Response and relapse rates of candidal esophagitis in HIV-infected patients treated with caspofungin

Caspofungin is a new antifungal drug of the echinocandin class. We analyzed the clinical efficacy of caspofungin (50 mg/day) in the treatment of HIV-infected adults with endoscopically documented Candida esophagitis and enrolled in four clinical trials of caspofungin. Symptoms were evaluated daily; a favorable outcome required complete resolution of all esophageal symptoms assessed at the time of discontinuation of therapy. Relapse was defined as recurrent symptoms during the subsequent 2 weeks. A multivariate logistic regression model was developed to identify potential factors (including severity of symptoms at presentation, CD4(+) cell count on entry, extent of disease [assessed endoscopically at baseline], causative Candida species, duration of therapy [overall and after resolution of symptoms], time on treatment before symptom resolution, and antifungal prophylaxis) that might predict symptomatic relapse in the 2 weeks following completion of therapy. The median CD4(+) lymphocyte count for the entire population was 31/mm(3). Candida albicans was isolated from 109 of 110 patient samples cultured for the pathogen and constituted the sole isolate in 77%. Extensive esophageal involvement was present in 55% of patients at the time of pretreatment endoscopy. The duration of therapy ranged from 7 to 20 days (median, 12 days). Symptoms resolved in 117 of 123 patients (95%; 95% confidence interval, 90-98%) with a median time of ~4 days. Response rates were 43 of 46 (93%) and 70 of 73 (96%) for patients with greater or fewer than 50 CD4(+) cells/mm(3), and 80 of 85 (94%) and 23 of 24 (96%) in infections caused by C. albicans alone or in association with non-albicans isolates, respectively. Symptoms recurred within 2 weeks of stopping caspofungin in 19 of 115 evaluable patients (17%), including 3 of 16 (19%) receiving antifungal prophylaxis. Relapse rates were similar for patients with greater or fewer than 50 CD4(+) cells/mm(3). In this relatively small number of patients, only symptom severity and extent of disease judged endoscopically at baseline were significantly (p < 0.10) associated with early relapse in the multivariate model.     

Incidence and management of perineal hernia after laparoscopic proctectomy

Perineal hernia (PH) is formed by the protrusion of intra-abdominal viscera through a defect in the pelvic floor. This is a rare complication after conventional abdominoperineal resection, pelvic exanteration, proctectomy, and other pelvic procedures. The purpose of the present paper is to report 4 cases of PH after laparoscopic abdominoperineal resection for rectal cancer and to review literature data about the incidence, predisposing factors, and treatment of this challenging problem. When added to other 3 cases previously reported in the Brazilian series of laparoscopic surgery, this group of 7 cases comprises a PH incidence of 3.5% after rectal resection procedures. Surgical treatment is indicated only in symptomatic patients with no signs of cancer recurrence. Proposed methods of surgical repair include abdominal, perineal, or combined approaches to the hernia in association with the use of autologous tissues or prosthetic meshes. Preventive measures are represented by closure of the pelvic peritoneum whenever possible, primary perineal suture and wound care to avoid infection.     

Acid-base disturbances in cardiogenic pulmonary edema

Eighty-one consecutive cases of uncomplicated cardiogenic pulmonary edema (CPE) were retrospectively graded for severity of chest roentgenogram (CXR) changes and grouped according to primary acid-base abnormalities, either single or mixed. Mean age was 72, 50 male, 31 female. Twenty-three percent had no acid-base disturbances (ABD). Isolated respiratory alkalosis was most common (41%), followed by metabolic acidosis, 22%; metabolic alkalosis, 10%, and respiratory acidosis, 9%. Age, sex, race distribution, morbidity and mortality were not significantly different between the groups. Overall mortality was 17%. Significantly higher mortality was associated with age over 70, pH less than 7.4, and presence of acute myocardial infarction. CXR scores did not correlate with pH, pCO2 or pO2, mortality or morbidity. Some patients with the most severe ABDs recovered while others, who had no ABD on presentation, eventually died. Thus, in 81 consecutive episodes of uncomplicated CPE, isolated respiratory alkalosis was the commonest ABD, occurring in 41%. No correlation was found between ABD and severity of CPE, morbidity or mortality.     

Hepatectomy for resectable colorectal cancer metastases--indicators of prognosis, definition of resectability, techniques and outcomes

The field of surgery for liver metastases is evolving rapidly. The proportion of patients viewed as amenable to resection is increasing with surgeons becoming more aggressive and systemic therapy more effective. Surgical resection is associated with low mortality and overall 5-year survival approaching 40%. Best candidates for resection are those with stage I or II colorectal cancer, fewer than 4 hepatic lesions, no lesions larger than 5 cm in diameter, no evidence of extra-hepatic disease, CEA level less than 5 ng/mL, and a disease-free interval of at least 2 years. Perioperative chemotherapy with or without biotherapies, in-situ ablation techniques, portal vein embolization, and staged hepatectomy have extended the indications without lessening the results of liver resection for colorectal metastases.     

2,5-Dimethyl-2'-hydroxy-9 alpha- and 9 beta-(3-methylbutyl)-6,7-benzomorphans and N-substituted compounds in the 9 alpha-(3-methylbutyl) series: chemistry, pharmacology, and biochemistry

2,5-Dimethyl-2'-hydroxy-9 alpha-(3-methylbutyl)-6,7-benzomorphan, the 9 beta-analogue, and 9 alpha-N-substituted (N-ethyl, propyl, butyl, pentyl, hexyl, phenylethyl, allyl, and cyclopropylmethyl) compounds were synthesized and evaluated biochemically and pharmacologically. The 9 beta N-methyl compound was found to be as potent as morphine in the mouse hot plate assay and had one-seventh the affinity of morphine for the opioid receptor. The N-alkyl and N-phenethyl 9 alpha-substituted compounds were either inactive or relatively ineffective as antinociceptive agents. None of the examined compounds substituted for morphine in single-dose suppression studies in the rhesus monkey. The N-cyclopropylmethyl compound in the 9 alpha series had half the narcotic antagonist potency of nalorphine and one-eighth of its affinity for the opioid receptor. The 9 alpha-(3-methylbutyl) moiety, unlike bulky substituents in the 9 beta position of 6,7-benzomorphans, generally lowers affinity for the mu opioid receptor and diminishes their in vivo activity as agonists or antagonists.     

Livaditis' circular myotomy does not decrease anastomotic leak rates and induces deleterious changes in anastomotic healing.

Considering that Livaditis' myotomy is still accepted as a good method for lengthening the esophagus to allow primary repair of long-gap esophageal atresia, the aim of this experimental study was to verify if this procedure decreases the incidence of leaks in anastomoses performed under severe tension. In addition, it was verified whether the myotomy promotes any morphological or biochemical change in the healing esophageal anastomosis. Sixty small dogs were submitted to a cervicotomy and resection of an esophageal segment (8.0 - 10.0 cm) resulting in an anastomosis under severe tension. The animals were divided into two groups (control group: only anastomosis; experimental group: anastomosis plus circular myotomy in the proximal esophageal segment). The animals were sacrificed on the 14th postoperative day, submitted to autopsy, and were evaluated as to the presence of leaks. Twelve scars of each group were collected for histological, histomorphometric (evaluation of scar thickness), electrophoretic and immunoblotting studies of collagen (total collagen and types of collagen determinations). Leak rates were the same in both groups. Histologic examination showed that the scar at the anastomosis was formed by fibrous tissue, without mucosa or muscular tissue. In the myotomy animals, a decreased number of newly formed small vessels was noted in comparison to control animals, and morphometric analysis showed that in the myotomy animals the anastomotic scar was thinner than in the control animals. Biochemical analysis of scars demonstrated that myotomy promoted a decrease in the soluble collagen content in comparison with the control animals and no alteration in the content of insoluble collagen. The electrophoretic separation of the types of collagen and characterization by immunoblotting demonstrated the presence of collagen types I, III, and V, and the quantification by densitometry of the bands showed a reduction in collagen type V (present in the blood vessels) in the myotomy animals in comparison to controls. This result is in accordance with the histological observation of a decrease in newly formed blood vessels. Circular myotomy does not decrease the possibility of anastomotic leaks, in addition to promoting deleterious changes in anastomotic healing.     

Problem-solving capacity for vitreoretinal diseases in a university health center

PURPOSE: To evaluate the effectiveness of the tertiary care delivered to patients with vitreoretinal diseases in a defined urban population; to substantiate the planning and allocation of resources in order to improve the tertiary eye care delivery system in a specific area. METHODS: Data were collected from consecutive first-time patients between June 1, 2003 and July 31, 2004 in the Department of Ophthalmology, State University of Campinas, S?o Paulo, Brazil. Problem-solving capacity values were calculated for vitreoretinal surgery and photocoagulation. Data were entered into the Statistical Package for the Social Sciences (version 10.0). RESULTS: Of the 7500 patients referred to the Department, 641 were deemed suitable for analysis. The diagnoses analyzed were retinal detachment (26.0%), diabetic retinopathy (21.0%), and vitreous hemorrhage (7.7%). The median ages were 52, 59 and 57.5, respectively. Of all patients referred for retinal detachment, 26.5% were inoperable. The values obtained for the problem-solving capacity (PSC) showed that 38.1%, 33.0% and 93.5% of those eligible for an ophthalmic intervention (for retinal detachment, vitreous hemorrhage and diabetic retinopathy) had obtained treatment. The main reason for not giving treatment was the unavailability of operating room time and photocoagulation time (87.1%). CONCLUSIONS: This was the first study of tertiary eye care service performance in Latin America. Sight-threatening conditions such as retinal detachment and diabetic retinopathy are not thoroughly covered by the health system in this area. Various ways to reduce the problem are considered. The study has provided valuable information on planning high-complexity eye services in the population in question.     

Efficacy of caspofungin against invasive Candida or invasive Aspergillus infections in neutropenic patients

BACKGROUND: Neutropenia is an indicator of poor prognosis in patients with fungal infections. All available clinical trial experience from the caspofungin development program was reviewed to ascertain the efficacy of caspofungin in neutropenic patients with documented invasive aspergillosis (IA) or invasive candidiasis (IC). METHODS: The review was limited to neutropenic patients with proven IC or proven/probable IA at caspofungin onset. Data were available from four clinical trials. All patients had an absolute neutrophil count < 500/mm(3) at the initiation of caspofungin. In all cases caspofungin was administered as monotherapy at a dose of 50 mg/day, after a 70-mg loading dose. In all patients efficacy was assessed at the completion of caspofungin therapy. Success included complete and partial responses. RESULTS: Sixty-eight neutropenic patients were identified with documented invasive infection, including 27 with IC and 41 with IA. Most patients had acute or chronic leukemia. A favorable response was noted in 63% (17 of 27 patients) of patients with IC, including a 58% (14 of 24 patients) response as first-line therapy and a 100% (3 of 3 patients) response as salvage therapy. Success in candidemia was 68% (17 of 25 patients). Outcomes across the different Candida species were similar. Favorable responses were noted in 39% (16 of 41 patients) of patients with IA, including a 42% (5 of 12 patients) response as first-line therapy and 38% (11 of 29 patients) response as salvage therapy. Success by site of IA was 40% for pulmonary (12 of 30 patients), 43% for sinus (3 of 7 patients), and 25% for skin/disseminated site (1 of 4 patients). CONCLUSIONS: A review of the caspofungin database demonstrates that this echinocandin is effective in neutropenic patients with documented cases of IC or IA.