New models for large prospective studies: is there a better way?

Large prospective cohort studies are critical for identifying etiologic factors for disease, but they require substantial long-term research investment. Such studies can be conducted as multisite consortia of academic medical centers, combinations of smaller ongoing studies, or a single large site such as a dominant regional health-care provider. Still another strategy relies upon centralized conduct of most or all aspects, recruiting through multiple temporary assessment centers.

Bombesin changes excitability of rat brain stem neurons sensitive to gastric distension.

The responses of single neurons in the dorsal vagal complex to physiological gastric distension were investigated in anesthetized control and capsaicin-treated rats. In both groups, the responses of brain stem neurons to close arterial injection of the regulatory peptide bombesin (BBS) were studied. These experiments observed whether selective chemical deafferentation by capsaicin caused any significant change in the central representation of responses to gastric distension and peripheral BBS administration.

Immunohistochemical localisation of a gastrin-releasing peptide-like material in area postrema, nucleus of the solitary tract and vagal motor nucleus in the brainstem of rat.

The presence of an endogenous gastrin-releasing peptide (GRP)-like peptide in the hindbrain of rat was demonstrated immunohistochemically using antisera directed against the N-terminus and C-terminus of GRP. N-terminal and C-terminal-like immunoreactive material were distributed throughout the nucleus of the solitary tract (NTS), dorsal motor nucleus of the vagus (DMV) and tractus solitarius (TS), as well as in areas postrema (AP) and substantia gelatinosa separating AP from NTS. Positive immunostaining was localised to a dense network of nerve fibres which project longitudinally along the neuraxis.

Capsaicin attenuates hindbrain neuron responses to circulating cholecystokinin.

Capsaicin is a neurotoxin that destroys small sensory neurons with unmyelinated axons, including a subpopulation of vagal sensory neurons. Capsaicin treatment attenuates suppression of food intake induced by systemic administration of cholecystokinin (CCK) but not by gastric distension. However, both gastric distension and intravascular CCK alter the discharge of dorsal hindbrain neurons by a vagal mechanism.

Central origin of vagal nerve fibres innervating the fundus and corpus of the stomach in rat.

The origin of vagal nerve fibres innervating the anterior and posterior walls of the fundus and corpus of the rat stomach was investigated using the axon tracing dye, Fast blue. The secretomotor nerve supply to the rat stomach was predominantly ipsilateral. A large majority (98-99%) of the vagal perikarya innervating the anterior fundus and corpus were located on the left side of the brainstem.

Physiological enteric stimulation elicits cardiovascular reflexes in the rat.

By use of anesthetized rats, parameters for the activation of cardiovascular reflexes by stimulation of gastric or hepatic receptors have been established. For reflex activation, the mean minimum intragastric volume was 4 ml, and the mean minimum rate of hepatic portal vein infusion was 0.3 ml/min.

Intracellular recordings from cells in the myenteric plexus of the rat duodenum.

Intracellular recordings were made in vitro from neurons in the myenteric plexus of freshly dissected preparations of the duodenum of the rat. Nearly one-quarter of neurons (18 out of 77) had long after-hyperpolarizations following their action potentials. Over 60% of neurons (20 out of 32) which were tested exhaustively by focal stimulation at seven points around the recording site were seen to receive fast excitatory synaptic inputs.

Intracellular recordings from myenteric neurones in the human colon.

1. Intracellular recordings were made from cells in the myenteric plexus of the human colon in freshly dissected tissue obtained from patients undergoing surgery for the removal of carcinomas or diverticular bowel. 2.

Convergence of sensory information from abdominal viscera in the rat brain stem.

This study was carried out to establish whether there was convergence of sensory information in the rat brain stem stimulated by physiological activation of gastric mechanoreceptors and hepatic glucoreceptors. Extracellular recordings were made from single neurons in the region of the dorsal vagal nucleus and nucleus of the solitary tract in the medulla. The responses of these neurons to gastric distension, hepatic portal vein perfusion of isotonic D-glucose, and hepatic portal vein infusion of isotonic saline were studied.

Sensation in the gastrointestinal tract.

There are similarities between sensation in the gastrointestinal tract (GI tract) and somatic sensation. This review concentrates on parasympathetic (vagal) components of GI sensation rather than the sympathetic (splanchnic) elements. A wide range of enteroceptors have been described over the whole length of the gut which subserve several different sensory modalities.

Central representation of arrival of nutrient in the duodenum.

This study was carried out to assess the extent to which the appearance of a nutrient (D-glucose) in the duodenum of the anesthetized rat is signaled within the medulla. Recordings were made from single neurons in the region of the dorsal vagal nucleus and the nucleus tractus solitarius during constant single-pass perfusion of the duodenum with isotonic saline or D-glucose at 37 degrees C. In some experiments, the response of medullary neurons to acute gastric distension was also recorded.

Causes of mortality in a subarctic settlement (York Factory, Man.), 1714-1946.

A 250-year retrospective mortality study of York Factory, on the shores of Hudson Bay, was undertaken. The daily journals of the Hudson's Bay Company and the records of the Anglican Church of Canada were the principal sources examined. From 1714 to 1801 the death rate among the Europeans was 0.

Cholecystokinin octapeptide and gastric mechanoreceptor activity in rat brain.

Extracellular unitary recordings were made from neurons in the rat dorsal vagal nucleus, and the response of these neurons to iontophoretically applied cholecystokinin octapeptide (CCK-OP) and proglumide (a novel CCK antagonist) was studied. The effect of CCK-OP and proglumide on the response of the neurons to gastric distension was also studied. Seventy-four percent (n = 39) of the neurons studied were excited by CCK-OP.

Central representation and opioid modulation of gastric mechanoreceptor activity in the rat.

The effects of gastric distension on single-unit activity recorded from the dorsal vagal nucleus in the rat medulla have been studied using microelectrodes in anesthetized animals. Out of 97 units studied, 64 responded to gastric distension in one of four characteristic ways. It was possible to modify these gastric distension responses by iontophoretic application of Leu-enkephalin and naloxone.

Slow waves and unitary activity evoked by cutaneous stimulation from the rat cuneate nucleus.

Depth profiles of averaged evoked potentials (AEPs) and simultaneously generated unitary activity have been recorded from the cuneate nucleus of the rat in response to controlled tactile stimulation of the ipsilateral forepaw. Four separate components of the AEPs were isolated, N1, N2, P, and N3. N1 corresponds to the classical N wave previously described by other workers; four fractions of N1 are described.