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PubMed1995

The potential of sheep for the study of osteopenia: current status and comparison with other animal models.

There is a great need to develop an animal model for postmenopausal osteoporosis; a model that will be useful for the understanding of the pathogenesis of the disease as well as the investigation of new therapies. The requirements for such an animal model are discussed and ones that have been used in the past include nonhuman primates, dogs, cats, rodents, rabbits, guinea pigs, and minipigs. Advantages and disadvantages of these models are briefly reviewed. Sheep are a promising model for various reasons; they are docile, easy to handle and house, relatively inexpensive, available in large numbers, spontaneously ovulate, and have hormone profiles similar to women. Ovariectomy results in a slight loss of bone from the ovine iliac crest, and biochemical markers such as osteocalcin are well characterized. Physiological disadvantages are lack of natural menopause, that normal estrus cycles are restricted to fall and winter and that they have a different gastrointestinal system. Sheep have cortical bone that is plexiform in structure although haversian remodeling is seen in older animals. When and if biomechanical incompetence of bone follows ovariectomy is presently unknown. There is no ideal model for the study of postmenopausal osteoporosis; all have advantages and disadvantages. Researchers in this field must recognize the limitations of the model they choose, and select one that will fulfill their needs.

Absorptiometry, Photon↗

PubMed2007

Local toxicity of hepatic arterial infusion of hexokinase II inhibitor, 3-bromopyruvate: In vivo investigation in normal rabbit model.

RATIONALE AND OBJECTIVES: 3-Bromopyruvate (3-BrPA), an hexokinase II inhibitor, is known to have high necrotic rate in hyperglycolytic liver tumor models without apparent damage to the normal liver parenchyma. The toxicity of intra-arterial delivery of 3-BrPA in various concentrations has not been specifically investigated using a normal rabbit model. MATERIALS AND METHODS: Twenty rabbits treated with intra-arterial 3-BrPA were divided into four groups according to its dose and infusion level: 1 mM at the left hepatic artery (group I), 5 mM at the left hepatic artery (group II), 25 mM at the left hepatic artery (group III), and 25 mM at the common hepatic artery (group IV). After selective catheterization, 30 ml of 3-BrPA was infused for 2 minutes. As a control group, five rabbits were treated with normal saline. During 1-week follow-up, toxicities were evaluated with blood laboratory results, mortality, and histopathologic examination. RESULTS: All 10 rabbits treated with 25 mM 3-BrPA and 2 rabbits treated with 5 mM 3-BrPA died within 3 days after treatment. In 10 of the 12 deaths, hemorrhagic pyloric or duodenal necrosis was noted. Hepatotoxicities on blood laboratory results were dose dependent but transient in the surviving rabbits. CONCLUSION: Selective intra-arterial administration of 25 mM 3-BrPA can cause considerable toxicities not only in the liver but also in the gastrointestinal system and are dose dependent and can cause death in high doses.

Animals↗

PubMed2004

Assessment of oral bisphosphonate use in elderly patients with varying degrees of kidney function.

BACKGROUND: Oral bisphosphonates are prescribed for millions of men and women in the United States who have osteopenia or osteoporosis. However, there are limited data on the use of oral bisphosphonates in patients with kidney impairment. OBJECTIVE: The purpose of this study was to evaluate changes in calculated creatinine clearance (CrCl) and reported adverse events in elderly patients with varying degrees of kidney function who were taking oral bisphosphonate therapy. METHODS: The present study was a retrospective review of the medical records of elderly patients (age range, 65-89 years) who were prescribed oral bisphosphonates for a diagnosis of osteoporosis or osteopenia at the University of Colorado Hospital Seniors Clinic during the period January 1999 through March 2003. Data on age, sex, body weight, height, blood urea nitrogen and serum creatinine concentrations, and adverse-reaction history were collected. Clinic notes were reviewed to determine whether patients had taken an oral bisphosphonate previously or whether bisphosphonate therapy was initiated during the study period. The Cockcroft-Gault equation was used to calculate CrCl. Rates of drug-related adverse events were compared in patients with and without severe kidney impairment. For the purposes of this study, severe kidney impairment was defined as a CrCl <35 mL/min. RESULTS: Data from 181 patients (88.4% female, 11.6% male; mean age, 79.2 years) who received oral bisphosphonates were included in the analysis. One hundred fourteen (63.0%) patients began bisphosphonate therapy during the study period. The mean duration of bisphosphonate therapy was 22.3 months. Thirty-one (17.1%) patients taking bisphosphonates had severe kidney impairment. There was no change in calculated CrCl after the initiation of oral bisphosphonate therapy in patients who started therapy during the study period. Adverse drug events, 19 of them related to the gastrointestinal system, occurred in 24 (13.3%) patients. Overall, 19.4% (6/31) of patients with severe kidney impairment and 12.0% (18/150) of those without severe kidney impairment experienced adverse events; the difference between groups was not statistically significant. No reported adverse drug event required hospitalization or emergency treatment. CONCLUSIONS: When prescribed for elderly patients with varying degrees of kidney function, oral bisphosphonate therapy was well tolerated and was not associated with a decline in calculated CrCl.

Administration, Oral↗

PubMed2006

Randomized controlled noninferiority trial to compare extended release acetaminophen and ibuprofen for the treatment of ankle sprains.

STUDY OBJECTIVE: To compare acetaminophen extended release 1,300 mg 3 times daily and ibuprofen 400 mg 3 times daily for treatment of signs and symptoms of grade I or II lateral ankle sprains. METHODS: Patients (N=260) 18 years or older and with grade I or II lateral ankle sprains were randomized to receive acetaminophen extended release 1,300 mg 3 times daily or ibuprofen 400 mg 3 times daily for 9 days. Primary endpoint was change from baseline at day 4 in pain on walking. Other endpoints included change from baseline at day 9 in pain on walking; change from baseline at days 4 and 9 in ability to walk and ankle swelling, bruising, and range of motion; satisfaction with treatment on days 4 and 9; percentage of patients with positive anterior drawer test on day 4; and time to resume normal activity. Safety assessments consisted of reported adverse events. This study had a noninferiority design in which the hypothesis was that acetaminophen extended release was not inferior to ibuprofen for treatment of signs and symptoms of grade I or II lateral ankle sprains. RESULTS: The difference in least squares means (acetaminophen extended release, ibuprofen) with respect to the primary endpoint within the per-protocol population was -0.88; acetaminophen extended release was comparable to ibuprofen for the primary endpoint because the upper limit (3.26) of the 1-sided 95% confidence interval (CI) for the difference in least squares means did not exceed the noninferiority limit of 6.90. The intention-to-treat population was used to test the second step of the 2-step testing process because the null hypothesis was rejected in the noninferiority test. For this analysis, the difference between acetaminophen extended release and ibuprofen in the least squares mean change from baseline for the primary endpoint was -1.63 (not significant). Results showed that acetaminophen extended release was noninferior to ibuprofen with respect to the secondary endpoints. No serious drug-related adverse events were reported. The most common adverse events, reported by 6.5% of patients, were in the gastrointestinal system (mainly nausea and upper abdominal pain). CONCLUSION: Acetaminophen extended release 3,900 mg daily was comparable to ibuprofen 1,200 mg daily for treatment of grade I or II lateral ankle sprains. Both treatments were well tolerated.

Acetaminophen↗

PubMed2004

Inverse gene expression patterns for macrophage activating hepatotoxicants and peroxisome proliferators in rat liver.

Macrophage activation contributes to adverse effects produced by a number of hepatotoxic compounds. Transcriptional profiles elicited by two macrophage activators, LPS and zymosan A, were compared to those produced by 100 paradigm compounds (mostly hepatotoxicants) using cDNA microarrays. Several hepatotoxicants previously reported to activate liver macrophages produced transcriptional responses similar to LPS and zymosan, and these were used to construct a gene signature profile for macrophage activators in the liver. Measurement of cytokine mRNAs in the same liver samples by RT-PCR independently confirmed that these compounds are associated with macrophage activation. In addition to expected effects on acute phase proteins and metabolic pathways that are regulated by LPS and inflammation, a strong induction was observed for many endoplasmic reticulum-associated stress/chaperone proteins. Additionally, many genes in our macrophage activator signature profile were well-characterized PPARalpha-induced genes which were repressed by macrophage activators. A shared gene signature profile for peroxisome proliferators was determined using a training set of clofibrate, WY 14643, diethylhexylphthalate, diisononylphthalate, perfluorodecanoic acid, perfluoroheptanoic acid, and perfluorooctanoic acid. The signature profile included macrophage activator-induced genes that were repressed by peroxisome proliferators. NSAIDs comprised an interesting pharmacological class in that some compounds, notably diflunisal, co-clustered with peroxisome proliferators whereas several others co-clustered with macrophage activators, possibly due to endotoxin exposure secondary to their adverse effects on the gastrointestinal system. While much of these data confirmed findings from the literature, the transcriptional patterns detected using this toxicogenomics approach showed relationships between genes and biological pathways requiring complex analysis to be discerned.

Animals↗

PubMed2006

Comparison of the effects of proton pump inhibitors on human plasma adrenocorticotropic hormone and cortisol levels under the starved condition.

The hypothalamo-pituitary-adrenal (HPA) axis is known to relate with energy homeostasis. Appetite and food intake are assumed to be regulated by the HPA axis. Among lots of medicines that act gastrointestinal system, we focused proton pump inhibitors, which are widely used to treat peptic ulcer, gastro esophageal reflux disease and eradication of Helicobacter pylori. In this study, we investigated that the effect of three proton pump inhibitors (omeprazole, lansoprazole and rabeprazole) on plasma adrenocorticotropic hormone (ACTH) and cortisol levels in healthy human subjects. Five healthy male volunteers were treated to omeprazole, lansoprazole, rabeprazole or placebo. Venous blood samples were taken repetitively from a forearm vein before and after administration. Plasma ACTH-like immunoreactive substance (IS) levels were measured using a sensitive enzyme immunoassay, and plasma cortisol levels were measured using a fluorescence polarization immunoassay. Single administration of lansoprazole caused significant (P<0.05) increase of ACTH-IS at 60 and 120-180 min, and cortisol at 180-240 min after administration, compared with placebo group. Rabeprazole also caused significant increase of ACTH-IS at 120 min and cortisol at 240-360 min, compared with placebo group. Omeprazole had no effect on plasma ACTH-IS and cortisol levels. Lansoprazole and rabeprazole increased plasma ACTH-IS and cortisol levels. Therefore, we hypothesized that the medicines might activate the HPA axis, and have effect to promote feeding. We considered that these results might be relevant to the development of new therapeutics in the treatment of psychiatric disorders involving dysregulation of appetite.

2-Pyridinylmethylsulfinylbenzimidazoles↗

PubMed2006

Safety and tolerability of tegaserod in patients with chronic constipation: pooled data from two phase III studies.

BACKGROUND & AIMS: Studies show that tegaserod effectively relieves the symptoms of chronic constipation/idiopathic constipation (CC). This pooled analysis assessed the safety and tolerability of tegaserod in a large dataset of CC patients. METHODS: Adverse event (AE) data were pooled from 2 double-blind, placebo-controlled phase III trials of 12 weeks' duration. Post hoc analysis was conducted for the most frequent AEs (incidence, >or=3%). RESULTS: Eight hundred eighty-one, 861, and 861 patients received tegaserod 6 mg twice a day, 2 mg twice a day, or placebo, respectively. Most AEs were mild/moderately severe. AE incidence was similar for the tegaserod 6 mg and 2 mg twice a day (57.1% and 56.3%, respectively) and placebo groups (59.6%) and most frequent in the gastrointestinal system (tegaserod 6 mg twice a day, 25.8%; 2 mg twice a day, 22.5%; placebo, 24.6%). Headache, the most common AE, was slightly more frequent in the placebo group (tegaserod 6 mg twice a day, 11.0%; 2 mg twice a day, 10.1%; placebo, 13.2%). Diarrhea (generally transient and resolved with continued treatment) was the only AE with a statistically significant difference between groups (tegaserod 6 mg twice a day 6.6% vs placebo 3.0%, P=.0005). Serious AE incidence (1.4% overall) was comparable across treatment groups, although abdominal surgery was less common in the combined tegaserod (0.5%) than the placebo group (1.0%). Discontinuation as a result of AEs was slightly higher in tegaserod 6 mg twice a day patients (5.7%; 2 mg twice a day, 3.3%; placebo, 3.7%), mainly because of diarrhea. Laboratory and electrocardiogram parameters were comparable across groups. CONCLUSIONS: Tegaserod is well tolerated by patients with CC during 12 weeks of treatment.

Administration, Oral↗

PubMed2004

Efficacy and tolerability of sustained-release tramadol in the treatment of symptomatic osteoarthritis of the hip or knee: a multicenter, randomized, double-blind, placebo-controlled study.

BACKGROUND: Opioid analgesics may be a useful alternative in patients with osteoarthritis who have not responded to first-line treatment with acetaminophen and in whom nonsteroidal anti-inflammatory drugs are contraindicated, ineffective, or poorly tolerated. OBJECTIVE: This study compared the efficacy and tolerability of tramadol LP 200 mg, a new once-daily,sustained-release formulation, with those of placebo in patients with osteoarthritis of the hip or knee. METHODS: In this multicenter, double-blind, placebo-controlled, parallel-group study, patients with osteoarthritis of the hip or knee (European League Against Rheumatism criteria) were randomized to receive either tramadol LP 200 mg once daily or placebo for 14 days. The primary efficacy end point was the change from baseline to the end of the study in scores on the Huskisson visual analog scale for pain. Secondary end points were change in the Lequesne functional discomfort index, global efficacy assessed by the patient and the investigator, time to improvement, and use of acetaminophen as rescue analgesic medication. Global tolerability was assessed by both patients and investigators at the end of the study The number and severity of adverse events occurring during the study and for 2 weeks thereafter were also recorded. RESULTS: Two hundred thirty patients (167 women, 63 men) were evaluable for efficacy and safety Demographic data for the tramadol and placebo groups were as follows: mean (SD) age, 67.1 (7.1) and 66.4 (92) years, respectively; female sex, 72.1% and 73.1%; and mean body weight, 74.7 (13.6) and 74.6 (14.8) kg. All patients were white. The completer analysis included 197 patients (85 tramadol, 112 placebo). Pain was significantly reduced in the tramadol LP group compared with the placebo group on day 7 (P = 0.002) and day 14 (P = 0.010). In the patient's assessment of global efficacy, 77.6% (66) of the tramadol LP group reported improvement by day 14, compared with 59.8% (67) of the placebo group; in the investigator's assessment, the efficacy of tramadol LP was rated very good or good for 612% (52) of patients, compared with 30.4% (34) for placebo. Improvement was reported before day 7 in 882% (75) of patients in the tramadol LP group, compared with 65.2% (73) in the placebo group (P = 0.021); the mean time from the initiation of treatment to reported improvement was 3 days for tramadol LP and 6 days for placebo (P < 0.001). Rates of response (defined as > or =30% pain reduction between days 0 and 14) were 64.7% (55) for tramadol LP and 50.0% (56) for placebo (P = 0.039); no rescue medication was used by 60.0% (51) of the tramadol LP group and 36.6% (41) of the placebo group (P - 0.001). One or more adverse event was reported by 45.0% (50) of the tramadol LP group, compared with 193% (23) of the placebo group (P < 0.001). As would be expected with an opiate agonist such as tramadol, the most common adverse events with this agent involved the gastrointestinal system (nausea, 22.5% [25] of patients; vomiting, 17.1% [19]) and the central nervous system (somnolence, 11.7% [13]). CONCLUSIONS: In this study, tramadol LP 200 mg was significantly more effective than placebo in alleviating pain in patients with osteoarthritis of the hip or knee. It appeared to be relatively well tolerated for an opioid compound.

Aged↗

PubMed2005

Gastroesophageal reflux.

Gastroesophageal reflux disease (GERD) is the most common disease of the gastrointestinal system. Heartburn, regurgitation, and dysphagia are the most common symptoms of GERD. However, chest pain, chronic cough, laryngitis, hoarseness, and other otolaryngologic manifestation can be the primary manifestations of the disease. Endoscopy, barium studies, and especially pH monitoring and therapeutic trials may help in establishing the diagnosis of GERD. The introduction of H2 antagonists and especially of proton pump inhibitors (PPI) has brought symptomatic relief in most patients. However, surgical procedures, especially laparoscopic fundoplication, are still required in some patients. Barrett's esophagitis is the most common complication of GERD and is associated with a high prevalence of esophageal adenocarcinoma. Whether or not treatment with either PPIs or H2 antagonists can prevent this complication is still under investigation.

Journal Article↗

PubMed2005

Disorders of potassium.

Potassium disorders are the most common electrolyte abnormality identified in clinical practice. Presenting symptoms are similar for both hypo- and hyperkalemia, primarily affecting the cardiac, neuromuscular, and gastrointestinal systems. Generally, mild hypokalemia is the most common potassium disorder seen clinically;however, severe complications can occur. Hyperkalemia is less common but more serious, especially if levels are rising rapidly. The etiologies and treatments for both hypo- and hyperkalemia are discussed, with special emphasis on the role medications play in the etiologies of each.

Acute Kidney Injury↗

PubMed2004

Behçet's disease: external ear involvement.

Behçet's disease is an autoimmune vasculitis characterized by recurrent episodes of oral and genital ulcerations, skin lesions and uveitis. It also affects neurological, vascular, articular and gastrointestinal systems. Although etiology and pathogenesis are under investigation, studies have shown that HLA-B51 influences genetic susceptibility. The development of the disease is associated to neutrophil activation. Treatment depends on the severity of the disease and immunosuppressive drugs are often used. Blindness and dementia are long-term concerns. We report an unprecedented case of a child with Behçet's disease presenting a skin lesion with necrosis of the external ear canal, facial paresis, Horner's syndrome and rupture of the internal carotid artery.

Behcet Syndrome↗

PubMed2005

Accidental cyanoacrylate glue ingestion.

Cyanoacrylates have a variety of medical and commercial applications as adhesives. They are commonly found as glue in the household. They can be swallowed accidentally by children. However, no case was reported so far in the English medical literature. Their effect on the mouth, pharynx, larynx, esophagus and the rest of gastrointestinal system is unknown. Here we report our own child who accidentally ingested cyanoacrylate glue without unwanted sequelae due to prompt intervention.

Accidents, Home↗

PubMed2005

Effect of melatonin on wound healing in normal and pinealectomized rats.

Melatonin usage is increasing gradually, but reports of its effects on wound healing are inconsistent. It has been shown that the hormone is synthesized in and secreted from the gastrointestinal system independently of the pineal gland. We have investigated, by means of a comparative study on the healing of incision and anastomotic wounds, whether melatonin has an effect on wound healing independent of the pineal gland. Rats were divided in five groups (n = 10), all of which were subjected to small intestine anastomosis. The first group (control) was otherwise untreated. Exogenous melatonin was given to the rats in second group. The calvaria was opened then closed in the third group (sham operated), whereas the fourth group was pinealectomized and the fifth group were pinealectomized and then treated with melatonin. After anastomosis bursting pressures and incision wound breaking strength were measured on the 7th postoperative day, tissue hydroxyproline levels were determined, and histopathological investigation was performed. It was found that while collagen deposition and epithelization increased concurrently in incision wounds after pinealectomy, only collagen deposition increased at the anastomosis line. Exogenous melatonin decreased collagen synthesis and epithelium proliferation and had negative effects on wound healing in both normal and pinealectomized rats.

Anastomosis, Surgical↗

PubMed2004

Retrospective analysis of adverse drug reactions induced by gemcitabine treatment in patients with non-small cell lung cancer.

Non-small cell lung cancer (NSCLC) is the leading cause of cancer death in the world. Traditional chemotherapy for advanced NSCLC is often considered excessively toxic. Recent clinical trials documented that gemcitabine may represent a good therapeutical option in patients with NSCLC. Aim of our research was to retrospectively evaluate the adverse effects induced by gemcitabine in patients with NSCLC from 1 January 1997 to 31 December 2002, in clinical records of Oncology Divisions of "S. Giovanni di Dio" Hospital of Crotone, "Ospedali Riuniti" Hospital of Reggio Calabria, Hospital of Paola, and in Pneumological Oncology Division of "Mariano Santo" Hospital of Cosenza, Italy. Clinical records of patients treated with gemcitabine (1000mgm(-2) on days 1 and 8) were reviewed and following data were obtained: sex and age of the patients, histologic diagnosis and disease stage, World Health Organisation (WHO) performance status and toxic effects induced by gemcitabine. We reported that 71.6% of NSCLC patients (age range 48-77 years; 135 males, 27 females; performance status 0=53, 1=109) were eligible for our study. Side effect of gemcitabine involved gastrointestinal system (nausea, vomiting and diarrhoea) and only in the last cycles (VIII-XI) emopoiethic system (leukopenia, neutropenia, thrombocytopenia and anemia). Grade IV vomiting occurred in three patients, thrombocytopenia in two. Grade III leukopenia was observed in three patients. Other toxicities were mild. None of the patients died during chemotherapy. In conclusion, these data showed that gemcitabine present a very good tolerability in patients with NSCLC. Therefore, it could be considered as a new therapeutic agents to use as first line therapy for this disease.

Aged↗

PubMed2006

Cholecystokinin- and gastrin-induced protein and amylase secretion from the parotid gland of the anaesthetized rat.

I.V. infusion of pentagastrin (20 microg/kg/h) or cholecystokinin (CCK)-8 (1 microg/kg/h) for 10 min caused secretion of salivary proteins from the parotid gland in the anaesthetized rat without any accompanying overt fluid secretion. This "occult" response was revealed by a subsequent wash-out injection of methacholine (5 microg/kg, I.V.) 10 min after the end of the infusion period (aiming at avoiding synergistic interactions). While the fluid response to methacholine was unaffected by the preceding infusion of pentagastrin and CCK-8, the output of protein increased by 147% (pentagastrin) and 74% (CCK-8) and that of amylase by 45% (CCK-8) compared to the responses to methacholine upon saline infusion. Those increases were abolished by the CCK-A receptor blocker (lorglumide), but not by the CCK-B receptor blocker (itriglumide). Evisceration, combined sympathetic and parasympathetic denervation of the glands and assay under adrenoceptor blockade excluded contribution from the gastro-intestinal tract, central or ganglionic mechanisms and circulating catecholamines to the increase in protein/amylase. Furthermore, Western blot demonstrated CCK receptors for both A and B subtypes in normal and chronically denervated glands. In the submandibular gland, both pentagastrin and CCK-8 evoked a trace secretion of saliva but, under the present experimental set-up, no statistically significant increase in protein output. Thus, in addition to the autonomic nervous system, gastrointestinal hormones may, in some types of glands, be involved in the secretion of salivary gland proteins.

Amylases↗

PubMed2005

Abrogation of the alloreactive responses of cadaveric donor intestinal lymphocytes by intraoperative Campath-1H exposure.

A number of recent reports in clinical and experimental intestinal transplantation have suggested that the donor lymphocytes present in and around the gastrointestinal system are potent mediators of graft-versus-host (GvH) reactivity and that GvH responses may contribute to posttransplant morbidity. Therefore, we have tested the proliferative and cytotoxic capabilities of gut-associated lymphocytes from cadaveric donors obtained prerevascularization (pre-r) and about 6 hours postrevascularization (post-r) in recipients pretreated with Campath-1H antibody (alemtuzumab). Mixed lymphocyte reactions (MLR) were performed with lymphoid cells isolated from intestinal epithelial mucosa, lamina propria, and lymph nodes. The pre-r lymphocytes responded strongly to both the recipient and third-party alloantigenic stimulating cells. However, similar preparations from the post-r samples responded in MLR at significantly lower levels (P < .01). This post-r decrease in responsiveness was not observed in similar lymphocyte samples obtained from donors of recipients not treated with Campath-1H. Both the pre-r and post-r samples had similar flow cytometric profiles, suggesting that there was no receptor loss in these lymphoid tissues by the short-term 6-hour exposure to Campath-1H given to the recipient. Conversely, in preliminary experiments where the donor were treated with Campath-1H, it was observed that very few lymphocytes could be obtained from intestinal tissues (n = 3). These results suggested that Campath-1H treatment of the recipient could bring about a drastic reduction in an otherwise strong GvH reactivity by the donor intestinal immune cells.

Alemtuzumab↗

PubMed2005

Tacrolimus plus low-dose mycophenolate mofetil in renal transplant recipients: better 2-year graft and patient survival than with a higher mycophenolate mofetil dose.

OBJECTIVES: Mycophenolate mofetil (MMF) has become more widely prescribed in recent years, but its adverse effects on the gastrointestinal system and bone marrow restrict its use in certain settings. The aim of this study was to compare the demographic features and clinical data for 173 renal transplant recipients who received tacrolimus (TAC) plus 1 g/d MMF (group I, n = 112) versus TAC plus 2 g/d MMF (group II, n = 61 patients) over a 2-year period. Each patient received similar TAC doses. METHODS: We compared demographic data and clinical data for each case: acute rejection (AR) episodes, chronic rejection (CR) episodes, death, graft loss, development of posttransplantation diabetes mellitus (PTDM), and posttransplantation hypertension rates. RESULTS: Demographic features were similar. There were also no significant differences between groups I and II with respect to number of AR episodes (17/112 vs 12/61, respectively), number of CR episodes (4/112 vs 1/61, respectively), PTDM, and hypertension rate (P > .05). Kaplan-Meier survival analysis revealed 2-year graft survival rates of 94% in group I versus 83% in group II. The corresponding 2-year patient survival rates were 100% in group I versus 91% in group II. The graft survival and patient survival rates in group I were significantly higher than those in group II (log-rank 0.005 and 0.001, respectively). CONCLUSIONS: The 2-year graft and patient survival rates for the renal transplant recipients in this study suggest that the combination of a full TAC dose with 1 g/d MMF is a better choice than 2 g/d MMF.

Adult↗

PubMedDate not supplied

Nutrient-induced changes in intestinal blood flow in the dog.

The cardiovascular response to feeding consists of two phases. The anticipation/ingestion phase is a brief, generalized cardiovascular response mediated by sympathetic neural activity. The digestive/absorptive phase is a longer, locally mediated vascular response to luminal nutrients. This post-prandial hyperaemia is localized primarily to the intestinal segment and tissue layer (mucosa) exposed to chyme. The stimuli for this hyperaemia are the digested products of food, and bile. Micellar fatty acids induce the greatest hyperaemia, followed by glucose. Individual amino acids have little effect, but by-products of protein digestion may increase blood flow. Bile enhances the glucose-induced hyperaemia and renders fatty acids and amino acids vasoactive. The mechanisms involved in the initiation and maintenance of the hyperaemia are complex and involve numerous factors that may vary with the type of nutrient. The factors involved include intestinal activity such as absorption, motility and secretion, tissue oxidative metabolism, adenosine, tissue oxygen tension, the enteric nervous system, gastrointestinal peptides such as vasoactive intestinal polypeptide, and paracrine substances such as histamine and prostanoids. The post prandial intestinal hyperaemia is probably the net result of the complex interaction of all these factors on the intestinal vascular smooth muscle.

Animal Feed↗