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PubMed1999

Extraesophageal autonomic dysfunction in patients with achalasia.

A disagreement exists as to whether extraintestinal parasympathetic autonomic function is altered in patients with esophageal achalasia. Therefore, we assessed autonomic dysfunction in esophageal achalasia and considered the most relevant parameters of parasympathetic autonomic function in these patients. In a prospective study, heart rate variation and pupillary function were investigated in 15 patients with achalasia of the esophagus and in 15 controls by application of a battery of standardized autonomic function tests. Significant differences between patients and controls were detected for various parameters of heart rate variation and pupillometry. When compared to values obtained from large groups of healthy subjects, none of the controls but 11 patients had at least one abnormal parameter of parasympathetic autonomic function. It is suggested that in esophageal achalasia parasympathetic dysfunction that extends beyond the gastrointestinal tract can be frequently detected. This finding supports the view of a generalized alteration of the autonomic nervous system in achalasia.

Adult↗

PubMed2000

Are anaphylactic reactions to snake bites immunoglobulin E-mediated?

BACKGROUND: Bites by poisonous European snakes of the genus Vipera lead to local tissue damage and systemic symptoms such as generalized oedema, hypotension, gastrointestinal symptoms, haemolysis and renal dysfunction. Not rarely anaphylactic symptoms like urticaria, localized angioedema and asthma are observed. OBJECTIVE: To look for snake venom-specific immunoglobulin (Ig) E antibodies in patients with a history of bites by European vipers and for cross-reactions with Hymenoptera venoms, that have a similar composition. METHOD: Ten patients with a history of bites by Vipera aspis or Vipera berus were investigated. Three patients had been bitten only once, and two of these had developed only local reactions. Four reported previous allergic reactions to Hymenoptera stings. All patients, 10 Hymenoptera venom-allergic and five nonallergic individuals who served as controls underwent i.c. skin test endpoint titration with snake (V. aspis, V. berus) and Hymenoptera venoms (honey bee, Vespula spp.) and were investigated for specific serum IgE antibodies to the same venoms. RESULTS: Seven of the eight patients with systemic snake bite reactions had both positive skin tests and serum IgE antibodies to snake venoms, while these tests were negative in the two patients with only local reactions to snake bites and all controls. Seven of the eight patients with systemic snake bite reaction also had positive skin tests and specific IgE with one or both Hymenoptera venoms. By RAST-inhibition with sera of four patients with high IgE to both Vipera and Hymenoptera venoms, partial cross-reactivity could be demonstrated in one. CONCLUSIONS: Anaphylactic reactions following snake bites may be IgE-mediated, especially in patients with repeated bites.

Adult↗

PubMed1998

Panic disorder: long-term pharmacotherapy and discontinuation.

This article compares panic disorder (PD) medications and discusses long-term therapy. In a review of the literature, monoamine oxidase inhibitors (MAOIs), selective serotonin reuptake inhibitors (SSRIs), and benzodiazepines prove effective in treating PD. MAOIs treat comorbid depression; frequent side effects are dizziness and orthostatic hypotension. SSRIs are better tolerated than MAOIs, producing mild anticholinergic effects, but also producing gastrointestinal side effects and sexual dysfunction. Benzodiazepines are generally well tolerated when titrated gradually; moderate sedation is the most common short-term side effect. Long-term risks are physical dependence and withdrawal reactions. One hundred six PD patients were enrolled in a double-blind, 8-month, placebo-controlled trial of alprazolam and imipramine. In the 8-week short-term phase, daily dosages were titrated up to 10 mg/day of alprazolam and 250 mg/day of imipramine. The greatest number of dropouts occurred during this phase (lack of improvement and/or side effects). Alprazolam patients had a significantly more rapid onset of improvement and lower adverse events and attrition rates. In the 6-month maintenance period, patients continued short-term treatment. Patients receiving either alprazolam or imipramine developed tolerance to some side effects. At maintenance-phase completion, 62% of the alprazolam-group patients and 26% of both the imipramine- and placebo-group patients were panic free (p<0.01). Dosages were tapered to zero over 3 weeks; one third of the alprazolam patients could not discontinue. During the unblinded, 15-month follow-up, patients received open treatment selected by personal physicians on an as-needed basis. At the end of follow-up, all patients were reassessed. Patients who had completed both short-term and maintenance phases were far more likely to be panic-free (85% vs. 55%; p<0.01). PD is chronic and recurrent, and 8 months is an effective treatment period. Maintenance treatment does not lead to tolerance, even with benzodiazepines. Dose tapering must be very gradual. Completion of a long-term maintenance program strongly predicts remission.

Alprazolam↗

PubMed1989

Autonomic neuropathy in familial amyloidotic polyneuropathy. A clinical study based on heart rate variability.

Familial amyloidotic polyneuropathy (FAP) is characterized by both sensimotor and autonomic dysfunction. Autonomic disturbance involving the gastrointestinal tract, the urinary bladder, the cardiac conduction system, and the peripheral circulation has been described. In this study simple, non-invasive tests of autonomic function based on heart rate variability were applied to 12 patients with FAP and 12 healthy volunteers. The heart rate variation during normal breathing, deep breathing and during tilt from recumbent to standing position was measured. All tests showed significantly less heart rate variation in patients than in controls and the heart rate variation decreased with increasing severity of neurological disability, but the small number of patients in our study does not allow any further comparison between subgroups. Our study thus indicates impaired cardiovascular autonomic function in patients with FAP and we believe that these findings might also be of importance in other forms of systemic amyloidosis.

Adult↗

PubMed2002

Cyclooxygenase-2--10 years later.

The enzyme cyclooxygenase (COX) catalyzes the first step of the synthesis of prostanoids. In the early 1990s, COX was demonstrated to exist as two distinct isoforms. COX-1 is constitutively expressed as a "housekeeping" enzyme in most tissues. By contrast, COX-2 can be up-regulated by various pro-inflammatory agents, including lipopolysaccharide, cytokines, and growth factors. Whereas many of the side effects of nonsteroidal anti-inflammatory drugs (NSAIDs) (e.g., gastrointestinal ulceration and bleeding, platelet dysfunctions) are caused by a suppression of COX-1 activity, inhibition of COX-2-derived prostanoids facilitates the anti-inflammatory, analgesic, and antipyretic effects of NSAIDs. During the past few years specific inhibitors of the COX-2 enzyme have emerged as important pharmacological tools for treatment of pain and arthritis. However, although COX-2 was initially regarded as a source of pathological prostanoids only, recent studies have indicated that this isoenzyme mediates a variety of physiological responses within the organism. The present review assesses recent advances in COX-2 research, with particular emphasis on new insights into pathophysiological and physiological functions of this isoenzyme.

Animals↗

PubMed1997

A maternally transmitted lethal neonatal progeroid syndrome with prominent genitourinary and gastrointestinal features.

Twin brothers and their maternal uncle with a previously undescribed neonatal progeroid syndrome are presented. In addition to progeroid features, they had pseudo-obstruction of the urinary and gastrointestinal tracts, severe leucocytosis, liver dysfunction, and low complex III and IV in muscle but not in liver. Previously described neonatal progeroid syndromes and syndromes featuring pseudo-obstruction are discussed. The two most likely aetiological mechanisms are an X linked single gene disorder or a mitochondrial disorder. The evidence for these possibilities is presented.

Abnormalities, Multiple↗

PubMed1997

A risk-benefit assessment of mirtazapine in the treatment of depression.

Mirtazapine is the first of a new class of antidepressants, the noradrenergic and specific serotonergic antidepressants (NaSSA). Its antidepressant effect appears to be related to its dual enhancement of central noradrenergic and serotonin 5-HT1 receptor-mediated serotonergic neurotransmission. Mirtazapine possesses a number of useful pharmacokinetic characteristics such as good absorption, linear pharmacokinetics over the recommended dosage range (15 to 80 mg/day), and an elimination half-life of 20 to 40 hours, thereby allowing once-daily administration. However, since the drug is extensively metabolised by the hepatic cytochrome P450 (CYP) system and is excreted mainly in the urine, its clearance may be reduced by hepatic or renal impairment. In vitro data suggest that from a clinical point of view it is unlikely that mirtazapine would inhibit the metabolism of coadministered drugs metabolised by CYP1A2, CYP2D6 or CYP3A4. In vivo data from a study in extensive and poor metabolisers of debrisoquine indicate that strong inhibitors of CYP2D6 would have no effect on the concentration of racemic mirtazapine. In some placebo-controlled studies mirtazapine showed an early onset of antidepressant action, with significant reductions in total Hamilton Depression Rating Scale and Montgomery-Asberg Depression Rating Scale scores (relative to placebo) noted as early as 1 week after starting treatment. This therapeutic advantage was subsequently maintained during treatment, with mirtazapine proving significantly superior to placebo at treatment end-point in the majority of studies. In comparative trials, the antidepressant efficacy of mirtazapine was comparable with that of tricyclic antidepressants such as amitriptyline, clomipramine and doxepin, and in 2 studies superior to that of trazodone and fluoxetine. Mirtazapine appears to have a broad spectrum of activity, reflected in its efficacy in a variety of clinical settings. Its additional beneficial effects on the symptoms of anxiety and sleep disturbance associated with depression may reduce the need for concomitant anxiolytic and hypnotic medication seen with some antidepressants. Mirtazapine has demonstrated superior tolerability to the tricyclic antidepressants and trazodone, primarily on account of its relative absence of anticholinergic, adrenergic and serotonin-related adverse effects, in particular gastrointestinal adverse effects and sexual dysfunction. It appears that increased sedation associated with the drug is related to subtherapeutic dosages, and that it is reported in substantially fewer patients when the drug is used in appropriate dosages (> or = 15 mg as a single evening dose) from the beginning of treatment. Although 2 cases of reversible severe symptomatic neutropenia have been reported in clinical trials, there have been no additional reports of symptomatic neutropenia since the introduction of this drug to various countries in September 1994. Currently available data and initial clinical experience suggest that with its combination of dual action, simple pharmacokinetics, and clinical efficacy and tolerability, mirtazapine appears to be an important advance in the pharmacotherapy of depression.

Adult↗

PubMed2004

Heat illness in athletes: the dangerous combination of heat, humidity and exercise.

In 1980, 1700 people died during a prolonged heat wave in a region under-prepared for heat illness prevention. Dramatically underreported, heat-related pathology contributes to significant morbidity as well as occasional mortality in athletic, elderly, paediatric and disabled populations. Among US high school athletes, heat illness is the third leading cause of death. Significant risk factors for heat illness include dehydration, hot and humid climate, obesity, low physical fitness, lack of acclimatisation, previous history of heat stroke, sleep deprivation, medications (especially diuretics or antidepressants), sweat gland dysfunction, and upper respiratory or gastrointestinal illness. Many of these risk factors can be addressed with education and awareness of patients at risk. Dehydration, with fluid loss occasionally as high as 6-10% of bodyweight, appears to be one of the most common risk factors for heat illness in patients exercising in the heat. Core body temperature has been shown to rise an additional 0.15-0.2 degrees C for every 1% of bodyweight lost to dehydration during exercise. Identifying athletes at risk, limiting environmental exposure, and monitoring closely for signs and symptoms are all important components of preventing heat illness. However, monitoring hydration status and early intervention may be the most important factors in preventing severe heat illness.

Adaptation, Physiological↗

PubMed2005

Hypermagnesemia induced by massive cathartic ingestion in an elderly woman without pre-existing renal dysfunction.

A 76-year-old woman was referred to our hospital for unresponsiveness and hypotension. She had developed constipation that had led to ileus and had received 34 g of magnesium citrate (Magcolol P) orally the day before. She was lethargic, her blood pressure was less than 50 mmHg, and electrocardiogram (ECG) revealed sinus arrest with junctional escape rhythm. Her serum concentration of magnesium (Mg) was markedly elevated (16.6 mg/dl =13.7 mEq/l). Emergency colonoscopy revealed ischemic colitis. As her condition ameliorated, her renal function returned to normal. Hence, the present case suggests that severe hypermagnesemia can occur in the absence of pre-existing renal dysfunction in elderly patients with gastrointestinal diseases.

Administration, Oral↗

PubMed2005

[Clinical study on severe acute pancreatitis associated with hypoalbuminemia in early stage].

OBJECTIVE: To investigate the occurring mechanism and clinical characteristics of severe acute pancreatitis (SAP) associated with hypoalbuminemia in early stage and its influence on prognosis of SAP and the preventive and therapeutic management of this disease. METHODS: One hundred and thirty-eight cases diagnosed as SAP complicated by hypoalbuminemia in early stage were accepted in our hospital from August 1, 2003 to December 31, 2004, and they were divided into 2 groups according to the level of plasma albumin: mild hypoalbuminemia (30 to 35 g/L) group and severe hypoalbuminemia (<30 g/L) group. The complications in the early stage, related parameters, and the incidence rate of infection and mortality in the later stage were evaluated respectively. RESULTS: The incidence rates of renal dysfunction, shock, cardiovascular failure and gastrointestinal hemorrhage, the score of acute physiology and chronic health evaluation II (APACHE II ) and the frequencies of pulse and breath in the severe hypoalbuminemia group were all higher than those in the mild hypoalbuminemia group (P<0.05 or P<0.01). The differences of incidence rate of hepatic failure and the scores of Ranson and Balthazar CT between these two groups had no statistical significance (P>0.05). The incidence rate of infection and the mortality in the severe hypoalbuminemia group were higher than those in the mild hypoalbuminemia group (P<0.01) in the later stage of SAP. CONCLUSION: Hypoalbuminemia in the early stage can accelerate the deterioration in pathophysiology of SAP. The lower level of the plasma albumin is in the early stage, the more complications and the higher incidence rate of infection and mortality will be in the later stage. To relieve the extent of systemic inflammatory response syndrome (SIRS) and abundant supplement of albumin, amino acid and lipid in time may be crucial to prevent the occurrence and deterioration of hypoalbuminemia.

Acute Disease↗

PubMed1991

[Adverse effects of interleukin 2].

Interleukin 2, has frequent and important side effects. Toxic effects observed are systemic (fever, chills, malaise), hemodynamic (capillary leak syndrome, hypotension), cardiac (arrhythmia, infarction), renal (renal dysfunction), infectious (septicemia), cutaneous, hematologic, gastrointestinal, endocrinologic and metabolic. Side effects are dose-dependent, generally reversible, with a mortality from 1 to 3%. Regimens of administration and other cytokine combinations affect interleukin 2 toxicity. If the treatment of these side effects is well known, selection of patients and specialized care unit remain always necessary.

Animals↗

PubMedDate not supplied

[Transfusion-associated graft-versus-host disease].

Transfusion-associated graft-versus-host disease (TA-GVHD) is rare but usually fatal complication of transfusion of any blood component containing viable T lymphocytes. TA-GVHD manifests as an acute syndrome characterized by the dysfunction of the skin, liver, gastrointestinal tract and bone marrow. The development of bone marrow aplasia increases the risk for hemorrhage and infection and most patients die within 1 month of transfusion. The risk associated with an individual transfusion depends on the number and viability of contaminated lymphocytes, the susceptibility of the patient's immune system to their engraftment and the degree of disparity in histocompatibility antigens between the donor and the patient. The risk of TA-GVHD are highest in recipients with immunodeficiency or immunosuppression. Prevention of TA-GVHD is of great importance as it cannot be treated successfully. Patients at risk must be identified and transfused with irradiated cellular blood products, as gamma irradiation inhibits the proliferation of donor lymphocytes and is currently the only recommended method for TA-GVHD prevention.

Graft vs Host Disease↗

PubMedDate not supplied

Mortality and survival in Down syndrome in Taiwan.

In order to investigate the morbidity and mortality in individuals with Down syndrome(DS), we reviewed 237 cases of DS visiting our hospital in a ten-year period. There were 150 males and 87 females with age range from newborn to 25 years. The major illnesses included: 1) congenital heart disease (CHD), 42.6%; with endocardial cushion defect, ventricular septal defect, atrial septal defect and patent ductus arteriosus as the common types; 2) frequent or major respiratory tract infections, 34.2%; 3) summer fever, 5.5%; 4) major infective episodes other than pneumonia, 5.0%. Other diseases such as seizure disorder, gastrointestinal tract anomalies and thyroid dysfunction were also noted. There were 28 deaths of them and the causes of mortality were 1) CHD with congestive heart failure (CHD with CHF) and pneumonia (46.9%); 2) CHD with CHF and sepsis (10.7%); 3) CHD with CHF (14.3%) and 4) acute leukemia with infection (10.7%) respectively. Most of the mortality occurred during the first year of life, especially in patients with CHD. In our series, the one year survival rate was 93.6%; the result indicates that life expectancy in DS is much better than generally believed.

Adolescent↗

PubMed1982

Diagnostic, pathogenetic, and therapeutic aspects of diabetic neuropathy.

Since nearly all patients with diabetes mellitus will manifest evidence of dysfunction of their peripheral and autonomic nerves, neuropathy can be considered to be the most common of the so-called "late complications of diabetes." Mononeuropathies are uncommon, but can affect virtually any cranial or nerve and are thought to be due to vascular occlusion. Distal symmetrical polyneuropathy usually begins insidiously with the development of sensory symptoms involving the feet. These symptoms progressively ascend and are accompanied by progressive motor dysfunction as well as cardiac, gastrointestinal, and genitourinary manifestations of autonomic neuropathy. Numerous biochemical abnormalities including impaired neural protein synthesis, abnormal axoplasmic transport, disturbed polyol pathway activity, and abnormal myo-inositol metabolism have been described and have been postulated to underlie the development of diabetic peripheral and autonomic neuropathies. At the present time, the available treatments for diabetic neuropathies are largely palliative and are not curative. In the future, a better understanding of the pathophysiologic basis of diabetic neuropathy will undoubtedly lead to the development of more rational therapeutic approaches.

Aging↗

PubMed1994

[Treatment of mild and moderate hypertension with fosinopril. Comparison of adverse effects with other antihypertensive agents].

PURPOSE: To evaluate the adverse reactions of fosinopril with other antihypertensives used as monotherapy. METHODS: Out-patients (n = 2,568) with diagnostic of mild to moderate hypertension, diastolic blood pressure (DBP) 95-115mmHg, with no antihypertensive treatment for 15 days, were included to treatment initially with fosinopril (F) 10mg, once daily, for six weeks. After this period, patients with DBP > 95mmHg had the dosage, once daily, increased to 20mg, while the others were maintained with the same dosage for six more weeks. Adverse reactions of 822 patients treated as monotherapy were grouped as absent, musculoskeletal, cardiovascular, cough, gastrointestinal, neurological, genital-urinary dysfunctions and dermatological and compared with 1,568 with F. Monotherapy consist in alpha-methyldopa (100 patients); beta-blocker (129); calcium blocker (106); diuretic (394); and another ACE inhibitors (93). RESULTS: At the end of the period without treatment, the blood pressure (BP), 165 +/- 16/105 +/- 7mmHg decreased significantly at 6th week to 144 +/- 15/91 +/- 9mmHg (p < 0.05 vs week 0) with further lowering to 139 +/- 13/86 +/- 7mmHg till the end of 12th week. BP response (DBP < or = 90mmHg) was obtained in 89% of the patients with F. Absence of adverse reactions were > or = 70% in patients with F compared to other drugs. CONCLUSION: Fosinopril has demonstrated therapeutic efficacy and less adverse reactions compared to antihypertensives used previously as monotherapy.

Adolescent↗

PubMed1996

Impaired small intestinal peristaltic reflexes and sensory thresholds are independent functional disturbances in patients with chronic unexplained dyspepsia.

OBJECTIVE: To study disturbances of gastrointestinal motility and afferent (sensory) dysfunction in functional (unexplained) dyspepsia, and the interrelationships between motility and sensory dysfunction. METHODS: Twelve patients with functional dyspepsia and 12 controls matched for age and gender were studied. Intestinal perception thresholds were tested by a standardized stepwise distension procedure in the third portion of the duodenum with a barostat device. Small intestinal motility was measured with a low compliance perfusion system proximal and distal to the distending balloon. RESULTS: First perception of duodenal balloon distension occurred at significantly (p <0.01) lower pressures in patients (23 +/- 3 mm Hg, mean +/- SEM) than in healthy controls (31 +/- 3 mm Hg). Patients had a lower maximal intestinal pain tolerance than controls (31 +/- 2 mm Hg vs. 39 +/- 1 mm Hg, p <0.05). Duodenal distension inhibited intestinal motility distal to the distending balloon (peristaltic reflex) more often in health controls (11/12) than in patients with functional dyspepsia (5/12, p <0.05). These alterations of small intestinal motility occurred at pressure values below the perception thresholds, and disturbed motility responses were not associated with perception thresholds. CONCLUSION: Disturbed peristaltic reflexes and decreased sensory thresholds for perception of intestinal sensations are prevalent but may be independent abnormalities in patients with unexplained dyspepsia.

Adult↗

PubMedDate not supplied

Mirtazapine: an antidepressant with noradrenergic and specific serotonergic effects.

Mirtazapine is a unique antidepressant that refines the specificity of effects on noradrenergic and serotonergic systems. It is an antagonist of presynaptic alpha 2-adrenergic autoreceptors and heteroreceptors on both norepinephrine and serotonin (5-HT) presynaptic axons, plus is a potent antagonist of postsynaptic 5-HT2 and 5-HT3 receptors. The net outcome of these effects is increased noradrenergic activity together with specific increased serotonergic activity, especially at 5-HT1A receptors. This mechanism of action maintains equivalent antidepressant efficacy but minimizes many of the adverse effects common to both tricyclic antidepressants and selective serotonin reuptake inhibitors. Mirtazapine has an onset of clinical effect in 2-4 weeks similar to other antidepressants, although sleep disturbances and anxiety symptoms may improve in the first week of treatment. It has minimal cardiovascular and anticholinergic effects, and essentially lacks serotonergic effects such as gastrointestinal symptoms, insomnia, and sexual dysfunction. Sedation, increased appetite, and weight gain are more common with mirtazapine than with placebo. An elimination half-life of 20-40 hours enables once-daily bedtime dosing. The recommended initial dosage is 15 mg once/day at bedtime, with an effective daily dosage range of 15-45 mg. Cases of overdose of up to 975 mg caused significant sedation but no cardiovascular or respiratory effects or seizures.

Antidepressive Agents, Tricyclic↗

PubMed1998

Gulf War syndrome--a model for the complexity of biological and environmental interaction with human health.

Since the end of the Gulf War, tens of thousands of American, Canadian and British soldiers who participated in that war have claimed to be suffering from a variety of incapacitating symptoms which are generally termed as Gulf War Syndrome (GWS). The symptoms are multiple but mainly consist of excessive tiredness, muscle and joint pain, loss of balance, sensory symptoms, neurobehavioural manifestations, diarrhoea, bladder dysfunction, sweating disturbances, and respiratory, gastrointestinal, musculoskeletal and skin manifestations. These veterans have been exposed to a variety of damaging or potentially damaging risk factors including environmental adversities, pesticides such as organophosphate chemicals, skin insect repellents, medical agents such as pyridostigmine bromide (NAPS), possible low-levels of chemical warfare agents, multiple vaccinations in combinations, depleted uranium, and other factors. A large number of basic research findings, clinical epidemiological studies, and case control studies are reviewed to try and link them together to produce a coherent picture and to demonstrate the complexity of the interaction of biological systems, environmental and genetic factors, combinations of drugs and toxins with human health. The findings of these studies so far have demonstrated that many of the previous assumptions made about the 'safety' of certain drugs and toxic substances or vaccines must be radically reviewed. Many of the findings have far reaching implications not only in terms of explanation of what might have gone wrong during the Gulf War, but also have wider implications for many occupational groups who are exposed daily to some of these risk factors. More open-mindedness and much less prejudice are required concerning the basic biology of interactions of the above factors and their effects on cell functions and wider intelligent research is urgently required with high priority. This review highlights the importance of intelligent research for answers for a new phenomenon, and demonstrates the necessity for a combination of this approach with high quality epidemiological research. The reader will notice an emerging clear picture that the majority (if not all) of these advances have been achieved from studies funded by independent or charity organizations rather than by the responsible authorities who are supposed and are duty bound to take on this task.

Chemical Warfare Agents↗