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Polyuria, peaking at 2000 ml/h, was seen in a patient after resuscitation of hemorrhagic shock and a brief period of oliguria. This unusual polyuria appears to be a consequence of renal tubular dysfunction that persisted after glomerular filtration rate had returned to normal.
BACKGROUND AND AIM: An increase in recto-sigmoid colon activity through electrical stimulation of the sacral dermatomes has previously been reported. It has not been evaluated whether or not sacral dermatome stimulation has beneficial effects on constipation symptoms and anorectal function in constipated patients. Our aim was to evaluate short-term effects of magnetic stimulation of the sacral dermatomes on constipation symptoms and anorectal function in patients with idiopathic slow transit constipation. METHOD: Fourteen patients with idiopathic slow transit constipation were enrolled. Constipation symptoms, stool form and anorectal function were assessed before treatment, and at 3 and 6 weeks of treatment. Six-week treatment consisted of either a 3-week period of sham treatment or a 3-week period of magnetic stimulation of the S2-S3 dermatomes, which was performed in a randomized cross-over design. RESULTS: During the stimulation period, the frequency score of spontaneous bowel movements decreased in eight of the 14 patients (2.9 [2-3]vs 1.4 [0-2]), whose threshold volumes for urge to defecate and maximum tolerable volumes were significantly greater than those of the non-responders, and significantly decreased at the end of treatment. The degree of straining on defecation also significantly decreased in the responders. Responders had shorter right colonic transit time and longer left colonic transit time compared to the non-responders. Sham treatment did not affect constipation symptoms, stool form and rectal sensation. CONCLUSION: Sacral dermatome stimulation may offer potential for therapeutic benefit for a subset of patients with idiopathic slow transit constipation, particularly constipated patients with rectal hyposensation or hindgut dysfunction.
Ulcerative colitis (UC) affects colonic motor function, but the mechanism responsible for this motor dysfunction is not well understood. We have shown that neurokinin A (NKA) may be an endogenous neurotransmitter mediating contraction of human sigmoid colonic circular muscle (HSCCM). To elucidate factors responsible for UC motor dysfunction, we examined the role of hydrogen peroxide (H(2)O(2)) in the decrease of NKA-induced response of HSCCM. As previously demonstrated, NKA-induced contraction or Ca(2+) increase of normal muscle cells is mediated by release of Ca(2+) from intracellular stores, because it was not affected by incubation in Ca(2+)-free medium (CFM) containing 200 microM BAPTA. In UC, however, CFM reduced both cell contraction and NKA-induced Ca(2+) increase, suggesting reduced Ca(2+) release from intracellular stores. In normal Ca(2+) medium, NKA and KCl caused normal Ca(2+) signal in UC cells but reduced cell shortening. The decreased Ca(2+) signal and contraction in response to NKA or thapsigargin were partly recovered in the presence of H(2)O(2) scavenger catalase, suggesting involvement of H(2)O(2) in UC-induced dysmotility. H(2)O(2) levels were higher in UC than in normal HSCCM, and enzymatically isolated UC muscle cells contained much higher levels of H(2)O(2) than normal cells, which were significantly reduced by catalase. H(2)O(2) treatment of normal cells in CFM reproduced the reduction of NKA-induced Ca(2+) release observed in UC cells. In addition, H(2)O(2) caused a measurable, direct release of Ca(2+) from intracellular stores. We conclude that H(2)O(2) may contribute to reduction of NKA-induced Ca(2+) release from intracellular Ca(2+) stores in UC and contribute to the observed colonic motor dysfunction.
OBJECTIVE: S-1 is a novel oral fluorouracil antitumor drug that combines three pharmacological agents: tegafur (FT), a prodrug of 5-fluorouracil (5-FU); 5-chloro-2,4-dihydroxypyridine (CDHP), an inhibitor of dihydropyrimidine dehydrogenase, and potassium oxonate (Oxo), a reducer of gastrointestinal toxicity. S-1 has safe and potent antitumor effects in patients with gastric cancer via these respective functions. However, the plasma 5-FU concentration is suspected to accumulate in patients with renal dysfunction, because 50% of the CDHP is excreted into the urine. There are no useful data on safety and efficacy of S-1 in chronic renal failure patients maintained on hemodialysis (HD). We examined the influence of HD on the pharmacokinetics (PK) of S-1 and its therapeutic efficacy in liver metastases from gastric cancer. METHODS: For the HD patient, the dose of S-1 in a single-administration study was set at 50 mg/body/day (41.7% of the recommended dose of 80 mg/m2/day). S-1 was given to the patient 24 h after HD. Blood samples were obtained before administration and 2, 4, 6, 8, and 24 h thereafter and 1, 2, 4, and 72 h after the following HD session. The PK parameters (5-FU, CDHP, Oxo, and FT) were measured, and Cmax, Tmax, AUC0-24, and T1/2 were calculated. The dose of consecutive or maintained administrations was determined. RESULTS: Both an increase in Cmax and an elongation of T1/2 for 5-FU, CDHP, and Oxo, but not for FT, occurred in this case as compared with controls. The AUC0-24 of 5-FU in this case was similar to that of controls at the standard dose. After HD, 87.8, 54.5, 77.4, and 66.2% of 5-FU, CDHP, Oxo, and FT, respectively, were eliminated. A slight accumulation of CDHP did not alter the 5-FU PK. Consecutive or maintained S-1 oral administration at the same dose showed similar effects on all PK parameters of a single-administration test. Liver metastases almost totally regressed with no adverse events 4 weeks after S-1 treatment (50 mg/body/day three times a week). CONCLUSION: Adjusted doses of S-1 according to the results of PK studies may provide therapeutic safety and high efficacy in liver metastases from gastric cancer, even in chronic renal failure patients maintained on HD.
Anticoagulation is a treatment with significant and life threatening complications requiring that the balance of risk and benefit be individually assessed in each patient. The risks are greater in the elderly and those with hypertension, falls and gastrointestinal disease. The use of anticoagulants is now established in patients with symptomatic non-rheumatic atrial fibrillation, especially older patients with hypertension, cardiac failure or a large left atrium or left ventricular dysfunction. There is, however, no place for the routine use of anticoagulants in acute stroke or as part of secondary prevention in patients in sinus rhythm. There may be a place, though as yet the evidence would not support this, for the limited use of anticoagulants in special situations such as cortical venous thrombosis or carotid dissection.
Experimental findings suggest that inhibition of neutrophil activation rather than suppression of prostaglandin formation may represent the principal mechanism of action of antiinflammatory drugs. This theory would account for the effectiveness of prostaglandin preserving agents, such as the nonacetylated salicylate salsalate, in the treatment of rheumatic disease. Results of the controlled clinical trials described in other papers contained in this supplement indicate that salsalate is equally effective as aspirin and the newer NSAID naproxen in relieving the signs and symptoms of rheumatoid arthritis. The damage to the gastric mucosa associated with NSAID use is believed to be attributable to impairment of mucosal defense mechanisms resulting from the inhibition of gastroprotective prostaglandins. Confirmation of neutrophil activation as the mechanism of action of NSAIDs would explain the efficacy of salsalate in light of its lower incidence of gastrointestinal side effects in controlled clinical trials with aspirin and naproxen. Establishment of such a mechanism would also suggest that the other adverse effects related to prostaglandin inhibition, such as hypersensitivity reactions, platelet dysfunction, and a reduction in renal function, are not necessary correlates of effective antiinflammatory therapy.
The anthelminthic agents chloxylum and prasiquantel were examined for their effects in patients with an above 5-year history of Opisthorchis invasion. The van de Kamer procedure revealed that chloxylum produced an inhibitory effect on absorption of d-xylose and fat. Prasiquantel failed to impair the absorptive function of the small intestine. Helminthological curing in patients with chronic opisthorchiasis was not shown to normalize dysfunction of the small intestine.
The motor response of the human colon to a meal is still poorly characterized. Such data as are available were obtained chiefly for the distal colonic portions with myoelectrical techniques. For these reasons, we investigated proximal and distal colonic motor responses to food ingestion in a rather large group of healthy subjects. Twenty-nine healthy volunteers were studied with a colonoscopically positioned multilumen manometric probe and low-compliance infusion system. Recordings were obtained for 2 h during fasting and for 3 h after the subjects had eaten a 1000-kcal standard mixed meal. During fasting, motility was quite low, and no significant differences between proximal and distal portions were seen. After eating, each portion significantly increased its motor activity throughout the subsequent recording period, but there were differences in the time course in the response to eating for different colonic segments. Proximal portions (especially the transverse colon) had first a sudden maximal increase and then a decrease, whereas the distal ones had a slower and more sustained increase in activity. These findings are of interest, especially for comparison with those of patients with suspected motor dysfunction of the large bowel.
Eleven academic institutions were selected to study mitoxantrone administered on a schedule of 10 mg/m2/d for five days initially and later at 12 mg/m2/d for five days, each given as a 30 minute intravenous (IV) infusion each day. Patients with acute or chronic leukemia were stratified by leukemic type and clinical status and included one group of patients considered to be in relapse after complete remission from previous chemotherapy and another group of patients considered refractory to standard induction and/or salvage chemotherapy. During the initial treatment schedule, complete remissions were obtained in two of seven patients with acute nonlymphoblastic leukemia, in one of three patients with acute lymphoblastic leukemia, but in none of the patients with chronic granulocytic leukemia in blast crisis. The durations of remission for these three patients were 22, 57, and 78 days, respectively. An increase in mitoxantrone dose to 12 mg/m2/d produced complete remissions in 8 of 19 evaluable patients with acute nonlymphoblastic leukemia, in one of ten patients with refractory acute nonlymphoblastic leukemia, and in one of four patients with chronic granulocytic leukemia in blast crisis. Each of these patients required only a single course of mitoxantrone to achieve remission; the median time to remission was 37 days (range 18 to 64 days). Remission duration ranged from 35 days (chronic granulocytic leukemia) to 186 days, with the median duration for those patients with acute nonlymphoblastic leukemia achieving remission being 135 days. Of the six patients with acute lymphoblastic leukemia, none achieved remission at the higher dose level. Drug-related gastrointestinal toxicity included mucositis (25%), diarrhea (21%), and nausea and vomiting (61%). Systemic infection (nonfatal) was experienced by 21% of patients and alopecia by 17%. Other side effects that occurred occasionally were hepatic dysfunction, decreased renal function, confusion, lethargy, anxiety, and fever. Possible drug-related phlebitis developed in one patient, and a single episode of minor epistaxis was reported in another. Cardiovascular toxicity was low. At a mitoxantrone dose of 10 mg/m2/d for five days, one patient developed hypotension, and one episode of congestive heart failure was reported in another. At the higher dose of 12 mg/m2/d, no drug-related hypotension, congestive heart failure, tachycardia, or chest pain were reported. These data indicate that mitoxantrone is a promising single drug for the treatment of acute nonlymphoblastic leukemia and possibly for acute lymphoblastic leukemia.
The study of GI motility is an area of great current interest and excitement. Our knowledge of normal and abnormal GI motility is expanding exponentially. Perhaps one of the most satisfying consequences of this new knowledge is the ability to reassure patients that their symptoms may not be functional but may be based on a specific physiologic dysfunction. Unfortunately, our ability to treat effectively these newly described disorders has lagged behind our ability to diagnose them, but progress is being made, with promising new therapeutic agents on the horizon. Gastroenterologists remain the best friends of surgeons; most of these patients can and should be managed without surgical intervention. Therapeutic nihilism is not justified, because a carefully considered and properly timed operation may be of tremendous symptomatic benefit to selected patients. As more information and follow-up results are gained, the proper role of surgical intervention in these disorders will be better defined.
Sensorimotor disturbances of the small bowel are implicated increasingly in the pathogenesis of the functional gastrointestinal disorders. In irritable bowel syndrome (IBS), alterations in both interdigestive and postprandial motility have been described, for example, the specific peristaltic contractions that are normally present in the ileum appear to occur more frequently and to be associated with abdominal pain in some patients. The latter finding is likely to be related to the selective mechanoreceptor hypersensitivity that has been demonstrated in the small bowel of IBS patients. The level of this afferent dysfunction has, however, not been established; some evidence suggests that personality traits, which predispose to a more severe and prolonged sympathetic response to stressors, may hasten the development of such sensorimotor disturbances.
BACKGROUND: Cyclosporine A (CsA) and tacrolimus (Tac) provide effective immunosuppression after orthotopic liver transplantation (OLT) but can cause renal dysfunction that may progress to end-stage renal failure (ESRF). Mycophenolate mofetil (MMF) is a newer immunosuppressant that does not affect renal function. Its long-term use in children with renal dysfunction after OLT has not yet been fully evaluated. METHODS: A retrospective analysis was performed of all children begun on MMF for renal dysfunction and followed up for at least 1 year. Renal dysfunction was defined as calculated glomerular filtration rate (cGFR) of less than 65 mL/min/1.73 m2. cGFR and liver function were measured before and after transfer. Data were analyzed using the Wilcoxon signed rank test. RESULTS: Forty-eight children (23 males) began MMF at a median age of 11.1 (0.9-18.1) years and at a median of 4.0 (0.3-12.4) years postOLT. Median baseline cGFR was 54 (range 29-65) mL/min/1.73 m2. Immunosuppression after transfer was MMF monotherapy in 36, MMF with steroids, in 4 and MMF with low-dose CsA or Tac in 8. In 44 (92%) patients, there was a statistically significant increase to a median cGFR of 69 (28-114) mL/min/1.73 m2 by 1 month and a further increase to a median cGFR of 77 (24-105) mL/min/1.73 m2 by 2 months of MMF treatment, after which time cGFR was maintained. Children aged less than 3 years at OLT or who were less than 5 years postOLT when MMF was begun demonstrated greater increases in cGFR. Four children with a median baseline cGFR of 34 (range 31-49) mL/min/1.73 m2 did not respond and progressed to ESRF. Mild side effects occurred in seven (15%) and gastrointestinal bleeding requiring discontinuation of MMF in one (2%). Liver function abnormalities occurred in seven (15%): transient transaminitis in three, acute rejection in two, and chronic rejection in two, of whom one required retransplantation. CONCLUSIONS: In 92% children with renal dysfunction after OLT, MMF treatment provided safe and effective immunosuppression and allowed CsA or Tac to be discontinued or reduced, leading to improvement of renal function. The improvement was greatest in younger children and those who began MMF early postOLT. Side effects were uncommon. Additional steroid cover during the transfer to MMF should be considered to prevent liver-allograft rejection.
Gastrointestinal manifestations in patients with primary Sjögren's syndrome (SS), which is an autoimmune exocrinopathy, include dysphagia, nausea, epigastric pain, dyspepsia and nutritional deficiencies. In this report, we are presenting the nature and incidence of esophageal, pancreatic and liver involvement in our primary SS patients. Esophageal motility was studied in 27 patients with primary SS and 25 normal age and sex matched volunteers. Esophageal dysfunction was detected in 11 of the 27 patients (40.71%). Individual analysis of the esophageal motility studies showed different patterns of esophageal dysfunction. These esophageal abnormalities did not correlate with the parotid flow rate, the degree of inflammatory infiltrate of the minor salivary glands, the extraglandular manifestations or the presence of autoantibodies. Sera from 25 patients with primary SS were studied for the total serum alpha-amylase activity and isoamylases. Sera from 81 normal age and sex matched volunteers were used as controls. None of these patients had abdominal pain or gastrointestinal symptoms at the time of blood collection. The presence of hyperamylasemia of P-type and S-type in 6/25 patients (24%) probably reflects a slow, subclinical, inflammatory process of the exocrine glands. Clinical and biochemical evaluation of the liver function was studied in 22 primary SS patients. One of them had abnormal liver function tests and another hepatomegaly and splenomegaly. Percutaneous liver biopsies in both revealed chronic active hepatitis.
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Two patients presented with similar peripheral neuropathic symptoms. Muscle denervation was shown by electromyography and muscle biopsy. Motor and sensory nerve conduction studies were normal. Both patients had intestinal giardiasis: 1 had asymptomatic steatorrhoea, and the other had diarrhoea and abdominal pain. Treatment with metronidazole abolished the gastrointestinal symptoms. After a delay of several months the neurological symptoms also gradually improved. No other cause of peripheral neuropathy was apparent on investigation, and the relationship between the intestinal giardiasis and the peripheral neuropathy is discussed.
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BACKGROUND: Many technical difficulties of the ileoanal reservoir operation have been overcome, allowing acceptable morbidity in the hands of both the frequent and less frequent operator. However, a minority of patients have persistently unsatisfactory pouch function, which can be a difficult problem to manage. METHODS: A Medline search was carried out to identify relevant papers published from November 1996 to January 1978. For clinical information more emphasis was given to recent publications with larger numbers. Where appropriate, information from other sources and some local data were included. RESULTS: Most patients empty the pouch four to eight times a day with perfect continence and no urgency, and are considered to have acceptable function with which they are satisfied. Patients who have poor function beyond an easily treated episode of pouchitis require the expertise of a multidisciplinary team offering some understanding of the anatomy, physiology and pathology of the gastrointestinal tract in general and of the ileal reservoir in particular. A thorough and persistent approach to difficult cases is often rewarded with a good outcome, with the exception of problems arising from postoperative sepsis. The temptation to use pouchitis as a waste-basket diagnosis for poorly understood dysfunction should be avoided. Problems causing poor function may originate in the pouch (including pelvic sepsis), the pouch outlet, or the small bowel above the pouch, and these areas need to be considered in each case. CONCLUSION: To optimize the benefits of restorative pouch surgery, both patients and physicians need to understand aspects of fine tuning of pouch function, including diet, medication and lifestyle. In managing ileoanal reservoir dysfunction the temptation to procrastinate should be resisted; an approach that is systematic and sympathetic should be adopted.
Emerging literature suggests that quality of life (QOL) after bone marrow transplantation is relatively good but is accompanied in some patients by a variety of residual difficulties. The studies supporting this finding, however, have been somewhat limited in scale, scope, design, and analysis. We comprehensively measured changes in multidimensional QOL in a 4-year longitudinal follow-up of 415 adult patients who received hematopoietic stem cell transplants at Fred Hutchinson Cancer Research Center. Questionnaire packets containing 271 items were mailed annually posttransplantation to patients' homes. Standard methods of analysis yielded conditional estimates depending on compliance and survival, whereas new, likelihood-based methods generated unconditional estimates applicable to the full intent-to-treat population. Typical QOL levels generally remained high over the entire study period. Most QOL functioning significantly improved over 4 years, with the remainder showing no important decrement. Although isolated problem areas, such as sexual dissatisfaction, did emerge, the level of dysfunction for most physical and psychological scales remained below 30% of scale maxima. Broadly similar results were obtained for conditional estimation, which may contain an optimistic bias, and for unconditional estimation, which largely avoids the bias. Because concurrence was obtained between the 2 types of estimation, we conclude that most patients really do experience good levels of QOL in the 4 years after transplantation. Although some problems can be anticipated, typical patients can look forward to a QOL after transplantation that is broadly comparable to that of the normal population.