Characteristics,anticoagulation, and outcomes of portal vein thrombosis after intra-abdominal surgery

BackgroundIntra-abdominal surgery is a cause of portal vein thrombosis; however, postsurgical portal vein thrombosis has not been extensively described.MethodsThis is a retrospective study of 107 patients with postsurgical portal vein thrombosis followed for a median 25 months (interquartile range 11–51). Outcomes were complete radiographic resolution of portal vein thrombosis and development of clinical portal hypertension.ResultsSurgeries associated with portal vein thrombosis included colectomy (n = 42), bariatric surgery (n = 25), and splenectomy (n = 11). Presentations were nonspecific, typically characterized by abdominal pain. Sixty-three patients (59%) achieved complete radiographic resolution. On univariable analysis, provoking surgery, occlusivity of portal vein thrombosis, and anticoagulant used were associated with complete radiographic resolution. Colectomy was associated with a complete radiographic resolution rate of 30/42 (71%), bariatric 10/25 (40%), splenectomy 2/11 (18%), and other 21/29 (72%), (log rank P = .0033). Nonocclusive thrombus was associated with a complete radiographic resolution rate of 44/62 (71%), occlusive thrombus 19/45 (42%), (log rank P = .0101). Direct oral anticoagulants were associated with a complete radiographic resolution rate of 27/35 (77%), enoxaparin 20/29 (69%), warfarin 14/31 (45%), and no anticoagulant 2/12 (17%), (log rank P = .0002). On multivariable analysis, only anticoagulant choice was significantly associated with complete radiographic resolution. Using direct oral anticoagulants as reference, no anticoagulant yielded an adjusted hazard ratio of 0.10 for complete radiographic resolution (95% confidence interval 0.023–0.44), warfarin 0.40 (95% confidence interval 0.20–0.78), and enoxaparin 0.64 (95% confidence interval 0.49–1.60). Failure to achieve complete radiographic resolution was associated with greater risk of future clinical portal hypertension. Twenty-three patients (21%) went on to develop clinical portal hypertension; 20 who failed to achieve complete radiographic resolution (45%), and only 3 who achieved complete radiographic resolution (5%), (log rank P < .0001).ConclusionThe natural history of postsurgical portal vein thrombosis is variable and influenced by type of surgery, degree of occlusion, and, most notably, type of anticoagulant used. Failure to recanalize the portal vein carries considerable risk of future clinical portal hypertension.     

Nitric oxide mediates inhibitory nerve effects in human esophagus and lower esophageal sphincter

The effect of inhibition of nitric oxide synthase on nonadrenergic, noncholinergic nerve-mediated responses in circular smooth muscle of the human esophageal body and lower esophageal sphincter (LES) was examinedin vitro. Tissues were obtained from 10 patients (eight esophageal resection for cancer, two transplant donors). Muscle strips from the LES developed significant spontaneous tension (11.6 ± 2.1 mN/mm²,N=6) and relaxed in response to electrical stimulation. The nitric oxide synthase inhibitor,N -nitro-l-arginine (NNA), at 10^–5 M, inhibited the relaxation, but had no significant effect on the spontaneous tension (13.0 ± 2.6 mN/mm²,P=0.07). Esophageal body strips developed little spontaneous tension, demonstrated an off contraction following the cessation of the electrical stimulus, and when contracted with 10^–5 M carbachol, relaxed during electrical stimulation. NNA (10^–5 M) inhibited the off contraction and the relaxation seen after carbachol and unmasked a prominent intrastimulus contraction. This intrastimulus contraction was enhanced by eserine and inhibited by atropine and tetrodotoxin. NNA showed similar potency in the esophageal body and LES and its effects were reversed byl-arginine, but notd-arginine. The results indicate that nitric oxide is an important mediator for nonadrenergic, noncholinergic nerve effects in the human esophagus and lower esophageal sphincter.This research was supported in part by an ICI Pharma/Medical Research Council of Canada Research Fellowship grant awarded to H.G. Preiksaitis and a Medical Research Council Program Grant PG8.     

The response to exercise with constant energy intake in identical twins

Seven pairs of young adult male identical twins completed a negative energy balance protocol during which they exercised on cycle ergometers twice a day, 9 out of 10 days, over a period of 93 days while being kept on a constant daily energy and nutrient intake. The total energy deficit caused by exercise above the estimated energy cost of body weight maintenance reached 244 +/- 9.8 MJ (Mean +/- SEM). Baseline energy intake was estimated over a period of 17 days preceding the negative energy balance protocol. Mean body weight loss was 5.0 kg (SEM = 0.6) (p < 0.001) and it was entirely accounted for by the loss of fat mass (p < 0.001). Fat-free mass was unchanged. Body energy losses reached 191 MJ (SEM = 24) (p < 0.001) which represented about 78% of the estimated energy deficit. Subcutaneous fat loss was slightly more pronounced on the trunk than on the limbs as estimated from skinfolds, circumferences, and computed tomograply (CT). The reduction in CT-assessed abdominal visceral fat was quite striking, from 81 cm2 (SEM = 5) to 52 cm2 (SEM = 6) (p < 0.001). At the same submaximal power output level, subjects oxidized more lipids than carbohydrates after the program as indicated by the changes in the respiratory exchange ratio (p < or = 0.05). Intrapair resemblance was observed for the changes in body weight (p < 0.05), fat mass (P < 0.01), percent fat (p < 0.01), body energy content (p < 0.01), sum of 10 skinfolds (p < 0.01), abdominal visceral fat (p < 0.01), fasting plasma triglycerides (p < 0.05) and cholesterol (p < 0.05), maximal oxygen uptake (p < 0.05), and respiratory exchange ratio during submaximal work (p < 0.01). We conclude that even though there were large individual differences in response to the negative energy balance and exercise protocol, subjects with the same genotype were more alike in responses than subjects with different genotypes particularly for body fat, body energy, and abdominal visceral fat changes. High lipid oxidizers and low lipid oxidizers during submaximal exercise were also seen despite the fact that all subjects had experienced the same exercise and nutritional conditions for about three months.     

Postexercise macronutrient oxidation: a factor dependent on postexercise macronutrient intake

BACKGROUND: It has been widely shown that exercise increases postexercise fat oxidation and energy expenditure. OBJECTIVE: The aim of this study was to investigate the effect of exercise on postexercise substrate oxidation and energy expenditure when the exercise-induced expenditure of energy and macronutrients oxidized is compensated by an equivalent intake immediately after exercise. DESIGN: Twenty-four-hour energy expenditure (24EE) and macronutrient oxidation of 8 young men were measured in a whole-body indirect calorimeter under the 2 following, randomly assigned conditions: 1) a control session of sedentary activities in the calorimeter for 61 h and 2) a similar session preceded by 60 min of exercise at 50% of maximal oxygen consumption. Immediately after exercising, subjects ingested a milk shake containing the same amount of energy (above resting metabolic rate) expended during exercise and with a food quotient corresponding to the mean exercise respiratory quotient. 24EE and substrate oxidation were compared between conditions on a day-to-day basis (days 1, 2, and 3) and for the 61-h observation period. RESULTS: There was no difference in 24EE between the 2 conditions. Moreover, the composition of the postexercise fuel mix oxidized, as reflected by the respiratory quotient, was strictly the same under the 2 conditions. CONCLUSION: Voluntary postexercise compensations in energy and macronutrient intakes play a major role in the ability of exercise to alter postexercise substrate utilization.     

Increased myogenic potential and fusion of matrilysin-expressing myoblasts transplanted in mice

The success of myoblast transplantation in clinical trials has been limited in part by the low dispersion of grafted cells outside the injection site. Our research group previously reported that the culture of myoblasts with concanavalin A, a stimulator of metalloproteinase production, increased their migration. Several lines of evidence also suggested that muscle cell fusion involves metalloproteinase-sensitive mechanisms. To determine whether the increased expression of metalloproteinases had an influence on myoblast fusion and dispersion through the muscle following transplantation, we generated a myoblast cell line expressing human matrilysin (MMP-7). The MMP-7-expressing myoblasts were obtained by the stable transfection of a matrilysin expression vector in a TnILacZ immortomouse myoblast clone. Matrilysin-expressing myoblasts showed a highly increased in vitro fusion index, forming seven times (p < 0.001) more myotubes than the control cell line and three times (p < 0.001) more myotubes than the Immortomyoblast parental clone. Single-site transplantation of matrilysin-expressing myoblasts generated more fibers (p < 0.001), over a greater surface (p < 0.001) than the control cell line. The cotransplantation of matrilysin-expressing myoblasts and of normal human myoblasts in SCID mice increased the number of human dystrophin-positive fibers and myotubes by sixfold. Although no significant increased migration of myoblasts outside the injection sites was observed, our results show that the metalloproteinase activity can improve the myogenic potential of myoblasts in vitro and the fusion of myoblasts with host fibers in vivo. MMP-7 expression may be useful in increasing myoblast transplantation success.     

Thermostable antigens from the bone marrow of several animal species.

Studies on bone marrow extracts from ten animal species have revealed the presence of thermostable antigens. Similar antigens were found in other organs as shown by immunodiffusion and cross-reactivity was demonstrated between the thermostable proteins from horse and dog and between cow and sheep proteins. Using an immunoenzymatic reaction with glucose oxidase as the marker, the thermostable antigens were localized in the blood and bone marrow polymorphonuclear leukocytes and the myeloid cell line.     

Detrusor sphincter dyssynergia,detrusor instability,and urethral sphincter spasticity as the urodynamic findings in the urethral syndrome: Role of treatment with a combined anticholinergic and alpha blocking agent,bladder drill,and antibiotics

The combined effect of isopropamide 5 mg plus trifluoperazine 1 mg (a combined anticholinergic and alpha-adrenergic antagonist) (Smith, Kline and French Canada Ltd, Ontario, Canada), antibiotics, and bladder drill was retrospectively assessed on 100 consecutive women, aged 16 to 47 years, presenting with the signs and symptoms of the urethral syndrome. Assessment included history, physical examination, routine bacterial and chlamydial cultures (cervical, urethral, vaginal, and urine), cystourethroscopy, and urodynamics. Urodynamic diagnoses included detrusor sphincter dyssynergia (n=84), detrusor instability (n =8), external urethral sphincter spasticity (n=4), and sensory urgency (n=1). Three patients with positive urine cultures were excluded. Urethrotrigonitis was visualized at cystourethroscopy in all patients. Only one case of chlamydial urethritis-cervicitis was identified by culture: 82% of patients had a history of prior antibiotic therapy for lower urinary tract symptoms and 21% were being treated with antibiotics at the time of their initial assessment.Following 1 month of treatment, 44 (45%) patients were cured of all symptoms, 49 (51%) were improved, 3 (3%) were unchanged and 1 (1%) was worse. Significant changes in uroflowmetry included a reduction in postvoid residual urine volume from 49 ± 28 ml to 14 ±21 ml (P=0.029) in the unstable bladder group and a conversion from intermittent to continuous uroflow patterns in the detrusor sphincter dyssynergia group (P <0.005, ²) and overall (P <0.005, ²). A statistically significant number of patients (P <0.025, ²) converted from increased to normal tracings on repeat perianal electromyography, suggesting that the pathophysiology of the urethral syndrome is urethral spasticity related to urethral inflammation rather than actual infection.We conclude that detrusor sphincter dyssynergia, bladder instability, and urethral sphincter spasticity are the common urodynamic findings in the urethral syndrome. A combination of anticholinergic and alpha blocking agent, antibiotics, and a bladder drill markedly improved (96%) symptoms in women with the urethral syndrome.     

An electron microscope study of synaptic contacts in the abdominal ganglion of Aplysia californica.

The fine structure of the abdominal ganglion of Aplysia californica has been studied in preparations fixed by immersion in aldehydes, either directly or after a survival of a few hours in artificial sea water. The central core of neuropil is surrounded by a rind of neuronal cell bodies floating in a subcapsular space containing a loose meshwork of neuronal and glial processes, separated by wide extracellular spaces. Large primary processes with deeply infolded membranes leave the neuronal perikarya and enter the neuropil where they branch into smaller processes containing either neurofilaments, neurotubules or both. Some have the appearance of initial segments. The neuropil is not a homogeneous structure. Rather, four types of zones can be distinguished: (1) zones of fibers of passage coursing together in the neuropil and making few synaptic contacts: (2) zones of neurosecretory fibers containing large granules and dense-core vesicles, again making few synaptic contacts: (3) zones with a great variety of synaptic contacts between medium size and small profiles; and (4) glomerular zones. The differentiated membranes of the synapses are characterized by a slight increase in density and by being regularly parallel to each other. Presynaptic densities are sometimes quite prominent but specialized dense cytoplasmic opacities have never been seen bordering the postsynaptic membranes, i.e., all synapses are of the symmetrical type. Interlemmal opacities vary considerably in density. In zone 3, the synaptic vesicles are of several sizes, are round, oval or flat, and are either clear or filled with different types of dense material. The population of vesicles within a single profile may consist either of a homogeneous group of similar vesicles or of various mixtures of two or three kinds of vesicles. In profiles with mixtures of clear and large dense-core vesicles, it is often only the clear vesicles which agglomerate towards the differentiated membranes. In such cases the large dense-core vesicles lie as a peripheral halo around the clear vesicles. Here, and especially in other large neuronal profiles not forming contact in the plane of section, they can be seen to associate specifically with mitochondria and glycogen. It is proposed that they do not contain neurotransmitters but are related to mitochondrial activities such as the storage of ATP or the movement of calcium ions. In profiles with mixtures of clear and small dense-core vesicles, both types of vesicles often touch the presynaptic membrane, suggesting the release of two transmitters or of a modulator or neurohormone with a transmitter, by a single terminal. Serial synapses are present in this zone. The glomerular zones contain small profiles forming many synaptic contacts, some of which are arranged in such a way as to suggest the existence of "reciprocal" serial synapses.     

Précipitation et prévention de l'abstinence chez le rat et la souris en état de dépendance aiguë. Comparaison de la naloxone,de la naltrexone et de la diprenorphine

Summary Abstinence signs were precipitated in rats by naloxone (1 mg·kg^-1 s.c.) injected at various times (from 1.5 to 16 h) after a single dose of morphine hydrochloride (15 or 50 mg·kg^-1 s.c.) administered incaqueous solution. Increasing the dose of morphine increased the latency of the phenomena and the duration of the underlying state shifts of signs as described by Bläsig et al. (1974) in chronically morphinized rats also occurred when increasing the dose of morphine and the time interval between the injections of morphine and of naloxone. Naltrexone and diprenorphine were also effective. These three antagonists, given before morphine, were able to prevent precipitated abstinence: however, naloxone was almost ineffective when the higher dose of morphine was used and when the time interval was long. In these latter conditions, naltrexone was definitely more effective and longer acting and diprenorphine still more so. The same characteristics were found for the protective action of the three antagonists in acutely morphinized mice and the same order for their potencies in precipitating abstinence in acutely morphinized mice. Like naloxone, naltrexone and diprenorphine facilitated a nociceptive reaction in normal mice.The abstinence signs precipitated in acutely morphinized rats or mice are probably not unmasked excitatory effects of morphine as such effects should have been increased rather than inhibited by previous administration of specific antagonists; they might correspond to potentiated effects of the antagonists themselves. The prevention by specific antagonists of the abstinence syndrome is most simply interpreted by antagonism (direct or indirect) of dependence induction, but other interpretations are not excluded.