unexpected consequences of the ACA on society and surgeons.

Pancreatoduodenectomy for Chronic Pancreatitis-Results of a Pain Relief and Quality of Life Survey 15 Years Following Operation.

BACKGROUND: Over the last 30 years, numerous developments in the management of chronic pancreatitis have occurred, leading to multiple surgical and non-surgical options. PATIENTS AND METHODS: All patients who underwent pancreatoduodenectomy for chronic pancreatitis from January 1976 to July 2013 were reviewed. Surviving patients were contacted for a follow-up questionnaire and Short Form (SF)-12 Quality of Life Survey administration. RESULTS: A total of 166 patients were identified (cohort 1:1976-1997(N = 105) and cohort 2:1998-2013(N = 61)). Prior to pancreatoduodenectomy, a higher proportion of patients in cohort 2 had undergone endoscopic stenting, 67 vs 10 % (p < 0.001) and/or celiac plexus block 15 and 5 % (p = 0.026). Median follow-up for all survey respondents was 15 years. On the SF-12, mean physical component score was 43.8 ± 11.8 and mental component score was 54.3 ± 7.9. Patients were significantly lower on the physical component score (p < 0.001) and significantly better on the mental component score (p = 0.001) than the general US population. Mean pain score out of 10 was significantly lower after surgery 1.6 ± 2.6 than before surgery 7.9 ± 3.5 (p < 0.001). Diabetes developed in 28 % of patients who were not diabetic prior to surgery. CONCLUSION: Although practice has changed so that patients have a longer time from presentation until surgery as less-invasive techniques are attempted, pancreatoduodenectomy appears to provide effective long-term pain relief and acceptable quality of life in appropriately selected patients with chronic pancreatitis and intractable pain.

Management of a delayed post-pancreatoduodenectomy haemorrhage using endovascular techniques.

BACKGROUND: A delayed post-pancreatoduodenectomy haemorrhage is associated with a significant increase in peri-operative mortality. Endovascular techniques are frequently used for a delayed haemorrhage. However, limited data exists on the short- and long-term outcomes of this approach. A retrospective review over a 10-year period at a quaternary-referral pancreatic centre was performed. METHODS: Between 2002-2012, 1430 pancreatoduodenectomies were performed, and 32 patients had a delayed haemorrhage (occurring >24 h post-operatively) managed by endovascular techniques. The clinicopathological variables related to a haemorrhage were investigated. RESULTS: A total of 42 endovascular procedures were performed at a median of 25 days, with the majority of delayed haemorrhages occurring after 7 days. There were four deaths (13%) with three occurring in patients with a grade C haemorrhage. Seven patients (22%) experienced rebleeding, and two patients developed hepatic abscesses. CONCLUSION: A delayed haemorrhage post-pancreaticoduodenectomy can be managed by endovascular techniques with acceptable morbidity and mortality. Rebleeding and hepatic abscesses may occur and can be managed non-operatively in most cases. The association of a delayed haemorrhage with a pancreatic fistula makes this a challenging clinical problem.

Laparoscopic pancreatoduodenectomy does not completely mitigate increased perioperative risks in elderly patients.

BACKGROUND: Elderly patients undergoing open pancreatoduodenectomy (OPD) are at increased risk for surgical morbidity and mortality. Whether totally laparoscopic pancreatoduodenectomy (TLPD) mitigates these risks has not been evaluated. METHODS: A retrospective review of outcomes in patients submitted to pancreatoduodenectomy during 2007-2014 was conducted (n = 860). Outcomes in elderly patients (aged ≥70 years) were compared with those in non-elderly patients with respect to risk-adjusted postoperative morbidity and mortality. Differences in outcomes between patients submitted to OPD and TLPD, respectively, were evaluated in the elderly subgroup. RESULTS: In elderly patients, the incidences of cardiac events (odds ratio [OR] 3.21, P < 0.001), respiratory events (OR 1.68, P = 0.04), delayed gastric emptying (DGE) (OR 1.73, P = 0.003), increased length of stay (LoS, 1 additional day) (P < 0.001), discharge disposition other than home (OR 8.14, P < 0.001) and blood transfusion (OR 1.48, P = 0.05) were greater than in non-elderly patients. Morbidity and mortality did not differ between the OPD and TLPD subgroups of elderly patients. In elderly patients, OPD was associated with increased DGE (OR 1.80, P = 0.03), LoS (1 additional day; P < 0.001) and blood transfusion (OR 2.89, P < 0.001) compared with TLPD. CONCLUSIONS: Elderly patients undergoing TLPD experience rates of mortality, morbidity and cardiorespiratory events similar to those in patients submitted to OPD. In elderly patients, TLPD offers benefits by decreasing DGE, LoS and blood transfusion requirements.

Clinical Risk Score to Predict Pancreatic Fistula after Pancreatoduodenectomy: Independent External Validation for Open and Laparoscopic Approaches.

BACKGROUND: A clinical risk score for pancreatic fistula (CRS-PF) was recently reported to predict postoperative pancreatic fistula (POPF) after pancreatoduodenectomy (PD). An independent external validation has not been performed. Our hypothesis was that CRS-PF predicts POPF after both laparoscopic and open PD. STUDY DESIGN: The CRS-PF was calculated from a retrospective review of patients undergoing PD from January 2007 to February 2014. Postoperative pancreatic fistula was graded using International Study Group of Pancreatic Fistula criteria. Grade B and C leaks were defined as clinically significant. Performance was measured based on sensitivity, specificity, positive and negative predictive value, accuracy, and R(2). RESULTS: There were 808 patients who met inclusion criteria; 539 (66.7%) had open and 269 (33.3%) had laparoscopic PD. The CRS-PF was high risk in 134 patients, intermediate in 492, low in 135, and negligible in 47. Postoperative pancreatic fistula occurred in 191 (23.6%) patients (grade A, 3.8%; B, 14.2%; and C, 5.6%), and it increased with risk category (R(2) = 0.935 all, 0.898 open, and 0.968 laparoscopic). High and intermediate risk categories were combined and classified as "test positive," and negligible and low risk categories were combined and classified "test negative," resulting in a CRS-PF with a sensitivity of 95% and a negative predictive value of 96% for predicting POPF. Contrary to previous studies, grade A POPF increased with increasing CRS-PF and POPF did not correlate with estimated blood loss (R(2) = 0.04). CONCLUSIONS: The CRS-PF was validated independently by predicting POPF for both laparoscopic and open PD. Predictive performance was at least as good for laparoscopic PD as for open PD. Lack of correlation with estimated blood loss suggests CRS-PF might be tailored for improved performance. The CRS-PF is a clinically useful tool for POPF risk stratification after PD and allows for targeted intra- and postoperative measures to address patients at increased risk.

Platelet-Derived Growth Factor Receptor-α Regulates Proliferation of Gastrointestinal Stromal Tumor Cells With Mutations in KIT by Stabilizing ETV1.

BACKGROUND & AIMS: In gastrointestinal muscles, v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog (KIT) is predominantly expressed by interstitial cells of Cajal (ICC) and platelet-derived growth factor receptor-α (PDGFRA) polypeptide is expressed by so-called fibroblast-like cells. KIT and PDGFRA have been reported to be coexpressed in ICC precursors and gastrointestinal stromal tumors (GISTs), which originate from the ICC lineage. PDGFRA signaling has been proposed to stimulate growth of GISTs that express mutant KIT, but the effects and mechanisms of selective blockade of PDGFRA are unclear. We investigated whether inhibiting PDGFRA could reduce proliferation of GIST cells with mutant KIT via effects on the KIT-dependent transcription factor ETV1. METHODS: We studied 53 gastric, small intestinal, rectal, or abdominal GISTs collected immediately after surgery or archived as fixed blocks at the Mayo Clinic and University of California, San Diego. In human GIST cells carrying imatinib-sensitive and imatinib-resistant mutations in KIT, PDGFRA was reduced by RNA interference (knockdown) or inhibited with crenolanib besylate (a selective inhibitor of PDGFRA and PDGFRB). Mouse ICC precursors were retrovirally transduced to overexpress wild-type Kit. Cell proliferation was analyzed by methyltetrazolium, 5-ethynyl-2'-deoxyuridine incorporation, and Ki-67 immunofluorescence assays; we also analyzed growth of xenograft tumors in mice. Gastric ICC and ICC precursors, and their PDGFRA(+) subsets, were analyzed by flow cytometry and immunohistochemistry in wild-type, Kit(+/copGFP), Pdgfra(+/eGFP), and NOD/ShiLtJ mice. Immunoblots were used to quantify protein expression and phosphorylation. RESULTS: KIT and PDGFRA were coexpressed in 3%-5% of mouse ICC, 35%-44% of ICC precursors, and most human GIST samples and cell lines. PDGFRA knockdown or inhibition with crenolanib efficiently reduced proliferation of imatinib-sensitive and imatinib-resistant KIT(+)ETV1(+)PDGFRA(+) GIST cells (50% maximal inhibitory concentration = 5-32 nM), but not of cells lacking KIT, ETV1, or PDGFRA (50% maximal inhibitory concentration >230 nM). Crenolanib inhibited phosphorylation of PDGFRA and PDGFRB, but not KIT. However, Kit overexpression sensitized mouse ICC precursors to crenolanib. ETV1 knockdown reduced KIT expression and GIST proliferation. Crenolanib down-regulated ETV1 by inhibiting extracellular-signal-regulated kinase (ERK)-dependent stabilization of ETV1 protein and also reduced expression of KIT and PDGFRA. CONCLUSIONS: In KIT-mutant GIST, inhibition of PDGFRA disrupts a KIT-ERK-ETV1-KIT signaling loop by inhibiting ERK activation. The PDGFRA inhibitor crenolanib might be used to treat patients with imatinib-resistant, KIT-mutant GIST.

FAM96A is a novel pro-apoptotic tumor suppressor in gastrointestinal stromal tumors.

The ability to escape apoptosis is a hallmark of cancer-initiating cells and a key factor of resistance to oncolytic therapy. Here, we identify FAM96A as a ubiquitous, evolutionarily conserved apoptosome-activating protein and investigate its potential pro-apoptotic tumor suppressor function in gastrointestinal stromal tumors (GISTs). Interaction between FAM96A and apoptotic peptidase activating factor 1 (APAF1) was identified in yeast two-hybrid screen and further studied by deletion mutants, glutathione-S-transferase pull-down, co-immunoprecipitation and immunofluorescence. Effects of FAM96A overexpression and knock-down on apoptosis sensitivity were examined in cancer cells and zebrafish embryos. Expression of FAM96A in GISTs and histogenetically related cells including interstitial cells of Cajal (ICCs), "fibroblast-like cells" (FLCs) and ICC stem cells (ICC-SCs) was investigated by Northern blotting, reverse transcription-polymerase chain reaction, immunohistochemistry and Western immunoblotting. Tumorigenicity of GIST cells and transformed murine ICC-SCs stably transduced to re-express FAM96A was studied by xeno- and allografting into immunocompromised mice. FAM96A was found to bind APAF1 and to enhance the induction of mitochondrial apoptosis. FAM96A protein or mRNA was dramatically reduced or lost in 106 of 108 GIST samples representing three independent patient cohorts. Whereas ICCs, ICC-SCs and FLCs, the presumed normal counterparts of GIST, were found to robustly express FAM96A protein and mRNA, FAM96A expression was much reduced in tumorigenic ICC-SCs. Re-expression of FAM96A in GIST cells and transformed ICC-SCs increased apoptosis sensitivity and diminished tumorigenicity. Our data suggest FAM96A is a novel pro-apoptotic tumor suppressor that is lost during GIST tumorigenesis.

Pancreaticoduodenectomy with major vascular resection: a comparison of laparoscopic versus open approaches.

BACKGROUND: Major vascular resection when necessary for margin control during pancreaticoduodenectomy is relatively universal with perioperative and oncological outcomes that are similar to those of patients undergoing a PD without venous involvement. The present study compares total laparoscopic pancreaticoduodenectomy (TLPD) versus open pancreaticoduodenectomy (OPD) with major vascular resection. METHODS: We reviewed data for all patients undergoing TLPD or OPD with vascular resection at Mayo Clinic Rochester, between the dates of July 2007 and July 2013. RESULTS: A total of 31 patients undergoing TLPD and 58 patients undergoing OPD with major vascular resection were identified. Mean operative blood loss was significantly less in the laparoscopic (842 cc) compared to the open group (1,452 cc) (p < 0.001), as was median hospital stay, 6 (4-118) versus 9 (6-73) days, respectively (p = 0.006). There was no significant difference in the total number of complications (lap 35%, open 48%) (p = 0.24) or severe complications (≥III) (lap 6.4%, open 3.4%) (p = 0.51) in the two groups. In-hospital mortality or 30-day mortality was not statistically different between the laparoscopic and open groups, 3.2 and 3.4%, respectively (p = 0.96). Patency of the reconstructed vessels on postoperative imaging was not significantly different between the TLPD (93%) and OPD groups (91%) (p = 0.76). In patients with a diagnosis of adenocarcinoma, there was no significant difference in overall survival between the two groups (p = 0.22). CONCLUSION: The present study clearly demonstrates that not only is TLPD with major vascular resection feasible and safe but that it can achieve results that are similar in morbidity and mortality as well as oncologic outcome compared to patients undergoing OPD with major vascular resection.

Identification and characterization of a novel promoter for the human ANO1 gene regulated by the transcription factor signal transducer and activator of transcription 6 (STAT6).

Anoctamin-1 (Ano1) is a widely expressed protein responsible for endogenous Ca(2+)-activated Cl(-) currents. Ano1 is overexpressed in cancer. Differential expression of transcriptional variants is also found in other diseases. However, the mechanisms underlying regulation of Ano1 are unknown. This study identifies the Ano1 promoter and defines a mechanism for regulating its expression. Next-generation RNA sequencing (RNA-seq) analysis in human gastric muscle found a new exon upstream of the reported exon 1 and identified a promoter proximal to this new exon. Reporter assays in human embryonic kidney 293 cells showed a 6.7 ± 2.1-fold increase in activity over empty vector. Treatment with a known regulator of Ano1 expression, IL-4, increased promoter activity by 1.6 ± 0.02-fold over untreated cells. The promoter region contained putative binding sites for multiple transcription factors including signal transducer and activator of transcription 6 (STAT6), a downstream effector of IL-4. Chromatin immunoprecipitation (ChIP) experiments on T84 cells, which endogenously express Ano1, showed a 2.1 ± 0.12-fold increase in binding of STAT6 to P0 after IL-4 treatment. These results were confirmed by mutagenesis, expression, and RNA interference techniques. This work allows deeper understanding of the regulation of Ano1 in physiology and as a potential therapeutic target in a variety of diseases.

Model to predict survival after surgical resection of intrahepatic cholangiocarcinoma: the Mayo Clinic experience.

BACKGROUND: The 7th edition of the American Joint Committee on Cancer (AJCC) staging system has recently been validated and shown to predict survival in patients with intrahepatic cholangiocarcinoma (ICC). The present study attempted to investigate the validity of these findings. METHODS: A single-centre, retrospective cohort study was conducted. Histopathological restaging of disease subsequent to primary surgical resection was carried out in all consecutive ICC patients. Overall survival was compared using Kaplan-Meier estimates and log-rank tests. RESULTS: A total of 150 patients underwent surgery, 126 (84%) of whom met the present study's inclusion criteria. Of these 126 patients, 68 (54%) were female. The median length of follow-up was 4.5 years. The median patient age was 58 years (range: 24-79 years). Median body mass index was 27 kg/m(2) (range: 17-46 kg/m(2) ). Staging according to the AJCC 7th edition categorized 33 (26%) patients with stage I disease, 27 (21%) with stage II disease, five (4%) with stage III disease, and 61 (48%) with stage IVa disease. The AJCC 7th edition failed to accurately stratify survival in the current cohort; analysis revealed significantly worse survival in those with microvascular invasion, tumour size of >5 cm, grade 4 disease, multiple tumours and positive lymph nodes (P < 0.001). A negative resection margin was associated with improved survival (P < 0.001). CONCLUSIONS: The AJCC 7th edition did not accurately predict survival in patients with ICC. A multivariable model including tumour size and differentiation in addition to the criteria used in the AJCC 7th edition may offer a more accurate method of predicting survival in patients with ICC.

Total laparoscopic pancreaticoduodenectomy for pancreatic ductal adenocarcinoma: oncologic advantages over open approaches?

OBJECTIVE: To directly compare the oncologic outcomes of TLPD and OPD in the setting of pancreatic ductal adenocarcinoma. BACKGROUND: Total laparoscopic pancreaticoduodenectomy (TLPD) has been demonstrated to be feasible and may have several potential advantages over open pancreaticoduodenectomy (OPD), including lower blood loss and shorter hospital stay. Whether potential advantages could allow patients to recover in a timelier manner and pursue adjuvant treatment options remains to be answered. METHODS: We reviewed data for all patients undergoing TLPD (N = 108) or OPD (N = 214) for pancreatic ductal adenocarcinoma at our institution between January 2008 and July 2013. RESULTS: Neoadjuvant therapy, tumor size, node positivity, and margin-positive resection were not significantly different between the 2 groups. Median length of hospital stay was significantly longer in the OPD group (9 days; range, 5-73 days) than in the TLPD group (6 days; range, 4-118 days; P < 0.001). There was a significantly higher proportion of patients in the OPD group (12%) who had a delay of greater than 90 days or who did not receive adjuvant chemotherapy at all compared with that in the TLPD group (5%; P = 0.04). There was no significant difference in overall survival between the 2 groups (P = 0.22). A significantly longer progression-free survival was seen in the TLPD group than in the OPD group (P = 0.03). CONCLUSIONS: TLPD is not only feasible in the setting of pancreatic ductal adenocarcinoma but also has advantages such as shorter hospital stay and faster recovery, allowing patients to recover in a timelier manner and pursue adjuvant treatment options. This study also demonstrated a longer progression-free survival in patients undergoing TLPD than those undergoing OPD.

Workforce shortage for general surgeons: results from the Society for Surgery of the Alimentary Track (SSAT) surgeon shortage survey.

BACKGROUND: Population shifts among surgeons and the general populous will contribute to a predicted general surgeon shortage by 2020. The Public Policy and Advocacy Committee of the Society for Surgery of the Alimentary Tract designed and conducted a survey to assess perceptions and possible solutions from important stakeholders: practicing surgeons of the society, general surgery residents, and medical students. RESULTS: Responses from 1,208 participants: 658 practicing surgeons, 183 general surgery residents, and 367 medical students, were analyzed. There was a strong perception of a current and future surgeon shortage. The majority of surgeons (59.3 %) and residents (64.5 %) perceived a current general surgeon shortage, while 28.6 % of medical students responded the same. When asked of a perceived general surgery shortage in 20 years, 82.4, 81.4, and 51 % said "yes", respectively. There were generational differences in responses to contributors and solutions for the impending shortage. Surgeons placed a high value on improving reimbursement, tort reform, and surgeon burnout, while residents held a strong interest in a national loan forgiveness program and improving lifestyle barriers. CONCLUSION: Our survey offers insight into possible solutions to ward off a surgeon shortage that should be addressed with programmatic changes in residency training and by reform of the national health care system.

Will there be a good general surgeon when you need one? (Part II) Solutions and taking back general surgery.

INTRODUCTION: Multiple reports have cited the looming shortage of physicians over the next decades related to increasing demand, an aging of the population, and a stagnant level in the production of new physicians. General surgery shares in this problem, and the specialty is "stressed" by a declining workforce related to increasing specialization that leaves gaps in emergency, trauma, and rural surgical care. SUMMARY: The Society of Surgery of the Alimentary Tract (SSAT) Public Policy and Advocacy Committee sponsored panel discussions regarding the general surgery workforce shortage at the Digestive Disease Week 2012 and 2013 meetings. The 2012 panel focused on defining the problem. This is the summation of the series with the solutions to the general surgery workforce shortage as offered by the 2013 panel.

STARTING A LAPAROSCOPIC SURGERY PROGRAMME IN THE SECOND LARGEST TEACHING HOSPITAL IN GHANA.

BACKGROUND: Komfo Anokye Teaching Hospital (KATH) is the second largest hospital in Ghana. Two years have elapsed after performance of the first laparoscopic cholecystectomy. OBJECTIVES: To examine our experience and lessons learned. DESIGN: Retrospective review. SETTING: Komfo Anokye Teaching Hospital (KATH). SUBJECTS: We reviewed leadership support, the role of a surgeon champion, training of physician and OR staff, influence of surgeons from outside Ghana and equipment status. The results of laparoscopic cholecystectomies performed from 2010-2012 were compared with information available from open cholecystectomies over the same period. RESULTS: Evidence of leadership support included equipment purchase and invitation of outside experts yearly from 2008. A KATH surgeon champion was identified in 2010. A dedicated OR team received training and exhibited excellent ownership of equipment preparation. Since 2010, 25 laparoscopic cholecystectomies have been performed, 17 independently by a single surgeon. Average operative time was 1.41 hours and length of stay (LOS) 1.5 days. Conversion rate was 4.0% (1/25). Complication rate was 20.0% (5/25), none involving haemorrhage or injuries to bile ducts or bowel. Median patient satisfaction score was 5 on a scale of 1-5 where 5 is most satisfied. Complication rates and hospital stay were lower than for open cholecystectomy (20.0% vs 34.5%, p > 0.05 and 1.5 days vs 6.6 days, p < 0.001 respectively). Operative times were on average 27 min onger for laparoscopic cholecystectomy (p < 0.01). CONCLUSION: Laparoscopic cholecystectomy at KATH has become a reality with less complications rates, shorter LOS, and trends towards improved patient satisfaction. Expanding laparoscopic surgery in Ghana requires its inclusion into residency training programmes and public education about its benefits for both patients and physicians.

Single-port and four-port laparoscopic cholecystectomy: difference in outcomes.

AIM: Patients prefer minimally invasive procedures with fast recovery, minimal pain and good cosmesis. Single-port cholecystectomy may decrease the need for narcotic pain medication and thus shorten recovery. Outcome-based evidence for this procedure is still being assembled. METHODS: Single-port cholecystectomy patients were matched based on age and gender with control patients undergoing four-port cholecystectomy during the same time. The primary endpoint was in hospital use of narcotic pain medication, measured by morphine equivalents. Secondary endpoints were operative time and length of stay. Statistical analysis was done by Student's t-test. RESULTS: Fifty patients (36 women, 14 men) underwent single port cholecystectomy between 11/2009-7/2012 and 50 patients underwent traditional cholecystectomy during the same time period. All patients were matched within 10 years of age. Morbidity was 4% for the single port group, 0% for the traditional cholecystectomy. There were no conversions to open cholecystectomy. The single-port group required a median of 29.0 mg (range, 8.7-180 mg) morphine equivalents of pain medication and the control group required a median of 33.2 mg (range, 0-185.7 mg) morphine equivalents (P=0.04). Single port cholecystectomy operative times were longer (median, 85 vs. 77 minutes, P=0.03). CONCLUSION: In this small study, there is a statistically significant difference in narcotic use during the initial hospital stay was measured between the two groups. After the initial ten cases, the operative time for single-port cholecystectomy approximated the standard four-port cholecystectomy. Prospective randomized controlled trials are necessary to investigate differences in outcomes between the two approaches.

Linfoma primario del sistema nervioso central en un paciente con sida / Primary central nervous system lymphoma in patient with AIDS

Se presenta una caso clínico de linfoma primario del sistema nervioso central (LPSNC) en una paciente con infección por virus de la inmunodeficiencia humana (VIH) en estadio sida. En este caso particular se destaca la confirmación por histopatología mediante intervención neuroquirúrgica de una lesión ocupante de espacio (LOE), lo que permitió instalar tratamiento oncoespecífico y terapia antirretroviral, lográndose buena evolución clínica. El obejtivo de la presente comunicación es realizar una revisión y actualización bibliográfica del LPSNC en pacintes con VIH destacando principalmente el aporte de los métodos diagnósticos y terapéuticos.

Acute stress-induced increases in thalamic CRH mRNA are blocked by repeated stress exposure.

Corticotropin-releasing hormone (CRH) coordinates multiple aspects of the stress response. Recently, CRH mRNA has been identified in two regions of the thalamus: the posterior nuclear group (Po), and a region located at the interface of the central medial and ventral posteromedial nucleus (parvicellular part) (CM-VPMpc). Previous studies demonstrated that in both regions CRH mRNA increases following 1 h of restraint stress, suggesting involvement of thalamic CRH in processing somatosensory and visceral information related to stress. The current study was proposed to further understand the effects of repeated and acute restraint stress on levels of thalamic CRH mRNA. Adult male rats were assigned to one of four groups in a 2 (repeated stress, no repeated) x2 (acute, no acute) design. Brain sections were processed for CRH mRNA in situ hybridization. ANOVA revealed no main effects of acute or repeated stress in either thalamic region. However, significant interactions between acute and repeated stress for levels of CRH mRNA were found for both regions of the thalamus. Compared to the no stress condition, acute restraint significantly increased CRH mRNA in the Po (39%) and the CM-VPMpc (32%). Repeated restraint did not alter baseline CRH mRNA levels, but blocked the acute restraint-induced effects. Thus, while acute stress increases levels of thalamic CRH mRNA, repeated exposure to the same stressor is without effect and prevents the acute response. These findings add to data establishing a role for thalamic CRH in the stress response and suggest a mechanism that may underlie habituation to repeated stress exposure.

Maternal glucocorticoid hormone influences nerve growth factor expression in the developing rat brain.

Rat pups nursed from birth by mothers with increased plasma corticosterone show long-lasting biochemical and behavioral modifications. Here we have investigated nerve growth factor (NGF) concentrations in the basal forebrain, prefrontal cortex and hippocampus of both male and female offspring at 11 days of age. Maternal hypercorticosteronemia was achieved by giving corticosterone-enriched water (200 microg/ml) from delivery. There was a significant increase of NGF in the basal forebrain of both sexes and no changes in the prefrontal cortex. In the hippocampus, an increase in NGF was found in males. These results indicate that a moderate increase of corticosterone in the lactating mother modulates NGF in the developing rat. We propose that these effects contribute directly to the long-lasting behavioral and biochemical modifications in pups nursed by hypercorticosteronemic mothers.

Corticotropin-releasing hormone messenger RNA distribution and stress-induced activation in the thalamus.

Corticotropin-releasing hormone plays a critical role in mediating the stress response. Brain circuits hypothesized to mediate stress include the thalamus, which plays a pivotal role in distributing sensory information to cortical and subcortical structures. In situ hybridization revealed neurons containing corticotropin-releasing hormone messenger RNA in the posterior thalamic nuclear group and the central medial nucleus of the thalamus, which interfaces with the ventral posteromedial nucleus (parvicellular part). These regions are of interest because they process somatosensory and visceral information. In the first experiment, the effect of acute stress on thalamic corticotropin-releasing hormone messenger RNA levels was assessed. Rats restrained for 1 h and killed 1 h later were found to have increased corticotropin-releasing hormone messenger RNA in the posterior thalamic nuclear group. The time course of these changes was examined in a second experiment in which rats were killed immediately or 3 h after restraint. While no changes occurred in the thalamus immediately after restraint, 3 h after restraint, increases in corticotropin-releasing hormone messenger RNA occurred in both the posterior thalamic nuclear group and the central medial-ventral posteromedial nucleus (parvicellular part) of the thalamus. A different pattern of activation was observed in the paraventricular nucleus of the hypothalamus with increased corticotropin-releasing hormone messenger RNA immediately after restraint, but not 1 or 3 h later. In addition to the stress-induced changes, a prominent decrease in baseline thalamic corticotropin-releasing hormone messenger RNA was observed from 1000 to 1300 h. These results show that the thalamus contains corticotropin-releasing hormone messenger RNA that increases after restraint stress, indicating a role for thalamic corticotropin-releasing hormone systems in the stress response. Stress-induced changes in thalamic corticotropin-releasing hormone messenger RNA expression appears to be regulated differently than that in the paraventricular nucleus of the hypothalamus, and may be influenced by diurnal mechanisms.