Partner symptom accommodation in generalized anxiety disorder: a preliminary examination of correlates with symptoms and cognitive behavioural therapy outcome.

BACKGROUND: Symptom accommodation is suggested to maintain anxiety pathology and interfere with treatment effectiveness for anxiety and related disorders. However, little is known about symptom accommodation in generalized anxiety disorder (GAD). AIM: This study investigated the associations between romantic partner symptom accommodation, GAD symptoms, intolerance of uncertainty (IU), relationship satisfaction, and cognitive behavioural therapy (CBT) outcomes from the perspective of the person with GAD. METHOD: One hundred and twelve people with GAD participated in group CBT and completed measures at pre- and post-treatment. RESULTS: All participants endorsed that their partner engaged in symptom accommodation to some extent, and the most commonly endorsed type was providing reassurance. Greater self-reported partner symptom accommodation was associated with greater GAD symptoms, chronic worry severity, IU, and relationship satisfaction at baseline. Partner symptom accommodation was found to significantly decrease over treatment; however, less improvement in symptom accommodation from pre- to post-treatment was associated with worse treatment outcomes. DISCUSSION: This study is the first to show that partner symptom accommodation is prevalent in adults with GAD and to elucidate the presentation and frequency of behaviours. The findings provide preliminary evidence that targeting partner symptom accommodation in treatment may improve CBT outcomes.

Effectiveness and predictors of group cognitive behaviour therapy outcome for generalised anxiety disorder in an out-patient hospital setting.

BACKGROUND: Cognitive behavioural therapy (CBT) is an empirically supported treatment for generalized anxiety disorder (GAD). Little is known about the effectiveness of CBT for GAD in real-world treatment settings. AIM: This study investigated the effectiveness of group CBT and predictors of treatment response in an out-patient hospital clinic. METHOD: Participants (n = 386) with GAD participated in 12 sessions of group CBT at an out-patient clinic. Of those who provided at least partial data (n = 326), 84.5% completed treatment. Most questionnaires were completed at pre- and post-treatment; worry severity was assessed weekly. RESULTS: Group CBT led to improvements in chronic worry (d = -0.91, n = 118), depressive symptoms (d = -1.22, n = 172), GAD symptom severity (d = -0.65, n = 171), intolerance of uncertainty (IU; d = -0.46, n = 174) and level of functional impairment (d = -0.35, n = 169). Greater pre-treatment GAD symptom severity (d = -0.17, n = 293), chronic worry (d = -0.20, n = 185), functional impairment (d = -0.12, n = 292), and number of comorbid diagnoses (d = -0.13, n = 299) predicted greater improvement in past week worry over treatment. Biological sex, age, depression symptom severity, number of treatment sessions attended, and IU did not predict change in past week worry over time. DISCUSSION: These findings provide support for the effectiveness of group CBT for GAD and suggest the outcomes are robust and are either not impacted or are slightly positively impacted by several demographic and clinical factors.

Objective and subjective vasomotor symptom outcomes in the CBT-Meno randomized controlled trial.

Objective: Vasomotor symptoms (hot flashes, night sweats) are common during the menopausal transition. Pharmacotherapy is effective but is associated with health risks for some women. There is an increasing demand for non-pharmacological interventions. The CBT-Meno protocol is a psychological intervention targeting a range of common menopausal symptoms. We compared the impact of CBT-Meno vs. waitlist on objective and subjective measures of vasomotor symptoms and on the relationship between vasomotor symptoms and sleep difficulties.Materials: The participants were 36 perimenopausal or postmenopausal women with co-occurring depressive symptoms who participated in the CBT-Meno trial (clinicaltrials.gov NCT02480192). Subjective measures included the Hot Flash Related Daily Interference Scale, the Greene Climacteric Scale, and the Pittsburgh Sleep Quality Inventory. Objective (physiological) and 'in-the-moment' measures of vasomotor symptoms were assessed with sternal skin conductance.Results: Greater improvements in vasomotor 'bothersomeness' and 'interference' were observed in the CBT-Meno condition compared to the waitlist condition. No between-group differences were observed in vasomotor frequency (subjectively or objectively recorded) or severity ratings. Sleep disturbance was unrelated to objectively measured vasomotor symptom frequency.Conclusion: The CBT-Meno trial improved subjective but not objective (physiological) measures of vasomotor symptoms. Self-reported sleep difficulties were unrelated to subjective or objective vasomotor symptoms.

Patient coping and expectations predict recovery after major orthopaedic trauma.

BACKGROUND: Persistent post-surgical pain and associated disability are common after a traumatic fracture repair. Preliminary evidence suggests that patients' beliefs and perceptions may influence their prognosis. METHODS: We used data from the Fluid Lavage of Open Wounds trial to determine, in 1560 open fracture patients undergoing surgical repair, the association between Somatic PreOccupation and Coping (captured by the SPOC questionnaire) and recovery at 1 yr. RESULTS: Of the 1218 open fracture patients with complete data available for analysis, 813 (66.7%) reported moderate to extreme pain at 1 yr. The addition of SPOC scores to an adjusted regression model to predict persistent pain improved the concordance statistic from 0.66 to 0.74, and found the greatest risk was associated with high (≥74) SPOC scores [odds ratio: 5.63; 99% confidence interval (CI): 3.59-8.84; absolute risk increase 40.6%; 99% CI: 30.8%, 48.6%]. Thirty-eight per cent (484 of 1277) reported moderate to extreme pain interference at 1 yr. The addition of SPOC scores to an adjusted regression model to predict pain interference improved the concordance statistic from 0.66 to 0.75, and the greatest risk was associated with high SPOC scores (odds ratio: 6.06; 99% CI: 3.97-9.25; absolute risk increase: 18.3%; 95% CI: 11.7%, 26.7%). In our adjusted multivariable regression models, SPOC scores at 6 weeks post-surgery accounted for 10% of the variation in short form-12 physical component summary scores and 14% of short form-12 mental component summary scores at 1 yr. CONCLUSIONS: Amongst patients undergoing surgical repair of open extremity fractures, high SPOC questionnaire scores at 6 weeks post-surgery were predictive of persistent pain, reduced quality of life, and pain interference at 1 yr. CLINICAL TRIAL REGISTRATION: NCT00788398.

Perioperative psychotherapy for persistent post-surgical pain and physical impairment: a meta-analysis of randomised trials.

BACKGROUND: Persistent post-surgical pain affects 10-80% of individuals after common operations, and is more common among patients with psychological factors such as depression, anxiety, or catastrophising. METHODS: We conducted a systematic review and meta-analysis of randomised, controlled trials to evaluate the efficacy of perioperative psychotherapy for persistent post-surgical pain and physical impairment. Paired independent reviewers identified studies, extracted data, and assessed risk of bias. The Grading of Recommendations, Assessment, Development and Evaluation system was used to assess the quality of evidence. RESULTS: Our search of five electronic databases, up to September 1, 2016, found 15 trials (2220 patients) that were eligible for review. For both persistent post-surgical pain and physical impairment, perioperative education was ineffective, while active psychotherapy suggested a benefit (test of interaction P=0.01 for both outcomes). Moderate quality evidence showed that active perioperative psychotherapy (cognitive-behaviour therapy, relaxation therapy, or both) significantly reduced persistent post-surgical pain [weighted mean difference (WMD) -1.06 cm on a 10 cm visual analogue scale for pain, 95% confidence interval (CI) -1.56 to -0.55 cm; risk difference (RD) for achieving no more than mild pain (≤3 cm) 14%, 95% CI 8-21%] and physical impairment [WMD -9.87% on the 0-100% Oswestry Disability Index, 95% CI -13.42 to -6.32%, RD for achieving no more than mild disability (≤20%) 21%, 95% CI 13-29%]. CONCLUSIONS: Perioperative cognitive behavioural therapy and relaxation therapy are effective for reducing persistent pain and physical impairment after surgery. Future studies should explore targeted psychotherapy for surgical patients at higher risk for poor outcome. CLINICAL TRIAL REGISTRATION: PROSPERO CRD42016047335.

Optimizing screening for depression, anxiety disorders, and post-traumatic stress disorder in inpatient addiction treatment: A preliminary investigation.

OBJECTIVE: Substance use disorders (SUD) are frequently comorbid with other psychiatric conditions, but a comprehensive diagnostic assessment is often not feasible clinically. Efficient psychometrically-validated screening tools exist for commonly comorbid conditions, but cutoff accuracies have typically not been evaluated in addiction treatment settings. This study examined the performance of several widely-used screening measures in relation to diagnostic status from a clinical interview to identify and validate cutoff scores in an inpatient SUD treatment setting. METHOD: Participants were 99 patients in a large residential SUD treatment program in Ontario, Canada. Participants completed a screening battery, including the Patient Health Questionnaire - 9 (PHQ-9), Generalized Anxiety Disorder - 7 (GAD-7), and Post-Traumatic Stress Disorder Checklist-5 (PCL-5), and underwent a semi-structured diagnostic clinical interview. Receiver operating characteristic curves were used to determine optimal cutoff scores on the screening tool against the interview-based diagnosis. RESULTS: Area under the curve (AUC) was statistically significant for all screens and were as follows: PHQ-9 = 0.70 (95% CI = 0.59-0.80), GAD-7 = 0.74 (95% CI = 0.63-0.84), and PCL-5 = 0.79 (95% CI = 0.66-0.91). The optimal accuracy cutoff scores based on sensitivity and specificity were: PHQ-9 ≥ 16, GAD-7 ≥ 9, the PCL-5 ≥ 42. CONCLUSIONS: In general, the candidate screeners performed acceptably in this population. However, the optimal cutoff scores were notably higher than existing guidelines for depression and PTSD, potentially due to the general elevations in negative affectivity among individuals initiating SUD treatment. Further validation of these cutoff values is warranted. PUBLIC HEALTH SIGNIFICANCE: This study provides modified screening cutoff scores for major depression, anxiety disorders, and post-traumatic stress disorder in addiction treatment settings.

Nosocomial acquisition of beta-lactamase--negative, ampicillin-resistant enterococcus.

BACKGROUND: A recent prospective study at the Department of Veterans Affairs Medical Center, Martinez, Calif, revealed that 9% of enterococcal clinical isolates were ampicillin resistant. We prospectively studied 100 patients hospitalized in one general medicine ward and in the medical intensive care unit to study determinants of acquisition of ampicillin-resistant enterococcus. METHODS: Rectal swabs and urine cultures were obtained from patients within 72 hours of admission to the study ward and twice weekly until discharge from the ward or the intensive care unit. Cultures were obtained from the hands of personnel and from environmental surfaces in the general medical ward and the intensive care unit. Ampicillin-resistant enterococcal isolates were examined for molecular relatedness by plasmid DNA analysis. RESULTS: The cultures from 23 patients yielded ampicillin-resistant enterococci. The rectal swabs yielded ampicillin-resistant enterococci before the urine cultures did except in one patient whose urine and rectal cultures were both positive on the same day. Acquisition of ampicillin-resistant enterococci was significantly associated with previous antimicrobial agents, Foley catheterization, and being bedridden. Resistant enterococci were not isolated from hospital personnel or environmental surfaces. Plasmid analysis by gel electrophoresis demonstrated nine strains, two of which predominated. Rectal and urine isolates from the same patient had identical plasmid electrophoresis patterns. CONCLUSIONS: We conclude that ampicillin-resistant enterococci are common in the rectal flora, can spread to the urinary system, are associated with patient characteristics that predipose to nosocomial infection, and may become an emerging clinical problem.

Perinephric abscess. Modern diagnosis and treatment in 47 cases.

The records of 47 patients with a perinephric abscess diagnosed from 1975 to 1986 at 8 San Francisco Bay Area hospitals were reviewed. The mean age was 51 years. Fifty-five percent were females and 45%, males. The left kidney was affected in 47% of cases, the right kidney in 40%, both in 4%, and a transplanted pelvic kidney in 9%. Fever (55%), chills or diaphoresis (47%), flank pain (40%), abdominal pain (40%), and nausea or vomiting (32%) were the most common presenting symptoms. About half the patients had symptoms for 1 week or less and 12% had no symptoms. Fever was documented before diagnosis in 88% of patients. Abdominal mass (13%) or tenderness (49%), and flank mass (9%) or tenderness (42%) were seen less frequently, and 11% of patients did not have fever, flank, or abdominal findings. The most frequent underlying conditions included previous urologic surgery (45%), previous urinary tract infection (38%), diabetes mellitus (36%), and urinary tract stones (36%). Cultures of perinephric abscesses yielded gram-negative aerobes in 52% of patients, primarily Escherichia coli. Staphylococcus aureus was isolated in 26% of patients and anaerobes in 17%. A single pathogen was isolated in 71% and multiple isolates in 29%. Of interest and great potential therapeutic importance was culture of anaerobes, primarily Bacteroides spp. in 17%, Enterococcus spp. in 7%, and Candida albicans in 7%. Positive blood and urine cultures identified perinephric abscess organisms exactly in 58% and 37% of cases, respectively. Routine laboratory tests such as the white blood cell count and urinalysis were insensitive and non-specific for perinephric abscess. Leukocytosis and anemia at admission were seen in slightly more than half of the patients. For radiologic diagnosis, computerized tomographic scanning was most helpful. Ultrasound and intravenous pyelography were falsely negative in about one-third of cases. Mortality (13%) was low in this series when compared with earlier studies, and probably reflects modern medical care. Six patients (13%) died during hospitalization, 2 of whom had diagnosis of PNA established only at autopsy. Drainage of the perinephric abscess was carried out by open surgical drainage in 64% of patients, percutaneous drainage in 19%, and both in 13%. The initial procedure, whether open surgical drainage or percutaneous catheter drainage, was usually successful. Late complications included nephrocutaneous fistulas in 3 patients and disseminated candidiasis in 1 patient.

Hospital survey of antimicrobial prophylaxis to prevent endocarditis in patients with prosthetic heart valves.

The American Heart Association (AHA) has published guidelines for use of prophylactic antibiotics to prevent bacterial endocarditis, but few data are available about physician compliance with these guidelines. A retrospective review was conducted of the use of prophylactic antibiotics in patients with prosthetic heart valves who were undergoing diagnostic or operative procedures or heart catheterization at three hospitals. Compliance with AHA recommendations was only 30 percent (14 of 46) for procedures considered high risk for patients with prosthetic heart valves. Six (23 percent) of 26 patients who underwent right or left heart catheterization received prophylactic antibiotics (not recommended by AHA). Antibiotics were given to 42 (74 percent) of 57 patients who underwent surgical procedures considered at low risk of bacteremia, but only 33 (58 percent) received antibiotics that cover organisms commonly present at the site of the procedure. The results indicate that clinicians frequently do not administer prophylactic antibiotics in patients with prosthetic heart valves who are undergoing invasive procedures or do not follow published AHA guidelines when antibiotics are administered.

Oral norfloxacin versus parenteral treatment of nosocomial urinary tract infection.

In a multiclinic, randomized trial, oral norfloxacin, a fluoroquinolone antibacterial, was compared with several standard parenteral regimens for the treatment of nonbacteremic, hospital-acquired urinary tract infections. Parenteral antibiotic agents included aminoglycosides alone; aminoglycosides in combination with either broad-spectrum penicillins or first-generation cephalosporins; or cefotaxime alone. Ninety-two percent of bacterial isolates were multiresistant gram-negative rods including Pseudomonas aeruginosa (31 percent), Escherichia coli (17 percent), Klebsiella/Enterobacter species (14 percent), and Serratia species (11 percent). In the first evaluable 94 patients, norfloxacin was comparable to the parenteral agents in eliminating infecting bacteria from the urine. Similarly, combined bacterial eradication and clinical cure or improvement occurred in 96 percent (76 percent with cures, 20 percent with improvement) of those treated with norfloxacin and 88 percent (67 percent with cures, 21 percent with improvement) of those treated with parenteral agents. A negative outcome (i.e., failure, superinfection, or reinfection) occurred in two (4 percent) norfloxacin-treated patients versus six (12 percent) parenterally treated patients. Adverse effects were few, infrequently drug related, and rarely serious (one with norfloxacin versus two with parenteral agents). Additionally, drug, preparation, and administration costs were substantially less with oral norfloxacin compared with the parenteral agents. The data suggest, therefore, that oral norfloxacin can be substituted for commonly used parenteral antibiotic regimens, without any compromise in efficacy, in the treatment of nonbacteremic patients with multiresistant, nosocomial urinary tract infections.

Open lung biopsy in patients with acute leukemia.

The results of open lung biopsy in 15 patients with acute leukemia, pulmonary infiltrates, neutropenia, and fever were reviewed. The patients averaged 26 hospital days of neutropenia and 20 hospital days of fever before open lung biopsy, and all patients received broad-spectrum antibacterial agents (mean 17 days) before open lung biopsy. Nine (67 percent) received amphotericin B prior to open lung biopsy (mean 22 days). Open lung biopsy yielded a specific clinically helpful diagnosis in six patients, but only two of these patients survived the hospitalization during which open lung biopsy was performed. Open lung biopsy detected fungus in four patients and leukemic infiltrates in two patients. Management was appropriately modified in these patients. In nine patients, a specific diagnosis of the pulmonary infiltrate was not obtained by open lung biopsy. Antimicrobial regimens were not changed substantially for these patients. In six patients, the results of open lung biopsy may have been misleading. Two patients had pulmonary fungal diseases at autopsy, undetected by open lung biopsy eight days and five weeks prior to death. Another patient had invasive aspergillosis and one had cytomegalovirus pneumonitis not detected by open lung biopsy. Two patients had false-positive preliminary histologic reports of pulmonary infection. On the basis of this experience, in this specific population of patients, open lung biopsy was often of little help in directing medical therapy or influencing clinical outcome.

The effects of cyclosporine on Toxoplasma gondii in vivo and in vitro.

We examined the effect of cyclosporine on Toxoplasma infection in vivo and in vitro. Administration to mice of 150 mg/kg/day cyclosporine variably affected mortality in four separate experiments. IgG (Sabin-Feldman dye test) and IgM enzyme-linked immunosorbent assay antibody titers were significantly depressed in mice treated with cyclosporine. These results suggested the possibility that cyclosporine possesses anti-Toxoplasma activity. Thus, macrophages were incubated with cyclosporine before and after infection with Toxoplasma. Treatment with 0.5, 1, and 5 micrograms cyclosporine/ml during or after challenge of macrophage monolayers with Toxoplasma inhibited replication of Toxoplasma (and resulted in killing of Toxoplasma). The effect of cyclosporine on development of activated macrophages was studied. Cyclosporine administered to mice at a dose of 150 mg/kg/day neither accelerated nor delayed activation of macrophages (assessed by inhibition of Toxoplasma replication in vitro) by i.v. injection of either Corynebacterium parvum or Toxoplasma. Cyclosporine affects mortality variably in murine toxoplasmosis, depresses synthesis of IgG and IgM Toxoplasma antibody in vivo, does not prevent activation of macrophages in vivo, and possesses anti-Toxoplasma activity in vitro and perhaps in vivo. Cyclosporine may be the preferred immunosuppressive agent for recipients of an organ transplant who are at high risk for toxoplasmosis (e.g., seronegative recipients who have received organ from seropositive donors).

International transoceanic kidney sharing.

The shortage of cadaver kidneys for transplantation persists in most regions of the United States. Because so many patients have preformed antibodies against prospective donors, identification of appropriate donor-recipient pairs is proving difficult in spite of computerized interregional sharing. To avoid wasting valuable human organs, we have shared 11 kidneys between Italy, the Soviet Union, West Germany and the USA, 10 of which resulted in successful transplants. Such sharing guarantees better utilization of kidneys bilaterally and aids in transplanting cytotoxic patients by increasing the total number of kidneys available.

Current recommendations and future prospects in the treatment of toxoplasmosis.

Toxoplasma infection is highly prevalent throughout the world and causes disease in diverse populations. Effective treatment regimens are available for each clinical entity of toxoplasma, but problems of incomplete clinical efficacy, drug potency, drug safety, and length of treatment remain. No well-controlled clinical trials in humans have been performed to evaluate the efficacy and safety of treatment. Primary treatment of toxoplasmosis is with the synergistic combination of pyrimethamine and sulphonamide. This is considered the treatment of choice for severe disease, disease in immunocompromised patients, and congenital toxoplasmosis. Spiramycin, a macrolide antibiotic, is frequently used alone or alternately with pyrimethamine and sulphonamide for pregnant women with the acute acquired infection to prevent congenital toxoplasmosis. Clindamycin is used frequently to treat acute flares of toxoplasmic chorioretinitis and as second-line therapy for toxoplasmic encephalitis in patients with the acquired immunodeficiency syndrome (AIDS). Inadequacies in the treatment of toxoplasmosis in immunosuppressed patients, exemplified by experience with AIDS patients, should provide the impetus for well-designed trials to find and evaluate more potent and better-tolerated agents. Classes of new drugs that have been investigated and show some promise include: (a) macrolides (roxithromycin, azithromycin); (b) folic acid antagonists (piritrexim and trimetrexate), and (c) purine analogues (arprinocid). Immunomodulators have attracted interest, and interferon-gamma alone and in combination with roxithromycin is effective in murine models. Interleukin-2 is also effective in the murine model.

Atypical presentations of Pneumocystis carinii pneumonia in patients receiving inhaled pentamidine prophylaxis.

Inhaled pentamidine is used commonly to prevent Pneumocystis carinii pneumonia (PCP) in patients with advanced human immunodeficiency virus infection. Case reports indicate that PCP can recur in patients who receive inhaled pentamidine and that clinical features may be atypical. To determine the magnitude of this problem, we reviewed retrospectively the medical records of patients with proven PCP during a 30-month period at two hospitals. Four (31 percent) of 13 patients with previous PCP who received inhaled pentamidine prophylaxis had recurrent P carinii infection, including one patient with widely metastatic extrapulmonary disease. Chest roentgenographic findings included cavities, pneumothoraces, bilateral and upper lobe interstitial infiltrates, and pleural effusion. False-negative bronchoalveolar lavage and induced sputum examinations were frequent. We conclude that recurrent PCP in patients maintained on a regimen of inhaled pentamidine prophylaxis occurs frequently, causes chest roentgenographic abnormalities other than interstitial infiltrates, and may be difficult to diagnose. Clinicians who choose to use this effective and convenient mode of prophylaxis should be aware of the problems attendant to its use.

Open lung biopsy in patients with non-Hodgkin's lymphoma and pulmonary infiltrates.

Patients with non-Hodgkin's lymphoma (NHL) are at increased risk for pulmonary infection with opportunistic pathogens associated with diminished cell mediated immunity. Open lung biopsy (OLB) frequently is recommended for diagnosis of pulmonary infiltrates in patients with NHL, but its usefulness for patient management and outcome has not been evaluated for patients with NHL. We reviewed the results of 20 consecutive OLB in 19 patients with previously diagnosed non-Hodgkin's lymphoma at Stanford University Medical Center during a nine-year period. Fifteen patients had known active lymphoma at time of OLB, and no patient had granulocytopenia. Ten of the 20 OLBs yielded specific diagnoses. A greater proportion of patients with stage I or II disease had specific diagnoses than patients with more advanced NHL. Five of 14 patients considered to have had a life threatening illness at the time of OLB had specific diagnoses from OLB vs five of six patients considered clinically stable. Chest roentgenograms that had discrete masses or nodules correlated with ability to establish a specific diagnosis by OLB. For patients in whom the results of OLB were nonspecific, management appeared unaffected by the OLB. The OLB in NHL appeared most useful for detecting recurrent NHL in clinically stable patients with discrete nodules or masses on chest roentgenogram. Pneumocystis pneumonia was the only infection identified by OLB.

In vivo and in vitro effects of cyclosporin A on Trypanosoma cruzi.

The in vivo and in vitro effects of cyclosporin A on T. cruzi were examined. Mice receiving 150 or 75 mg/kg/day of cyclosporin A and infected with T. cruzi 48 hr later had significantly higher parasitemias and earlier mortality than controls. Mice receiving cyclosporin A after infection had parasitemias similar to controls. Infections with both the reticulotropic Y and the miotropic CL strains of T. cruzi were enhanced by cyclosporin A. The in vitro replication of epimastigotes, but not the intracellular replication of amastigotes, in mouse macrophages was inhibited by 5 micrograms cyclosporin A/ml. Enhancement of the infection by cyclosporin A was not due to an effect on macrophages since the drug did not prevent development of activated macrophages capable of killing intracellular T. cruzi.

In vitro and in vivo effects of itraconazole against Trypanosoma cruzi.

The synthetic imidazole, itraconazole, was examined for in vitro and in vivo activity against Trypanosoma cruzi. Mice treated with concentrations as low as 15 mg itraconazole/kg/day were completely protected against death due to infection with any of three different and highly virulent strains of T. cruzi. Treatment of infected mice with 120 mg itraconazole/kg/day for seven to nine weeks apparently resulted in the parasitologic cure as determined by negative hemocultures and subinoculations, negative serology for T. cruzi, and absence of parasites in histologic sections following completion of therapy. Peak serum levels of itraconazole after treatment of mice with the dose of the drug that provided protection against death were less than 1 microgram/ml. Experiments in vitro revealed that concentrations of itraconazole as little as 0.001 microgram/ml inhibited replication of intracellular amastigotes in macrophages. These results indicate that itraconazole has a remarkable activity against T. cruzi. Further investigation of intraconazole as a therapeutic agent for Chagas' disease may be warranted.

Ketoconazole protects against infection with Trypanosoma cruzi in a murine model.

The oral administration of ketoconazole to mice protected them against death caused by infection with Trypanosoma cruzi. The addition of ketoconazole to cultures of macrophages infected with the organism markedly inhibited the intracellular multiplication of amastigotes. These observations suggest that ketoconazole may be a potent agent against T. cruzi and should be evaluated more extensively as a chemotherapeutic agent for Chagas' disease.

Treatment of recurrent urinary tract infection with norfloxacin versus trimethoprim-sulfamethoxazole.

Norfloxacin, a broad-spectrum antimicrobial analog of nalidixic acid, was evaluated by comparing it to trimethoprim-sulfamethoxazole in 93 office patients with recurrent urinary tract infections. In this prospective randomized study, norfloxacin and trimethoprim-sulfamethoxazole were given on the same dosage schedule with the former drug given as a 400-mg tablet twice daily and the latter drug given as a double strength tablet twice daily. Overall, 50 patients received norfloxacin and 43 patients received trimethoprim-sulfamethoxazole with a cure rate of 96 percent and 79 percent, respectively. Whether a patient had one infection or multiple previous infections, norfloxacin appeared to be superior to trimethoprim-sulfamethoxazole. Only minor side effects were noted in either group, and no patient withdrew from this study as a direct result of these side effects. Minor complaints of nausea, dizziness, and headache were found in the norfloxacin group (24%) and in the trimethoprim-sulfamethoxazole group (16%). Both agents are effective in treating urinary tract infections but norfloxacin is superior to trimethoprim-sulfamethoxazole in patients with either recurrent complicated infections or one previous uncomplicated urinary tract infection.