Small bowel obstruction in pregnancy is a complex surgical problem with a high risk of fetal loss.

INTRODUCTION: Small bowel obstruction (SBO) in pregnancy is rare and is most commonly caused by adhesions from previous abdominal surgery. Previous literature reviews have emphasised the need for prompt laparotomy in all cases of SBO because of the significant risks of fetal loss and maternal mortality. We undertook a review of the contemporary literature to determine the optimum management strategy for SBO in pregnancy. METHODS: The MEDLINE® and PubMed databases were searched for cases of SBO in pregnancy between 1992 and 2014. Two cases from our own institution were also reviewed. RESULTS: Forty-six cases of SBO in pregnancy were identified, with adhesions being the most common aetiology (50%). The overall risk of fetal loss was 17% and the maternal mortality rate was 2%. In cases of adhesional SBO, 91% of cases were managed surgically, with 14% fetal loss. Two cases (9%) were managed conservatively with no complications. Magnetic resonance imaging (MRI) was used to diagnose SBO in 11% of cases. CONCLUSIONS: Based on our experience and the contemporary literature, we recommend that urgent MRI of the abdomen should be undertaken to diagnose the aetiology of SBO in pregnancy. In cases of adhesional SBO, conservative treatment may be safely commenced, with a low threshold for laparotomy. In other causes, such as volvulus or internal hernia, laparotomy remains the treatment of choice.

Measurement of anal cushions in continent women.

AIM: Anal cushions are connective tissue complexes thought to be involved in anal continence. This study aimed to assess them in continent subjects. METHOD: Continent women undergoing a transvaginal ultrasound scan for gynaecological reasons were included. The anal cushions were visualized at the mid-canal level. The cross-sectional area within the internal anal sphincter (Area 1) and the area enclosed within the anal cushions (Area 2) were measured and a Cushion:Canal (C:C) ratio was derived for each patient. The measurements were repeated in the semi-erect position. RESULTS: One hundred and two patients with a median age of 41 (IQR 32-49) years were included. The median C:C ratio was 0.68 (IQR 0.61-0.73). Inter-observer error was 0.98 and intra-observer error was 0.99. There was no significant correlation between age and C:C ratio. The C:C ratio was significantly higher in parous than in nulliparous women (P = 0.04). A history of obstetric trauma or minimal haemorrhoidal symptoms did not influence C:C ratio. There was a significant increase in C:C ratio in the erect position. (P = 0.04). CONCLUSION: There was a wide range of variability in the measurement of anal cushions in normal continent women. These were not influenced by age.

Effects of rolipram on adult rat oligodendrocytes and functional recovery after contusive cervical spinal cord injury.

Traumatic human spinal cord injury (SCI) causes devastating and long-term hardships. These are due to the irreparable primary mechanical injury and secondary injury cascade. In particular, oligodendrocyte cell death, white matter axon damage, spared axon demyelination, and the ensuing dysfunction in action potential conduction lead to the initial deficits and impair functional recovery. For these reasons, and that oligodendrocyte and axon survival may be related, various neuroprotective strategies after spinal cord injury are being investigated. We previously demonstrated that oligodendrocytes in the adult rat epicenter ventrolateral funiculus (VLF) express 3'-5'-cyclic adenosine monophosphate-dependent phosphodiesterase 4 (PDE4) subtypes and that their death was attenuated up to 3 days after contusive cervical SCI when rolipram, a specific inhibitor of PDE4, was administered. Here, we report that (1) there are more oligodendrocyte somata in the adult rat epicenter VLF, (2) descending and ascending axonal conductivity in the VLF improves, and that (3) there are fewer hindlimb footfall errors during grid-walking at 5 weeks after contusive cervical SCI when rolipram is delivered for 2 weeks. This is the first demonstration of improved descending and ascending long-tract axonal conductivity across a SCI with this pharmacological approach. Since descending long-tract axonal conductivity did not return to normal, further evaluations of the pharmacokinetics and therapeutic window of rolipram as well as optimal combinations are necessary before consideration for neuroprotection in humans with SCI.

Measurement of anal cushions in idiopathic faecal incontinence.

BACKGROUND: Faecal incontinence affects a heterogeneous population and aetiology can be multifactorial. In a subset of patients the aetiology remains idiopathic despite standard investigations. Anal cushions are important in normal continence, but have rarely been studied. The aim of this study was to measure the size of the anal cushions and to evaluate their role in patients with idiopathic faecal incontinence. METHODS: Women in whom idiopathic faecal incontinence was diagnosed after standard anorectal investigations underwent transvaginal ultrasonography. The area of the anal cushions was measured and a cushion : canal (C : C) ratio derived, which was compared with that in a control group of women without faecal incontinence. RESULTS: Some 21 patients with incontinence (median age 60 years) and 102 asymptomatic controls (median age 41 years) underwent scanning. The median (interquartile range) C : C ratio in the symptomatic group was significantly lower than that for controls (0.57 (0.54-0.66) versus 0.68 (0.61-0.73) respectively; P = 0.001). C : C ratio was not influenced by age (r = 0.023, P = 0.821). CONCLUSION: The C : C ratio was reduced in patients with idiopathic faecal incontinence.

Morbidity and mortality after closure of loop ileostomy.

BACKGROUND: A temporary loop ileostomy is commonly used to protect low pelvic anastomoses. Closure is associated with morbidity and mortality. This study investigated patterns of complications after loop ileostomy closure and factors associated with morbidity and mortality. METHOD: A review was performed of patients who underwent loop ileostomy closure between 1999 and 2005. RESULTS: Three hundred and twenty-five patients underwent closure of loop ileostomy. Reasons for primary surgery were: anterior resection for cancer (n = 160, 49%), ileal pouch-anal anastomosis (n = 114, 35%), diverticular disease (n = 25, 8%), Crohn's colitis (n = 4, 1%) and other conditions (n = 22, 7%). Overall mortality was 2.5% (n = 8) and morbidity was 22.8% (n = 74). Thirty-two patients (10%) developed small bowel obstruction, of whom seven required operative intervention. Overall, the re-operation rate in this series was 28 patients (8.6%). Thirteen (4%) patients had an anastomotic leak of whom 12 patients had re-operation. Preoperative anaemia was significantly associated with leakage (Hb < 11 g/dl; n = 65, P = 0.033). The leakage rate was lower after a stapled anastomosis than a hand-sutured anastomosis (4/203 vs 9/122; P = 0.039). Hypo-albuminaemia (albumin < 34 g/l) was significantly associated with mortality (n = 46, P < 0.001). CONCLUSIONS: Loop ileostomy closure is associated with morbidity and mortality. Anaemia and hypo-albuminaemia may be associated with poor outcome.

Oral antioxidant supplementation for fatigue associated with primary biliary cirrhosis: results of a multicentre, randomized, placebo-controlled, cross-over trial.

BACKGROUND: We have previously reported, in an uncontrolled trial, an improvement in fatigue scores in patients with primary biliary cirrhosis given oral antioxidant supplementation. We now present data from a controlled trial. PATIENTS AND METHODS: Sixty-one patients with primary biliary cirrhosis-associated fatigue were randomized into a double-blind, placebo-controlled, cross-over trial. Participants received 12 weeks each of placebo and antioxidant supplementation (vitamins A, C and E, selenium, methionine and ubiquinone) in random order, separated by a 4-week washout period. The primary trial outcome (fatigue) was assessed using the Fisk scale. Other symptoms of primary biliary cirrhosis were measured using Likert and visual analogue scales. RESULTS: Forty-four patients completed both arms of the trial. No significant changes in fatigue were recorded in the active phase of treatment (median improvement in Fisk score, 1; P = 0.61). Small improvements in Fisk scores were recorded during placebo therapy (median improvement, 4; P = 0.03). Neither medication was associated with improvement in any other symptoms related to primary biliary cirrhosis. Adverse effects were more common during active therapy and were mild and self-limiting. One patient died from unrelated causes during active treatment. CONCLUSIONS: Although oral antioxidant supplementation appears to be safe, we could not find any evidence for a beneficial effect on fatigue or other liver-related symptoms.

Incidence rates and populations at risk for spinal cord injury: A regional study.

STUDY DESIGN: A 6 year retrospective study was conducted. OBJECTIVES: The populations at risk for spinal cord injury (SCI) in the northwestern Kentucky (KY) and southern Indiana (IN) regions were identified following examination of the causes and factors associated with SCI. SETTING: The database included patients primarily from the surrounding KY and IN counties admitted to the University of Louisville (U of L) Hospital. METHOD: Specification of SCI patient demographics, injury causes and related factors was achieved utilizing the hospital's trauma institute database and an extensive review of patient medical records. RESULTS: An adjusted average incidence rate of 27.1 cases per million per year was obtained for this region. A high rate of SCI was found for the youngest age group, 14-24 year olds, and for African Americans. A high frequency of injuries was also observed for adults between the ages of 25-39 years. Motor vehicle accidents (MVA) were the leading cause of SCI. Contributing factors included alcohol and widespread non-use of vehicle safety precautions. CONCLUSIONS: In addition to the high proportion of youth at risk for SCI, a higher proportion of older adults with SCI was observed for this region compared to other studies. Because the primary source of transportation in this area is the use of private vehicles, rather than public transportation, greater effort is warranted in emphasizing the potential risks of combining driving with alcohol consumption and non-use of seatbelts.

A topical mixture for preventing, abolishing, and treating autophagia and self-mutilation in laboratory rats.

The dysesthesia and paresthesia that occurs in laboratory rats after spinal cord injury and peripheral nerve injury results in autophagia and self-mutilation. This self-destructive behavior interferes with functional assessments in designed studies and jeopardizes the health of the injured rat. We developed a topical mixture that prevents, abolishes, and treats autophagia and self-mutilation. When the mixture is applied to the limb, its bitterness effectively prevents the rat from licking and biting the limb. In addition, the mixture has antiseptic properties.

Embryonic brain precursors transplanted into kainate lesioned rat spinal cord.

Embryonic day 14 rat cerebral cortex-derived precursors were expanded with FGF2 and labeled with BrdU prior to being transplanted into the kainic acid-lesioned adult rat spinal cord. While these precursors give rise to cells with neuronal, astrocytic and oligodendroglial phenotypes vitro, they remained largely undifferentiated up to 12 weeks in vivo. Numerous BrdU-labeled cells were found in injured gray matter, and also lining the dilated central canal that sometimes accompanies these lesions. BrdU-labeled cells never co-expressed Map2ab, rarely co-expressed GFAP but often co-expressed nestin, even after 12 weeks in vivo. These observations suggest that the environment of the kainic acid-injured spinal cord is not hostile to transplanted embryonic cerebral cortex-derived precursors, but also is not conducive to their neuronal differentation.

Lasting paraplegia caused by loss of lumbar spinal cord interneurons in rats: no direct correlation with motor neuron loss.

OBJECT: The aims of this study were to investigate further the role played by lumbar spinal cord interneurons in the generation of locomotor activity and to develop a model of spinal cord injury suitable for testing neuron replacement strategies. METHODS: Adult rats received intraspinal injections of kainic acid (KA). Locomotion was assessed weekly for 4 weeks by using the Basso, Beattie, and Bresnahan (BBB) 21-point locomotor scale, and transcranial magnetic motor evoked potentials (MMEPs) were recorded in gastrocnemius and quadriceps muscles at 1 and 4 weeks. No changes in transcranial MMEP latency were noted following KA injection, indicating that the descending motor pathways responsible for these responses, including the alpha motor neurons, were not compromised. Rats in which KA injections included much of the L-2 segment (10 animals) showed severe locomotor deficits, with a mean BBB score of 4.5 +/- 3.6 (+/- standard deviation). Rats that received lesions rostral to the L-2 segment (four animals) were able to locomote and had a mean BBB score of 14.6 +/- 2.6. Three rats that received only one injection bilaterally centered at L-2 (three animals) had a mean BBB score of 3.2 +/- 2. Histological examination revealed variable loss of motor neurons limited to the injection site. There was no correlation between motor neuron loss and BBB score. CONCLUSIONS: Interneuron loss centered on the L-2 segment induces lasting paraplegia independent of motor neuron loss and white matter damage, supporting earlier suggestions that circuitry critical to the generator of locomotor activity (the central pattern generator) resides in this area. This injury model may prove ideal for studies of neuron replacement strategies.

The role of directly applied hypothermia in spinal cord injury.

STUDY DESIGN: The effect of intense local hypothermia was evaluated in a precision model of spinal canal narrowing and spinal cord injury in rats. The spinal cord injury was cooled with a custom cooling well used over the epidural surface. Basso, Beattie, and Bresnahan (BBB) motor scores and transcranial magnetic motor-evoked potential (tcMMEP) responses were used after injury to accurately evaluate neurologic recovery. OBJECTIVE: This study was undertaken to determine whether the prognosis for neurologic recovery in a standardized rat spinal cord injury model is altered by the direct application of precisely controlled hypothermia to the area of injury. SUMMARY OF BACKGROUND DATA: The role of hypothermia in the treatment of spinal cord injuries with neurologic deficits remains undefined. Hypothermia may decrease an area of spinal cord injury and limit secondary damage, therefore improving neurologic recovery. However, it has been difficult to consistently apply localized cooling to an area of spinal cord injury, and the use of systemic hypothermia is fraught with complications. This fact, along with the unavailability of a precise spinal cord injury model, has resulted in inconsistent results, both clinically and in the laboratory. In a rat model of spinal cord injury, 37 C and 19 C temperatures were used to study the role of hypothermia on neurologic recovery. METHODS: Male Spraque-Dawley rats (n = 52; weight, 277.7 g) were anesthetized with pentobarbital and subjected to laminectomy at T10. The rats were divided into three groups: 1) placement of a 50% spacer in the epidural space (16 rats), 2) severe (25 g/cm) spinal cord injury (16 rats), 3) 50% spacer in combination with spinal cord injury (16 rats). Eight rats in each group were tested at two temperatures: normothermic (37 C) and hypothermic (19 C). With the use of a specially designed hypothermic pool placed directly over the spinal cord for 2 hours, epidural heating to 37 C, and epidural cooling to 19 C was accomplished. Simultaneous measurements of spinal cord and body temperatures were performed. The rats underwent behavior testing using the BBB motor scores and serial tcMMEPs for 5 weeks. Statistical methods consisted of Student's t tests, one-way analysis of variance, Tukey post hoc t tests and chi2 tests. RESULTS: There was a significant improvement in motor scores in rats subjected to hypothermia compared with those that were normothermic after insertion of a 50% spacer. This improvement was observed during the 5-week duration of follow-up. In the severe spinal cord injury group and the spinal cord injury-spacer groups, no significant improvement in motor scores were obtained when the spinal cord was exposed to hypothermia. CONCLUSION: The results demonstrate that there is a statistically significant (P < 0.05) improvement in neurologic function in rats subjected to hypothermia (19 C) after insertion of a spacer that induced an ischemic spinal cord injury. This indicates that directly applied hypothermia may be beneficial in preventing injury secondary to ischemic cellular damage. The data demonstrated minimal therapeutic benefit of hypothermia (19 C) after a severe spinal cord injury.

Magnetic motor evoked potential monitoring in the rat.

OBJECT: The authors conducted a study to provide an objective electrophysiological assessment of descending motor pathways in rats, which may become a means for predicting outcome in spinal cord injury research. METHODS: Transcranial magnetic motor evoked potentials (TMMEPs) were recorded under various conditions in awake, nonanesthetized, restrained rats. Normative data were collected to determine the reproducibility of the model and to evaluate the effect of changing the stimulus intensity on the evoked signals. In addition, an experiment was performed to determine if the TMMEPs produced were the result of auditory startle response (ASR) potentials elicited by the sound generated by the movement of the copper coil inside its casing during magnetic stimulation. Transcranial magnetic motor evoked potentials were elicited after magnetic stimulation. At 100% stimulus intensity, the mean forelimb onset latency was 4.2 +/- 0.39 msec, and the amplitude was 9.16 +/- 3.44 mV. The hindlimb onset latency was 6.5 +/- 0.47 msec, and the amplitude was 11.47 +/- 5.25 mV. As the stimulus intensity was decreased, the TMMEP onset latency increased and the response amplitude decreased. The ASR potentials were shown to have longer latencies, smaller amplitudes, and were more variable than those of the TMMEPs. CONCLUSIONS: These experiments demonstrate that TMMEPs can be recorded in awake, nonanesthetized rats. The evoked signals were easy to elicit and reproduce. This paper introduces noninvasive TMMEPs as a new technique for monitoring the physiological integrity of the rat spinal cord.

Psoralen plus UVA protocol for Compositae photosensitivity.

BACKGROUND: Patients allergic to sesquiterpene lactones found in Compositae plants may develop severe photosensitivity, which can result in persistent light reaction. Treatment of these exquisitely photosensitive individuals can be very difficult, often requiring hospitalization. Although some treatment regimens have used psoralen plus UVA (PUVA) therapy, no specific outpatient protocol has been established OBJECTIVE: The purpose of this study was to develop an effective PUVA outpatient regimen to treat compositae photosensitivity. METHODS: A prednisone-assisted PUVA protocol was established in which the prednisone does was decreased weekly, and the PUVA dose was increased during the same time interval. RESULTS: Both patients enrolled in the study experienced dramatic improvement in their previously unresponsive eruptions. CONCLUSIONS: Two men aged 66 and 80 years were subjected to this protocol. Both men had chronic photodistributed dermatitis that resolved with this treatment and in one instance has remained clear for 18 months without needing further PUVA therapy.

Use of the Miniscreen assay to screen novel compounds for bacterial mutagenicity in the pharmaceutical industry.

In vitro assays for mutagenicity are an important feature of pre-clinical testing and form part of the current regulatory testing conducted early in drug development. They can also play a part in compound selection since mutagenic compounds can be eliminated from a range of potential candidates. Bacterial tests are particularly useful in this area because they generate results quickly, though their use may be limited because they can require up to 4 g of material. A scaled-down version of the Ames test has been developed which requires only approximately 20 mg of material. Initial experiences with this assay using a range of known mutagens and novel compounds have shown that the Miniscreen has similar sensitivity to the Ames test. The major exception is for those mutagens preferentially detected with strains TA1537 and TA1535, which, because of their low spontaneous counts, are not employed in the Miniscreen.

Evaluation of pyrazole and ethanol induced S9 fraction in bacterial mutagenicity testing.

A major constitutive enzyme in the liver of the uninduced rat is cytochrome P450-2E1. This isozyme has been shown to metabolize a number of carcinogens, including low molecular weight nitrosamines and a number of compounds normally regarded as non-mutagenic in the Ames test, e.g. aniline, urethane and benzene. Using the standard induction procedures [Aroclor 1254 or a combination of phenobarbitone (PB) and beta-naphthoflavone (beta-NF)] the level of CYP2E1 in rat liver is actually suppressed and it has been suggested that this may account for the negative findings with these compounds in the Ames test. S9 fractions were prepared from rats pre-treated with pyrazole or ethanol (inducers of CYP2E1) and then used in the Ames test (or pre-incubation modification) with urethane, acetaminophen, aniline, benzene, procarbazine and N-nitrosopyrrolidine. Both pyrazole and ethanol induced S9 were superior to PB/beta-NF-S9 and uninduced-S9 for the activation of N-nitrosopyrrolidine, a known CYP2E1 substrate. However, there was no evidence of mutagenic activity with urethane, aniline, benzene, procarbazine or acetaminophen. As these compounds have demonstrated genotoxicity in vivo, additional important metabolic pathways must be required which are not present in rat liver S9 fraction.

Oral tobramycin in ulcerative colitis: effect on maintenance of remission.

Oral tobramycin for 7 days has been shown to be of benefit as an adjunct to conventional medication in acute ulcerative colitis. Eighty-one patients (40 who had received tobramycin; 41 placebo) who had been enrolled in a double-blind placebo-controlled trial of this drug in acute disease were subsequently followed to determine whether this short-term benefit persisted. Relapse was defined as a liquid stool frequency of three times daily with rectal bleeding. Results were analysed by the log-rank test on Kaplan-Meier survival curves. Treatment failure was defined as a lack of response by the end of the acute trial period, or subsequent relapse. In a second analysis, only those entering remission at the end of the acute trial were considered, and followed to relapse. Although at the start of the follow-up period significantly fewer patients in the tobramycin group had failed (failed: tobramycin 9, placebo 24; not failed tobramycin 31; placebo 17; P = 0.001), the failure-free survival curves subsequently converged and did not differ significantly. After 1 and 2 years, the failure-free survival rates were 40% (S.E. = 7.8%) and 20% (S.E. = 6.3%) for the tobramycin group and 24% (S.E. = 6.7%) and 12% (S.E. = 5.1%) for the placebo group. When only those entering remission were considered, there was no significant difference in the relapse rates in the two groups. Benefit from tobramycin is therefore short-lived and may reflect short-term changes in the faecal flora.

Double blind trial of oral fluticasone propionate v prednisolone in the treatment of active ulcerative colitis.

Fluticasone propionate is a corticosteroid with the potential for topical treatment of ulcerative colitis because of low systemic bioavailability. The drug was compared with prednisolone in the management of active left sided or total ulcerative colitis. Two hundred and five patients were studied in the multicentre four week double blind study. Prednisolone was given in a dose of 40 mg daily orally, reducing over four weeks to 10 or 20 mg. Fluticasone propionate was given in an oral daily dose of 20 mg. The primary end point was the investigator's overall assessment of response. Patient's assessment, sigmoidoscopic appearance, and histology were also studied. Patients improved more rapidly with prednisolone. Differences between the two groups were significant at two weeks. At four weeks differences were not significant, but there was a trend in favour of prednisolone. Corticosteroid side effects were minimal in the fluticasone propionate group, and there was minimal suppression of the hypothalamic pituitary adrenal axis. Fluticasone propionate 20 mg daily is not as effective in the treatment of active ulcerative colitis as prednisolone tapering from 40 mg daily to 10 or 20 mg. The complete absence of suppression of the corticoadrenal axis by fluticasone propionate was encouraging, however, and a higher dosage schedule should be assessed.

A method of enhancing verocytotoxin production by Escherichia coli.

The number of verocytotoxin producing Escherichia coli (VTEC) present in the faeces during an infection may be very low, making their detection difficult. We report a method for enhancing toxin production by VTEC using mitomycin C as an inducing agent with the aim of improving the detection of VTEC. In pure culture, mitomycin C enhanced toxin production up to 100-fold. When applied to mixed faecal culture, toxin could be detected in mitomycin C treated samples when standard cultures were negative and when substantially fewer verocytotoxin-producing bacteria were present. Use of this method may aid in the detection of VTEC and is appropriate for use in the routine diagnostic laboratory.

The effect of glutamine-enriched TPN on gut immune cellularity.

Prolonged parenteral feeding with standard nutrient solutions results in significant alteration in the structural, hormonal, and immunological composition of the intestinal tract. The purpose of the following study was to evaluate the effect of glutamine-supplemented parenteral nutrition on the immune cellularity of the gut. Twenty-one Fischer rats were randomized to three groups of seven animals each. Group I was fed rat chow and water ad lib, Group II was fed a standard solution of total parenteral nutrition (TPN) (D25/4.25% amino acids) via a central venous catheter, and Group III was fed the standard solution of TPN with 2% glutamine which was isonitrogenous and isocaloric to Group II. Animals were fed their respective diets for 1 week and bile was collected and assayed for secretory IgA (s-IgA) and IgM. The terminal ileum was stained and assayed for IgA+, IgM+, IgG+, CD4+, and CD8+ plasma cells and lymphocytes. Results indicate that the feeding of a standard parenteral diet results in a significant decrease in biliary s-IgA and IgA+ plasma cells in the gut lamina propria compared to chow-fed animals (S-IgA: chow, 858 +/- 23 micrograms/ml; TPN, 494 +/- 41 micrograms/ml; IgA cells: chow, 35.7 +/- 1.8; TPN, 8.6 +/- 0.9 cells/hpf). In addition a marked depletion of CD4+ and CD8+ lymphocytes was observed with standard solutions of parenteral nutrition compared to chow (CD4+: chow, 36.8 +/- 6.6; TPN, 14.9 +/- 6.0; CD8+: chow, 18.8 +/- 5.6; TPN, 5.7 +/- 2.7 cells/hpf). The addition of glutamine to the standard TPN solution maintained both B and T cell populations at levels similar to chow-fed animals.(ABSTRACT TRUNCATED AT 250 WORDS)