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Acute iliopsoas and adductor brevis abscesses presenting with proximal leg muscle weakness.

Pyomyositis is a bacterial infection of skeletal muscle. We describe the clinical case of a 77-year-old woman affected by gait disturbance, repetitive falls, low back pain and left thigh and groin pain, but without symptoms of systemic infection. Computed tomography and magnetic resonance imaging of the abdomen and pelvis showed abscesses in the left psoas and adductor brevis muscles. Investigations of urogenital tract and gastrointestinal system were normal. Systemic antibiotic treatment alone was not efficient, while surgical drainage improved the clinical picture. The aetiological organism, isolated from the abscess, was Staphylococcus aureus. We suggest that this patient had a primary pyomyositis rather than a secondary form. This is the first report of concomitant abscesses of psoas and adductor brevis muscles with early neurological involvement.

Aged↗

General pharmacology of a Pseudomonas vaccine prepared from outer-membrane fractions of Pseudomonas aeruginosa.

CFC-101 is a novel Pseudomonas vaccine with high effectiveness against Pseudomonas infection and is currently under clinical evaluation. The general pharmacological properties of this vaccine were evaluated in mice, rats, guinea pig ileum, and dogs. In vivo doses of 0.2, 2.0 and 20 mg/kg given by intramuscular route, or in vitro concentrations up to 50 micrograms/ml were used. Intramuscular administration of CFC-101 vaccine had no effect on the central nervous system except that the body temperature of rats was slightly decreased at the highest dose, 20 mg/kg. CFC-101 vaccine did not affect the function of smooth muscles, gastrointestinal system, and cardiovascular and respiratory systems. In water and electrolytes excretion test, a decrease in urine output and an elevation of the excretion of Na+, Cl- and total protein at the highest dose (20 mg/kg) were observed. In summary, CFC-101 vaccine had no pharmacological effect in these studies even up to the 100-fold clinical dose, 2 mg/kg.

Animals↗

The corticotropin-releasing factor system as a mediator of the appetite-suppressing effects of stress in fish.

A characteristic feature of the behavioural response to intensely acute or chronic stressors is a reduction in appetite. In fish, as in other vertebrates, the corticotropin-releasing factor (CRF) system plays a key role in coordinating the neuroendocrine, autonomic, and behavioural responses to stress. The following review documents the evidence implicating the CRF system as a mediator of the appetite-suppressing effects of stress in fish. Central injections of CRF or the related peptide, urotensin I (UI), or pharmacological treatments or stressors that result in an increase in forebrain CRF and UI gene expression, can elicit dose-dependent reductions in food intake that are at least partially reversed by pre-treatment with a CRF receptor antagonist. In addition, the appetite suppressing effects of various environmental, pathological, physical, and social stressors are associated with elevated levels of forebrain CRF and UI gene expression and with an activation of the hypothalamic-pituitary-interrenal (HPI) stress axis. In contrast, although stressors can also be associated with an increase in caudal neurosecretory system CRF and UI gene expression and an endocrine role for CRF-related peptides has been suggested, the physiological effects of peripheral CRF-related peptides on the gastrointestinal system and in the regulation of appetite have not been investigated. Overall, while CRF and UI appear to participate in the stress-induced changes in feeding behaviour in fish, the role of other know components of the CRF system is not known. Moreover, the extent to which the anorexigenic effects of CRF-related peptides are mediated through the hypothalamic feeding center, the HPI axis and cortisol, or via actions on descending autonomic pathways remains to be investigated.

Animals↗

Food entrainment modifies the c-Fos expression pattern in brain stem nuclei of rats.

When food is restricted to a few hours daily, animals increase their locomotor activity 2-3 h before food access, which has been termed food anticipatory activity. Food entrainment has been linked to the expression of a circadian food-entrained oscillator (FEO) and the anatomic substrate of this oscillator seems to depend on diverse neural systems and peripheral organs. Previously, we have described a differential involvement of hypothalamic nuclei in the food-entrained process. For the food entrainment pathway, the communication between the gastrointestinal system and central nervous system is essential. The visceral synaptic input to the brain stem arrives at the dorsal vagal complex and is transmitted directly from the nucleus of the solitary tract (NST) or via the parabrachial nucleus (PBN) to hypothalamic nuclei and other areas of the forebrain. The present study aims to characterize the response of brain stem structures in food entrainment. The expression of c-Fos immunoreactivity (c-Fos-IR) was used to identify neuronal activation. Present data show an increased c-Fos-IR following meal time in all brain stem nuclei studied. Food-entrained temporal patterns did not persist under fasting conditions, indicating a direct dependence on feeding-elicited signals for this activation. Because NST and PBN exhibited a different and increased response from that expected after a regular meal, we suggest that food entrainment promotes ingestive adaptations that lead to a modified activation in these brain stem nuclei, e.g., stomach distension. Neural information provided by these nuclei to the brain may provide the essential entraining signal for FEO.

Animals↗

[Massive gastrointestinal bleeding in Henoch-Schoenlein purpura in an adult].

Henoch-Schoenlein syndrome in an adult patient, localised only to the gastrointestinal system is very rare. A 50 year old male was treated in our Intensive Department because of acute respiratory distress syndrome (ARDS) and renal failure. After temporary improvement massive gastrointestinal bleeding developed with shock. Blood was found in the descending duodenum without evident pathology at endoscopy. Angiogram showed bleeding at the hepatic flexure of the colon, which was successfully treated by a coil and bleeding was also present in the terminal part of the small intestine. The catheter was left in situ and the bleeding part of the bowel was painted intraoperatively, so we could resect the stained part of the intestine. Because of rebleeding, bowel resection was performed an other two occasions in the same way. The histology of the bowel showed Henoch-Schoenlein syndrome in each specimen. Our patient was totally non-responsive to treatment, which is usually successful in this disease. After the resections the bleeding stopped temporarily, but as the underlying disease was unmanageable the patient died but we have not found any surgical complication at autopsy. We think that this method in the surgical treatment of massive intestinal bleeding is very useful and effective.

Diagnosis, Differential↗

Liposomal oxaliplatin in the treatment of advanced cancer: a phase I study.

BACKGROUND: Lipoxal is a liposomal oxaliplatin, which reduces the cytotoxic agent's adverse reactions without reducing effectiveness. Our objectives were to determine the adverse reactions, dose-limiting toxicity (DLT) and the maximum tolerated dose (MTD) of lipoxal. PATIENTS AND METHODS: Twenty-seven patients with advanced disease of the gastrointestinal system were included in the study. All patients had been pretreated with standard chemotherapy according to established guidelines. At entry, all patients had recurrent or progressive disease (stage IV gastrointestinal cancers: colorectal, gastric and pancreatic). Six lipoxal dose levels (100 mg/m2, 150 mg/m2, 200 mg/m2, 250 mg/m2, 300 mg/m2 and 350 mg/m2) were set and at least 3 patients were included at each level. Eight patients were treated at 300 mg/m2 (MTD). The treatment was given once weekly for 8 weeks. RESULTS: No serious side-effects were observed at the first 4 dose levels (100-250 mg/m2). At levels 5 and 6, mild myelotoxicity and nausea were observed. The most common adverse reaction was grade 2-3 peripheral neuropathy, observed in all 4 patients treated at 350 mg/m2. The 350 mg/m2 dose level was therefore considered as DLT and the 300 mg/m2 level as the MTD. Of the 27 patients, 3 achieved partial response and 18 had stable disease for 4 months, (range 2-9 months). CONCLUSION: The most common toxicity was peripheral neuropathy at the 300 and 350 mg/m2 dose levels. Lipoxal was well-tolerated and greatly reduced all the other side-effects of oxaliplatin, especially myelotoxicity and gastrointestinal tract toxicities. These preliminary results showed adequate effectiveness in pretreated patients.

Adult↗

Postoperative management of patients who undergo aortic surgery.

Because patients with occlusive or aneurysmal disease of the aorta frequently have coexisting disease in other important organ systems, complications after aortic surgery usually relate to the heart, lungs and kidneys. Postoperative care thus requires attention, in an intensive-care milieu, to respiratory, cardiac, renal and gastrointestinal systems, coagulation and, in rare instances, psychiatric problems.

Aged↗

Physiology of skin.

One of Montagna's greatest contributions to study of the biology of the skin has been his demolition of the artificial walls that traditionally separated the histologist from the physiologist. He has shown that only by relating function with structure can we shed light on the workings of the skin. He has stressed the fallacy of studying a single structural or functional unit in isolation from others. The skin represents an organization of many different functional units, and physiology of skin is the study of this organization. My purpose is to make a personal commentary on the achievements, failures, and prospects of understanding some aspects of the organization of the functional units. Twenty-five years ago, the importance of relating skin to internal organs and systems received much attention. We have long been aware that skin sometimes reacts to internal disease, but only recently has the impact of skin disorders on the circulatory, renal, and gastrointestinal systems been recognized. As a result, our patients are now less likely to suffer from neglect of the whole which follows narrow over-specialized attention to the part. Increased interest in endocrine effects on the skin has revealed that several important physiologic activities of the skin are either partly or wholly regulated by hormones secreted by endocrine glands. Nevertheless, some physiologic activities in skin seems to be independent, their regulation being carried out by local mediating hormones. Other activities involve both central and local regulation. The nature and roles of these two control mechanisms and their interrelation constitute by far the most promising physiologic research in skin.

Animals↗

Field and clinical observations of exertional heat stroke patients.

Exertional heatstroke (EH) occurs when heat production, generated by muscular exercise, exceeds the body's heat dissipation capacities. This illness has been reported among young, active individuals, laborers, and religious pilgrims. Although EH includes a rectal temperature above 39.5 degrees C (depending on the timing of the measurement) and elevation of serum enzymes, altered mental status is the universally accepted sign which distinguishes EH from heat exhaustion. Once EH is suspected, cooling therapy should be initiated immediately and investigation of multiple-system involvement should be undertaken. Delay in diagnosis occurs more commonly in moderate environments, when suspicion of EH is low. Complications of EH include the central nervous, cardiovascular, pulmonary, and gastrointestinal systems, often with renal and hematologic involvement. Treatment at the point of collapse should focus on clearing the airway, measurement of rectal temperature, whole body cooling, intravenous therapy, and prompt evacuation. Hospital treatment should emphasize whole body cooling, control of convulsions, monitoring of acid-base status, cardiac function, and renal function. The incidence of EH has been reduced markedly in Israel, by using the following simple guidelines: rest periods during exercise in heat, medical monitoring of strenuous activities, use of meteorological indices, and evaluation of medical history.

Heat Exhaustion↗

Distribution and reactivity of inhaled 14C-labeled toluene diisocyanate (TDI) in rats.

Inhalation exposure to toluene diisocyanate (TDI) can result in a variety of airway diseases. Concern has been expressed that a putative carcinogenic potential of TDI exists as a result of the formation of toluenediamine (TDA) by hydrolysis of the isocyanate in the body. Results from long-term bioassays (TDI inhalation versus gavage in rats and mice) are contradictory and discrepancies do exist concerning the interpretation of adverse effects. This study was performed to analyze the distribution and reactivity of radioactively-labeled TDI using vapor exposure in a rat model system. Rats were exposed to 14C-TDI vapors at concentrations ranging from 0.026 to 0.821 ppm for 4 h. All tissues examined showed detectable quantities of radioactivity, with the airways, gastrointestinal system and blood having the highest levels which increased with exposure concentration. The concentration of radioactivity in the bloodstream after exposure was linear with respect to dose. The majority (74-87%) of the label associated with the blood was recovered in the plasma, and of this, 97-100% of the 14C existed in the form of biomolecular conjugates. Analysis of stomach contents shows that the majority of the label is also associated with high (> 10 kDa) molecular weight species. While a larger percentage (28%) of the label is found in the low molecular weight fraction relative to blood, this low molecular weight labeled material represents at least eight different components. Thus, over the vapor exposure concentrations and time tested, it appears that conjugation is the predominant reaction and that free TDA is not a primary in vivo reaction product under the conditions tested.

Administration, Inhalation↗

[X-ray examination of the gastrointestinal tract in systemic cutaneous disease].

An X-ray examination of the gastrointestinal tract was performed on 56 patients with systemic cutaneous disease that is often considered associated with internal malignancies. Found were one case of esophageal cancer, two cases of gastric cancer, and two cases of colon cancer. The prevalence of gastric and colon cancer in these patients showed a statistically significant increase compared to the general population. The rate of gastric cancer was 16.26 times higher than the general population and that of colon cancer 32.26. X-ray examination of the gastrointestinal tract in patients with systemic cutaneous disease is useful for detecting malignancy.

Aged↗

Gastric myoelectrical activity as an index of emotional arousal.

Autonomic nervous system parameters such as electrodermal activity, heart rate, and facial EMG have been utilized extensively as measures of emotional arousal. One measure that has rarely been employed in this setting is gastric myoelectrical activity, despite the fact that "gut feelings" have an obvious and even profound role in everyday emotional life. It has been shown that the gastrointestinal system changes wall tonus and contraction rate during stressful tasks. However, the effects of emotionally salient stimuli on gastrointestinal motility have scarcely been studied. In the current study, emotional film clips designed to elicit happiness, disgust, fear, sadness, or no emotion (neutral) were presented to 16 normal participants. Electrogastrogram (EGG), skin conductance, and heart rate were measured while the participants viewed the film clips, and participants rated subjective arousal intensity and pleasantness of the film clips. We found that emotional film clips reliably induced the intended subjective feeling states. Also, EGG peak amplitudes in fear, disgust, sadness and happiness were higher than in the no emotion condition. There was a strong positive correlation (r=0.64) between EGG peak amplitude and subjective ratings of arousal. This is the first evidence that gastric myoelectrical activity is strongly correlated with arousal ratings to emotionally salient stimuli, and it suggests that EGG may add useful information about how the body contributes to the phenomenology of emotion and feeling.

Adult↗

Megatherapy combining I(131) metaiodobenzylguanidine and high-dose chemotherapy with haematopoietic progenitor cell rescue for neuroblastoma.

Despite the use of aggressive chemotherapy, stage 4 high risk neuroblastoma still has very poor prognosis which is estimated at 25%. Metabolic radiotherapy with I(131) MIBG appears a feasible option to enhance the effects of chemotherapy. Seventeen patients having MIBG-positive residual disease received 4.1-11.1 mCi/kg of I(131) MIBG 7-10 days before initiating the high-dose chemotherapy cycle consisting of busulphan 16 mg/kg and melphalan 140 mg/m(2) followed by PBSC infusion. We compared the toxicity in these patients to that seen in 15 control subjects with neuroblastoma who underwent a PBSC transplant without MIBG therapy. We observed greater toxic involvement of the gastrointestinal system in children treated with I(131) MIBG: grade 2 or 3 mucositis developed in 13/17 patients treated with I(131) MIBG and in 9/15 treated without it. Grade 1-2 gastrointestinal toxicity occurred in 12/17 children given MIBG and in 5/15 of the controls. One child receiving I(131) MIBG developed transient interstitial pneumonia. Another child who also received I(131) MIBG after PBSC rescue developed fatal pneumonia after the third course of metabolic radiotherapy. Our experience indicates that MIBG can be included in the high-dose chemotherapy regimens followed by PBSC rescue for children with residual neuroblastoma taking up MIBG. Attention should be paid to avoiding lung complications. Prospective studies are needed to demonstrate the real efficacy of this treatment.

3-Iodobenzylguanidine↗

General pharmacological properties of the new angiotensin II receptor antagonist (+/-)-1-(cyclohexyloxycarbonyloxy)ethyl 2-ethoxy-1-[[2'-(1H-tetrazol-5-yl) biphenyl-4-yl]methyl]-1H-benzimidazole-7-carboxylate. Part I: Effects on central nervous system and other properties.

The effects of TCV-116 ((+/-)-1-(cyclohexyloxycarbonyloxy)ethyl 2-ethoxy-1-[[2'-(1H-tetrazol-5-yl) biphenyl-4-yl]methyl]-1H-benzimidazole-7-carboxylate, CAS 145040-37-5), a nonpeptide angiotensin II receptor antagonist, on the central nervous and autonomic nervous systems, isolated smooth muscle and digestive system were investigated in various experimental animals. TCV-116 at 1000 mg/kg (p.o.) produced a slight decrease in body tone in mice, but at 300 mg/kg did not affect spontaneous locomotor activity, skeletal muscle coordination, tonic extensor convulsions, pentobarbital-induced sleeping time, frequency of acetic acid-induced writhing, or body temperature in mice or rats. TCV-116 (at 300 mg/kg p.o.) did not affect the spontaneous EEG in conscious, unrestrained cats, or (at 100 mg/kg i.d.) the spinal reflex in anesthetized cats. CV-11974, the active metabolite of TCV-116, did not inhibit neuromuscular transmission in isolated rat phrenic nerve-diaphragm preparations (10(-5) mol/l and 10(-4) mol/l). In anesthetized cats, TCV-116 at 100 and 300 mg/kg (i.d.) slightly reduced the pressor response to carotid occlusion, but had no effect on the bradycardic response to stimulation of the cervical vagus nerve, contraction of the nictitating membrane induced by electrical stimulation of the cervical sympathetic preganglionic nerve, or the changes in blood pressure in response to acetylcholine, histamine, norepinephrine, or bradykinin. CV-11974 had no effect on agonist-induced contraction of guinea pig ileum. In isolated smooth muscle preparations, CV-11974 even at 10(-4) mol/l did not affect the spontaneous motility of the rabbit ileum or the rat uterus, or KCl-induced tension in guinea pig trachea. TCV-116 at 300 mg/kg (p.o.) had no significant effect on gastric emptying or intestinal transport of a semisolid meal in rats, or on gastric secretion in pylorus-ligated rats. TCV-116 (30-300 mg/kg p.o.) had no effect on carrageenin-induced paw edema in rats. The results suggest that TCV-116 exerts no notable pharmacological effects on the central nervous system, autonomic nervous system, gastrointestinal function or smooth muscle function.

Analgesics↗

Adverse events associated with pyrazinamide and levofloxacin in the treatment of latent multidrug-resistant tuberculosis.

BACKGROUND: The current Canadian and US guidelines for the treatment of multidrug-resistant latent tuberculosis infection advocate the use of pyrazinamide and a fluoroquinolone as a first-line treatment option. However, there is very little information in the literature that describes the use of these agents together. This case series describes the probable association between multiple adverse events and the use of pyrazinamide and levofloxacin in the treatment of individuals with suspected latent multidrug-resistant tuberculosis infection. METHODS: We studied a case series of 17 individuals with suspected latent multidrug-resistant tuberculosis infection in Hamilton, Ont., who were being treated with pyrazinamide and levofloxacin. The Naranjo scale was used to assess patients for musculoskeletal, central nervous system, gastrointestinal and dermatological adverse events. Hepatocellular events were assessed and defined using criteria established by the Council for International Organizations of Medical Sciences. Laboratory abnormalities and adverse events that were documented during combination drug therapy were evaluated to determine the likelihood of an association. RESULTS: Fourteen individuals developed musculoskeletal adverse effects (11 were deemed to be probably related to combination therapy). There were 8 reports of central nervous system effects (5 of which were assessed as being probably associated with therapy). Hyperuricemia and gastrointestinal and dermatological effects were also common; the use of pyrazinamide and levofloxacin was believed to be probably responsible for the emergence of these adverse effects. There were 5 cases of hepatocellular injury. Therapy was discontinued in all individuals. INTERPRETATION: The combination of pyrazinamide and levofloxacin appears to be a poorly tolerated regimen. The mechanism of a possible interaction is not yet understood. Given the severity of some of the adverse events, a better understanding of dosing and clearer guidelines for monitoring therapy are imperative if these drugs are to be prescribed together.

Adolescent↗

Role of the innate immune system and host-commensal mutualism.

Host organisms live in intimate contact with indigenous microflora. The interactions between the host and commensal microbiota are highly complex and heterogeneous. A growing body of evidence indicates that commensal symbionts provide many benefits to the host physiology, particularly in the gastrointestinal system. The molecular mechanisms of the mutualistic interactions between the host and commensals are largely unknown but can be due either to bioactivity of the commensals or to the reaction of the host immune system to the commensal-derived products. Recent advances in our understanding of the innate immune system allow re-evaluation of some of the older findings regarding the mechanisms of benefits conferred by microflora. Here we review the examples of the benefits of host-commensal interactions that are due to recognition of commensal microbial products by the host innate immune system.

Animals↗

Nutritional aspects of nitric oxide: human health implications and therapeutic opportunities.

Nitric oxide (NO), the most potent natural vasorelaxant known, has close historical ties to cardiovascular physiology, despite NO's rich physiologic chemistry as an ubiquitous, signal-transducing radical. Aspects of NO biology critical to gastrointestinal health and, consequently, nutritional status are increasingly being recognized. Attempts are underway to exploit the gastrointestinal actions of NO for therapeutic gain. Cross-talk between NO and micronutrients within and outside the gastrointestinal system affects the establishment or progression of several diseases with pressing medical needs. These concepts imply that NO biology can influence nutrition and be nutritionally modulated to affect mammalian (patho)physiology. At least four nutritional facets of NO biology are at the forefront of contemporary biomedical research: 1) NO as modulator of feeding behavior and mediator of gastrointestinal homeostasis; 2) NO supplementation as a therapeutic modality for preserving gastrointestinal health; 3) interactions among elemental micronutrients (e.g., zinc), NO, and inflammation as potential contributors to diarrheal disease; and 4) vitamin micronutrients (e.g., vitamins E and C) as protectors of NO-dependent vascular function. Discussion of extant data on these topics prompts speculation that future research will broaden NO's nutritional role as an integrative signaling molecule supporting gastrointestinal and nutritional well-being.

Animals↗