Absorption kinetics of rectal formalin instillation

Formalin instillation has become an accepted treatment of radiation-induced hemorrhagic cystitis and proctitis since the initial report by Brown in 1969 (Med. J. Aust. 1:23, 1969). Although its use is widespread, no studies have been performed to determine the safest, volume or duration of formalin exposure. The purpose of our study was to determine the optimum technique for instillation and the safety margin regarding the maximum time that formalin can be in contact with the rectal mucosa without causing serum toxicity. In a pilot canine study, 4% neutral buffered formalin was instilled into the rectum in 30 ml aliquots for 60 seconds each after which each aliquot was withdrawn; a total volume of 400 ml was used. Our subsequent experiment involved rectal instillation of a single formalin bolus of 100 ml for 1 hour without removal during this time. Formalin metabolites were measured in the blood and urine to assess toxicity. Results indicate that with the latter technique serum formic acid reaches toxic levels within 15 minutes of instillation and may stay elevated for several hours. Metabolites in the urine similarly increase within 15 minutes, lagging only shortly behind the rise in serum levels. Performing formalin instillation in a series of 30 ml aliquots appears to be a safer treatment, as toxic serum levels were not reached and their slight rise above baseline returned to normal within 3 hours.     

Formalin treatment of refractory hemorrhagic cystitis in systemic lupus erythematosus

Hemorrhagic cystitis is a potentially life-threatening complication in systemic lupus erythematosus (SLE). No safe, effective and conservative treatment exists for patients who fail to respond to standard therapy. We report a 17-year-old girl with SLE who suffered from severe hemorrhagic cystitis. Initially, she received frequent red blood cell and platelet transfusions, continuous bladder irrigation, and blood clots were evacuated. Numerous kinds of treatment were tried, including electrocoagulation of bleeding foci, prostaglandin E1 bladder instillation, and hyperbaric oxygen. However, she remained severely anemic and thrombocytopenic necessitating daily transfusions of blood products. After intravesical formalin instillation was performed twice, the hematuria ceased completely.     

Comparison of the uroprotective efficacy of mesna and HBO treatments in cyclophosphamide-induced hemorrhagic cystitis

The aim of this research was to compare the protective effects of mesna, hyperbaric oxygenation (HBO), and their combination in cyclophosphamide-induced hemorrhagic cystitis in guinea pigs. Following one dose of i.p. 21.5 mg./kg. mesna administration 20 minutes before i.p. 68.1 mg./kg. cyclophosphamide, 3 additional doses of mesna were given every three hours. A total of 8 HBO exposures, 5 of which were applied prophylactically before cyclophosphamide, were performed at 2.8 ATA for 90 minutes 2 times a day. Although mesna or HBO provided significant protection for cyclophosphamide-cystitis in animal bladders, there was also significant damage compared with controls. The combination of mesna and HBO, which act through independent mechanisms, resulted in complete protection, since mean histological scores and hematuria levels in this group were not different from controls (p >0.05). Therefore, this combination may be a useful tool in the prophylaxis and treatment of cyclophosphamide-induced hemorrhagic cystitis.     

The efficacy of intravesical Tice strain bacillus Calmette-Guerin in the treatment of interstitial cystitis: a double-blind, prospective, placebo controlled trial

PURPOSE: Interstitial cystitis is a debilitating bladder disease of unknown etiology with no cure. A recent report suggested that bacillus Calmette-Guerin (BCG) may be effective in the treatment of interstitial cystitis. A randomized, prospective, double-blind, placebo controlled trial to evaluate the safety and efficacy of intravesical BCG in treating interstitial cystitis was done. MATERIALS AND METHODS: Patients meeting the National Institute of Arthritis, Diabetes and Digestive and Kidney Diseases criteria for interstitial cystitis received 6 weekly instillations of Tice strain BCG or placebo. Periodic questionnaires, voiding diaries and cystometrograms were obtained. A total of 30 evaluable subjects was enrolled in the study with a mean followup of 8 months (range 6 to 13). Based on an exit questionnaire a responder was defined as one who rated the interstitial cystitis symptoms as moderately improved or better. RESULTS: A 60% BCG response rate was noted, compared to a 27% placebo response rate. Minimum voided volume and quality of life improved in the BCG group compared to placebo. Adverse events were similar in each group, mostly irritative in nature, and no significant systemic events were noted. CONCLUSIONS: Intravesical Tice strain BCG appears to be safe and efficacious in the treatment of interstitial cystitis. Additional studies must be performed to confirm the results of this pilot study.     

Post radiation hemorrhagic cystitis: MR findings

We report on the magnetic resonance findings in two patients with hemorrhagic cystitis secondary to radiation therapy. One patient's bladder wall was high in signal intensity on T1-weighted fat-suppressed spoiled gradient echo and low in signal intensity on T2-weighted fat-suppressed spin echo images, findings consistent with intracellular methemoglobin in the setting of subacute intramural hemorrhage. The second patient's bladder wall had regions that were low in signal intensity on T1-weighted fat-suppressed spin echo and high in signal intensity on T2-weighted fat-suppressed spin echo, and other regions that were high in signal intensity on T1-weighted fat suppressed spin echo and on T2-weighted fat-suppressed spin echo images, findings that were consistent with active bleeding and late subacute hemorrhage, respectively. Imaging findings correlated with the patients' clinical picture. Our two cases illustrate that magnetic resonance images may demonstrate changes of hemorrhagic cystitis and may permit determination of disease acuity.     

Interstitial pneumonia treated with intermittent cyclophosphamide pulse therapy

A 52-year-old woman was admitted to the hospital because of polyarthralgia and dry coughing. A chest X-ray film showed bilateral diffuse reticulo-nodular shadows. A specimen obtained by transbronchial lung biopsy revealed alveolar septal thickening and infiltration by mononuclear cells. Interstitial pneumonia associated with rheumatoid arthritis was diagnosed. Interstitial pneumonia relapsed soon after the first pulse of corticosteroid therapy. Cyclophosphamide pulse therapy was given in addition to a second pulse of corticosteroid therapy; 700 mg of cyclophosphamide (500 mg/m2) was administered intravenously every month and the dose of steroids was gradually reduced. Cyclophosphamide pulse therapy was repeated three times and the dose of oral corticosteroids was reduced from 60 mg to 35 mg. There was no bone marrow suppression or hemorrhagic cystitis after the cyclophosphamide pulses. Eventually, corticosteroid therapy was stopped with no clinical deterioration. This case suggests that intermittent cyclophosphamide pulse therapy can be effective for treatment of interstitial pneumonia unresponsive to corticosteroids.     

Utilization of a direct sandwich ELISA kit for rapid diagnosis of adenovirus hemorrhagic cystitis in a patient with adult T-cell leukemia

We report on a case of adenovirus hemorrhagi cystitis that developed in a 49-year-old woman during intensive chemotherapy for adult T-cell leukemia. Although rapid etiologic diagnosis is essential for the effective management of viral hemorrhagic cystitis, the isolation of adenovirus from urine is often too time-cousuming. We detected the adenovirus antigen in the patient's urine using an Adenoclone direct sandwich ELISA kit (Cambridge Bio Science), which is commonly employed for the diagnosis of adenovirus conjunctivitis. Treatment consisted of intravenous vidarabine and bladder irrigation, which resulted in prompt clinical improvement. The Adenoclone kit was useful for the rapid etiologic diagnosis of adenovirus hemmorrhagic cystitis.     

Aspirin and risk of hemorrhagic stroke: a meta-analysis of randomized controlled trials

CONTEXT: Aspirin has been widely used to prevent myocardial infarction and ischemic stroke but some studies have suggested it increases risk of hemorrhagic stroke. OBJECTIVE: To estimate the risk of hemorrhagic stroke associated with aspirin treatment. DATA SOURCES: Studies were retrieved using MEDLINE (search terms, aspirin, cerebrovascular disorders, and stroke), bibliographies of the articles retrieved, and the authors' reference files. STUDY SELECTION: All trials published in English-language journals before July 1997 in which participants were randomized to aspirin or a control treatment for at least 1 month and in which the incidence of stroke subtype was reported. DATA EXTRACTION: Information on country of origin, sample size, duration, study design, aspirin dosage, participant characteristics, and outcomes was abstracted independently by 2 authors who used a standardized protocol. DATA SYNTHESIS: Data from 16 trials with 55462 participants and 108 hemorrhagic stroke cases were analyzed. The mean dosage of aspirin was 273 mg/d and mean duration of treatment was 37 months. Aspirin use was associated with an absolute risk reduction in myocardial infarction of 137 events per 10000 persons (95% confidence interval [CI], 107-167; P<.001) and in ischemic stroke, a reduction of 39 events per 10000 persons (95% CI, 17-61; P<.001). However, aspirin treatment was also associated with an absolute risk increase in hemorrhagic stroke of 12 events per 10000 persons (95% CI, 5-20; P<.001). This risk did not differ by participant or study design characteristics. CONCLUSIONS: These results indicate that aspirin therapy increases the risk of hemorrhagic stroke. However, the overall benefit of aspirin use on myocardial infarction and ischemic stroke may outweigh its adverse effects on risk of hemorrhagic stroke in most populations.     

Intraoperative radiotherapy combined with external beam radiation for prostate cancer without metastasis

Between 1989 and 1996, 35 patients with prostate cancer without metastasis received intraoperative radiotherapy combined with external beam radiation. 10 of 16 stage B patients and all of 19 stage C patients received additional endocrine therapy for the initial treatment. The radiation therapy included 25-30 Gy of intraoperative radiotherapy for prostate and 30 Gy of external beam radiotherapy for small pelvic region. One patient of stage C was dead for cancer and 4 patient were dead for other causes during 15-99 (mean: 41.6) months follow up period. The overall actuarial survival at 5 years by Kaplan-Meier method were 92.3% for stage B and 87.2% for stage C. Although cystitis, proctitis and anal bleeding were observed as the adverse effects of radiotherapy, both acute and chronic symptoms were not critical. In conclusion, intraoperative radiotherapy combined with external beam radiotherapy was revealed as an effective treatment for prostate cancer without metastasis.     

Prevention of hemorrhage and dental treatment of patients with congenital or acquired coagulopathies

The physiopathology of the hemorrhagic blood coagulation disorders caused by genetic or aquired problems is described. Among the former the most frequent ones include the hemophilia of type A-B and the von Willebrand disease, among the latter the use of oral anticoagulant constitutes the most frequent cause. If the are not subjected to an adequate haemostatic prophylaxis, both patients with hemophilia and von Willebrand disease present a serious haemorrhagic risk as a consequence of dental practice. As far as the use of anticoagulants is concerned, a periodical monitoring of the time of prothrombin (PT) is needed to find the right dosage (TP between 20%-30% or INR--international normalized radio between 2 and 3.5). Values over this range cause an increase of the hemorrhagic risk, while lower values involve an increased risk of thrombotic events. According to the authors the patients with the hemorrhagic diathesis show a precise handicap, caused both by his illness and by environmental elements, such as the fear of doctors for the haemorrhagic complications consequent to a therapeutical operation, fear that often leads to neglect important medical measures, in particular dental measures. The specialized dental surgeon has to mantain a strict cooperation with the hematologist in order to arrange an appropriate procedure of the prophylaxis. As far as the hemostatic prophylaxis is concerned, the use of the dermopressin (DDAVP), in patients with hemophilia A and von Willebrand disease, guarantees the realisation of dental practice without hemorrhagic risk. On the contrary, the use of the tranhexanic acid on patients in an anticoagulant oral treatment gives hemostatic security and makes it possible to carry on the therapy and the out-patient treatment.     

Combined warfarin and antiplatelet therapy after St. Jude Medical valve replacement for mitral valve disease

OBJECTIVES: The clinical effect of combined warfarin and antiplatelet therapy on the incidence of stroke and postoperative complications after mitral (plus aortic) valve replacement was studied and compared with that observed with warfarin therapy alone. BACKGROUND: It has been reported that combined warfarin and antiplatelet therapy may be effective but may be associated with an increased hemorrhagic risk. Therefore, definite benefits of the treatment in patients with an implanted prosthetic valve have not been clearly documented. METHODS: Between January 1980 and December 1992, 195 patients with a St. Jude Medical valve at the mitral (plus aortic) position were assigned to receive treatment with either warfarin alone (125 patients) or warfarin plus antiplatelet agents (70 patients), such as dipyridamole (150 or 300 mg daily, 14 patients) or ticlopidine (200 or 400 mg daily, 56 patients). A minimal dose of aspirin (10 to 40 mg) was added (29 patients) if the maximal platelet aggregation rate by collagen was not reduced. The target thrombotest level was 10% to 20%. RESULTS: The two treatment groups were similar with regard to gender and age distribution. The number of patients with atrial fibrillation, left atrial thrombus, history of previous stroke, simultaneous aortic valve operation and previously performed valve procedures were comparable in the two groups. Actuarial survival rate at 10 years was 98.3 +/- 1.7% (mean +/- SD) in the warfarin plus antiplatelet group and 90.3 +/- 3.2% in the warfarin group (p < 0.05 at 1 and 9 to 12 years). The actuarial stroke-free rate at 10 years was 95.3 +/- 3.4% and 84.3 +/- 3.8%, respectively (p < 0.05 by the generalized Wilcoxon test). The actuarial complication-free rate at 10 years was 89.4 +/- 4.3% and 67.9 +/- 4.8%, respectively (p < 0.05 by the generalized Wilcoxon test). No hemorrhagic complications were seen in the warfarin plus antiplatelet group. CONCLUSIONS: The results strongly indicate the effectiveness and safety of combined warfarin plus antiplatelet treatment after St. Jude Medical valve replacement for mitral (plus aortic) valve disease.     

Intraarterial chemotherapy combined with radiation therapy for advanced cancer of the uterine cervix

The results of intraarterial chemotherapy (IACT) combined with definitive radiation therapy for 23 advanced and bulky carcinomas of uterine cervix are reported. IA-CT with cisplatin 50 mg and doxorubicin 30 mg was administered by one shot method in bilateral internal iliac arteries. The protocol consisted of one to three treatment session every 3 weeks. Nine of eleven patients with clinical stage III achieved a complete local response (82%), and the 3- and 5-year survival in these cases were 72% and 72%, respectively. These results were superior to the response (58%), 3- and 5-year survivals (68%, 58%) obtained in 19 patients treated mainly with radiation therapy alone. The side effect of grade 2 and 3 for the intestine, such as ileus and hemorrhagic colitis, was noted in 3 patients (15%). In addition, 3 of 8 patients with radical surgery and postoperative radiation therapy after IA-CT developed insufficient fracture of pelvic bone. These complications accompanied by IA-CT combined with radiation therapy and/or surgery increased slightly, compared with that by the previous therapy without IA-CT, but were not critical. The results suggest that IA-CT following radiation therapy is effective to improve the prognosis of patients with Stage III cervical cancer.     

Serum thrombomodulin levels in patients receiving allogeneic bone marrow transplantation

It has been reported that serum levels of thrombomodulin (TM) reflect endothelial damages in various diseases. We measured serum TM levels between day-10 and day 100 in 6 patients receiving allogeneic bone marrow transplantation. Serum TM levels were increased when patients had transplant related complications including graft versus host disease, hemorrhagic cystitis and interstitial pneumonitis. In patient without complications, serum TM levels were within normal limits. These results suggest that the serum TM level serves as a useful marker of treatment related toxicity and a predictor of complications after BMT.     

Neurogenically mediated cystitis in rats: an animal model

PURPOSE: Pseudorabies virus (PRV) is a useful tool for mapping the control circuitry of the spinal cord. In the process of mapping CNS regulatory pathways for the lower urinary tract, a hemorrhagic change in the bladder was observed that was not overtly evident in other pelvic organs. The relationship between the appearance of hemorrhagic changes in the bladder and the evolution of PRV induced changes in the spinal cord was therefore explored. MATERIALS AND METHODS: Sprague-Dawley rats were injected with PRV into the ACD tail-muscle. Bladder and CNS fixation were achieved by transcardial perfusion with formaldehyde. Multi-level sections were obtained from T8 through S4. Fixed tissue was stained and evaluated by light microscopy. Immunohistochemical stains were carried out for PRV and iNOS on spinal cord tissue. We were therefore able to evaluate the relationship between the manifestation of the hemorrhagic cystitis, appearance of the PRV in the spinal cord and evidence of CNS inflammation. RESULTS: The evolution of hemorrhagic cystitis paralleled the evidence of inflammation in the thoraco-lumbar and sacral cord. These bladders contained 5 to 9 ml. of bloody urine (a normal rat bladder contains 1 to 2 ml.). On cystomanometry (CMG) the bladders were acontractile. No PRV could be cultured in the hemorrhagic bladders. The histological changes observed in the bladder represent true inflammation. CONCLUSION: There was no obvious explanation for these changes other than the associated inflammatory changes in the spinal cord. The findings are consistent with the hypothesis that a spinal cord stress, via an unknown metabolic pathway, can result in dramatic, neurogenically mediated changes in the bladder.     

Can acupuncture prevent cystitis in women?

67 adult women with a history of recurrent lower urinary tract infection (UTI) were randomized for acupuncture treatment, sham acupuncture, or no treatment. The incidence rate of UTI over the following six months was noted. In the acupuncture group a total of 85% was free of cystitis during the six-month observational period, as compared to 58% in the sham group (p < 0.05), and 36% in the control group (p < 0.01). Compared to the acupuncture group, twice as many incidents of cytitis occurred in the sham group, and three times as many in the control group (p < 0.05). Acupuncture seems a worthwhile alternative in the prevention of frequently recurring cystitis in women.     

Amitriptyline in the treatment of interstitial cystitis

Limited data and an accumulated body of anecdotal experience with the tricyclic class of antidepressants suggest that this group of drugs (especially amitriptyline) may be an effective treatment modality in nonulcerative interstitial cystitis. Both the ease of administration and the relatively rapid onset of relief make these types of drugs appropriate to consider for first-line therapy after bladder distention has failed.     

The diagnosis of interstitial cystitis revisited: lessons learned from the National Institutes of Health Interstitial Cystitis Database study

PURPOSE: The lack of a precise working definition of interstitial cystitis may have resulted in the de facto use of the National Institute of Diabetes, Digestive and Kidney Diseases (NIDDK) "research" definition by clinicians. We evaluated these strict criteria in light of the broader inclusion criteria for patients evaluated in the Interstitial Cystitis Database study to determine their utility in clinical practice as a useful basis for the diagnosis of interstitial cystitis. MATERIALS AND METHODS: A total of 379 women who completed screening for the Interstitial Cystitis Database before January 1, 1996 met the basic criteria of urinary frequency, urgency or pain for at least 6 months in duration without a diagnosable etiology. Of these patients 148 underwent cystoscopy and hydrodistention of the bladder as a part of the evaluation. All patients were followed for a minimum of 1 year. Comparisons were made between patients judged to have a clinical diagnosis of interstitial cystitis and those who met the NIDDK research definition of the syndrome. RESULTS: Almost 90% of patients potentially meeting NIDDK criteria are believed by experienced clinicians to have interstitial cystitis, confirming the research value of these criteria in defining a homogeneous population for study. However, strict application of NIDDK criteria would have misdiagnosed more than 60% of patients regarded by researchers as definitely or likely to have interstitial cystitis. CONCLUSIONS: The NIDDK criteria are too restrictive to be used by clinicians as the diagnostic definition of interstitial cystitis.     

Influence of various antithrombotic therapy methods on the incidence of subacute coronary stent occlusions, hemorrhagic complications and length of hospitalization

BACKGROUND: The clinical benefit of coronary stenting is reduced by the risk of thrombotic stent occlusion as well as hemorrhagic complications of intensive antithrombotic therapy. We compared the influence of different antithrombotic therapies on the incidence of post-interventional complications and in-hospital stay duration. METHODS: After successful placement of a coronary stent, 334 consecutive patients were given different antithrombotic treatments in addition to aspirin 100 mg/d indefinitely: (1) phenprocoumon for 3 months (n = 47), (2) low molecular weight heparin 2 x 100 U/kg/d s.c. for 4 weeks (n = 90), (3) ticlopidine 2 x 250 mg/d and low molecular weight heparin 2 x 100 U/kg/d s.c. for 4 weeks (n = 72) and (4) ticlopidine 2 x 250 mg/d for 4 weeks (n = 125). RESULTS: Major events were subacute stent thrombosis in 17 patients (5%), and severe hemorrhagic complication in 20 patients (5.9%). The incidence of subacute stent thrombosis in groups 1 to 4 was 10.6%, 11%, 1.4% and 0.8% respectively. The use of ticlopidine was associated with a significant lowering of stent occlusions in univariate and multivariate analysis (p = 0.0013). Additional uni- and multivariate predictors were stent placement as a "bail-out" procedure (p = 0.033) and in patients with acute coronary syndrome (p = 0.049). Anticoagulant therapy was associated with a higher incidence of severe hemorrhagic complications (p < 0.01) and a prolonged in-hospital stay (p = 0.01). CONCLUSIONS: These results confirm that anti-thrombotic therapy with aspirin and ticlopidine combines low rates of subacute stent occlusion and hemorrhagic complications. Treatment with phenprocoumon and low molecular weight heparin does not improve the rate of subacute stent occlusion but increases hemorrhagic complications. Very low rates of stent occlusion permit short in-hospital stays with concomitant reduction in cost.     

Current aspects in the diagnosis and treatment of chronic cystitis in women

Chronic cystitis (CC) in females is annually encountered now in 15,000-20,000 per 1,000,000. Etiological and pathogenetic factors in CC are closely related. Bacteriologically, CC is represented primarily by Enterobacter. The infection, as a rule, ascends the lower urinary tracts. The contributing factors are: weak local antibacterial mechanisms of the urogenital system, anatomical variants and anomalies of the urethra and introitus, sexual activity, impaired urodynamics of the lower urinary tracts. The diagnosis of chronic inflammation of the bladder is made mainly endoscopically, with obligatory endovesical multifocal biopsy of the bladder followed by histological examination. The treatment of CC includes antibacterial, general and local antiinflammatory therapy, measures to normalize urodynamics of the lower urinary tracts, correction of hygienic and sexual factors, immunostimulation. 16 nonresponders to conservative treatment of interstitial cystitis with progressive contraction of the bladder were subjected to supratrigonal or subtotal resection of the bladder with one-stage ileocystoplasty.     

Stroke and use of low-dose oral contraceptives in young women: a pooled analysis of two US studies

BACKGROUND AND PURPOSE: The available data on low-dose oral contraceptive pill (OCP) use and stroke risk in US women are limited by small numbers. We sought more precise estimates by conducting a pooled analysis of data from 2 US population-based case-control studies. METHODS: We analyzed interview data from 175 ischemic stroke cases, 198 hemorrhagic stroke cases, and 1191 control subjects 18 to 44 years of age. RESULTS: For ischemic stroke, the pooled odds ratio (pOR) adjusted for stroke risk factors for current use of low-dose OCPs compared with women who had never used OCP (never users) was 0.66 (95% confidence interval [CI], 0.29 to 1.47) and compared with women not currently using OCPs (nonusers) the pOR was 1.09 (95% CI, 0.54 to 2.21). For hemorrhagic stroke, the pOR for current use of low-dose OCPs compared with never users was 0.95 (95% CI, 0.46 to 1.93) and compared with nonusers the pOR was 1.11 (95% CI, 0.61 to 2.01). The pORs for current low-dose OCP use and either stroke type were not elevated among women who were >/=35 years, cigarette smokers, obese, or not receiving medical therapy for hypertension. pORs for current low-dose OCP use were 2.08 (95% CI, 1. 19 to 3.65) for ischemic stroke and 2.15 (95% CI, 0.85 to 5.45) for hemorrhagic stroke among women reporting a history of migraine but were not elevated among women without such a history. Past OCP use (irrespective of formulation) was inversely related to ischemic stroke but unrelated to hemorrhagic stroke. CONCLUSIONS: Women who use low-dose OCPs are, in the aggregate, not at increased risk of stroke. Studies are needed to clarify the risk of stroke among users who may be susceptible on the basis of age, smoking, obesity, hypertension, or migraine history.