Novel use of the Bakri balloon to minimize empty pelvis syndrome following laparoscopic total pelvic exenteration.

AIM: Pelvic exenteration is the only surgical option for locally advanced pelvic malignancies infiltrating the surrounding organs. The resultant pelvic void after the procedure is responsible for a number of complications, collectively termed empty pelvis syndrome (EPS). We aim to show how EPS can be minimized by presenting a case series demonstrating the surgical technique of laparoscopic total pelvic exenteration with bilateral pelvic node dissection along with a novel use of the Bakri balloon. METHOD: This is a case series of three successive patients undergoing laparoscopic total pelvic exenteration for locally advanced primary, nonmetastatic rectal adenocarcinoma over a period of 1 month in a specialized colorectal unit at a tertiary cancer centre. The Bakri balloon was deployed in all three patients and retained for variable time intervals postoperatively. Features of EPS were prospectively documented. RESULTS: In the first patient, the Bakri balloon was completely deflated and removed on postoperative day (POD) 5. The patient developed subacute intestinal obstruction which resolved with conservative management by POD 12. In the second and third patients, the Bakri balloon was deflated in a sequential manner, beginning on POD 8, until it was finally removed on POD 11. Neither of these patients had any abdominal complaints. A postoperative CT scan of both these patients showed the small bowel loops clearly above the pelvic inlet. CONCLUSIONS: The Bakri balloon is a simple, safe and cost-effective method to reduce the complications of EPS following laparoscopic total pelvic exenteration. A prospective study is ongoing to objectively quantify the benefits of this technique.

Psychiatric comorbidity in new daily persistent headache: A cross-sectional study.

BACKGROUND: New daily persistent headache (NDPH) is a type of chronic daily headache. NDPH can have migrainous (NDPH-CM) or tension-type character (NDPH-CTTH). Recently, NDPH patients have shown to have associated anxiety and depression. We compared anxiety, depressive symptoms, somatization and pain catastrophization among NDPH, healthy controls and patients with chronic low-back pain and between NDPH-CM and NDPH-CTTH. METHODS: We assessed the study population for depressive symptoms by Patient Health Questionnaire-9, anxiety by Generalized Anxiety Disorder Scale - 7, somatoform disorder using DSM IV (TR) criteria and pain catastrophizing by using Pain Catastrophizing Scale. RESULTS: Fifty-five patients each with NDPH (mean age 28.24 ± 12.05 years, 45.5% females) and age/sex matched healthy individuals and patients with chronic low-back pain were enrolled. Among NDPH patients, somatoform disorder was seen in 32.7%, severe anxiety in 65.5%, severe depressive symptoms in 40%, significant pain catastrophization in 85.5%. NDPH patients had significantly higher frequency of all psychiatric co-morbidities as compared to healthy controls and patients with chronic low-back pain. NDPH-CM patients had significantly higher frequency of depression and pain catastrophizing behaviour as compared to NDPH-CTTH. CONCLUSION: Anxiety, depressive symptoms, somatization and pain catastrophizing were significantly more prevalent in NDPH when compared to healthy individuals and patients with chronic low back pain. Such effects should be sought for, as they might contribute to refractoriness to treatment. SIGNIFICANCE: Anxiety, depressive symptoms, somatization and pain catastrophizing were significantly more prevalent in new daily persistent headache when compared to healthy individuals and patients with chronic low back pain. Such effects should be sought for, as they might contribute to refractoriness to treatment.

Polymorphisms of IL-17 and ICAM-1 and their expression in Guillain-Barré syndrome.

PURPOSE: Guillain-Barré syndrome (GBS) is an acute inflammatory, autoimmune disorder of peripheral nervous system. Interleukin-17 (IL-17) and intercellular adhesion molecule-1 (ICAM-1) polymorphisms with higher expression levels have already been studied in many inflammatory and autoimmune diseases. However, the possible role of IL-17 and ICAM-1 polymorphisms in GBS remains unknown. Therefore, the current study investigated IL-17 (His161Arg and Glu126Gly) and ICAM-1 (Gly241Arg) polymorphisms. MATERIALS AND METHOD: In this study, total 80 GBS patients and 75 normal healthy controls were included. IL-17 (His161Arg and Glu126Gly) and ICAM-1 (Gly241Arg) polymorphisms were performed using polymerase chain reaction -restriction fragment length polymorphism analysis. Further, the expression of ICAM-1 and IL-17 was determined by reverse-transcriptase PCR and enzyme-linked immunosorbent assay. RESULTS: IL-17 (Glu126Gly) mutant and ICAM-1 (Gly241Arg) heterozygous genotypes were strongly associated with increased risk of GBS (p < 0.016; OR = 3.706, 95% CI = 1.28-10.67; p < 0.001; OR = 4.148, 95% CI = 2.119-8.119, respectively). IL-17 and ICAM-1 genes showed significantly higher expression in GBS when compared with healthy controls. CONCLUSION: IL-17 and ICAM-1 polymorphisms showed significant association with GBS and their enhanced expressions have possible role in GBS development. IL-17 and ICAM-1 polymorphisms could be genetic markers to GBS susceptibility.

Association of NOD1 and NOD2 polymorphisms with Guillain-Barré syndrome in Northern Indian population.

BACKGROUND: Nucleotide oligomerization domain (NOD) proteins are cytosolic pattern recognition receptors that respond to bacterial substrate and induce NF-κB activation in host. Association of NOD polymorphisms have been studied in many autoimmune disorders, however its role in Guillain-Barré syndrome (GBS) remains unknown. We have investigated NOD1 Glu266Lys and NOD2 (Arg702Trp and Gly908Arg) gene polymorphisms among patients with GBS. MATERIALS AND METHOD: Polymorphisms in NOD-1 (Glu266Lys) and NOD-2 (Arg702Trp and Gly908Arg) genes were studied using polymerase chain reaction-restriction fragment length polymorphism in 105 patients with GBS and 100 healthy controls. RESULTS: Homozygous genotype (Lys/Lys) of NOD1 was significantly associated with GBS (p=0.013); and its subtypes viz. acute motor axonal neuropathy (AMAN) and acute inflammatory demyelinating polyneuropathy (AIDP) (p=0.008 and p=0.024 respectively) than controls. In NOD2 (Arg702Trp and Gly908Arg) polymorphisms, only heterozygous genotype (Arg/Trp and Gly/Arg) showed significant association with GBS (p=0.001 and p=0.01 respectively); subtypes AMAN, acute motor-sensory axonal neuropathy (AMSAN) and AIDP showed association with heterozygote Arg702Trp (p=0.001; p=0.029 and p=0.001 respectively) whereas only AIDP was associated with heterozygote genotype Gly908Arg (p=0.003). CONCLUSION: NOD1 (Glu266Lys) and NOD2 (Arg702Trp and Gly908Arg) polymorphisms were associated with an increased susceptibility to GBS. These polymorphisms could be genetic marker to GBS susceptibility.

T1-weighted dynamic contrast-enhanced MR evaluation of different stages of neurocysticercosis and its relationship with serum MMP-9 expression.

BACKGROUND AND PURPOSE: Epileptogenesis in NCC is associated with perilesional inflammation and disruption in BBB. We quantified BBB in different stages of NCC by using DCE-MR imaging to look for the differences in perfusion indices and to correlate these indices with serum MMP-9 expression. MATERIALS AND METHODS: DCE-MR imaging along with conventional MR imaging was performed in 57 single cysticercous brain lesions to quantify the kep, K(trans), and ve around the lesions, which were in different stages of evolution. There were 6 lesions in the vesicular stage and 17 lesions each in the colloidal, granular-nodular, and calcified stages. Serum MMP-9 was quantified from all patients, whereas perfusion indices were quantified from all stages except for the vesicular stage. RESULTS: We observed significant differences among the 3 stages of NCC in serum MMP-9 expression as well as DCE-derived kep values. In addition, kep showed a strongly significant positive correlation with MMP-9 expression when modeled with the individual stage of the disease as well as with all stages when pooled together. Other DCE-derived hemodynamic and pharmacokinetic parameters showed inconsistent differences with each stage of the disease. The correlation of DCE-derived parameters with serum MMP-9 expression and edema volume also showed inconsistency with the stage of the disease. CONCLUSIONS: We conclude that kep correlates best with serum MMP-9 expression among the pharmacokinetic indices and most closely represents the degree of BBB breakdown, which is highest in the colloidal stage and lowest in the calcified stage. kep may be used as a noninvasive image biomarker of BBB breakdown in different stages of NCC.

Understanding epileptogenesis in calcified neurocysticercosis with perfusion MRI.

OBJECTIVES: Calcified cysticercus larva with perilesional abnormality is thought to be responsible for seizures in patients with neurocysticercosis (NCC). However, it is not well understood why some calcified cysts are associated with seizures even without perilesional abnormality. METHODS: The study group consists of 30 subjects from an ongoing survey for disease burden estimation of a swine farming community who had a single calcified lesion without any perilesional abnormality with or without presentation of seizures. Each group consisted of 15 patients with calcified cysts and was labeled as asymptomatic and symptomatic. We performed dynamic contrast-enhanced (DCE) MRI on all these subjects and determined serum matrix metalloproteinase-9 (MMP-9) levels and MMP-9 gene polymorphisms. RESULTS: DCE-MRI-derived rate transfer constant (k(ep)) and serum MMP-9 levels showed significant differences between symptomatic and asymptomatic subjects. We observed an increase in the MMP-9 levels, k(ep), and the volume transfer coefficient (k(trans)) in these lesions. We also observed a significant increase in MMP-9 (R279Q) gene polymorphism in symptomatic subjects compared with asymptomatic and control subjects. CONCLUSIONS: Perilesional inflammation, which varies from symptomatic to asymptomatic subjects, can be quantified using DCE-MRI in calcified cysticercosis and may help distinguish these 2 groups with similar imaging findings. The observed increase in k(ep) with serum MMP-9 levels suggests that the former may serve as a biomarker of MMP-9 levels in these subjects. The significant MMP-9 (R279Q) gene polymorphism in symptomatic subjects might explain the differences in the observed DCE-MRI indices between symptomatic and asymptomatic subjects.

Neuromyotonia masquerading as tetanus.

Neuromyotonia, or Isaac's syndrome, is a rare neuromuscular disorder of peripheral nerve hyperexcitability characterized by muscle stiffness, muscle hypertrophy, pseudomyotonia, myokymia and electromyographic evidence of myokymic or neuromyotonic discharges. A young boy with neuromyotonia is presented who was diagnosed with tetanus for severe muscle spasms, trismus and ophisthotonos. We discuss differentiation of neuromyotonia from tetanus and other disorders with similar features on clinical and electrophysiological examination.

Diffusion tensor MR imaging in children with pantothenate kinase-associated neurodegeneration with brain iron accumulation and their siblings.

BACKGROUND AND PURPOSE: It has been reported that iron concentration influences DTI metrics in deep gray matter nuclei. We hypothesized that increased FA in the deep gray nuclei may indicate abnormal iron accumulation in patients with PKAN and their siblings. MATERIALS AND METHODS: Seven patients with the characteristic "eye-of-the-tiger sign," their 5 siblings, and 5 age-matched controls were prospectively studied. One-way ANOVA with Bonferroni post hoc multiple comparisons was used to compare DTI metrics (FA and MD) among subject groups in the putamen, CN, GP, SN, and ALIC. In addition, hypointense and hyperintense regions of the eye-of-the-tiger sign were segmented, and their DTI metrics were compared. In the patient group, the values of DTI metrics in hypointense regions were also compared with those of the ALIC. RESULTS: A significant increase in FA values of the GP and SN from controls to the patient group to siblings was observed. In the GP, MD values were significantly higher in patients compared with controls and siblings. The patients showed significantly increased FA with decreased MD in hypointense compared with hyperintense regions of the eye-of-the-tiger sign. No difference in FA values were observed between the ALIC and hypointense regions of the eye-of-the-tiger sign in patients. CONCLUSIONS: High FA values in siblings of patients with PKAN suggest the presence of abnormal iron in deep gray matter nuclei, even in the absence of its demonstration on T2*-weighted GRE.

Delayed diagnosis of brain tumor in a patient with flexor spasms and spastic foot drop.

Flexor spasms are involuntary muscle contractions comprising dorsiflexion at the ankle and flexion at the knee and the hip, occurring as a result of nociceptive spinal release reflex. The presence of flexor spasms generally suggests a lesion in the spinal cord. Foot drop is usually seen with lesions of lumbosacral roots, peripheral nerves or muscles. We hereby present a patient with a rare combination of spastic foot drop and flexor spasms due to a brain tumor. The possible underlying pathophysiological mechanisms resulting in flexor spasms due to a cerebral lesion are briefly discussed.

Formation of 1D-nanowires and 2D nanophases in heteroepitaxy of Sb on high index Si(5 5 12) surface.

The surface topography of high index Si(5 5 12) presents a single-domain planar reconstruction that is composed of (225) and (337) regions with nanoscale widths and row like trenches and provides an unique template for the growth of nanostructures. In this study, Sb has been adsorbed on this Silicon surface to form various superstructural phases by steering the kinetic parameters and post growth annealing of the surface. Different pathways adopted have shown the formation of stabilized ordered superstructural phases corresponding to various coverages and substrate temperatures and are probed in-situ by complementary surface sensitive techniques such as Low Energy Electron Diffraction (LEED), Auger Electron Spectroscopy (AES), and Electron Energy Loss Spectroscopy (EELS). The growth of Sb at 300 degrees C substrate temperature and annealing the formed system to different temperatures upto 820 degrees C leads to the formation of low dimensional phases having anisotropicity along the (110) direction like atomic wires. The results also demonstrate the pathways in tailoring 1 D and 2D nanostructure formation, on this technologically and scientifically important interface.

Deficiency in beta(2)-microglobulin, but not CD1, accelerates spontaneous lupus skin disease while inhibiting nephritis in MRL-Fas(lpr) nice: an example of disease regulation at the organ level.

When mutations that inactivate molecules that function in the immune system have been crossed to murine lupus strains, the result has generally been a uniform up-regulation or down-regulation of autoimmune disease in the end organs. In the current work we report an interesting dissociation of target organ disease in beta(2)-microglobulin (beta(2)m)-deficient MRL-Fas(lpr) (MRL/lpr) mice: lupus skin lesions are accelerated, whereas nephritis is ameliorated. beta(2)m deficiency affects the expression of classical and nonclassical MHC molecules and thus prevents the normal development of CD8- as well as CD1-dependent NK1(+) T cells. To further define the mechanism by which beta(2)m deficiency accelerates skin disease, we studied CD1-deficient MRL/lpr mice. These mice do not have accelerated skin disease, excluding a CD1 or NK1(+) T cell-dependent mechanism of beta(2)m deficiency. The data indicate that the regulation of systemic disease is not solely governed by regulation of initial activation of autoreactive lymphocytes in secondary lymphoid tissue, as this is equally relevant to renal and skin diseases. Rather, regulation of autoimmunity can also occur at the target organ level, explaining the divergence of disease in skin and kidney in beta(2)m-deficient mice.

IL-12 is produced by antigen-presenting cells stimulated with soluble alphabeta TCR and restores impaired T(h)1 responses.

Contact sensitivity (CS) is a cutaneous T(h)1 response that is induced by skin painting with reactive hapten. In prior in vivo studies of CS, we showed that recombinant soluble alphabetaTCR (sTCR) acted non-specifically to protect CS-effector T cells from suppression, but no molecular mechanism was determined. In the current study, we employed an in vitro system to investigate the mechanism of how sTCR protect CS-effector T cells from suppression. Immune CS-effector cells and appropriate hapten-conjugated antigen-presenting cells (APC) were incubated together with down-regulatory culture supernatant produced by suppressive spleen cells from mice tolerized i.v. with specific hapten, which produced strong inhibition of IFN-gamma production by the CS-effector cells. Importantly, addition of two different sTCR, of unrelated specificity, reversed this down-regulation and thus restored IFN-gamma production. We found that the APC, and not the CS-effector T cells, were the locus of the sTCR-mediated protection and showed direct binding of sTCR to APC by flow cytometry. Further, addition of anti-IL-12 showed that sTCR protection was due to IL-12 induced by sTCR and released by the APC, and was confirmed by ELISA measurement of IL-12 induced in APC supernatants by sTCR incubation. These results indicated a possible new regulatory loop in which suppression was reversed by IL-12 derived from APC, following direct surface binding of sTCR, and enhanced by IFN-gamma production from the T(h)1 CS-effector cells.

A new paradigm of T cell allergy: requirement for the B-1 cell subset.

BACKGROUND: We have uncovered a role for B-1-B-cell-produced IgM antibody, in the initiation of contact sensitivity (CS) in mice. CS and delayed-type hypersensitivity (DTH) involve recruitment of T cells to the tissues, to be activated by antigen-presenting cells (APC), and then make cytokines. Little is known about low recruitment is initiated. In CS, soon after immunization, the unique B-1 cell subset, responsible for the formation of most IgM, is activated to produce antigen (Ag)-specific IgM for export to tissues. IgM forms complexes with challenge Ag, activating the classical complement (C) pathway, generating C5a, to activate endothelium directly, or indirectly via C5a receptors (R) on mast cells and platelets, that release vasoactive amines (serotonin) and cytokines (TNF-alpha). These act together to induce vasodilatation, vascular permeability and expression of endothelial adhesion molecules to promote optimal T cell recruitment. METHODS AND RESULTS: New findings that established this pathway include: (1) absent CS response in C-deficient, or C-inhibited mice; (2) local generation of C5a in CS tissue extracts; (3) absent CS in C5aR-/- mice; (4) decreased CS in B cell and B-1-cell-deficient mice, and (5) reconstitution of CS by transfer of B-1 cells, or hapten-specific IgM. CONCLUSION: These findings indicate that the B-1 subset producing Ag-specific IgM is required early in CS to activate C, to induce vasoactive mediators that initiate local T recruitment.

Aggregated immunoglobulin protects immune T cells from suppression: dependence on isotype, Fc portion, and macrophage FcgammaR.

We determined the regulatory properties of heat-aggregated immunoglobulins (HA-Ig) that possess many activities of immune complexes (IC), such as binding and activation of cells via immunoglobulin Fc gamma receptors (FcgammaR). HA-Ig protected contact sensitivity (CS) effector T cells from antigen-specific immunosuppression, while monomeric IgG were inactive. This anti-suppressive activity of HA-Ig was antigen non-specific, and depended on the species from which Ig was derived, i.e. mouse and rat HA-Ig were protective in mice, and of other species were inactive. The protecting activity of HA-Ig was confined to IgG2a and IgG3, and to a lesser degree to IgG1 isotypes, and resided in the Fc domain. Removal of phagocytic cells from the CS-immune target cells, or blocking with anti-FcgammaR mAb, abolished HA-Ig protection of CS-effector T cells from suppression. We suggest that HA-Ig multimers acted via Fc domains, in one of two ways: by binding to FcgammaR of macrophages to produce positive-acting cytokines, or by blocking FcgammaR on macrophages, to compete with suppressive factors that can also bind to FcgammaR. If HA-Ig protection of T cells is generalized, it is likely that IC in vivo may non-specifically overcome suppression of responses to antigen that normally are under the control of T suppressive cells, and thus may contribute to the development of autoimmunity.

Recombinant soluble alphabeta T cell receptors protect T cells from immune suppression: requirement for aggregated multimeric, disulfide-linked alphabeta heterodimers.

Recombinant soluble T cell receptors (sTCR) protected contact sensitivity (CS) effector T cells from down-regulation or immunosuppression. CS-protecting sTCR were released enzymatically from the surface of thymoma cells transfected with cDNAs encoding TCR-alpha and -beta extracellular domains that were expressed with a phosphatidylinositol linkage. sTCR affinity purified on anti-TCR-alpha and anti-TCR-beta mAb columns had identical CS-protective activity, as did sTCR from a CD4+ Th2 clone or from a CD8+ cytotoxic clone. Reduced sTCR alpha- and beta-chains had no CS-protective activity, but this was restored when the TCR chains were rejoined into disulfide-linked alphabeta heterodimers. sTCR CS protection was Ag nonspecific, MHC unrestricted, and not influenced by the relevant synthetic peptide specific for the TCR complexed with appropriate MHC. CS protection may have resided in the sTCR constant region. When heated at 62 degrees C for 30 min, sTCR formed a CS-protecting aggregate, with a molecular mass of 481 +/- 37 kDa, corresponding to an alphabeta TCR pentamer. HPLC gel filtration essentially confirmed the molecular mass at 516 kDa for the multimer, while the monomer, which was an alphabeta TCR heterodimer, had an expected molecular mass of approximately 104 kDa and no bioactivity. In summary, the pentameric sTCR may bind to and activate lymphoid cells, perhaps via constant domains, resulting in protection of CS effector T cells from down-regulation. The ability of sTCR to protect CS effector T cells from down-regulation/suppression, if generalized, could overcome immunosuppression accompanying infectious diseases, particularly AIDS, or in tumors.

Delayed-type hypersensitivity in mast cell-deficient mice: dependence on platelets for expression of contact sensitivity.

Previous studies of cutaneous T cell-mediated responses in mice have obtained pharmacologic, morphologic, and immunologic evidence pointing to a critical role for local mast cells in release of the vasoactive amine serotonin (5-HT) to mediate early, initiating events that are required for elicitation of these responses. However, the role of mast cells in initiating these T cell-mediated cutaneous responses has been questioned due to the presence of relatively intact delayed-type hypersensitivity responses, such as contact sensitivity (CS), in mast cell-deficient mice whose skin contains only 1 % normal mast cell numbers. The contribution of other potential local sources of 5-HT, such as circulating platelets, at the site of a delayed-type hypersensitivity or CS response in these mast cell-deficient strains, has not been investigated. Therefore, we studied the effect of systemic platelet depletion, produced with an anti-platelet Ab, on blood and tissue levels of 5-HT, and on in vivo T cell-mediated cutaneous sensitivity responses, in W/Wv and Sl/Sld mast cell-deficient mice. The results showed that: 1) platelet depletion severely reduced whole blood 5-HT; 2) tissue levels of 5-HT, in mast cell-deficient mice, depended in large part on the presence of circulating platelets, and 3) specific depletion of platelets markedly suppressed CS responses in both W/Wv and Sl/Sld mast cell-deficient mice, and only moderately reduced CS in normal +/+ congenic mast cell-sufficient controls, but did not decrease CS in beige mice, with platelet granules that are defective in storage of 5-HT. We concluded that platelets may provide 5-HT crucial for the initiation of cutaneous T cell-mediated immune responses, such as CS.