Temporary faecal diversion in ileocolic resection for Crohn's disease: is there an impact on long-term surgical recurrence?

AIM: Temporary faecal diversion after ileocolic resection (ICR) for Crohn's disease reduces postoperative anastomotic complications in high-risk patients. The aim of this study was to assess if this approach also reduces long-term surgical recurrence. METHOD: This was a multicentre retrospective review of prospectively maintained databases. Patient demographics, medical and surgical details were collected by three specialist centres. All patients had undergone an ICR between 2000 and 2012. The primary end-point was surgical recurrence. RESULTS: Three hundred and twelve patients (80%) underwent an ICR without covering ileostomy (one stage). Seventy-seven (20%) had undergone an ICR with end ileostomy/double-barrel ileostomy/enterocolostomy followed by closure (two stage). The median follow-up was 105 months [interquartile range (IQR) 76-136 months]. The median time to ileostomy closure was 9 months (IQR 5-12 months). There was no significant difference in surgical recurrence between the one- and two-stage groups (18% vs 16%, P = 0.94). We noted that smokers (20% vs 34%, P = 0.01) and patients with penetrating disease (28% vs 52%, P < 0.01) were more likely to be defunctioned. A reduced recurrence rate was observed in the small high-risk group of patients who were smokers with penetrating disease behaviour treated with a two-stage strategy (0/10 vs 4/7, P = 0.12). CONCLUSION: Despite having higher baseline risk factors, the results in terms of rate of surgical recurrence over 9 years are similar for patients having a two-stage compared with a one-stage procedure.

Cause of Cambrian Explosion - Terrestrial or Cosmic?

We review the salient evidence consistent with or predicted by the Hoyle-Wickramasinghe (H-W) thesis of Cometary (Cosmic) Biology. Much of this physical and biological evidence is multifactorial. One particular focus are the recent studies which date the emergence of the complex retroviruses of vertebrate lines at or just before the Cambrian Explosion of ∼500 Ma. Such viruses are known to be plausibly associated with major evolutionary genomic processes. We believe this coincidence is not fortuitous but is consistent with a key prediction of H-W theory whereby major extinction-diversification evolutionary boundaries coincide with virus-bearing cometary-bolide bombardment events. A second focus is the remarkable evolution of intelligent complexity (Cephalopods) culminating in the emergence of the Octopus. A third focus concerns the micro-organism fossil evidence contained within meteorites as well as the detection in the upper atmosphere of apparent incoming life-bearing particles from space. In our view the totality of the multifactorial data and critical analyses assembled by Fred Hoyle, Chandra Wickramasinghe and their many colleagues since the 1960s leads to a very plausible conclusion - life may have been seeded here on Earth by life-bearing comets as soon as conditions on Earth allowed it to flourish (about or just before 4.1 Billion years ago); and living organisms such as space-resistant and space-hardy bacteria, viruses, more complex eukaryotic cells, fertilised ova and seeds have been continuously delivered ever since to Earth so being one important driver of further terrestrial evolution which has resulted in considerable genetic diversity and which has led to the emergence of mankind.

Population Structure Among and Within Iowa, Missouri, Ohio, and South Dakota Populations of Phytophthora sojae.

Phytophthora root and stem rot, caused by Phytophthora sojae, is an economically important disease of soybean throughout the Midwestern United States. This disease has been successfully managed with resistance (Rps) genes; however, pathogen populations throughout the Midwest have developed virulence to many Rps genes, including those that have not been deployed. To gain a better understanding of the processes that influence P. sojae evolution, the population genetic structure was compared among populations using one isolate collected from 17, 33, and 20 fields in Iowa, Ohio, and South Dakota, respectively, as well as multiple isolates from individual fields in Iowa, Ohio, and Missouri. Genotypic diversity was measured using 21 polymorphic microsatellite (simple-sequence repeat) markers. and pathotype diversity using 15 soybean differentials. For all but three of the populations with low sample size, there was a high level of pathotype diversity and a low to moderate level of genotypic diversity among the populations for both comparisons between states and within-field variation. None of the Rps-gene differentials were resistant to all of the isolates. There were 103 unique multilocus genotypes identified in this study and only 2 were identified from the same field. Although no clones were identified in more than one field, pairwise FST indicated that some gene flow within neighboring fields does occur but not across the region, including fields from neighboring states. These results suggest that there is a strong probability that each state may have their own or several regional populations, as well as provide further evidence of high diversity within this homothallic pathogen which may be due, in part, to limited gene flow, mutation, or outcrossing, and this likely affects the success of deployment of resistance.

Outcomes in consecutive hospitalized UK patients with bacteraemia or fungaemia caused by medical devices and procedures.

BACKGROUND: There is a lack of outcome data on hospitalized patients with bacteraemia or fungaemia caused by medical devices or procedures. AIM: To determine the association between death and bacteraemia or fungaemia caused by medical devices and procedures. METHODS: From December 2012 to November 2013, demographic, clinical, and microbiological data were collected on consecutive inpatients with bacteraemia or fungaemia. Multivariate analysis, using generalized estimating equations, was used to define the association. FINDINGS: A total of 594 bacteraemic or fungaemic episodes occurred in 500 patients. Among patients with episodes caused by medical devices or procedures, 7-day and 30-day mortality were 7/167 [4.2%; 95% confidence interval (CI): 1.7-8.4] and 12/167 (7.2%; CI: 3.8-12.2) respectively. After adjustment, the association between death and bacteraemic or fungaemic episodes related to medical devices and procedures was non-significant as 7- and 30-day mortality odds ratios (OR) were 2.86 (95% CI: 0.80-10.12) and 1.72 (95% CI: 0.71-4.16) respectively. The difference between 30-day mortality associated with Escherichia coli and Staphylococcus aureus bacteraemia demonstrated a trend towards significance [6/47 (12.8%; CI: 4.8-25.7) vs 0/24; P = 0.067]. Thirty-day mortality associated with bacteraemia or fungaemia in patients with urinary catheter infections (often E. coli-associated) was significantly higher than intravascular device-associated infections (often S. aureus-associated) [4/51 (7.8%; 95% CI: 2.2-18.8) vs 1/62 (1.6%; 95% CI: 0.0-8.7); P = 0.028]. CONCLUSION: Special attention is required to prevent medical device- or procedure-related bacteraemia caused by E. coli. Greater attention should be placed on preventing infections caused by urinary catheters.

Three-Dimensional Anorectal Manometry Findings in Primigravida.

BACKGROUND: Vaginal delivery is an identified risk factor for anal sphincter injury. Therefore, to identify postpartum injury, an antepartum value or a normal range is required. However, at present, the normal values of 3D manometry are not available for primigravida or pregnant mothers. AIMS: Our study aims at describing normal values of 3D manometry in primigravida. METHODS: We analyzed 3DARM data of 101 consecutive primigravid mothers in the third trimester. 3DARM was performed using the Given Imaging(®) ManoScan system. RESULTS: The mean age was 24.7 (SD 5.1) years. All patients had a normal Cleveland Clinic Incontinence Score. The mean resting pressure (RP) was 87.02 (SD 18.43) mmHg and the maximum squeeze pressure (SP) was 179.21 (SD 52.96) mmHg. The mean length of the high-pressure zone (HPZ) was 3.67 (SD 0.52) cm. Mean volumes for initial rectal sensation, urge, and discomfort were 50.36 (± 25.57), 76.70 (± 35.17), and 143.40 (± 66.26) ml, respectively. The pressure asymmetry was highest in the lower anal sphincter and lowest in the mid-sphincter. There was a statistically significant relationship between the HPZ and RP (Pearson ρ -0.23, p = 0.01), height (Pearson ρ 0.22, p = 0.028), and weight (Pearson ρ 0.25, p = 0.012). There were no statistically significant correlations between age, height, or weight with RP, SP, or balloon fill volumes. The characteristic appearance of the normal RP and SP was clearly visualized in all patients. CONCLUSIONS: Normal 3DARM values for Sri Lankan primigravid mothers have been established. These may be used as reference values by other investigators.

Heavy metal mediated immunomodulation of the Indian green frog, Euphlyctis hexadactylus (Anura:Ranidae) in urban wetlands.

Impacts of heavy metal toxicity on the immune system of the Indian green frog, Euphlyctis hexadactylus, in Bellanwila Attidiya, an urban wetland polluted with high levels of heavy metals, compared to the reference site in Bolgoda, in Sri Lanka was investigated. Significantly higher accumulation of selected heavy metals, copper (Cu), zinc (Zn), lead (Pb), and cadmium (Cd) were detected by AAS in frog liver and gastrocnemius muscle, in the polluted site than in the reference site. Non-functional immunotoxicity tests; total WBC, splenocyte and bone marrow cell counts, spleen weight/body weight ratio, neutrophil/lymphocyte ratio and basal immunoglobulin levels, and phagocytic capacity of peritoneal macrophages (immune functional test) were carried out using standard methodology. Test parameters recorded significantly lower values for frogs of the polluted site compared with their reference site counterparts, indicative of lowered immune response of frogs in the former site. In vitro phagocytic assay based on NBT dye reduction, measured the stimulation index (SI) of E. hexadactylus blood leukocytes, splenocytes and peritoneal macrophages, where SIs of frogs in the polluted site were significantly lower. Also, in vitro exposure of frog phagocytes to Cu, Zn, Pb and Cd at 10(-2)-10(-10)M, showed immunomodulation i.e. low concentrations stimulated phagocytosis while increased concentrations showed a trend towards immunosuppression. IC50 values indicated Cd>Zn>Cu>Pb as the decreasing order of the potential of phagocytosis inhibition. In conclusion, this study clearly demonstrated immunomodulation of E. hexadactylus, stimulated by heavy metals. In-vitro studies evidently suggested the use of phagocytosis as a biomarker in Ecoimmunotoxicology to detect aquatic heavy metal pollution.

A comparison of endoanal ultrasound and computed tomography in staging rectal cancer and in clinical decision making - a preliminary study.

INTRODUCTION: The treatment options and the prognosis of rectal cancer (RC) depend mainly on the stage. Computed tomography (CT) has been the main staging tool in RC but endoanal ultrasound (EAUS) is thought to be more accurate. METHODS: Patients with histologically proven rectal cancer presenting for the first time were staged using CT and EAUS. TNM staging was used to stage the rectal cancer. RESULTS: 24 patients (M:F 1:1) with a mean age of 57.3 (range = 23-80, SD = 15.3) years were included. The majority had a tumour of stage IIA/T3N0M0 (CT = 10, EAUS = 12). The staging of the tumour was the same in both investigations in 11 patients, while in 8 patients, EAUS staging was higher. The agreement for the T and N stages were kappa 0.24 and 0.5 respectively. There was a moderate and fair agreement between the overall TNM staging (weighted kappa 0.435) and the treatment strategies (weighted kappa 0.226) respectively, based on each imaging method. Of the 13 patients whose staging was different, the management changed in 6 (25%) patients (p = 0.016). CT identified distal metastases in 2 patients. CONCLUSIONS: EAUS and CT have only a fair to moderate agreement for staging and deciding treatment. However,EAUS has a significant influence when deciding treatment protocols.

Lymphoedema and its management in cases of lymphatic filariasis: the current situation in three suburbs of Matara, Sri Lanka, before the introduction of a morbidity-control programme.

Using in-depth interviews, information on the current state of lymphoedema management was collected from 101 cases of lymphatic filariasis with lymphoedema in three suburbs of Matara. The interviews were conducted prior to the introduction of a programme of community home-based care (CHBC) that incorporates modern lymphoedema-management strategies. Thirty-two of the interviewees had severe lymphoedema (of grade III or above). The male interviewees had significantly more entry lesions than the female. Most of the subjects had suffered from episodes of limb pain with fever, although the incidence of these episodes appeared unrelated to the severity of the lymphoedema. The frequency of the episodes of limb-pain/fever in the 12 months prior to the interviews appeared unrelated either to the level of daily hygiene, which was generally poor, or to the frequency of bathing. Many (65%) of the subjects paid no attention to limb care when bathing, and 44% did not use footwear. Over 80% made no effort to keep their afflicted limbs elevated, and 95% did not exercise. Most of the female interviewees felt shameful of their condition and were, in consequence, less likely to attend government clinics, for treatment, than the male interviewees. The drug treatment that the interviewees had received was often inadequate, and most had stopped seeking treatment because they had not perceived any significant treatment-attributable improvement in their condition. Modern lymphoedema-management strategies (based on regular washing, careful drying, and treatment, with antifungal, antibiotic or emollient creams, of the affected limbs, limb elevation, exercise, and use of footwear) had not reached the study communities and the local physicians were not aware of them. When dermatology life-quality indexes (DLQI) were calculated for the interviewees, the 26 most impaired subjects gave scores of 5-15 (mean=8.6). The DLQI for these subjects will be regularly re-evaluated, as a measure of the effectiveness of the CHBC programme that has now begun.

Prenatal testing and pregnancy termination in Sri Lanka: views of medical students and doctors.

INTRODUCTION: Prenatal diagnosis and pregnancy termination generate complex ethical issues. Surveys conducted in Sri Lanka among doctors and medical students in 1986 supported a change in law in favour of pregnancy termination when gross genetic defects are detected antenatally. A new generation of prenatal tests has focused attention again on the topic of termination and under what circumstances it might be legally done. The present survey contributes to the debate by means of a survey of doctors and medical students. METHOD: A self-administered questionnaire given to doctors and medical students. RESULTS: Ninety three per cent of doctors and 81% of students accept pregnancy termination as an appropriate course of action if a gross genetic defect is detected antenatally, and 87% of doctors and 80% of students support a change in the law to allow termination of the pregnancy. The corresponding figures in previous surveys were 80%, 69% and 96%, 88% respectively. CONCLUSIONS: A majority of doctors and medical students support a change in law in favour of liberalising pregnancy termination when a genetic defect is detected antenatally.

Knowledge on lymphatic filariasis and the response to July 2002 mass treatment campaign in two communities in the Galle district.

OBJECTIVE: To ascertain the knowledge on filariasis and response to the July 2002 mass treatment campaign in two sample populations. DESIGN: Application of pre-tested questionnaire by direct interviews of individuals from randomly selected streets. METHODS: Study areas were a coastal community in Unawatuna (population sample 381), and an inland community in Baddegama (population sample 236) in the Galle district. They were interviewed twice, 4 weeks before the mass drug administration (MDA) and 4 to 7 days after. RESULTS: The sample population of Unawatuna had a greater awareness of the clinical and parasitological features of the disease (p = 0.0003) and the drug treatment (p = 0.00380 than that of Baddegama. Only 5.5% of the combined sample attributed the cause of filariasis to a parasitic worm. However, over 70.0% of them knew that transmission was through mosquito bites. Volunteers formed 87.5% of the work force used for drug distribution in Unawatuna and 70.1% in Baddegama. The balance work force were Grama Niladaris and Public Health Midwives. Drugs were received by 76.9% of the Unawatuna sample compared with 89.0% at Baddegama (p < 0.001). Among those who received the drugs, consumption was 91.8% in Unawatuna and 96.2% in Baddegama. Taking the two communities together adverse effects were experienced by 22.9%. These effects in night time drug consumers (10.4%) were significantly less than in day time consumers (19.8%) (p < 0.005). The adverse effects were sleepiness (37.8%), malaise (28.2%), headache (16.8%), vomiting (5.1%), nausea (4.5%) and fever (3.9%). The message of mass treatment was carried to the community by the people themselves on the eve and on the day of drug distribution. Over 95% agreed that in future programs drugs should be delivered to their homes.

Structure and promoter activity of the mouse CDC25A gene.

CDC25A is a member of a group of highly related, dual-specificity phosphatases that promote cell cycle phase transitions by regulating the activity of cyclin-dependent kinases. Here we report the cloning and genomic sequence of 21,067 nucleotides encompassing the mouse CDC25A gene. The coding sequence is expressed from 17,904 bp of genomic DNA comprising 15 exons. We also mapped the transcription initiation site to a consensus initiator element proximal to an SP1 site. Approximately 1 kb of sequence upstream of the transcription initiation site confers promoter activity and cell type specificity to a reporter gene construct. Surprisingly, transcription from this promoter was repressed by over-expression of catalytically active but not catalytically inactive CDC25A protein. We also show, using NIH 3T3 cells, that murine CDC25A mRNA levels fluctuate only modestly over the cell cycle. Our findings provide insights into the regulation of CDC25A expression and have facilitated construction of gene knock-out vectors.

The four cdc25 genes from the nematode Caenorhabditis elegans.

During eukaryotic evolution, multicellular organisms have evolved multiple members of gene families that may display unique, partially overlapping, or redundant functions during development. More than 75% of the C. elegans genome has been sequenced, which represents approximately 95% of the coding sequences. This provides a unique opportunity to identify most, if not all, of the members of a given gene family. We have searched the C. elegans genome database for members of a key family of cell cycle regulators, the CDC25 phosphatases, and have identified four genes. The four C. elegans genes represent a larger family within a single organism than has been reported so far in Drosophila, mice and humans. An amino acid comparison revealed a high degree of similarity and identity within the phosphatase domain. This analysis also identified an expanded consensus sequence that can be used to discover new members of the CDC25 phosphatase family. However, the four C. elegans sequences display a few novel amino acid substitutions in the residues surrounding the invariant catalytic motif CX5R. These data demonstrate the value of genome database searching for identifying new members of known gene families, understanding genetic diversity, and for studying gene structure.

Two CDC25 homologues are differentially expressed during mouse development.

The cdc25 gene product is a tyrosine phosphatase that acts as an initiator of M-phase in eukaryotic cell cycles by activating p34cdc2. Here we describe the cloning and characterization of the developmental expression pattern of two mouse cdc25 homologs. Sequence comparison of the mouse genes with human CDC25 genes reveal that they are most likely the mouse homologs of human CDC25A and CDC25B respectively. Mouse cdc25a, which has not been described previously, shares 84% sequence identity with human CDC25A and has a highly conserved phosphatase domain characteristic of all cdc25 genes. A glutathione-S-transferase-cdc25a fusion protein can hydrolyze para-nitro-phenylphosphate confirming that cdc25a is a phosphatase. In adult mice, cdc25a transcripts are expressed at high levels in the testis and at lower levels in the ovary, particularly in germ cells; a pattern similar to that of twn, a Drosophila homolog of cdc25. Lower levels of transcript are also observed in kidney, liver, heart and muscle, a transcription pattern that partially overlaps, but is distinct from that of cdc25b. Similarly, in the postimplantation embryo cdc25a transcripts are expressed in a pattern that differs from that of cdc25b. cdc25a expression is observed in most developing embryonic organs while cdc25b expression is more restricted. An extended analysis of cdc25a and cdc25b expression in preimplantation embryos has also been carried out. These studies reveal that cdc25b transcripts are expressed in the one-cell embryo, decline at the two-cell stage and are re-expressed at the four-cell stage, following the switch from maternal to zygotic transcription which mirrors the expression of string, another Drosophila homolog of cdc25. In comparison, cdc25a is not expressed in the preimplantation embryo until the late blastocyst stage of development, correlating with the establishment of a more typical G1 phase in the embryonic cell cycles. Both cdc25a and cdc25b transcripts are expressed at high levels in the inner cell mass and the trophectoderm, which proliferate rapidly prior to implantation. These data suggest the cdc25 genes may have distinct roles in regulating the pattern of cell division during mouse embryogensis and gametogenesis.