On the origin of rhythmic contractile activity of the esophagus in early achalasia, a clinical case study
Bibliographic record
Abstract
A patient with early achalasia presented spontaneous strong rhythmic non-propulsive contractions at ~7/min, independent of swallows. Our aim was to evaluate characteristics of the rhythmic contractions, provide data on the structure of pacemaker cells in the esophagus and discuss a potential role for interstitial cells of Cajal (ICC) in the origin of rhythmicity. We hypothesize that intramuscular ICC (ICC-IM) are the primary pacemaker cells. The frequency but not the amplitude of the rhythmic contractions was inhibited by the phosphodiesterase inhibitor drotaverine consistent with cAMP inhibiting pacemaker currents in ICC-IM. The frequency increased by wet swallows but not dry swallows, consistent with stretch causing increase in slow wave frequency in ICC-IM. New studies on archival material showed that ICC-IM were present throughout the human esophageal musculature and were not diminished in early achalasia. Although ICC-IM exhibited a low density, they were connected to PDGFRα-positive fibroblast-like cells with whom they formed a dense gap junction coupled network. Nitrergic innervation of ICC was strongly diminished in early achalasia because of the loss of nitrergic nerves. It therefore appears possibly that ICC-IM function as pacemaker cells in the esophagus and that the network of ICC and PDGFRα-positive cells allows for coupling and propagation of the pacemaker activity. Loss of nitrergic innervation to ICC in achalasia may render them more excitable such that its pacemaker activity is more easily expressed. Loss of propagation in achalasia may be due to loss of contraction-induced aboral nitrergic inhibition.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.002 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.003 | 0.001 |
| Science and technology studies | 0.002 | 0.001 |
| Scholarly communication | 0.001 | 0.002 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.003 | 0.002 |
| Insufficient payload (model declined to judge) | 0.002 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".