Changing paradigm of sacral neuromodulation and external anal sphincter repair for faecal incontinence in specialist centres.

AIM: The aim of this study was to determine whether the paradigm of surgical intervention for faecal incontinence (FI) has changed between 2000 and 2013. METHOD: This was a multi-centre retrospective study of patients who had undergone either sacral neuromodulation (SNM) or delayed sphincter repair or sphincteroplasty (SR) as a primary surgical intervention for FI in five centres in Europe and one in the United States. The flow of patients according to the intervention, sustainability of the treatment at a minimum follow-up of 5 years, complications and requirement for further interventions were recorded. RESULTS: A total of 461 patients (median age 56 years, range 24-90 years, 41 men) had either SNM or SR as an index operation during the study period [SNM 284 (61.6%), SR 177 (38.4%)]. Among SNM patients, there were 169 revisional operations (change of battery and/or lead, re-siting or removal). At the time of last follow-up 203 patients (71.4%) continued to use SNM. Among SR patients, 30 (16.9%) had complications, most notably wound infection (22, 12.4%). During follow-up 32 patients (18.1%) crossed over to SNM. Comparing two 4-year periods (2000-2003 and 2007-2010), the proportion of patients operated on who had a circumferential sphincter defect of less than 90° was 48 (68%) and 45 (46%), respectively (P = 0.03), while those who had SNM as the primary intervention increased from 29% to 89% (P < 0.05). CONCLUSION: The paradigm of surgical intervention for FI has changed with increasing use of SNM.

Adverse obstetric history is not a risk factor for poor outcome after ventral rectopexy for obstructive defaecation syndrome.

AIM: Ventral rectopexy (VR) has gained popularity in the management of obstructive defaecation syndrome (ODS) due to a symptomatic rectocele ± intussusception. Data on the efficacy and safety of VR are variable and there are few predictors of successful outcome. This study aimed to examine whether or not an adverse obstetric history influenced the functional outcome following VR for ODS. METHOD: This was a retrospective study of a cohort of 76 consecutive patients who had undergone VR for ODS at a tertiary referral centre between 2012 and 2015. Patients were followed up by telephone questionnaire. The obstetric history and pre- and postoperative symptoms of ODS and faecal incontinence (FI) were obtained from telephone interviews. RESULTS: In this cohort, symptoms of ODS were significantly improved by surgery, with 56% of patients showing a reduction of symptoms of 50% or more (P < 0.001). Subgroup analysis demonstrated that a lower body mass index (BMI; 24.4 vs 27.3 kg/m2 ; P < 0.05) and shorter duration of symptoms (7 vs 10 years; P < 0.05) led to a better outcome. VR had no effect on FI. Obstetric factors such as foetal weight, instrumental delivery, episiotomy, perineal tear and total number of deliveries did not influence outcomes. CONCLUSION: Patients with a less straightforward obstetric history can be reassured that this should not adversely influence the functional outcome after VR for ODS. Colorectal surgeons who offer this surgery should warn patients with an elevated BMI or with longstanding symptoms that the operation may be less successful than for those with a lower BMI or shorter duration of symptoms.

Self-expanding metallic stent insertion in the proximal colon.

OBJECTIVE: Colonic obstruction may be relieved by the insertion of a self-expanding metallic stent (SEMS), either for permanent palliative relief or as a bridge to surgery. Lesions proximal to the descending colon can be more difficult to intubate and stent [1]. SEMS placement in the more proximal colon lesions has been reported in only a few cases [2,4]. The aim of this study was to review the outcome of SEMS for obstruction at the splenic flexure and above. METHOD: A study of all colonic stents inserted in one specialist unit was undertaken. Patients' demographics, site and aetiology of the underlying obstruction, success or other outcome of the procedures were collected. Thirty-day morbidity and mortality were documented. RESULTS: Seven patients had proximal lesions: four in the transverse colon and three at the splenic flexure. Six patients had colorectal carcinoma and one had extrinsic compression from a gastric carcinoma. Six of the SEMS were inserted for permanent palliation, and one as a bridge to surgery. Stent placement was technically successful in six of the seven patients. In the seventh patient, there was a failure of expansion of the stent, after successful intubation of the lesion, which was in the distal transverse colon. One patient suffered from minor self-limiting abdominal pain in the first 24 h after the procedure. There was no other SEMS related morbidity or mortality. All of the successfully stented patients were discharged from the surgical ward within 3 days after the procedure. Median survival time was 4.3 months (range 3-12 months). Three patients are still alive. CONCLUSION: The SEMS is a useful tool in managing acute bowel obstruction. Placement of colonic stents proximal to the descending colon is safe, feasible and effective.

Outcomes of the rectal remnant following colectomy for ulcerative colitis.

OBJECTIVE: Controversy surrounds the optimal surgical management of the distal rectal remnant during colectomy for ulcerative colitis (UC) and the potential benefit from the placement of a rectal catheter for remnant drainage. This study reviews the clinical outcomes of patients who have undergone colectomy for UC with intra-peritoneal closure of the rectal remnant. METHOD: Analysis of prospective data lodged on Lothian Surgical Audit databases from patients treated in a tertiary coloproctology unit over 11 years. RESULTS: One hundred and fifty-nine patients were identified, the mean age was 41.9 years, 63% were men. Failure of maximal medical therapy necessitated surgery for 78.1% patients, while 12.6% had acute perforation and 11.9% had toxic megacolon. Complications included five (3.1%) stump dehiscences, eight (5.0%) intra-abdominal/pelvic collections, four (2.5%) significant wound infections, three (1.9%) small bowel obstructions and three (1.9%) deaths. Within the follow-up period, 62.3% patients had an ileo-pouch anal anastomosis (IPAA), 7.5% patients had a completion proctectomy, 10.1% patients within the series had a retained rectal remnant after 1 year follow up, the remaining patients had less than 1 year follow up. CONCLUSION: The intra-peritoneal rectal stump following colectomy for UC is associated with low rates of pelvic sepsis and a high proportion of patients successfully proceeding to IPAA.

Studies of influenza virus infection in newborn ferrets.

Influenza virus infection by the intranasal route was found to be invariably fatal in newborn ferrets. Some obviously died of influenza pneumonia; others died of aspiration pneumonia or showed only minimal or non-specific changes in the lungs. All, however, had severe lesions in the upper respiratory tract, and it is suggested that obstruction of airways and oesophageal passages, in combination with feeding difficulties, played a major role in causing death. The relevance of the findings to the pathology of cot deaths in human infants is briefly discussed.

Comparison of Immobilon-N membrane and other membranes for the detection of HIV-1 genome in high risk patients using PCR.

The polymerase chain reaction (PCR) was used for detection of the HIV-1 genome from the peripheral blood lymphocytes of high risk patients. The gag regions of HIV-1 (SK38-SK39) were chosen to amplify viral DNA and the amplified products were spotted onto membrane filters and hybridized with a 32P-labeled SK19 probe. Nitrocellulose, nylon and polyvinylidene difluoride (PVDF) membrane filters were used and compared in dot-blot hybridization. PVDF (Immobilon-N, trade name) filter membranes were demonstrated to be the best membranes on the basis of hybridization data and showed a stronger signal on autoradiograms than the other two types (nitrocellulose and nylon).

Regional distribution of Ginkgo biloba-induced c-Fos immunoreactivity.

A growing literature supports the notion that Ginkgo biloba has cognitive enhancing and anxiolytic properties; however, its effects on neuronal populations have yet to be characterized. The present study used c-Fos immunoreactivity (Fos-IR) to characterize functional activity in selected brain regions following administration of a standardized Ginkgo biloba extract. Because Ginkgo is typically consumed orally, Exp 1 sought to identify patterns of neural activity induced by oral administration. To ensure that the alterations in functional neural activity observed in Exp 1 were not simply due to novel gustatory experience, Exp 2 characterized patterns of Fos-IR following intraperitoneal administration of Ginkgo. Rats were habituated to handling and experimental conditions. In Exp 1, rats self-administered 150 mg/kg Ginkgo or vehicle alone (strawberry jam) orally. In Exp 2, rats were injected with Ginkgo (2.5 or 25 mg/kg, i.p.) or vehicle (0.3% gum Arabic). Animals were anaesthetized and perfused transcardially. Brains were sectioned, immunostained using a c-Fos antibody, then the number of labelled cells was quantified microscopically in selected brain regions. In both experiments Ginkgo increased Fos-IR in numerous brain regions including the insular cortex and amygdala. Intraperitoneal administration induced Fos-IR in some additional regions including the nucleus accumbens and dentate gyrus. Results provide important preliminary data serving to identify several candidate neural sites involved in the cognitive enhancing and anxiolytic effects of Ginkgo biloba.

Influence of antigen dose on antibody production of intact and splenectomised Xenopus laevis.

Antigen persistence and serum antibody production in intact Xenopus were monitored using human gamma globulin (HGG), in adjuvant, in various immunisation schedules. Retention of HGG in spleen and serum was directly related to the quantity injected. However, antibody responses to a dose range between 1 mu-g-6 mg antigen were similar in intensity. These were detected in the serum two weeks after injection and at this stage were exclusively mercapto-ethanol (ME) sensitive; ME-resistant antibodies had appeared by four weeks. No antibodies were detected below a dose of 100 ng HGG. The effect of splenectomy on antibody levels was tested using HGG/adjuvant or sheep erythrocytes (SRBC) in saline. Splenectomised toads showed impairment of antibody responses only to threshold doses of HGG (100 ng) but to a wider range of SRBC doses.

Functional and morphological changes associated with the ageing of primary cultures of embryonic adrenal gland cells derived from the Pekin duck.

The morphological and functional changes associated with ageing were studied in adrenal steroidogenic cells derived from duck embryos. Cells grown for not more than three days had structural characteristics similar to their counterparts in vivo; they contained numerous lipid droplets and mitochondria, an abundant smooth endoplasmic reticulum, an even network of microtubules, and microfilaments that formed extensive and elaborate systems of parallel stress fibers. After the 3rd day of growth in culture, many of the cells started to decrease in size and become elongated; the older cells showed less well-defined actin filaments and contained elongated mitochondria, fewer lipid droplets, less smooth endoplasmic reticulum, and swollen cisternae of rough endoplasmic reticulum. The proliferative capacity of the cells was the same when they were cultured in either the presence or the absence of 1-24 ACTH. After the first day of growth in culture, the steroidogenic capacity of the cells declined and the addition of 1-24 ACTH to the growth medium did not prevent changes in their structure and function. The decline in steroidogenic capacity occurred both in terms of the amount of hormone released into the culture medium and in the ability of the cells to respond when incubated in buffer containing 1-24 ACTH. Since the basal unstimulated rates of corticosteroid production also declined as the cells aged, it is probable that the steroidogenic deficiency occurs at a site distal to the corticotropin receptor; this is also consistent with the ultrastructural observations that suggest a relationship between the morphological changes and the decline in steroidogenic capacity as the cells age.

A comparison of the responses of dispersed steroidogenic cells derived from embryonic adrenal tissue from the domestic chicken (Gallus domesticus), the domestic Pekin duck and the wild mallard duck (Anas platyrhynchos), and the domestic muscovy duck (Cairina moschata).

The steroidogenic responsiveness of adrenal cell suspensions prepared from domestic chicken adrenal tissue at the end of embryogenesis was compared to the responses of similar preparations derived from the wild and domesticated mallard duck (Anas platyrhynchos), and the domesticated muscovy duck (Cairina moschata). In all cases, the masses of corticosterone (B), aldosterone (Aldo), and deoxycorticosterone (DOC) released from cells incubated in medium containing 1-24 ACTH exceeded the estimated hormone content of the freshly dispersed cells; the induced rates of corticosteroid release were, therefore, presumed to reflect de novo hormone synthesis. When chicken cells were incubated in medium containing 1-24 ACTH, there were progressive, dose-dependent increases in B and DOC synthesis over a range of concentrations spanning two orders of magnitude; only small, non-dose-related, albeit significant, increases in Aldo release were observed. The 1-24 ACTH-induced increases in B and Aldo synthesis by the mallard and Pekin duck cells exposed to the same range of concentrations were up to 40 and 60 times greater than the corresponding responses of the chicken cells. The rates of 1-24 ACTH-induced B and DOC release from muscovy duck cells were similar to those from the Pekin duck cells; compared with the mallard duck cells, however, the muscovy duck cells were less sensitive and the maximum inducible rate of B release was significantly lower. The pattern of 1-24 ACTH-induced Aldo release from the muscovy duck cells was indistinguishable from that of the mallard duck cells, although the maximum inducible increase occurred at a lower concentration. Angiotensin II (AII) induced very small, but significant increased in B, Aldo, and DOC release from the chicken cells but in a nondose-related fashion. In contrast, mallard, Pekin, and muscovy duck cells all responded in a dose-dependent manner when incubated in medium containing AII. In each instance the maximum rate of Aldo synthesis induced by AII was about one-tenth of the corresponding rate induced by 1-24 ACTH. The maximum rates of B synthesis induced by AII, however, were extremely low compared with the rates induced by 1-24 ACTH. Thus, when maximally stimulated with AII the B:Aldo output ratio ranged from 1.0 to 1.9, whereas the corresponding ratio was between 9.0 and 17.0 when the cells were maximally stimulated with 1-24 ACTH.

Association of foetal wastage with influenza infection during ferret pregnancy.

Inoculation of influenza virus into pregnant ferrets during the late gestational period was investigated. Foetal resorption followed intracardial inoculation of a large dose of influenza virus (10(9.4) EBID50) and a 100-fold lower dose caused lower litter sizes at birth. The possible role of fever in foetal resorptions was largely discounted by 2 observations: a non-pyrexic dose inoculated intracardially into the pregnant ferret still had detrimental effects on foetal viability; influenza virus inoculated intranasally caused a pyrexia but did not affect the progeny. The potential of the ferret as a model for studying the possible adverse effects of influenza during pregnancy is discussed.

Infection of neonatal and adult mice with non-passaged influenza viruses. Brief report.

In contrast to adult mouse influenza, infection of neonates with non-passaged influenza viruses (7a and 64c) resulted in approximately 50 per cent mortality. Virus predominated in the upper respiratory tract though the neonatal lung infection was greater than in adults.

Sensitivity to pyrexial temperatures: a factor contributing to virulence differences between two clones of influenza virus.

The influence of pyrexia on the differential persistence of a virulent and an attenuated clone of influenza virus in the respiratory tract of ferrets has been further studied. Clone 64d, an attenuated clone of a recombinant virus (A/PR/8/34-A/England/939/69 (H3N2)) grown in organ cultures of ferret nasal turbinates, was inactivated at pyrexial temperatures more readily than a virulent Clone 7a. In addition, replication of Clone 64d was restricted at pyrexial temperatures to a greater extent than that of Clone 7a in organ cultures of both ferret nasal turbinate and lung tissue. The greater adverse effects of pyrexial temperatures on Clone 64d appears to explain the earlier reduction of upper respiratory tract infection seen in ferrets infected with this attenuated clone. Also, the differential influence of pyrexial temperatures may be the reason for the virtual lack of lung infection with Clone 64d in vivo in contrast to the consistent infection found with Clone 7a. The relevance of these findings to human infection and to markers of attenuation of influenza virus is discussed.

Antibody production to lipopolysaccharide in thymectomized Xenopus.

Xenopus toadlets, some of which had been thymectomized as larvae, were immunized with E. coli lipopolysaccharide. Antibody titers were similar in thymectomized and intact toadlets. Antibody was exclusively IgM. The results suggest that a division into thymus-dependent and thymus-independent anti-body responses extends at least as far back in phylogeny as the amphibians.

Cytoskeletal changes accompanying ACTH-induced steroidogenesis in cultured embryonic adrenal gland cells from the Pekin duck.

Cells derived from the adrenal glands of duck embryos immediately prior to hatching were grown in culture and used to study the morphological and cytoskeletal changes and steroidogenic responses induced by 1-24 ACTH. Changes in the cytoskeletal components were observed by rhodamine-phalloidin staining for actin and by staining the tubulin immunoreactive components with FITC. The cultures were comprised of a small population of chromaffin cells and a larger population of steroidogenic cells. The chromaffin cells were distinguished by their tyrosine hydroxylase immunoreactivity. The steroidogenic cells were characterized by the presence of sudanophilic lipid droplets, numerous mitochondria, abundant smooth endoplasmic reticulum, microtubules distributed as a fairly even network throughout the cytoplasm, and microfilaments that formed an extensive and elaborate system of stress fibers with many parallel arrays. The cells readily responded to stimulation with ACTH by releasing corticosterone, aldosterone and deoxycorticosterone. Stimulation with ACTH also induced changes in both the cell morphology and the cytoskeleton. Exposure of the cells to Krebs-Henseleit buffer containing 1-24 ACTH caused them to form numerous fine filopodia, to lose their stress fibers, and to form a thick ring of actin at the periphery of the cell. In addition, many cells became extremely arborized with many long branched dendritic processes. The morphological changes appeared to be related to a redistribution of the actin components, and may be explained only in part by the rounding up or retraction of the cytoplasm. The results strongly suggest an involvement of the actin components of the cytoskeleton in the steroidogenic response to corticotropic stimulation.

Distribution of viral antigen with the lower respiratory tract of ferrets infected with a virulent influenza virus: production and release of virus from corresponding organ cultures.

Using fluorescent antibody techniques, a semi-quantitative survey has been made of the distribution of influenza virus antigen in the trachea, main bronchi, and three zones (hilar, intermediate and alveolar) of all four lung lobes of ferrets following intranasal inoculation of a virulent clone (7a) of the recombinant influenza virus A/PR/8/34-A/England/939/69 (H3N2). The results confirm the indications from our previous quantitative surveys of infectious virus and histological damage in these areas, namely that infection is confined largely to airway epithelium and is rare in the alveoli. Furthermore, in the lung zones, viral antigen resided mainly in the bronchial rather than bronchiolar epithelium. In attempts to identify the reasons for lack of alveolar involvement organ cultures of alveolar tissue, from which all major airways had been removed, produced levels of virus similar to cultures of bronchus and trachea and the hilar and intermediate lung zones which contain airway and alveolar tissue. Hence, the lack of alveolar infection in vivo must be due to factors which prevent virus attack of susceptible alveolar cells. However, these organ culture experiments showed that a contributing factor could be very poor release of virus from any alveolar cells that do become infected. In contrast, although cultures of bronchi produced less virus than those of nasal turbinates (the most susceptible tissue in vivo) they released a high proportion of their yield and this ease of release may contribute to spread of infection in vivo.

The role of naturally-acquired bacterial infection in influenza-related death in neonatal ferrets.

Concomitant, naturally-acquired bacterial infection was the cause of some deaths occurring in neonatal ferrets infected with the attenuated influenza virus A/Puerto Rico/8/34, these being prevented by antibiotic therapy. Bacterial infection played an insignificant role in the greater number of deaths following inoculation with the virulent clone 7a (of the recombinant influenza virus A/Puerto Rico/8/34-A/England/939/69/(H3N2]. As seen previously with clone 7a some ferret neonates infected with A/PR/8/34 died either from obstruction in the upper respiratory tract or from viral pneumonia, but with the latter virus, both types of lesion were probably attributable to the bacterial superinfection.

The effects of maternal influenzal viraemia in late gestation on the conceptus of the pregnant ferret.

Pregnant ferrets were inoculated intra-cardially on day 30 of gestation with influenza virus. The animals were sacrificed on days 5 to 11 after inoculation and the products of conception including the uterus were examined virologically and histopathologically. The results indicate that the initial site of infection of the conceptus is the haemophagous organ and that spread occurs from this site to the endometrium, placental labyrinth and fetus. Lesions in the fetus are confined to the liver and respiratory tract. In the liver they may represent either a viral hepatitis or a secondary response to placental damage resulting in the stimulation of erythropoiesis. In the respiratory tract they first occur in the nasal sinuses and upper airways suggesting that infection is via the amniotic fluid rather than via the blood stream. The relevance of these findings to human pregnancy is discussed.