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Chiropractic management of cow's milk protein intolerance in infants with sleep dysfunction syndrome: a therapeutic trial.

OBJECTIVE: In addition to the more usual cutaneous, gastrointestinal, and respiratory problems, infants with cow's milk intolerance (CMI) may present with a disturbed sleep pattern. Frustrated mothers may turn to their doctor of chiropractic for assistance. This pilot study shows how a therapeutic trial may offer a realistic, noninvasive approach to the chiropractic management of infants with this clinical problem. METHODS: A pilot study to describe the presentation and treatment of infants presenting with disturbed sleep patterns to a chiropractic clinic was undertaken. Infants fulfilling a clinical screening protocol for CMI were selected for a therapeutic trial. The sleep behavior of subjects was monitored over a 4-week period during which they were managed by dietary change and a high-impulse, low-amplitude whole-of-body chiropractic management protocol. RESULTS: Fifty-nine infants presented with disturbed sleep. Of these, 19 met the clinical criteria used to establish the diagnosis CMI. The mothers of breast-fed infants were counseled on how to implement a dairy-free diet, and those infants who were artificially fed were changed from cow's milk-based formulae to either a partially or wholly hydrolyzed formula. Fourteen achieved a stable sleep pattern within the study period. In 5 instances, the sleep pattern remained problematic, but other clinical evidence of hypersensitivity reactions attributable to CMI disappeared. By the end of the study, no subject had demonstrable evidence of either biomechanical derangement or functional neurologic imbalance. CONCLUSION: CMI should be considered as a possibility in infants with disturbed sleep patterns who present for chiropractic care. This study describes how a therapeutic trial involving dietary modification, parental counseling, and comprehensive chiropractic care may offer a noninvasive approach to excluding and/or managing this condition. Further research is required before definitive recommendations can be made.

Counseling↗

Failure to thrive, hepatic dysfunction, hypotonia, and cerebellar atrophy.

A 2-year-old with cerebrellar and gastrointestinal difficulties is presented. The differential diagnosis of this combination of clinical features is difficult but recently several of the conditions under consideration have been more precisely characterized from a molecular standpoint.

Cerebellar Cortex↗

Review article: botulinum toxin in the therapy of gastrointestinal motility disorders.

Since 1980, botulinum toxin has been employed for the treatment of various voluntary muscle spastic disorders in the fields of neurology and ophthalmology. More recently, botulinum toxin has been proved to be effective in the therapy of dyskinetic smooth muscle disorders of the gastrointestinal tract. Achalasia and anal fissure are the gastrointestinal disorders in which botulinum toxin therapy has been most extensively investigated. Botulinum toxin is the best treatment option for achalasia in patients whose condition makes them unfit for pneumatic dilation or surgery. In anal fissure, botulinum toxin is highly effective and may become the treatment of choice. In the future, botulinum toxin application in the gastrointestinal tract will be extended to many other gastrointestinal disorders, such as non-achalasic motor disorders of the oesophagus, dysfunction of Oddi's sphincter, achalasia of the internal anal sphincter and others. This article describes the mechanism of action, rationale of employment, indications and side-effects of botulinum toxin application in smooth muscle disorders of the gastrointestinal tract, and compares the results of different techniques of botulinum toxin therapeutic application.

Anti-Dyskinesia Agents↗

[Evaluation of autonomic dysfunction by novel methods].

The autonomic nervous system innervates every organ in the body. Since autonomic disturbances affect patient survival, an understanding and recognition of these disturbances are important. We adopted several new methods to evaluate autonomic function accurately. 123I-metaiodobenzylguanidine scintigraphy can assess the cardiac autonomic function even in the presence of cardiac arrhythmia. Laser-Doppler flowmetry, ultrasonographic study in the vessels and near-infrared spectrophotoscopy techniques serve as useful markers for screening the dysfunction of vasomotor neurons and blood circulation. Electrogastrography and the circadian rhythms of protein C secretion could be markers of the visceromotor nerves in the abdomen. Electrogastrography is a particularly useful tool for reflecting on functional changes in gastrointestinal motility. The evaluation of anemia could be a marker of autonomic dysfunction in the kidney and bone marrow in patients with familial amyloidotic polyneuropathy, pandysautonomia, and multiple system atrophy. Normocytic and normochromic anemia correlated with the severity of autonomic dysfunction were shown in these patients. We also evaluated the dysfunction of the neuroendocrine system and sudomotor neuron using our new autonomic function tests. The glucose-tolerance test could become one of the most useful clinical tools for detecting autonomic dysfunction in the endocrine system. Microhydrography and thermography could be useful tools for diagnosing the lesion site of dyshidrosis. Moreover, it is clinically important to check the systemic circulation and autonomic function in patients treated with sildenafil citrate and organ transplantation to save their lives. Our new autonomic function tests, such as laser-Doppler flowmetry and 123I-metaiodobenzylguanidine scintigraphy, are crucial tools in supplying the best symptomatic treatment for such patients.

3-Iodobenzylguanidine↗

Gastrointestinal motility in obesity.

Gastrointestinal motility is closely linked to the rate at which nutrients become systemically available. Regulation of gastric emptying represents the most important brake against delivery of nutrients to the intestine in excess of digestive and absorptive capacity. In man, gastric emptying is slowed in proportion to the energy density of the meal, which will level out the rate of energy delivery to the duodenum. Studies suggest a more rapid gastric emptying in obesity, although the opposite has been reported in some experimental settings. Moreover, gastric volume is larger in obese individuals and appropriate satiety signals are not triggered in response to gastric distension. Postprandial intestinal transit time in obesity is similar to that in normal-weight subjects, however, despite this fact, intestinal absorption of nutrients is more efficient in obesity. Several regulatory mechanisms for gastrointestinal motility, such as the autonomous and enteric nervous systems and gastrointestinal regulatory peptides, are also of importance for feeding behaviour and metabolism. Dysfunction of the autonomous nervous system has been observed, the sensitivity to cholecystokinin is decreased in obesity, and plasma concentrations of somatostatin and neurotensin are lower than in normal-weight subjects. These changes in regulatory mechanisms favour rapid gastrointestinal transit of ingested nutrients and promote rapid intestinal absorption in obesity and decreased satiety in response to ingested food. It is presently not known whether the observed changes in gastrointestinal motility in obesity represent a primary feature linked to the pathogenesis of such disease.

Autonomic Nervous System↗

Guts and their motions (gastrointestinal motility in health and disease).

In the last decade, a much greater understanding of human upper intestinal motility has been obtained. The existence of a cyclical fasting pattern is now recognized, associated with intermittent secretion and propulsion of material through the stomach and small intestine. This pattern changes after the ingestion of food, the duration of the disruption depending upon both quality and quantity of nutrient ingested. The present clinical relevance of this phenomenon is twofold. 1) In normal fasting persons, the passage and absorption by the small intestine of food and drugs may be influenced by such periodic changes. 2) Motility abnormalities in disease states may account for associated gastrointestinal symptoms. While the number of disorders showing clinically relevant motor dysfunction is small, continuing study will undoubtedly bring others to light, and may even provide a rational basis for therapy.

Bacterial Infections↗

Stress signaling pathways activated by weaning mediate intestinal dysfunction in the pig.

Weaning in the piglet is a stressful event associated with gastrointestinal disorders and increased disease susceptibility. Although stress is thought to play a role in postweaning intestinal disease, the mechanisms by which stress influences intestinal pathophysiology in the weaned pig are not understood. The objectives of these experiments were to investigate the impact of weaning on gastrointestinal health in the pig and to assess the role of stress signaling pathways in this response. Nineteen-day-old pigs were weaned, and mucosal barrier function and ion transport were assessed in jejunal and colonic tissues mounted on Ussing chambers. Weaning caused marked disturbances in intestinal barrier function, as demonstrated by significant (P < 0.01) reductions in transepithelial electrical resistance and increases in intestinal permeability to [3H]mannitol in both the jejunum and colon compared with intestinal tissues from age-matched, unweaned control pigs. Weaned intestinal tissues exhibited increased intestinal secretory activity, as demonstrated by elevated short-circuit current that was sensitive to treatment with tetrodotoxin and indomethacin, suggesting activation of enteric neural and prostaglandin synthesis pathways in weaned intestinal tissues. Western blot analyses of mucosal homogenates showed increased expression of corticotrophin-releasing factor (CRF) receptor 1 in the jejunum and colon of weaned intestinal tissues. Pretreatment of pigs with the CRF receptor antagonist alpha-helical CRF(9-41), which was injected intraperitoneally 30 min prior to weaning, abolished the stress-induced mucosal changes. Our results indicate that weaning stress induces mucosal dysfunction mediated by intestinal CRF receptors and activated by enteric nerves and prostanoid pathways.

Animals↗

Long-term results of radiotherapy for early-stage testicular seminoma.

PURPOSE: We conducted an outcome and complications analysis of patients treated with adjuvant radiotherapy (RT) for early-stage testicular seminoma over a 35-year period at the University of Florida. METHODS AND MATERIALS: All 73 patients had the classic seminoma histology. No patient received chemotherapy as initial treatment. There were 57, 14, and 2 patients with Royal Marsden stage I, IIA, and IIB disease, respectively. All received RT to the paraaortic (PAN) and pelvic fields. One-third of the patients received prophylactic RT to mediastinal/supraclavicular fields. RESULTS: Median follow up was 15 years. Median RT dose to PAN and pelvic fields was 25 Gy. Local control and cause-specific survival at 20 years were 95% and 96%, respectively. Of the 3 recurrences, 1 was salvaged with chemotherapy. Subset analysis of 41 patients revealed 1 patient who developed peptic ulcer disease and 11 patients with gastrointestinal reflux symptoms after RT. Thirty-two patients fathered a child before or after RT. Cardiovascular complications were not greater in those treated with prophylactic RT to the mediastinal region. The rate of nontesticular second malignancy for the overall group was 8% at 15 years. CONCLUSIONS: Patients treated with adjuvant low-dose RT to the paraaortic and pelvic fields for treatment of early-stage seminoma enjoy an excellent long-term cure rate with minimal risk of late RT complications.

Adult↗

Long term tolerance of high dose three-dimensional conformal radiotherapy in patients with localized prostate carcinoma.

BACKGROUND: The current study was undertaken to evaluate the incidence and predictors of late toxicity in patients with localized prostate carcinoma treated with high dose three-dimensional conformal radiotherapy (3D-CRT). METHODS: A total of 743 patients with prostate carcinoma classified as T1c-T3 were treated with 3D-CRT that targeted the prostate and seminal vesicles. A minimum tumor dose of 64.8 gray (Gy) was given to 96 patients (13%), 70.2 Gy to 266 patients (365), 75.6 Gy to 320 patients (43%), and 81.0 Gy to 61 patients (8%). The median follow-up time was 42 months (range, 18-109 months). Late toxicity was graded according to the Radiation Therapy Oncology Group morbidity scoring scale. RESULTS: Late gastrointestinal (GI) and urinary (GU) toxicities were absent or minimal (Grade 0 or 1) in 90% of patients. The 5-year actuarial likelihood of the development of Grade 2 and 3 late GI toxicities was 11% and 0.75%, respectively. A multivariate analysis identified doses > or =75.6 Gy (P<0.001), history of diabetes mellitus (P = 0.01), and the presence of acute GI symptoms during treatment (P = 0.02) as independent predictors of Grade > or =2 late GI toxicity. The 5-year actuarial likelihood of the development of Grade 2 and 3 late GU toxicities was 10% and 3%, respectively. Doses > or =75.6 Gy (P = 0.008) and acute GU symptoms (P<0.001) were independent predictors of Grade > or =2 late GU toxicity. Among 544 patients who were potent before treatment (73% of all patients), 211 (39%) became impotent after 3D-CRT. The 5-year actuarial risk of potency loss was 60%. Doses > or =75.6 Gy (P<0.001) and the use of neoadjuvant androgen deprivation (P = 0.01) were independent predictors of posttreatment erectile dysfunction. CONCLUSIONS: The incidence of severe late complications after high dose 3D-CRT was minimal. Radiation doses > or =75.6 Gy and the presence of acute treatment-related symptoms during 3D-CRT correlated with a higher incidence of Grade > or =2 late GI and GU toxicities. In addition to higher doses, the use of androgen deprivation therapy increased the likelihood of permanent impotence in these patients. Intensity-modulated radiotherapy, which makes it possible to enhance the conformality of the dose distribution, has recently been implemented in an attempt to reduce the incidence of moderate grade toxicities in patients receiving high dose 3D-CRT.

Adenocarcinoma↗

Tegaserod: a novel, selective 5-HT4 receptor partial agonist for irritable bowel syndrome.

Irritable bowel syndrome (IBS) is a common functional bowel disorder of unknown aetiology. It is defined by the presence of gastrointestinal (GI) symptoms including abdominal pain/discomfort, bloating and bowel motor dysfunction. No available therapy is yet effective against all the symptoms of the disorder. Current treatments therefore target individual symptoms but may be accompanied by unpleasant side-effects. Tegaserod is a novel selective serotonin receptor type-4 (5-HT4) partial agonist with structural similarity to 5-HT Tegaserod stimulates small bowel and colonic motility and helps to normalise GI function. Clinical trials using a patient's assessment of efficacy demonstrate that tegaserod significantly improves key symptoms of IBS: abdominal pain/discomfort, bloating and constipation. Tegaserod is well tolerated with an excellent safety profile and represents a significant treatment advance in this difficult-to-treat disorder.

Clinical Trials, Phase III as Topic↗

Gastrointestinal and hepatic complications affecting patients with renal allografts.

Of 126 renal allograft recipients, 34 were found to have gastrointestinal and hepatic complications. In order of frequency, these included: mild liver dysfunction, severe hepatitis usually associated with cytomegalovirus infection, peptic ulceration complicated by bleeding, intestinal obstruction, and pancreatitis. These complications did not appear to influence the long-term survival or function of the renal allograft, but proved to be fatal when massive infection of cytomegalovirus affected the gastrointestinal tract and especially the liver. Gastrointestinal and pancreatic complications occurring in renal allograft recipients can be managed in the same manner as in patients who are not receiving immunosuppression. When surgical intervention is required, it should be performed promptly. The fact that these patients are receiving immunosuppressive therapy should not be a contraindication to early surgical intervention. When the presence of ulcerative lesions of the gastrointestinal mucosa, pancreatitis, or hepatitis is confirmed, the possibility of these lesions being caused by viral agents, especially cytomegalovirus, should be considered and attempts to confirm this diagnosis should be made. If cytomegalovirus infection is confirmed and the patient is experiencing rejection of the allograft, careful consideration should be given to immediate discontinuation of immunosuppressive therapy followed by removal of the renal allograft. In this way the relentless and fatal course of the cytomegalovirus infection seen in some of the patients reported in this study may be avoided.

Adult↗

Hepatic dysfunction in patients with extrahepatic portal venous obstruction.

BACKGROUND: Extrahepatic portal venous obstruction (EHPVO) developing due to thrombotic occlusion of the portal vein in children is generally considered a benign disease. Whether hepatic dysfunction develops in these patients in the absence of a gastrointestinal bleed has not been well studied. MATERIALS AND METHODS: Forty-three patients with EHPVO who had not bled in the last 3 months were studied. Patients were divided into those with (group I) or without ascites (group II). Matched cirrhotic patients with ascites (group III) served as controls. Clinical, biochemical, ultrasonographic, and histopathological evaluation was carried out. Portal biliopathy was assessed in five patients in group I and in 12 patients in group II by cholangiography. RESULTS: Of 43 EHPVO patients, ascites was seen in nine (21%) patients (group I). Thirty-four patients had no ascites (group II). Serum ALT (54 +/- 24 vs. 34 +/- 10 IU/l, P < 0.01), albumin (3.2 +/- 0.3 vs. 3.7 +/- 0.4 g/dl, P < 0.01), and prothrombin time difference (9.0 +/- 4.5 vs. 2.4 +/- 1.9 s, P < 0.05) were deranged in patients in group I compared with group II. Patients in group I were 4 years older, and the duration of portal hypertension was longer than in group II (11.5 vs. 5.6 year, P < 0.05). Portal biliopathy changes were significantly more severe in group I than in group II patients. Ascites was high gradient in all the patients in group I and the serum-ascitic albumin gradient was comparable between groups I and III. None of the EHPVO patients, but four cirrhotic patients, developed spontaneous bacterial peritonitis during a follow-up of 11 +/- 4 months. CONCLUSIONS: Hepatic dysfunction in the form of ascites and deranged liver functions is not uncommon in patients with EHPVO, more so in patients with prolonged portal hypertension. Based on our data it would be worthwhile to study whether prolonged portal vein thrombosis in EHPVO patients could lead to progressive liver disease.

Adolescent↗

Acid-base disorders in medicine.

The practice of internal medicine involves daily exposure to abnormalities of acid-base balance. A wide variety of disease states either predispose patients to develop these conditions or lead to the use of medications that alter renal, gastrointestinal, or pulmonary function and secondarily alter acid-base balance. In addition, primary acid-base disease follows specific forms of renal tubular dysfunction (renal tubular acidosis). We review the acid-base physiologic functions of the kidney and gastrointestinal tract and the current understanding of acid-base pathophysiologic conditions. This includes a review of whole animal and renal tubular physiologic characteristics and a discussion of the current knowledge of the molecular biology of acid-base transport. We stress an approach to diagnosis that relies on knowledge of acid-base physiologic function, and we include discussion of the appropriate treatment of each disorder considered. Finally, we include a discussion of the effects of acidosis and alkalosis on human physiologic functions.

Acid-Base Equilibrium↗