Treatment of Chronic Anal Fissure by Application of l-Arginine Gel: A Phase II Study in 15 Patients

PURPOSE Local application of exogenous nitric oxide donors, such as isosorbide dinitrate and glyceryl trinitrate, promotes fissure healing by reducing anal resting pressure and improving anodermal blood flow. The major drawback of these nitric oxide donors is headache. The overall incidence of this side effect is approximately 40 percent. Recently we have shown in healthy volunteers that l-arginine, being an intrinsic precursor of nitric oxide, reduces anal resting pressure without headache as a side effect. The aim of the pres-ent study was to evaluate the effect of l-arginine on anal resting pressure, anodermal blood flow, and fissure healing in patients with chronic anal fissure.METHODS Fifteen patients with a chronic anal fissure were included in the present study. Before entering the study 10 patients were unsuccessfully treated by local application of isosorbide dinitrate. Six of these patients experienced severe headache during treatment with isosorbide dinitrate. All patients were treated for at least 12 weeks by local application of a gel containing l-arginine 400 mg/ml five times a day. In patients with a persistent fissure, treatment was continued until 18 weeks. Anal manometry and laser Doppler flowmetry of the anoderm were performed before treatment, 20 minutes after local application of the first dose, and after 12 weeks of treatment. A visual analog scale was used to assess fissure-related pain and headache.RESULTS One patient dropped out after one day of treatment, and one was excluded because of violation of the study protocol. After 12 weeks of treatment complete fissure healing was observed in 3 of 13 (23 percent) patients, and after 18 weeks the healing rate was 8 of 13 (62 percent) patients. None of the 13 patients experienced typical nitric oxide-induced headache. The pressure recordings showed a significant reduction of maximum anal resting pressure (mean ± SD): pretreatment 89 ± 17 mmHg; 20 minutes after application of the first dose 67 ± 17 mmHg; 12 weeks after treatment 74 ± 14 mmHg (P < 0.005). Recordings of anodermal blood flow showed a significant increase in flow: pretreatment 0.36 ± 0.25 volts; 20 minutes after application of the first dose 0.59 ± 0.27; 12 weeks after treatment 0.64 ± 0.33 (P < 0.005).CONCLUSIONS Local application of l-arginine promotes fissure healing without headache as a side effect, and l-arginine is effective even in patients not responding to isosorbide dinitrate treatment.Norgine Research Ltd. Northwood, United Kingdom, financially supported the study.Reprints are not available.Read at the annual meeting of The American Society of Colon and Rectal Surgeons, Chicago, Illinois, June 3 to 8, 2002.     

A new variant of type II von Willebrand disease with aberrant multimeric structure of plasma but not platelet von Willebrand factor (type IIF)

A patient with a lifelong bleeding disorder was diagnosed as having Type II von Willebrand disease. The larger multimers of von Willebrand factor were absent from her plasma but present in platelets. A high- resolution electrophoretic technique was used to study the complex structure of individual von Willebrand factor multimers. In normal plasma, each multimer could be resolved into five bands: a more intense central one and four less intense, two moving faster and two slower than the central band. In normal platelets, each multimer could also be resolved into five bands. The central one had a mobility similar to that in plasma, whereas the four satellite bands had a mobility that differed from that of the corresponding plasma bands. In the patient, platelet von Willebrand factor antigen content and ristocetin cofactor activity were normal, and von Willebrand factor showed the same structure of individual multimers as seen in normal platelets. On the other hand, plasma von Willebrand factor antigen and ristocetin cofactor activity were decreased, and the structure of individual von Willebrand factor multimers was different from that of normal plasma and similar to that seen in normal and patient's platelets. After infusion of 1-deamino-8-D-arginine vasopressin, the largest von Willebrand factor multimers, as well as new satellite bands with a mobility similar to those in normal plasma, appeared in the patient plasma, and the levels of von Willebrand factor antigen and ristocetin cofactor activity became normal. Yet no relevant change in the prolonged bleeding time was observed. This new variant of von Willebrand disease, therefore, is characterized by the presence of a dysfunctional von Willebrand factor molecule that exhibits unique structural abnormalities in plasma but appears to be normal in platelets. The designation of Type IIF is proposed for this type of von Willebrand disease in accordance with the terminology that has been previously used.     

Spontaneous platelet aggregation in type IIB Tampa von Willebrand disease is inhibited by the 52/48-kDa fragment of normal von Willebrand factor, which contains the GPIb binding domain

The association of Type IIB von Willebrand disease (vWD) with chronic persistent thrombocytopenia and spontaneous platelet aggregation has recently been recognized. It has been shown that IIB von Willebrand factor (vWF) can initiate platelet aggregation by binding to the platelet glycoprotein (GP) lb receptor and inducing exposure of the GpIIb/IIIa fibrinogen receptor. In this study we demonstrate the increased binding of Type IIB Tampa vWF with normal platelets when compared with nonthrombocytopenic Type IIB vWF. Studies further demonstrate that spontaneous platelet aggregation initiated by IIB Tampa vWF can be blocked by a 52/48-kDa fragment of normal vWF, which contains the binding domain.     

Crohn''s Colitis Complicated by Superimposed Invasive Amebic Colitis

The clinical characteristics and endoscopic appearance of inflammatory bowel disease (IBD) may be very similar to those of amebic colitis. Physicians, especially in areas in which amebiasis is endemic, are familiar with this difficulty. Moreover, in individual cases, it may even be impossible to distinguish between the two conditions, since stool specimens, bowel biopsies, and serological studies may be negative for Entamoeba histolytica, even in the presence of invasive amebic colitis. Invasive amebiasis may rarely be superimposed on IBD, which further complicates the issue. We report here a young patient with a 7-yr history of Crohn's colitis proven histologically who developed invasive amebic colitis during steroid and 6-mercaptopurine treatment for active disease. Stool specimens, mucosal biopsies, and serological studies were negative for E. histolytica, and the diagnosis was established on pathological examination of a surgically resected bowel. Anti-amebic therapy should be considered in endemic areas in cases of persistent IBD.     

The diagnostic laboratory tests for histoplasmosis: analysis of experience in a large urban outbreak

Of 495 patients reported in a large urban histoplasmosis outbreak, we studied 276 whose serologic tests were done in a single laboratory. Serologic test results were positive in 96% of these patients (compared with less than 5% of controls from an endemic area), cultures were positive in 22%, and special stains in 19%. The immunodiffusion test results were negative in 13% of patients who had positive findings by complement fixation, and 1% had positive results only by immunodiffusion. The complement fixation test was almost twice as sensitive as the immunodiffusion test in patients with subclinical infection. The serologic response differed significantly among the clinical syndromes with higher titers in cavitary and lower titers in disseminated disease. Factors associated with titers of 1:64 or greater to both antigens were black race and immunocompetence. High mycelial titers were also associated with more intense exposure, and high yeast titers were associated with age less than 36 years. No prognostic significance could be proved for fourfold titer rises or falls or persistence of precipitins.     

Skin lesions treated with azathioprine and prednisone. Comparison of nontransplant patients and renal transplant recipients.

Cutaneous complications were studied in 120 patients who received azathioprine and prednisone for six months to ten years. Questionnaire, chart review, and physical examination were used to assess skin infections, rash, verrucae, herpes zoster, tumors, condylomata acuminata, hair loss, and color changes. One hundred patients with renal allografts were compared with 20 nontransplant patients with systemic disease. Dermatologic problems were more frequent in transplant recipients (P less than .02) than in nontransplant patients. Verrucae were more frequent in transplant recipients (P less than .001). There was no significant increase in the total number of skin manifestations with increasing length of therapy, although warts and herpes zoster increased with time. This study suggests that the increase in the total number of skin lesions noted in previous studies of renal transplant recipients is not as prevalent in nontransplant patients who receive azathioprine and prednisone, due primarily to fewer verrucae in nontransplant patients.     

Experts recommend minimum nurse staffing standards for nursing facilities in the United States

The experts concluded that current data show that the average nurse staffing levels (for RNs, LVN/LPNs, and NAs) in nursing homes are too low in some facilities to provide high quality of care. Caregiving, the central feature of a nursing home, needs to be improved to ensure high quality of care to residents. Because detailed time studies have not been conducted on the amount of time that is required to provide high quality of care to residents, expert opinion is currently the best approach to addressing the problem of inadequate staffing. Increases in the education level and training of nursing staff are also strongly recommended as a step to improving quality of care and reducing turnover rates in nursing homes. These recommendations are designed for consideration by Congress, HCFA regulators, policymakers, nursing home administrators, and nurses. Ideally, Congress would pass legislation establishing these recommendations as minimum standards for all nursing homes or direct HCFA to establish detailed minimum nurse staffing standards to ensure that staffing levels take into account the number and the case-mix of the residents. Alternatively, HCFA could introduce minimum staffing standards through the regulatory process. In 1999 there were a number of efforts at the state level to increase minimum staffing levels. Mohler (1999) surveyed selected states and found that 21 states had either proposed new legislation or were considering proposals for new legislation or new regulations. In California, for example, in 1999 the state budget approved $31 million in new state funds (to be matched with $31 million in federal Medicaid dollars) to increase nursing home staffing minimum requirements from 2.8 to 3.2 hr per resident day and to increase wage rates. Overall, nursing facilities need to be held accountable by HCFA for providing adequate levels and types of staffing to meet the needs of their residents, especially because government is paying for 61% of the expenditures. Adopting these minimum standards will have an important impact on improving the quality of the nation's nursing home care. Additional research is needed to determine appropriate levels and types of staff to provide high quality of care to residents. These studies could test the proposed staffing standards against existing staffing levels to examine the impacts on quality. As new data become available on staffing levels, revisions of staffing standards should be made if necessary to ensure that high standards are maintained.     

Gender differences in recovery after coronary artery bypass graft surgery

This study examined the effect of gender on symptom evaluation, symptom response, and physical functioning following coronary artery bypass graft surgery. Symptom evaluation and symptom response were measured at baseline and 2, 4, and 6 weeks and 3 months following surgery, and physical functioning was measured at baseline, 6 weeks, and 3 months. The sample included 46 men and 19 women randomly assigned to the routine care group of a larger study examining symptom management intervention influence on recovery outcomes in elderly coronary artery bypass graft patients. No significant differences were found in symptom evaluation, symptom response, or physical functioning by gender over time. Women reported consistently higher symptom evaluation scores for shortness of breath, fatigue, depression, sleep disturbance, swelling, and anxiety and lower mean physical and vitality subscale scores than men at every time point. Gender-specific symptom management strategies should be developed and tested to address the differences in the reporting of symptoms by men and women.