‘ An investigation of the nervous control of defecation ’ by Denny-Brown and Robertson: a classic paper revisited

In 1935 two young neurologists, Derek Denny-Brown and E. Graeme Robertson, published an article explaining the mechanisms underlying human defaecation based on a manometric study in patients with sacral root and spinal cord lesions, and normal subjects. This article is still routinely cited in studies of rectal and sphincter ani function. Unfortunately, however, the article itself is not written well, being composed of long convoluted sentences and containing 79 often indecipherable figures. Difficult-to-understand articles were common to the publications of Denny-Brown, who became one of the most prominent neurologists of the twentieth century. In accord with our prior work explaining Denny-Brown and Robertson's earlier paper on micturition, we provide here what we hope is a clear explanation of the methods and results in their study on defaecation.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73905/1/j.1463-1318.2004.00636.x.pd

Laser-Evoked Vertex Potentials Predict Defensive Motor Actions

The vertex potential is the largest response that can be recorded in the electroencephalogram of an awake, healthy human. It is elicited by sudden and intense stimuli, and is composed by a negative-positive deflection. The stimulus properties that determine the vertex potential amplitude have been well characterized. Nonetheless, its functional significance remains elusive. The dominant interpretation is that it reflects neural activities related to the detection of salient stimuli. However, given that threatening stimuli elicit both vertex potentials and defensive movements, we hypothesized that the vertex potential is related to the execution of defensive actions. Here, we directly compared the salience and motoric interpretations by investigating the relationship between the amplitude of laser-evoked potentials (LEPs) and the response time of movements with different defensive values. First, we show that a larger LEP negative wave (N2 wave) predicts faster motor response times. Second, this prediction is significantly stronger when the motor response is defensive in nature. Third, the relation between the N2 wave and motor response time depends not only on the kinematic form of the movement, but also on whether that kinematic form serves as a functional defense of the body. Therefore, the N2 wave of the LEP encodes key defensive reactions to threats

Anorectal motility in patients with achalasia of the esophagus: recognition of an esophago-rectal syndrome

BACKGROUND: During my study of constipation, I encountered patients who had achalasia of the esophagus (AE) as well. The possibility of an existing relationship between the 2 conditions was studied. METHOD: Investigations to study the anorectal motility in 9 AE patients included: the intestinal transit time, anorectal manometry, rectoanal inhibitory reflex, defecography and electromyography (EMG) of external anal sphincter and levator ani muscle. Anorectal biopsy was done. The study comprised 8 healthy volunteers as controls. RESULTS: 6/9 AE patients had constipation presenting as strainodynia (excessive prolonged straining at stool). Rectocele was present in 4 of them. The 6 constipated patients showed significantly high rectal neck pressure (p < 0.05), absent rectoanal inhibitory reflex and aganglionosis in the anorectal biopsy. The EMG revealed diminished activity in 4 of the 6 constipated patients. The remaining 3 patients with AE had normal anorectal function. Heller's myotomy with Nissen's fundoplication improved the dysphagia, but not the constipation which was, however, relieved after performance of anorectal myectomy. CONCLUSION: The high incidence of constipation with AE postulates a relationship between the 2 conditions. Both have the same pathologic lesion which is aganglionosis. This study is preliminary and requires further studies on a larger number of patients

Socio-cultural influences on the behaviour of South Asian women with diabetes in pregnancy: qualitative study using a multi-level theoretical approach

BACKGROUND: Diabetes in pregnancy is common in South Asians, especially those from low-income backgrounds, and leads to short-term morbidity and longer-term metabolic programming in mother and offspring. We sought to understand the multiple influences on behaviour (hence risks to metabolic health) of South Asian mothers and their unborn child, theorise how these influences interact and build over time, and inform the design of culturally congruent, multi-level interventions. METHODS: Our sample for this qualitative study was 45 women of Bangladeshi, Indian, Sri Lankan, or Pakistani origin aged 21-45 years with a history of diabetes in pregnancy, recruited from diabetes and antenatal services in two deprived London boroughs. Overall, 17 women shared their experiences of diabetes, pregnancy, and health services in group discussions and 28 women gave individual narrative interviews, facilitated by multilingual researchers, audiotaped, translated, and transcribed. Data were analysed using the constant comparative method, drawing on sociological and narrative theories. RESULTS: Key storylines (over-arching narratives) recurred across all ethnic groups studied. Short-term storylines depicted the experience of diabetic pregnancy as stressful, difficult to control, and associated with negative symptoms, especially tiredness. Taking exercise and restricting diet often worsened these symptoms and conflicted with advice from relatives and peers. Many women believed that exercise in pregnancy would damage the fetus and drain the mother's strength, and that eating would be strength-giving for mother and fetus. These short-term storylines were nested within medium-term storylines about family life, especially the cultural, practical, and material constraints of the traditional South Asian wife and mother role and past experiences of illness and healthcare, and within longer-term storylines about genetic, cultural, and material heritage - including migration, acculturation, and family memories of food insecurity. While peer advice was familiar, meaningful, and morally resonant, health education advice from clinicians was usually unfamiliar and devoid of cultural meaning. CONCLUSIONS: 'Behaviour change' interventions aimed at preventing and managing diabetes in South Asian women before and during pregnancy are likely to be ineffective if delivered in a socio-cultural vacuum. Individual education should be supplemented with community-level interventions to address the socio-material constraints and cultural frames within which behavioural 'choices' are made

Regulatory Variation at Glypican-3 Underlies a Major Growth QTL in Mice

The genetic basis of variation in complex traits remains poorly understood, and few genes underlying variation have been identified. Previous work identified a quantitative trait locus (QTL) responsible for much of the response to selection on growth in mice, effecting a change in body mass of approximately 20%. By fine-mapping, we have resolved the location of this QTL to a 660-kb region containing only two genes of known function, Gpc3 and Gpc4, and two other putative genes of unknown function. There are no non-synonymous polymorphisms in any of these genes, indicating that the QTL affects gene regulation. Mice carrying the high-growth QTL allele have approximately 15% lower Gpc3 mRNA expression in kidney and liver, whereas expression differences at Gpc4 are non-significant. Expression profiles of the two other genes within the region are inconsistent with a factor responsible for a general effect on growth. Polymorphisms in the 3′ untranslated region of Gpc3 are strong candidates for the causal sequence variation. Gpc3 loss-of-function mutations in humans and mice cause overgrowth and developmental abnormalities. However, no deleterious side-effects were detected in our mice, indicating that genes involved in Mendelian diseases also contribute to complex trait variation. Furthermore, these findings show that small changes in gene expression can have substantial phenotypic effects