Effects of enteral feedback inhibition on motility,luminal flow,and absorption of nutrients in proximal gut of minipigs

We wanted to clarify whether the postprandial intestinal feedback control activated by nutrients in the distal gut exerts different effects on motility, transit of digesta, and absorption of nutrients in the proximal gut. Additionally, interrelationships among motility, transit, and absorption were to be elucidated because these relationships have only been investigated in the fasted state. In five minipigs, a 150-cm segment of the proximal jejunum was isolated by two cannulas. Motility of the jejunal segment was recorded by multiple strain gauges and analyzed by computerized methods. Markers (Cr- and Cu-EDTA) were used for the measurement of the flow rate, transit time, and absorption of nutrients. After a meal, the test segment was perfused with 2 kcal/min of an elemental diet over a period of 90 min. A feedback inhibition was activated by infusion of nutrients into the midgut at rates of 1–4 kcal/min. Saline was infused as control. With increasing energy loads infused into the midgut, the motility index and the length of contraction waves decreased, whereas the incidence of stationary contractions increased, ie, the motility changed from a propulsive to a segmenting pattern. These modulations of motility were associated with a linear decrease in the flow rate and a linear increase in transit time. Flow and transit were linearly correlated with each other. Additionally, the reduction in flow rate and the delay in luminal transit were associated with a linear increase in the absorption of nutrients. However, the increase in absorption induced by the feedback mechanism was small (7.3–13.4%) compared to the marked inhibition of the motility parameters (54–64%), the flow rate (59%), and the delay of transit (5.8-fold). Feedback control primarily modulated motor patterns and luminal flow, whereas the small increase in absorption was only a side effect due to the longer contact time of the nutrients with the mucosa.The study was supported by the Deutsche Forschungsgemeinschaft, grant Eh 64/6-3.     

Absorption of Propranolol in Humans Following Oral,Jejunal, and Heal Administration

Pharmaceutical Research -     

Comparison of the Permeability Characteristics of a Human Colonic Epithelial (Caco-2) Cell Line to Colon of Rabbit,Monkey, and Dog Intestine and Human Drug Absorption

The in vitro permeabilities of Caco-2 monolayers and permeabilities in tissue sections from colon of monkey, rabbit, and dog were compared using a series of compounds. The selected compounds differed in their physicochemical properties, such as octanol/water partition coefficient, water solubility, and molecular weight. Their structure included steroids, carboxylic acids, xanthins, alcohols, and polyethylene glycols. A linear permeability relationship was established between Caco-2 and colon tissue from both rabbit and monkey. The results suggest that Caco-2 is twice as permeable as rabbit and five times as permeable as monkey colon. However, no clear relationship could be established between Caco-2 monolayers and dog colon permeability. A relationship between permeability in Caco-2 monolayers and human absorption was found. The results suggest that within certain limits, permeability of Caco-2 monolayers may be used as a predictive tool to estimate human drug absorption.     

BILIARY HYPERPRESSURE IN RAT EXTRAHEPATIC CHOLESTASIS ALTERS HORSERADISH PEROXIDASE BILIARY EXCRETION

1. The authors investigated the effect of two extrahepatic cholestasis models (one by bile duct ligation and the other by choledocho-jugular fistula) on the hepatic clearance of horseradish peroxidase in male Sprague-Dawley rats divided into four groups. 2. In groups A (n = 5 rats) and B (n = 5), bile duct ligation was performed, while a choledocho-jugular fistula was created in groups C (n = 5) and D (n= 7). A 10 mg intravenous bolus of horseradish peroxidase was injected after 24 h (groups A and C), 48 h (groups B and D) or 1 h (Group E; five sham-operated rats). Serum and bile samples were then serially collected for 2 h. 3. In all groups, serum horseradish peroxidase levels increased soon after injection and then rapidly decreased, the curves being similar. Biliary excretion increased for 30 min and then slowly decreased. The highest horseradish peroxidase biliary concentrations and outputs were found in Group B followed by Group A; both groups had significantly higher levels than Group E. No difference was found between horseradish peroxidase biliary excretion of groups C and D and that of sham-operated rats. 4. When each group was considered separately, sampling times correlated with the corresponding ratios of bile/ plasma HRP. Significant differences were found between the relative slopes of groups A, B and E, but not between those of groups C, D and E. 5. In conclusion, bile duct obstruction greatly affects the plasma-bile transfer of fluid phase markers, such as horseradish peroxidase, while single retention, caused by choledocho-jugular fistula, has no influence. The increased biliary hyperpressure related to the duration of cholestasis may account for the degree of horseradish peroxidase transfer which, in turn, probably depends on an enhanced paracellular passage.     

Interactions between peripheral blood CD8 T lymphocytes and intestinal epithelial cells (iEC)

Intestinal intraepithelial lymphocytes (iIEL) are primarily CD8 cells and most of them have a CD28^? phenotype, the phenotype of effector cytotoxic T cells. We asked whether the predominance of CD8⁺ CD28^? T cells in the gut may result from peripheral blood T cells preferentially migrating to the iIEL compartment and adhering to iEC. Compared with CD4 cells, adhesion of resting CD8⁺ T cells to iEC cell lines was significantly higher. Adhesion could be blocked with a MoAb to gp180, a molecule expressed on iEC which is known to interact with CD8/lck. No significant difference in the level of adhesion was observed between CD8⁺ CD28⁺ and CD8⁺ CD28^? T cells. Thus CD8 cells may preferentially migrate to the iIEL compartment, but loss of CD28 expression could occur in situ after migration. Consistent with this hypothesis, the CD8⁺ CD28^? cells became enriched after co-culturing T cells with iEC cell lines and primary iEC. Induction of the CD8⁺ CD28^? phenotype in cord blood and adult T cells was observed in co-cultures with iEC and also with mitogens and superantigens. In the latter case, CD28 down-modulation was seen specifically in the Vβ subset targeted by the superantigen, indicating that loss of CD28 expression is a direct result of T cell receptor (TCR)-mediated stimulation. The combined results suggest that CD8⁺ CD28^? T cells are antigen experienced T cells, and that they may have a survival advantage in the presence of gut epithelial cells in vitro. This may contribute to the predominance of CD8⁺ CD28^? T cells in the iIEL compartment.     

A new operational approach for the piriform sinus fistula

It has been well documented that piriform sinus fistulae often cause suppurative thyroditis; however, when a piriform sinus fistula does not present this symptom, making a correct diagnosis is very difficult. We have experienced 11 cases of a piriform sinus fistula. The conventional operational approach was performed in the initial eight patients, among which there were four recurrences in two patients. Therefore, a new operational approach was introduced for the three most recent cases and one recurrent case. First, the existence of the internal orifice of the fistula is confirmed with a laryngoscope, after which a transverse incision on the neck is made and the abscess dissected. The side wall of the piriform sinus is then opened with the help of a laryngoscope and the bottom part of the mucosa of the sinus transected with the internal orifice of the fistula, after which the fistula is removed en bloc with the bottom part of the sinus and abscess cavity. Using this operation, we experienced no complications and there has been no recurrence so far.This paper was presented at the 23rd Annual Meeting of Pacific Association of Pediatric Surgeons, June 1990 in Kona, Hawaii.     

AN UNUSUAL CAUSE OF RECTOVAGINAL FISTULA

An unusual case of rectovaginal fistula is reported. An 81 year old woman presented to the geriatric team with a request to review her faecal incontinence. It was discovered that she had a predilection for placing foreign objects in her vagina. In this instance a carbonated drink top had formed a rectovaginal fistula.     

Vesicocutaneous fistula: An unusual complication of inguinoscrotal hernia

Involvement of the urinary bladder in an inguinal hernia is common, but massive bladder hernia is rare. Most urinary bladder herniations are discovered and repaired during surgery. We report a case of large incarcerated inguino-scrotal hernia, which was reduced only to present as a scrotal abscess and vesicocutaneous fistula; an unusual complication. The patient was managed conservatively due to underlying comorbidities.     

Off-pump resection of a coronary arterial fistula using the Harmonic Scalpel

Off-pump surgery was performed in a patient with post-infarction angina complicated with aneurysmal coronary-pulmonary arterial fistula. Epicardial echocardiography localized the artery feeding the fistula in the myocardium, which had not been revealed by visual inspection, palpation, or transesophageal echocardiography. The patient underwent off-pump coronary artery bypass grafting concomitant with aneurysmectomy. The feeding arteries were dissected easily using a Harmonic Scalpel and ligated. The flow in the aneurysm disappeared immediately and aneurysmectomy was performed without bleeding.     

小儿乙状结肠冗长症病理特点分析

目的 探讨小儿乙状结肠冗长症的病理特点，以提高对该症病理特点的认识。方法 分析我科1993～2002年间经手术治疗12例小儿乙状结肠冗长症的临床病理资料。结果 小儿乙状结肠冗长症病理特点与先天性巨结肠同源病相似。主要表现为乙状结肠肠壁肥厚，部分肌纤维变性。结肠黏膜萎缩，黏膜下充血水肿；肌间神经丛减少，均可见神经节细胞发育幼稚，且数量减少或体积变小，呈固缩或空泡变性。结论 小儿乙状结肠冗长症大多有肠神经元发育异常。