Laparoscopic versus open ventral hernia repair in the elderly: a propensity score-matched analysis.

BACKGROUND: Ventral hernia repair is common in the expanding aging population, but remains challenging due to their frequent comorbidities. The purpose of this study is to compare the surgical outcomes of open vs. laparoscopic ventral hernia repair in elderly patients. METHODS: Patients ≥ 65 years of age that underwent elective open or laparoscopic ventral hernia repair were identified from the American College of Surgeons National Surgical Quality Improvement Project (NSQIP) database. To reduce potential selection bias, propensity scores were created for the likelihood of undergoing laparoscopic surgery based on patients' demographics and comorbidities. Patients were matched based on the logit of the propensity scores. Thirty-day surgical outcomes were compared after matching using Chi-square test for categorical variables and the Wilcoxon Rank-Sum test for continuous variables. RESULTS: 35,079 (71.1%) and 14,270 (28.9%) patients underwent open and laparoscopic ventral hernia repairs, respectively. Laparoscopic surgery was associated with a lower overall morbidity (5.9% vs. 9.1%; p < 0.001) compared to open repair. The incidence of surgical site infections (1.1% vs. 3.5%; p < 0.001), post-operative infections (2.7% vs. 3.6%; p < 0.001), and reoperation (1.7% vs. 2.1%; p = 0.009) were all lower after laparoscopic repair. All other major surgical outcomes were either better with laparoscopy or comparable between both treatment groups except for operative time. CONCLUSION: Although open surgery remains the most prevalent in the elderly population, the results of this study suggest that laparoscopic surgery is safe and associated with a lower risk of overall morbidity, surgical site infections, and reoperation.

Fas-induced caspase denitrosylation.

Only a few intracellular S-nitrosylated proteins have been identified, and it is unknown if protein S-nitrosylation/denitrosylation is a component of signal transduction cascades. Caspase-3 zymogens were found to be S-nitrosylated on their catalytic-site cysteine in unstimulated human cell lines and denitrosylated upon activation of the Fas apoptotic pathway. Decreased caspase-3 S-nitrosylation was associated with an increase in intracellular caspase activity. Fas therefore activates caspase-3 not only by inducing the cleavage of the caspase zymogen to its active subunits, but also by stimulating the denitrosylation of its active-site thiol. Protein S-nitrosylation/denitrosylation can thus serve as a regulatory process in signal transduction pathways.

Integrating simulation into a surgical residency program: is voluntary participation effective?

OBJECTIVE: Surgical training programs nationwide are struggling with the integration of simulation training into their curriculum given the constraints of the 80-h work week. We examine the effectiveness of voluntary training in a simulation lab as part of the surgical curriculum. METHODS: The ProMIS simulator was introduced into the general surgery residency at Boston University Medical Center. All categorical residents (28) and non-categorical residents (23) were offered a 2-h training session and curriculum review. After the introductory session, time spent in the lab was encouraged, but voluntary. Use of the simulator was tracked for all residents. Participation in the simulation curriculum was defined as three or more uses of the simulator. After 3 months, all residents completed a survey regarding the simulation lab and their simulator usage. RESULTS: Twenty-six (93%) categorical residents and three (6%) non-categorical residents completed the introductory simulator training session. Over a 3 month period, use of the simulator at least once was 31% among all eligible residents; 80% of postgraduate year (PGY)1, 40% of PGY2, 60% of PGY3, and 0% of PGY4 and PGY5. Four residents (14%) participated in the simulation curriculum. Overall, 70% of simulator usage was during working hours, and 30% was completed post-call or when the resident was off duty. Most residents agreed that the simulator was easy to use and that its use improved their operative skills, but they did not think it was a good substitute for actual operative experience. Reported reasons for not using the simulator included off-site rotation (44%), no time (30%), and no interest (11%). CONCLUSIONS: Voluntary use of a surgical simulation lab leads to minimal participation in a training curriculum. Participation should be mandatory if it is to be an effective part of a residency curriculum.

Increased incidence of p53 mutations is associated with hepatic metastasis in colorectal neoplastic progression.

Within a panel of 15 colon carcinoma cell lines we have characterized the p53 gene status using immunocytochemistry (ICC), SSCP and direct sequence analysis. Extension of this analysis to the use of ICC on 104 colonic lesions, representative of different stages of colonic neoplastic progression, showed an absence of detectable p53 nuclear staining in preneoplastic polyp lesions (20 cases) with staining of 52% (25/48) of primary colon carcinomas and 81% (29/36) of hepatic metastases, suggestive of an increased incidence of p53 mutations in late stage lesions of colonic cancer. To address this issue more directly, we analysed 18 primary colon carcinomas and hepatic metastases excised coincidentally from the same patients. In ICC, p53 nuclear staining was recorded in matching lesions from eight individuals where direct sequencing revealed identical mutations in each case. In four individuals no ICC staining was detected in either lesion and molecular analysis revealed wild type sequence in exons 4-9. In six individuals p53 nuclear staining was observed in the hepatic metastases of patients but not the primary lesion. Molecular analysis revealed point mutation events in hepatic metastases from these patients which were not detected in the primary tumor. The point mutations identified in colon carcinomas were predominantly transition events (83%) located in previously characterized colon hotspot regions. These results demonstrate an increased incidence of p53 mutations associated with secondary lesions of colorectal tumors suggestive of a role for p53 in the establishment of colorectal hepatic metastases.

Anatomical demonstration of ocular segregation in the retinogeniculocortical pathway of the New World capuchin monkey (Cebus apella).

We describe the architecture of the dorsal lateral geniculate nucleus and primary visual cortex (striate cortex; area 17) of the New World capuchin monkey (Cebus apella) on the basis of the distribution of cell bodies and cytochrome oxidase histochemistry. Changes in staining for cytochrome oxidase following unilateral enucleation served to indicate the organization of the representation of the two eyes in the retinogeniculocortical pathway. The number and disposition of eye-specific layers within the lateral geniculate nucleus of Cebus are consistent with the common plan of geniculate organization in anthropoid primates, and the radial organization of area 17 fits the pattern common to New World squirrel and Old World macaque monkeys, including the presence of cytochrome-oxidase-rich zones in supragranular and deeper cortical layers (Horton: Philos. Trans. R. Soc. Lond. [Biol.] 304:199-253, '84). Our principal finding is that cytochrome oxidase histochemistry following unilateral eye removal unequivocally reveals ocular dominance columns in the striate cortex of Cebus. As in the macaque (Hubel: Nature 292:762-764, '82), ocular dominance columns extend through the thickness of cortex and blobs are centered on columns, but the array of columns viewed tangentially is less orderly or more mosaic than in the macaque, and there is apparently significant overlap between columns. The presence of well-defined ocular dominance columns in Cebus, as in Ateles (Florence, Conley, and Casagrande: J. Comp. Neurol. 243:234-248, '86) but not in other New World monkeys examined previously, emphasizes the phylogenetic lability of binocular segregation in the primate visual cortex. In addition, the present results indicate significant differences with respect to the tangential organization of the ocular dominance domain between primate species in which ocular dominance columns are present.

Modification of cysteine residues within G(o) and other neuronal proteins by exposure to nitric oxide.

Nitric oxide (NO), a free-radical gas produced endogenously by some neurons, functions as a diffusible intercellular messenger and appears to play a role in activity-dependent modification of synaptic efficacy in the mammalian CNS. The molecular targets and mechanisms of action of NO in neurons remain largely uncharacterized. Employing in vitro brain slices and isolated synaptosomes, we show here that exposure to exogenous or endogenously generated NO results in the modification of cysteine residues within neuronal proteins, as revealed by reduced binding of agents which react with cysteine sulfhydryls. In particular, exposure of synaptosomes to NO inhibits subsequent thiol-linked ADP-ribosylation of the heterotrimeric G-protein, G(o), by pertussis toxin. Our results demonstrate directly that NO may exert its neuronal effects through modification of protein cysteine thiols, and identify G(o) as a potential synaptic target of NO.

The tecto-olivo-cerebellar pathway in the rat.

The olivo-cerebellar projection to the vermis of cerebellar lobule VII, and the projection of the midbrain tectum onto the inferior olive (IO), were examined in the rat employing, respectively, retrograde and anterograde transport of horseradish peroxidase (HRP). Olivary neurons afferent to lobule VII vermis are located in a restricted region of the contralateral, caudomedial, medial accessory olive (MAO). The termination of the olivary projection demonstrated after HRP placement in the superior colliculus (SC), corresponds closely with this region.

5'-Nucleotidase of cerebellar molecular layer: reduction in Purkinje cell-deficient mutant mice.

The molecular layer of the cerebellar cortex contains high levels of the enzyme 5'-nucleotidase (EC 3.1.3.5), localized predominantly to Bergmann glia. In the present study, histochemical methods have been employed to examine the distribution of cerebellar 5'-nucleotidase in mice of two separate mutant strains in which Purkinje cells are eliminated selectively. In homozygous 'Purkinje cell degeneration' (pcd) and 'nervous' (nr) mice, molecular layer 5'-nucleotidase is greatly reduced and residual enzyme activity in colocalized with surviving Purkinje cells. These results suggest strongly that the expression of 5'-nucleotidase activity by Bergmann glia is under the inductive influence of their associated Purkinje cells.

Chemoarchitectonic zonation of the monkey cerebellum.

The modular organization of the monkey cerebellum is revealed in normal material by histochemical methods for demonstrating the presence of the enzymes acetylcholinesterase (AChE) and cytochrome oxidase (CO). In the cerebellar white matter, AChE- and CO-rich fibers are distributed in longitudinal compartments, which are aligned with AChE- and CO-rich bands in the granule cell layer, and with narrower AChE-rich strips in the molecular layer. The number and disposition of zones demonstrated histochemically are consistent with, and extend, the basic scheme of cerebellar zonation established by Voogd and Voogd and Bigaré.

The distribution of cholinesterase and cytochrome oxidase within the dorsal lateral geniculate nucleus of the squirrel monkey.

Within the dorsal lateral geniculate nucleus (dLGN) of the squirrel monkey, acetylcholinesterase (AChE) and cytochrome oxidase (CO) are distributed preferentially in the magnocellular layers. Butyrylcholinesterase (BuChE) activity is comparatively weak, but higher in the parvocellular than in the magnocellular layers. The different patterns of distribution of AChE within the dLGN in different primate species signify differences in geniculate organization, which may reflect adaptation to different visual habitats.

In vitro stimulation of ovarian tumour-associated lymphocytes with a peptide derived from HER2/neu induces cytotoxicity against autologous tumour.

The proto-oncogene HER2/neu encodes for a 185 kDa transmembrane protein with extensive homology to the epidermal growth factor (EGF) receptor. We have previously shown a correlation between HER2/neu expression and the level of in vitro cytotoxicity of tumour-associated lymphocytes (TAL) versus autologous tumour. In addition, we have recently demonstrated that tumour-associated cytotoxic T-lymphocytes (CTL) from ovarian and breast cancer patients can recognize a HER2/neu derived peptide epitope when presented in the context of HLA-A2. Since repeated tumour stimulation of CTL enhances both proliferation and cytotoxicity against autologous tumour, we hypothesized that repeated peptide antigen stimulation would have a similar effect. To be therapeutically useful, the peptide antigen must meet the following conditions: (1) the peptide must be immunogenic and cause a proliferation of CTL to adequate therapeutic numbers, and (2) the peptide-specific CTL which are generated must be cytotoxic against autologous tumour. To test our hypothesis, T-lymphocytes isolated from the ascites of four consecutive HER2/neu+ ovarian cancer patients were initially stimulated with solid phase anti-CD3 antibody and divided into three groups: (1) treatment with recombinant interleukin-2 (IL-2) alone, (2) IL-2 plus weekly stimulation with irradiated autologous tumour cells, and (3) IL-2 plus weekly stimulation with a HER2/neu derived peptide. Peptide-stimulated and tumour-stimulated CTL showed similar increases in proliferation with both groups consistently reaching therapeutic numbers. Peptide-stimulated CTL demonstrated significantly enhanced cytotoxicity against autologous tumour in 4-h chromium release assays as compared to the IL-2 alone group.(ABSTRACT TRUNCATED AT 250 WORDS)

A retinal whole-mount method useful in detecting retrogradely-labeled ganglion cells.

The present report describes a simple retinal whole-mount method that is compatible with horseradish peroxidase histochemistry. The retina is removed unfixed, flattened and fixed. Histochemical procedures are carried out with the retina free-floating, prior to affixing it to the slide with formaldehyde vapor. The method consistently yields whole-mounts free of pigment epithelium and firmly affixed to the slide, with good preservation of retinal morphology and surface topography.

Relation of depot-specific adipose inflammation to insulin resistance in human obesity.

BACKGROUND: A low-grade state of adipose tissue inflammation associated with obesity has been linked to mechanisms of systemic metabolic dysfunction. However, the relation of clinical phenotypes to depot-specific inflammation has not been well examined in human obesity. OBJECTIVE: To characterize the inflammatory status of subcutaneous and visceral fat depots, as assessed by tissue presence of macrophage crown-like structures (CLS) as a hallmark of chronic inflammation, and determine the relation of systemic insulin resistance to inflammatory abnormalities in subcutaneous and visceral fat. METHODS: We collected adipose tissue simultaneously from subcutaneous and visceral (omental and mesenteric) depots in 92 obese participants (age 42±11 years; BMI30 kg m(-2)) during planned bariatric surgery. Using immunohistochemistry, we categorized individuals as CLS(+) or CLS(-) based on the presence or absence, respectively, of macrophage CLS in subcutaneous (CLSs), omental (CLSo) and mesenteric (CLSm) adipose depots. RESULTS: The majority of participants exhibited adipose tissue inflammation manifest by the presence of CLS (CLS(+)) in both subcutaneous and intra-abdominal visceral depots. CLS status in subcutaneous fat was highly sensitive and modestly specific for inflammation of visceral fat. In multivariable models, plasma insulin and homeostatis model assessment levels were positively associated with CLS(+) status in all depots independent of age, waist circumference, BMI and type 2 diabetes, and worsened with the increasing number of adipose regions involved. CONCLUSIONS: In severely obese participants, systemic insulin resistance is linked to adipose inflammation in both subcutaneous and visceral depots. The findings suggest that examination of subcutaneous regions that are more easily accessible by transcutaneous biopsy may prove useful in clinical studies designed to investigate adipose phenotypes in relation to human disease.

Multiple-unit activity evoked in dorsal cap of inferior olive of the rabbit by visual stimulation.

1. Microelectrode recordings of multiple-unit activity were made from the dorsal cap of the inferior olive of anesthetized and unanesthetized rabbits during vestibular and optokinetic stimulation. 2. A large field potential could be evoked in the dorsal cap by photic stimulation of the contralateral eye when the rabbit was anesthetized with sodium pentobarbital or chloralose-urethan. This field potential could not be evoked in rabbits that were anesthetized with halothane or in unanesthetized rabbits. 3. Dorsal cap neurons were maximally excited by large, contrast-rich stimuli presented to the contralateral eye, moving in the posterior-anterior direction at a velocity of 1--2 degrees/s. The discharge rate of dorsal cap neurons was decreased by stimuli moving in the opposite direction. 4. The activity of dorsal cap neurons was not modulated by vestibular stimulation when visual inputs were excluded. 5. Dorsal cap neurons were sensitive to retinal slip velocity and higher derivatives of optokinetic stimulation. Their activity was related to eye movements only when the eye movements affected movement of optokinetic images on the retina.