Tube Feed Necrosis after Major Gastrointestinal Oncologic Surgery: Institutional Lessons and a Review of the Literature.

BACKGROUND: Small bowel necrosis after enteral feeding through a jejunostomy tube (tube feed necrosis, TFN) is a rare, serious complication of major abdominal surgery. However, strategies to reduce the incidence and morbidity of TFN are not well established. Here, in the largest series of TFN presented to date, we report our institutional experience and a comprehensive review of the literature. METHODS: Eight patients who experienced TFN from 2000 to 2014 after major abdominal surgery for oncologic indications at the University of Cincinnati were reviewed. Characteristics of post-operative courses and outcomes were reviewed prior to and after a change in tube-feeding protocol. The existing literature addressing TFN over the last three decades was also reviewed. RESULTS: Patients with TFN ranged from 50 to 74 years old and presented with upper gastrointestinal tract malignancies amenable to surgical resection. Six and two cases of TFN occurred following pancreatectomy and esophagectomy, respectively. Prior to TF protocol changes, which included initiation at a low rate, titrating up more slowly and starting at one-half strength TF, three of six cases of TFN (50%) resulted in mortality. With the new TF protocol, there were no deaths, goal TF rate was achieved 3 days later, symptoms of TFN were recognized 3 days earlier, and re-operation was conducted 1 day earlier. CONCLUSION: This case series describes a change in clinical practice that is associated with decreased morbidity and mortality of TFN. Wider implementation and further refinement of this tube-feeding protocol may reduce TFN incidence at other institutions and in patients with other conditions requiring enteral nutrition.

Hesperetin exerts apoptotic effect on A431 skin carcinoma cells by regulating mitogen activated protein kinases and cyclins.

Dietary agents and phytochemicals have been utilised for the management of cancer for many years. Hesperetin, a dietary flavonoid found abundantly in citrus fruits, was evaluated for its cytotoxic and pro-apoptotic activities in A431 human skin carcinoma cells. Effect of hesperetin in regulating MAPK (Mitogen-Activated Protein Kinase) signalling pathway and levels of various cyclins and other downstream apoptotic proteins were investigated. Its critical role in regulating other apoptotic proteins especially p21, Bcl-2 and Bax were also assessed. Hesperetin stimulated alterations in MAPK (Mitogen-Activated Protein Kinase) signalling pathway by modulating the expression levels of ERK (Extracellular signal Regulated Kinase), JNK (c-Jun NH2-terminal Kinase) and p38; thereby induced apoptosis in A431 cells. Hesperetin regulated the levels of cyclin A2, B1, D1, D3 and E1. It also modulated the levels of various proteins involved in apoptotic pathway especially p21, Bcl-2 and Bax. The study revealed the efficiency of hesperetin against human skin carcinoma cells and proposed its mechanism of action; there by opens up new avenues for the use of this dietary flavonoid against skin malignancies.

Scientific Insights in the Preparation and Characterisation of a Lead-based Naga Bhasma.

Naga bhasma is one of the herbo-metallic preparations used in Ayurveda, a traditional Indian System of Medicine. The preparation of Naga bhasma involves thermal treatment of 'Naga' (metallic lead) in a series of quenching liquids, followed by reaction with realgar and herbal constituents, before calcination to prepare a fine product. We have analysed the intermediates obtained during different stages of preparation to understand the relevance and importance of different steps involved in the preparation. Our results show that 'Sodhana' (purification process) removes heavy metals other than lead, apart from making it soft and amenable for trituration. The use of powders of tamarind bark and peepal bark maintains the oxidation state of lead in Jarita Naga (lead oxide) as Pb(2+). The repeated calcination steps result in the formation of nano-crystalline lead sulphide, the main chemical species present in Naga bhasma.

Variations in physicochemical properties of a traditional mercury-based nanopowder formulation: need for standard manufacturing practices.

Rasasindura is a mercury-based nanopowder synthesized using natural products through mechanothermal processing. It has been used in the Ayurvedic system of medicine since time immemorial for various therapeutic purposes such as rejuvenation, treatment of syphilis and in genital disorders. Rasasindura is said to be composed of mercury, sulphur and organic moieties derived from the decoction of plant extracts used during its synthesis. There is little scientific understanding of the preparation process so far. Though metallic mercury is incorporated deliberately for therapeutic purposes, it certainly raises toxicity concerns. The lack of gold standards in manufacturing of such drugs leads to a variation in the chemical composition of the final product. The objective of the present study was to assess the physicochemical properties of Rasasindura samples of different batches purchased from different manufacturers and assess the extent of deviation and gauge its impact on human health. Modern characterization techniques were employed to analyze particle size and morphology, surface area, zeta potential, elemental composition, crystallinity, thermal stability and degradation. Average particle size of the samples observed through scanning electron microscope ranged from 5-100 nm. Mercury content was found to be between 84 and 89% from elemental analysis. Despite batch-to-batch and manufacturer-to-manufacturer variations in the physicochemical properties, all the samples contained mercury in the form of HgS. These differences in the physicochemical properties may ultimately impact its biological outcome.

Formation and properties of composites comprised of calcium-deficient hydroxyapatites and ethyl alanate polyphosphazenes.

Composites comprised of calcium-deficient hydroxyapatite (HAp) and biodegradable polyphosphazenes were formed via cement-type reactions at physiologic temperature. The composite precursors were produced by blending particulate hydroxyapatite precursors with 10 wt% polymer using a solvent/non-solvent technique. HAp precursors having calcium-to-phosphate ratios of 1.5 (CDH) and 1.6 (CDS) were used. The polymeric constituents were poly[bis(ethyl alanato)phosphazene] (PNEA) and poly[(ethyl alanato)(1) (p-phenylphenoxy)(1) phosphazene] (PNEA(50)PhPh(50)). The effect of incorporating the phenyl phenoxy group was evaluated as a means of increasing the mechanical properties of the composites without retarding the rates of HAp formation. Reaction kinetics and mechanistic paths were characterized by pH determination, X-ray diffraction analyses, scanning electron microscopy, and infrared spectroscopy. The mechanical properties were analyzed by compression testing. These analyses indicated that the presence of the polymers slightly reduced the rate HAp formation. However, surface hydrolysis of polymer ester groups permitted the formation of calcium salt bridges that provide a mechanism for bonding with the HAp. The compressive strengths of the composites containing PNEA(50)PhPh(50) were superior to those containing PNEA, and were comparable to those of HAp produced in the absence of polymer. The current composites more closely match the structure of bone, and are thus strongly recommended to be used as bone cements where high loads are not expected.

Mantoux and contact positivity in tuberculosis.

OBJECTIVE: To study the role of Mantoux and contact history in various forms of Childhood tuberculosis. METHODS: 605 children registered with TB clinic of Institute of Child Health and Hospital for Children, Chennai over a 5 year period from January 2000 to October 2005 with various forms of tuberculosis were recruited in the study. Clinical examination findings, basic investigations, chest skiagrams, computerized tomography (CT) wherever warranted, sputum or gastric aspirates for AFB smear, histopathology wherever possible were analyzed. RESULTS: The study showed that Mantoux positivity in various forms of tuberculosis studied is 34.7%. The positivity of Mantoux was highest in lymph node tuberculosis (53%) and the lowest with CNS tuberculosis (21.2%). Among the other forms, Mantoux positivity was 36.4% in TB abdomen, 44.4% in Skeletal TB, 30.3% in pulmonary tuberculosis. The contact positivity was 30.4% in the sample studied. CONCLUSION: The study also reflects that the extra pulmonary forms of tuberculosis seems to be more common in the pediatric population which constituted 79.8% of the cases included in the study.

Role of splenectomy in chronic idiopathic thrombocytopenic purpura.

AIM OF THE STUDY: To evaluate the usefulness of splenectomy and factors which predict long term remission in chronic idiopathic thrombocytopenic purpura (ITP). METHODS: We reviewed the data of 364 patients diagnosed as chronic ITP between January 1983 to December 1996 of whom 71 patients underwent splenectomy. The patients were followed up for an average period of 58 months and the short and long term response to splenectomy were analyzed at the end of one month and 60 months, respectively. RESULTS: At the end of one month after splenectomy, 82% had complete response, 7% partial response and 11% had no response. At the end of 60 months, 42% maintained complete response, 7% partial response, 34% had no response and 17% were lost to follow up. The results were statistically evaluated by using non-parametric test (Chi-square test) to age, sex, platelet count prior to treatment, initial response to steroids, time interval between diagnosis and splenectomy and post-operative platelet count. Of these factors only preoperative response to steroids (p value = 0.018303) and postoperative platelet count (p value = 0.013536) were found to be significant, statistically to predict long term remission. Age, sex, initial platelet count and time interval between diagnosis and splenectomy didn't seem to be statistically significant. CONCLUSION: This study suggests, that patients with an initial complete response to steroids and a post-operative platelet count > 300 x 10(9)/L at the time of discharge were associated with a long term remission. Splenectomy in ITP is a safe procedure with minimal morbidity and mortality and gives a good long term remission in steroid- failure patients with chronic ITP.

Acute, short-term, and subchronic oral toxicity of 1,1,1-trichloroethane in rats.

1,1,1-Trichloroethane (TRI) is a widely used solvent that has become a frequent contaminant of drinking water supplies in the U.S. There is very little information available on the potential for oral TRI to damage the liver or to alter its P450 metabolic capacity. Thus, a major objective of this investigation was to assess the acute, short-term, and subchronic hepatotoxicity of oral TRI. In the acute study, male Sprague-Dawley (S-D) rats were gavaged with 0, 0.5, 1, 2, or 4 g TRI/kg bw and killed 24 h later. No acute effects were apparent other than CNS depression. Other male S-D rats received 0, 0.5, 5, or 10 g TRI/kg po once daily for 5 consecutive days, rested for 2 days, and were dosed for 4 additional days. Groups of the animals were sacrificed for evaluation of hepatotoxicity 1, 5, and 12 days after initiation of the short-term experiment. This dosage regimen caused numerous fatalities at 5 and 10 g/kg, but no increases in serum enzymes or histopathological changes in the liver. For the subchronic study, male S-D rats were gavaged 5 times weekly with 0, 0.5, 2.5, or 5.0 g TRI/kg for 50 days. The 0 and 0.5 g/kg groups were dosed for 13 weeks. A substantial number of rats receiving 2.5 and 5.0 g/kg died, apparently due to effects of repeated, protracted CNS depression. There was evidence of slight hepatocytotoxicity at 10 g/kg, but no progression of injury nor appearance of adverse effects were seen during acute or short-term exposure. Ingestion of 0.5 g/kg over 13 weeks did not cause apparent CNS depression, body or organ weight changes, clinical chemistry abnormalities, histopathological changes in the liver, or fatalities. Additional experiments did reveal that 0.5 g/kg and higher doses induced hepatic microsomal cytochrome P450IIE1 (CYP2E1) in a dose- and time-dependent manner. Induction of CYP2E1 activity occurred sooner, but was of shorter duration than CYP2B1/2 induction. CYP1A1 activity was not enhanced. In summary, 0.5 g/kg po was the acute, short-term, and subchronic NOAEL for TRI, for effects other than transient CYP2E1 induction, under the conditions of this investigation. Oral TRI appears to have very limited capacity to induce P450s or to cause liver injury in male S-D rats, even when administered repeatedly by gavage in near-lethal or lethal dosages under conditions intended to maximize hepatic effects.

Silicon nitride Micromesh Bolometer Array for Submillimeter Astrophysics.

We present the design and performance of a feedhorn-coupled bolometer array intended for a sensitive 350-mum photometer camera. Silicon nitride micromesh absorbers minimize the suspended mass and heat capacity of the bolometers. The temperature transducers, neutron-transmutation-doped Ge thermistors, are attached to the absorber with In bump bonds. Vapor-deposited electrical leads address the thermistors and determine the thermal conductance of the bolometers. The bolometer array demonstrates a dark noise-equivalent power of 2.9 x 10(-17) W/ radicalHz and a mean heat capacity of 1.3 pJ/K at 390 mK. We measure the optical efficiency of the bolometer and feedhorn to be 0.45-0.65 by comparing the response to blackbody calibration sources. The bolometer array demonstrates theoretical noise performance arising from the photon and the phonon and Johnson noise, with photon noise dominant under the design background conditions. We measure the ratio of total noise to photon noise to be 1.21 under an absorbed optical power of 2.4 pW. Excess noise is negligible for audio frequencies as low as 30 mHz. We summarize the trade-offs between bare and feedhorn-coupled detectors and discuss the estimated performance limits of micromesh bolometers. The bolometer array demonstrates the sensitivity required for photon noise-limited performance from a spaceborne, passively cooled telescope.

Mechanisms of ordering in striped patterns.

We have studied the ordering dynamics of the striped patterns of a single layer of cylindrical block copolymer microdomains in a thin film. By tracking disclinations during annealing with time-lapse atomic force microscopy, we observe a dominant mechanism of disclination annihilation involving three or four disclinations (quadrupoles). Pairwise disclination annihilation events are suppressed as a result of the topological constraints in this system. The kinetic scaling laws with exponents observed here are consistent with topologically allowed annihilation events involving multiple disclinations. The results provide insight into two-dimensional pattern formation and may lead to the successful application of block copolymer lithography.

Intimal thickness and layering, and smooth muscle cell phenotypes in aorta of youth.

Proneness to the lesions of atherosclerosis varies along the length and circumferential topography of the aorta. Smooth muscle cells, in particular those of the 'modulated' synthetic phenotype which are able to proliferate and synthesize matrix proteins, are considered to play an important role in lesion progression. We report on a study of the aortic intima at a lesion-prone site from abdominal aorta and a lesion-resistant site from thoracic aorta in young humans to determine (1) whether the histologic structure and the smooth muscle cell composition show quantitative differences between lesion-prone and lesion-resistant aortic sites; (2) whether there are gender differences, and (3) whether any differences increase in degree with increasing age in this young population. Material for this study was obtained as part of the NIH-funded multicenter study on Pathobiological Determinants of Atherosclerosis in Youth (PDAY) from autopsies of male and female subjects between the ages of 15 and 34, victims of unexpected sudden death, usually from trauma. The samples consisted of strips of abdominal and thoracic aorta, all derived from the same anatomical sites standardized in the PDAY studies. The thickness of total intima (TI) and its elastic hyperplastic (EH) layer was measured. Smooth muscle cells of all types (SMC) and separately those of the synthetic phenotype (SynSMC) were quantified in each site using immunohistochemical procedures in replicate sections of uniform thickness. The intima of the atherosclerotic lesion-prone dorsal half of the abdominal aorta (AD) shows significant differences from the lesion-resistant ventral half of thoracic aorta (TV) in that (1) its EH layer is significantly thicker; (2) its EH layer has a comparatively higher number of both total SMC and SynSMC, even when adjusted for intimal thickness, and (3) the age-related increase in thickness of both TI and EH layer of AD is much greater than that of TV.

Cytogenetic and molecular genetic studies on Indian patients with chronic lymphocytic leukemia.

This is the first cytogenetic and molecular genetic study to find any specific genetic abnormalities in Indian patients with chronic lymphocytic leukemia (CLL). Cytogenetic studies on 18 patients indicated that their karyotypes were relatively simple and trisomy 12 was seen on karyotype evolution in one patient. Fluorescence in situ hybridization (FISH) revealed abnormal clones of trisomy 12 in nine cases and RB gene deletion in 14 of the 29 cases analyzed. Three patients had both clones. Immunoglobulin genes were rearranged in all the cases and TCR beta in none of the 18 cases Southern blotted. BCL-1 was rearranged in one case. No rearrangement of BCL-2 gene was seen in any case. Genetic changes in Indian CLL were more similar to Western CLL than to Japanese CLL, even though India is supposed to be a low incidence area. Therefore, factors (such as HLA and other genetic markers) other than these routine parameters must be studied to explain the low incidence of CLL in India.

Furazolidone in multi-resistant childhood typhoid fever.

Multi-drug-resistant Salmonella typhi infection is an emerging public health problem in most developing countries. Fifty children up to the age of 12 years whose blood cultures were positive for S. typhi, mostly drug-resistant ones, were treated with oral furazolidone in a prospective year-long study. Defervescence occurred in 96% of the treated group with a mean duration for response of 5.9 days. No clinically significant side-effects were noted. Furazolidone was found to be efficacious, safe and cost-effective in the treatment of most cases of childhood typhoid fever caused by multi-resistant S. typhi.

Analysis of karyotype, SCE, and point mutation of RAS oncogene in Indian MDS patients.

Thirty Indian patients diagnosed as having primary myelodysplastic syndrome as per the French-American-British classification were investigated, on admission, for the frequencies of nonrandom karyotype abnormalities, sister chromatid exchange, and point mutations of the RAS oncogene. Successful karyotype analysis was possible in 24 patients, of whom 9 (37.5%) showed nonrandom karyotypic changes. Anomalies of chromosomes 5, 7, and 8 were detected in their bone marrow (BM). In addition, two new anomalies, del(8)(q22) and +19, were observed for the first time in our series. Six MDS patients were studied for SCE in either BM or peripheral blood. These data revealed a normal SCE incidence. Of the 10 MDS patients studied for point mutations of NRAS 12 and 61 and KRAS 12 and 61, one patient exhibited a base substitution at position 1 of the 12th codon of the KRAS gene. These data, gathered for the first time on the Indian patients, throw some light on the nature of genetic changes in MDS of our country.

Specific Skin Involvement in Leukaemias and Lymphomas.

Four cases of leukemia, 5 cases of non-Hodgkin's lymphoma and 3 cases of Hodgkin's lymphoma, developed maculo-papular rashes, papules, nodules, urticarial skin lesions and a plaque. Each of these on histopathology, showed a specific skin infiltrate corresponding to the malignancy.