[Clinical analysis of the correlation between gallbladder adenomyomatosis and occult pancreaticobiliary reflux].

Objective: To explore the association between gallbladder adenomyomatosis (GA) and occult pancreaticobiliary reflux (OPBR). Methods: A total of 81 patients with GA who underwent cholecystectomy in Shanghai East Hospital from December 2020 to January 2022 were enrolled, including 48 cases of fundal type, 28 cases of segmental type and 5 cases of diffuse type. Patient's intraoperative bile was coltected and tested for amylase. According to gallbladder bile amylase level, patients were divided into OPBR group (bile amylase>110 U/L) and the control group (bile amylase≤110 U/L). Results: Among 81 patients, 32 were male and 49 were female, and aged (49.1±13.2) years; there were 66 cases in control group, including 27 males and 39 females, and aged (50.0±12.9)years; there were 15 patients in the OPBR group, including 5 males and 10 females, and aged (45.1±14.2) years. In terms of the clinical features of the two groups, there was no significant difference (all P>0.05), except for a significant increase in biliary amylase in the OPBR group compared with the control group (P<0.001). However, the incidence of OPBR was significantly different in the three types of GA, with a lower incidence of OPBR in the fundal type (10.4%, 5/48) than in the segmental type (28.6%, 8/28) and diffuse type (2/5) (P=0.038). In addition, segmental GA was more likely to be combined with gallbladder stones (85.7%, 24/28) than fundal GA (58.3%, 28/48) and diffuse GA (3/5) (P=0.031). Univariate and multivariate logistic regression analyses showed OPBR [OR (95%CI)=3.410 (1.010 to 11.513), P=0.048] and combined gallbladder stones [OR (95%CI)=2.974 (1.011 to 8.745), P=0.048] indepenclently correlated with segmental and diffuse GA. Conclusions: The incidence of OPBR is higher in segmental and diffuse GA, and gallstones and OPBR are independently associated with the occurrence of segmental and diffuse GA. These results suggest that OPBR may be the initiating factor for the occurrence and carcinogenesis of segmental and diffuse GA.

Innate and adaptive immune system cells implicated in tendon healing and disease.

Tendons perform a critical function in the musculoskeletal system by integrating muscle with skeleton and enabling force transmission. Damage or degeneration of these tissues lead to impaired structure and function, which often persist despite surgical intervention. While the immune response and inflammation are important drivers of both tendon healing and disease progression, there have been relatively few studies of the diverse immune cell types that may regulate these processes in these tissues. To date, most of the studies have focused on macrophages, but emerging research indicate that other immune cell types may also play a role in tendon healing, either by regulating the immune environment or through direct interactions with resident tenocytes. The present review synthesises the literature on innate and adaptive immune system cells that have been implicated in tendon healing or disease, in the context of animal injury models, human clinical samples or in vitro experiments.

Axin2-lineage cells contribute to neonatal tendon regeneration.

PURPOSE: Tendon injuries are a challenging clinical problem with few treatment options. Identifying the molecular regulators of tendon is required for the development of new therapies. While the Wnt pathway is critical for the maintenance and differentiation of many tissues, the role of Wnt signaling in tendon cell biology remains largely unexplored. METHODS: The effects of Wnt activation were tested in vitro using neonatal tendon-derived cells cultured in 2D and 3D conditions. The inducible Axin2CreERT2 was then used to label Axin2+ cells in vivo and cells were traced during neonatal tendon regeneration. RESULTS: We showed that activation of Wnt signaling results in proliferation of neonatal tendon cells. While tendon marker expression was inhibited by Wnt activation under 2D conditions, Scx expression was not affected under 3D uniaxial tension, suggesting that the microenvironment contextualizes tendon cell response to Wnt signaling. Using an in vivo model of neonatal tendon regeneration, we further showed that Wnt signaling cells comprise a subpopulation of tenocyte and epitenon cells that proliferate after injury and are recruited during regeneration. DISCUSSION: Collectively, these studies suggest that Wnt signaling may play a role in tendon cell proliferation, differentiation, and regeneration.

Clinical characteristics and disease burden in prurigo nodularis.

BACKGROUND: Prurigo nodularis (PN) is a chronic inflammatory skin disease characterized by intense pruritus, but information on patient experience and impact on quality of life (QoL) remains understudied. AIM: To characterize disease characteristics and QoL in a global sample of patients with PN. METHODS: An anonymous survey was distributed via patient support groups for PN. RESULTS: In total, 231 members responded to the survey. The majority of respondents reported itch localized both to nodules and to intervening skin (67.0%). Associated symptoms included prickling, pain, stinging and burning. The extensor lower legs (69% right, 67.3% left) and flexor forearms (66.1% right, 62% left) were the most common sites of itch. Participants reported frequent healthcare utilization, with 36.3% visiting a doctor ≥ 10 times in the past year. Physician-diagnosed anxiety (45.4%), depression (16.4%) and the atopic triad (18.7%) were commonly reported. Patients with PN had mean scores of 16.4, 11.6 and 16.8 on the Dermatology Life Quality Index, Pittsburgh Sleep Quality Index and 5-Dimensions Itch, respectively. CONCLUSIONS: Severe pruritus with accompanying pain, stinging and burning is characteristic of PN, with the majority of patients experiencing itch in both nodular and interlesional skin. Patients further report decreased QoL scores and impaired sleep. Patient experiences should guide future management of PN.

[Clinicopathologic features of solitary fibrous tumor in urogenital system].

OBJECTIVE: To study the clinicopathologic features and differential diagnosis of solitary fibrous tumor (SFT) in the urogenital system. METHODS: The clinical data and pathologic characteristics of eight cases of SFT in the urogenital system were analyzed, and the relevant literature was reviewed. RESULTS: The cohort included six male and two female patients, with age of onset ranging from 25 to 80 years. Five occurred in the kidney (three in the right kidney), one case each occurred in the bladder, the prostate and the spermatic cord. Most patients showed no obvious clinical symptoms or only had low back pain and swelling. The diameter of the tumor was ranged from 2.5 to 11.8 cm (median 5.2 cm). Microscopy showed at low magnification, the tumor cells were spindle-shaped and arranged in bundles or helicoid pattern. The regional mesenchymal fibroblasts showed hyperplasia, with obvious collagenization and formed hemangiopericytoma-like structure. One case showed increased mitotic figures (>5 cells/10 HPF) and focal necrosis. By immunohistochemistry, the tumor cells were positive for CD34 and STAT6 in all eight cases, CD99 and vimentin in six cases, bcl-2 in four cases and SMA in one case. All seven cases with follow-up did not show any tumor recurrence or metastasis. CONCLUSIONS: SFT is rare in the urogenital system and most patients show good prognosis. SFT expresses CD34 and STAT6 and needs to be distinguished from other spindle cell tumors.

Long noncoding RNA SNHG14 promotes breast cancer cell proliferation and invasion via sponging miR-193a-3p.

Since this article has been suspected of research misconduct and the corresponding authors did not respond to our request to prove originality of data and figures, "Long noncoding RNA SNHG14 promotes breast cancer cell proliferation and invasion via sponging miR-193a-3p, by S.-D. Xie, C. Qin, L.-D. Jin, Q.-C. Wang, J. Shen, J.-C. Zhou, Y.-X. Chen, A.-H. Huang, W.-H. Zhao, L.-B. Wang, published in Eur Rev Med Pharmacol Sci 2019; 23 (6): 2461-2468. DOI: 10.26355/eurrev_201903_17393. PMID: 30964172" has been withdrawn. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/17393.

Macromer density influences mesenchymal stem cell chondrogenesis and maturation in photocrosslinked hyaluronic acid hydrogels.

OBJECTIVE: Engineering cartilage requires that a clinically relevant cell type be situated within a 3D environment that supports cell viability, the production and retention of cartilage-specific extracellular matrix (ECM), and eventually, the establishment of mechanical properties that approach that of the native tissue. In this study, we investigated the ability of bone marrow derived mesenchymal stem cells (MSCs) to undergo chondrogenesis in crosslinked methacrylated hyaluronic acid hydrogels (MeHA) of different macromer concentrations (1, 2, and 5%). DESIGN: Over a 6 week culture period under pro-chondrogenic conditions, we evaluated cartilage-specific gene expression, ECM deposition within constructs and released to the culture media, and mechanical properties in both compression and tension. Further, we examined early matrix assembly and long term histological features of the forming tissues, as well as the ability of macromolecules to diffuse within hydrogels as a function of MeHA macromer concentration. RESULTS: Findings from this study show that variations in macromer density influence MSC chondrogenesis in distinct ways. Increasing HA macromer density promoted chondrogenesis and matrix formation and retention, but yielded functionally inferior constructs due to limited matrix distribution throughout the construct expanse. In 1% MeHA constructs, the equilibrium compressive modulus reached 0.12MPa and s-GAG content reached nearly 3% of the wet weight, values that matched or exceeded those of control agarose constructs and that are 25 and 50% of native tissue levels, respectively. CONCLUSIONS: These data provide new insight into how early matrix deposition regulates long term construct development, and defines new parameters for optimizing the formation of functional MSC-based engineered articular cartilage using HA hydrogels.

Localization of enzymes within microbodies.

Microbodies from rat liver and a variety of plant tissues were osmotically shocked and subsequently centrifuged at 40,000 g for 30 min to yield supernatant and pellet fractions. From rat liver microbodies, all of the uricase activity but little glycolate oxidase or catalase activity were recovered in the pellet, which probably contained the crystalline cores as many other reports had shown. All the measured enzymes in spinach leaf microbodies were solubilized. With microbodies from potato tuber, further sucrose gradient centrifugation of the pellet yielded a fraction at density 1.28 g/cm(3) which, presumably representing the crystalline cores, contained 7% of the total catalase activity but no uricase or glycolate oxidase activity. Using microbodies from castor bean endosperm (glyoxysomes), 50-60% of the malate dehydrogenase, fatty acyl CoA dehydrogenase, and crotonase and 90% of the malate synthetase and citrate synthetase were recovered in the pellet, which also contained 96% of the radioactivity when lecithin in the glyoxysomal membrane had been labeled by previous treatment of the tissue with [(14)C]choline. When the labeled pellet was centrifuged to equilibrium on a sucrose gradient, all the radioactivity, protein, and enzyme activities were recovered together at peak density 1.21-1.22 g/cm(3), whereas the original glyoxysomes appeared at density 1.24 g/cm(3). Electron microscopy showed that the fraction at 1.21-1.22 g/cm(3) was comprised of intact glyoxysomal membranes. All of the membrane-bound enzymes were stripped off with 0.15 M KCl, leaving the "ghosts" still intact as revealed by electron microscopy and sucrose gradient centrifugation. It is concluded that the crystalline cores of plant microbodies contain no uricase and are not particularly enriched with catalase. Some of the enzymes in glyoxysomes are associated with the membranes and this probably has functional significance.

Surface structure and properties of plant seed oil bodies.

Storage triacylglycerols (TAG) in plant seeds are present in small discrete intracellular organelles called oil bodies. An oil body has a matrix of TAG, which is surrounded by phospholipids (PL) and alkaline proteins, termed oleosins. Oil bodies isolated from mature maize (Zea mays) embryos maintained their discreteness, but coalesced after treatment with trypsin but not with phospholipase A2 or C. Phospholipase A2 or C exerted its activity on oil bodies only after the exposed portion of oleosins had been removed by trypsin. Attempts were made to reconstitute oil bodies from their constituents. TAG, either extracted from oil bodies or of a 1:2 molar mixture of triolein and trilinolein, in a dilute buffer were sonicated to produce droplets of sizes similar to those of oil bodies; these droplets were unstable and coalesced rapidly. Addition of oil body PL or dioleoyl phosphatidylcholine, with or without charged stearylamine/stearic acid, or oleosins, to the medium before sonication provided limited stabilization effects to the TAG droplets. High stability was achieved only when the TAG were sonicated with both oil body PL (or dioleoyl phosphatidylcholine) and oleosins of proportions similar to or higher than those in the native oil bodies. These stabilized droplets were similar to the isolated oil bodies in chemical properties, and can be considered as reconstituted oil bodies. Reconstituted oil bodies were also produced from TAG of a 1:2 molar mixture of triolein and trilinolein, dioleoyl phosphatidylcholine, and oleosins from rice (Oryza sativa), wheat (Triticum aestivum), rapeseed (Brassica napus), soybean (Glycine max), or jojoba (Simmondsia chinensis). It is concluded that both oleosins and PL are required to stabilize the oil bodies and that oleosins prevent oil bodies from coalescing by providing steric hindrance. A structural model of an oil body is presented. The current findings on seed oil bodies could be extended to the intracellular storage lipid particles present in diverse organisms.

Dynamic tracking of cardiac vulnerability by complex demodulation of the T wave.

A link is found between T wave alternans and vulnerability to ventricular fibrillation, and a new approach is provided for quantification of susceptibility to malignant arrhythmias. Complex demodulation reveals that alternation of the electrocardiogram is concentrated during the first half of the T wave, coinciding with the vulnerable period of the cardiac cycle. During myocardial ischemia and reperfusion, there are marked increases in the degree of T wave alternans that parallel the established time course of changes in vulnerability. The influence of the sympathetic nervous system in arrhythmogenesis is also accurately detected. Ultimately, complex demodulation of the electrocardiogram could provide a technique for identification and management of individuals at risk for sudden cardiac death.

Long noncoding RNA SNHG14 promotes breast cancer cell proliferation and invasion via sponging miR-193a-3p.

OBJECTIVE: Breast cancer (BC) is one of the most ordinary fatal cancers. Recent studies have identified the vital role of long noncoding RNAs (lncRNAs) in the development and progression of BC. In this research, lncRNA SNHG14 was studied to identify how it functioned in the development and metastasis of BC. PATIENTS AND METHODS: SNHG14 expression of tissues was detected by Real Time-quantitative Polymerase Chain Reaction (RT-qPCR) in 50 paired patients with BC. And cell proliferation assay, colony formation assay, and transwell assay were enrolled to observe the biological behavior changes of BC cells through gain or loss of SNHG14. In addition, luciferase assays and RNA immunoprecipitation assay (RIP) were performed to discover the potential targets of SNHG14 in BC cells. RESULTS: SNHG14 expression level of BC samples was higher than that of adjacent ones. Besides, cell growth ability and cell invaded ability of BC cells were inhibited after SNHG14 was silenced, while cell growth ability and cell invaded ability of BC cells were promoted after SNHG14 was overexpressed. In addition, miR-193a-3p was upregulated after silence of SNHG14 in BC cells, while miR-193a-3p was downregulated after overexpression of SNHG14 in BC cells. Furthermore, luciferase assays and RNA immunoprecipitation assay (RIP) showed that miR-193a-3p was a direct target of SNHG14 in BC. CONCLUSIONS: Our study uncovers a new oncogene in BC and suggests that SNHG14 could enhance BC cell proliferation and invasion via sponging miR-193a-3p, which provided a novel therapeutic target for BC patients.

Tensile properties of engineered cartilage formed from chondrocyte- and MSC-laden hydrogels.

OBJECTIVE: The objective of this study was to determine the capacity of chondrocyte- and mesenchymal stem cell (MSC)-laden hydrogel constructs to achieve native tissue tensile properties when cultured in a chemically defined medium supplemented with transforming growth factor-beta3 (TGF-beta3). DESIGN: Cell-laden agarose hydrogel constructs (seeded with bovine chondrocytes or MSCs) were formed as prismatic strips and cultured in a chemically defined serum-free medium in the presence or absence of TGF-beta3. The effects of seeding density (10 vs 30 million cells/mL) and cell type (chondrocyte vs MSC) were evaluated over a 56-day period. Biochemical content, collagenous matrix deposition and localization, and tensile properties (ramp modulus, ultimate strain, and toughness) were assessed biweekly. RESULTS: Results show that the tensile properties of cell-seeded agarose constructs increase with time in culture. However, tensile properties (modulus, ultimate strain, and toughness) achieved on day 56 were not dependent on either the initial seeding density or the cell type employed. When cultured in medium supplemented with TGF-beta3, tensile modulus increased and plateaued at a level of 300-400 kPa for each cell type and starting cell concentration. Ultimate strain and toughness also increased relative to starting values. Collagen deposition increased in constructs seeded with both cell types and at both seeding densities, with exposure to TGF-beta3 resulting in a clear shift toward type II collagen deposition as determined by immunohistochemical staining. CONCLUSIONS: These findings demonstrate that the tensile properties, an important and often overlooked metric of cartilage development, increase with time in culture in engineered hydrogel-based cartilage constructs. Under the free-swelling conditions employed in the present study, tensile moduli and toughness did not match that of the native tissue, though significant time-dependent increases were observed with the inclusion of TGF-beta3. Of note, MSC-seeded constructs achieved tensile properties that were comparable to chondrocyte-seeded constructs, confirming the utility of this alternative cell source in cartilage tissue engineering. Further work, including both modulation of the chemical and mechanical culture environment, is required to optimize the deposition of collagen and its remodeling to achieve tensile properties in engineered constructs matching the native tissue.

Hypoperfusion of the myocardium relative to myocardial metabolism during delayed coronary constriction.

OBJECTIVE: The aim was to test the hypothesis that the myocardium becomes hypoperfused, relative to its metabolic demands, during the delayed coronary constriction which is observed following termination of a period of sympathetic stimulation. METHODS: This was tested by beat by beat analysis of the ratio of coronary blood flow to the product of heart rate and systolic blood pressure (HR x SBP), an index of myocardial metabolism, in acutely instrumented open chest canine preparations, before, during, and after direct electrical stimulation of the left stellate ganglion. RESULTS: Myocardial metabolism increased in response to stellate stimulation, as evidenced by increases in heart rate, aortic blood pressure, and HR x SBP. These were accompanied by increased blood flow and decreased vascular resistance in the left anterior descending coronary artery. Delayed coronary constriction, defined as the period with the lowest coronary blood flow observed after the end of the stimulation, occurred 1 to 3 min after stimulation was terminated and was characterised by recovery of heart rate, blood pressure, HR x SBP, and coronary blood flow toward control levels, while coronary vascular resistance overshot to above control levels. The ratio of coronary blood flow to HR x SBP fell progressively in the poststimulation period to significantly less (mean 0.715, range of +/- 1 SEM 0.638 to 0.800, p < 0.05) than control (1.0, by definition) in experiments performed with partial prestenosis of the left anterior descending coronary artery. In a selected subgroup of observations with a mean reduction in coronary blood flow during delayed coronary constriction comparable to that reported previously, the flow/metabolism ratio was even lower (mean 0.239, range of +/- 1 SEM 0.202 to 0.284). CONCLUSIONS: The phenomenon of delayed coronary constriction clearly involves a mismatch between myocardial supply and demand: coronary blood flow becomes inappropriately low for the prevailing level of myocardial metabolism.

Hyperthermia induces doxorubicin release from long-circulating liposomes and enhances their anti-tumor efficacy.

PURPOSE: To examine the possibility that hyperthermia would accelerate drug release from long-circulating liposomes, and enhance their antitumor activity. METHODS AND MATERIALS: Liposomes were prepared by thin film hydration technique. Hyperthermia was induced by ultrasound apparatus and a water bath heating system. The antitumor efficacy of treatment against RIF-1 tumor in C3H mice was evaluated by the tumor growth delay assay. RESULTS: In vitro drug release experiments demonstrated that increase in temperature from 37 degrees C to 41 degrees C resulted in about a sixfold increase in doxorubicin (DOX) release in a 1-h period. Increasing the temperature to 43 degrees C, resulted in only a modest additional drug release. Drug uptake studies showed that local hyperthermic treatment immediately following the drug administration dramatically enhanced Stealth liposome-encapsulated doxorubicin (S-DOX) uptake by tumors, but did not do so for free DOX. At 42 degrees C and at a dose of 10 mg/kg, the accumulation of S-DOX was about 10-fold and 2.5-fold higher than that with free drug and S-DOX at 37 degrees C, respectively. The antitumor efficacy study confirmed our hypothesis that the addition of hyperthermia to the treatment of RIF-1 tumors with doxorubicin encapsulated in long-circulating liposomes would enhance antitumor effects. Two hyperthermia treatments given at 24-h intervals appeared to be the most promising method of combining heat and long-circulating liposomes. The increased antitumor activity was not accompanied by increased toxicity, as determined by the body weight of the mice. CONCLUSION: Local hyperthermic treatment is able to accelerate DOX release from long-circulating liposomes, increase tumor uptake, and enhance their antitumor efficacy. The combination of local hyperthermia and long-circulating liposomes appears to show considerable promise in the treatment of localized diseases.

Relationship between coronary hemodynamic changes and the phasic events of rapid eye movement sleep.

Previous studies in dogs showed dramatic increases in coronary blood flow associated with episodes of sinus tachycardia during rapid eye movement (REM) sleep. The present study demonstrates that 90% of these surges in heart rate and coronary flow are concentrated during periods of phasic REM sleep and only 10% in tonic REM sleep. Intensely phasic REM was distinguished from moderately phasic REM sleep by the degree of phasic eye movement. The surges were three times more frequent during intensely phasic REM than in moderately phasic REM sleep. However, the magnitudes of heart rate (37% +/- 3%) and coronary flow (25% +/- 3%) surges were unaffected by the specific substage of REM sleep. The incidence of surge events was almost eleven times greater in epochs of phasic REM that also contained a muscle twitch than in those that did not. During REM sleep, muscle twitches accompanying surges were not associated with any additional elevations in coronary flow or myocardial demand. Our data indicate that the sinus tachycardia-associated surges in coronary flow represent integrated autonomic responses intrinsic to phasic periods of REM sleep in dogs.

The selection of triple therapy for Helicobacter pylori eradication in chronic renal insufficiency.

AIM: To establish a triple therapy regimen for Helicobacter pylori eradication in patients with chronic renal insufficiency. METHODS: Eighty-eight patients with chronic renal insufficiency and H. pylori infection were evenly randomized into two groups receiving 1-week lansoprazole, 30 mg, clarithromycin, 500 mg, and either amoxicillin, 750 mg, or metronidazole, 500 mg, twice daily. The adverse events and compliance with triple therapy were reviewed at the week 1 visit. Patients provided stool samples at week 6 to assess the success of H. pylori eradication by H. pylori-specific stool antigen. The serum creatinine levels were monitored at enrollment, at weeks 1, 2 and 6 and on any unscheduled visit after triple therapy. RESULTS: The success of H. pylori eradication was higher in the lansoprazole-clarithromycin-metronidazole group than in the lansoprazole-clarithromycin-amoxicillin group (intention-to-treat analysis: 84% vs. 66%, P < 0.05: per protocol analysis: 93% vs. 76%, P < 0.05). Complete drug compliance was also better in the lansoprazole-clarithromycin-metronidazole group than in the lansoprazole-clarithromycin-amoxicillin group (77% vs. 52%, P < 0.05). Patients in the lansoprazole-clarithromycin-metronidazole group had a lower risk of acute renal failure than those in the lansoprazole-clarithromycin-amoxicillin group (2% vs. 18%, P < 0.05; relative risk, 0.128, 95% confidence interval, 0.016-0.979). CONCLUSIONS: Triple therapy with metronidazole and clarithromycin, but not amoxicillin, can be used for H. pylori eradication in patients with chronic renal insufficiency, because it is more effective, well tolerated and less likely to cause deterioration of renal function.

Quadruple therapy containing amoxicillin and tetracycline is an effective regimen to rescue failed triple therapy by overcoming the antimicrobial resistance of Helicobacter pylori.

AIM: To identify optimal antibiotics for second-line quadruple therapy of Helicobacter pylori after failed 1-week triple therapy. METHODS: One hundred patients were enrolled in this study after the failure of 1-week triple therapy. They were randomized to receive 1-week quadruple therapy consisting of amoxicillin, omeprazole and bismuth salts, plus either metronidazole or tetracycline. Before quadruple therapy, the H. pylori culture of each patient was tested for metronidazole resistance or clarithromycin resistance by E-test. Six weeks later, an endoscopy or 13C-urea breath test was used to define the success of H. pylori eradication. RESULTS: The H. pylori eradication rates by intention-to-treat and per protocol analysis were higher in the tetracycline group than in the metronidazole group (intention-to-treat: 78% vs. 58%, P < 0.05; per protocol: 89% vs. 67%, P < 0.05). In the metronidazole group, but not in the tetracycline group, the per protocol eradication rate of quadruple therapy was lower for the infected isolates with metronidazole resistance than for those without metronidazole resistance (77% vs. 33%, P < 0.05). CONCLUSION: Quadruple therapy, including tetracycline and amoxicillin, improves the H. pylori eradication rate after failed triple therapy.

Local attenuation of systemically mediated splanchnic vasoconstriction during shock due to cholera.

Hypovolemic shock, most often due to hemorrhage, is typically associated with intense splanchnic vasoconstriction. This can be severe enough to impair the functional and structural integrity of the gastrointestinal tract. Paradoxically, with cholera the structure of the gastrointestinal tract is preserved, and the intestine continues to secrete fluid delivered to it in the circulating blood in spite of severe hypovolemic shock. This suggests that splanchnic blood flow is maintained at higher levels in hypovolemic shock due to cholera than in hypovolemic shock due to hemorrhage. Our hypothesis is that cholera toxin in the intestinal lumen activates local mechanisms that attenuate systemically mediated splanchnic vasoconstriction. Blood flow to an isolated ileal segment in situ in the anesthetized rabbit was measured continuously (ultrasound transit-time volume flow probe) for 5 to 6 h after instillation of cholera toxin into the isolated intestinal lumen. Norepinephrine was infused selectively into the mesenteric artery supplying the segment to elicit local responses uncomplicated by compensatory changes secondary to systemic effects of norepinephrine. Baseline vascular conductance increased gradually and became significantly greater in cholera toxin experiments than in vehicle experiments 5 h after treatment (P < 0.035). Animals treated with cholera toxin were less responsive to norepinephrine than vehicle treated animals were (P < 0.05) and became more so over time (P < 0.001). Our conclusion is that cholera toxin activates local mechanisms that attenuate systemically mediated splanchnic vasoconstriction, at least in part by reducing vascular responsiveness to a systemic vasoconstrictor, norepinephrine.

An evaluation of antithrombin III laboratory tests.

Three laboratory tests for the measurement of antithrombin III (AT III) were evaluated. The tests measured functional AT III in serum and plasma, and the third measured AT III antigen in plasma. Normal values for each method were obtained by testing samples from 20 normal subjects. Each test was then performed on specimens from 15 patients clinically suspected of having hypercoagulable states. Each determination was run in duplicate. The hypercoagulable states included disseminated intravascular coagulation, pulmonary embolism, and pregnancy. Two-thirds of these patients were found to have antithrombin III levels below the normal range by all three of the methods studied. Patients who had decreased AT III activity in the functional assays also had decreased AT III antigen.