Comparative bioavailability of two cefadroxil formulations in healthy human volunteers after a single-dose administration

OBJECTIVE: To compare the bioavailability of two cefadroxil capsule (500 mg) formulations (Cefadroxila from Eurofarma Laboratórios Ltd, Brazil, as test formulation and Cefamox from Bristol-Myers Squibb, Brazil S.A. as reference formulation) in 24 volunteers of both sexes. MATERIAL AND METHODS: The study was conducted open with randomized two-period crossover design and a 1-week washout period. Plasma samples were obtained over a 12-h interval. Cefadroxil concentrations were analysed by combined reversed-phase liquid chromatography and tandem mass spectrometry (LC-MS-MS) with positive ion electrospray ionization using a selected ion monitoring method. From the cefadroxil plasma concentration versus time curves the following pharmacokinetic parameters were obtained: AUC(last), AUC(0-infinity) and C(max). RESULTS: Geometric mean of Cefadroxila/Cefamox 500 mg individual percent ratio was 103.97% for AUC(last), 104.08% for AUC(0-infinity) and 95.23% for C(max). The 90% confidence intervals (CI) were 98.14-110.16%, 98.37-110.12%, and 85.59-105.96%, respectively. CONCLUSION: Since the 90% CI for C(max), AUC(last) and AUC(0-infinity) were within the 80-125% interval proposed by the Food and Drug Administration, it was concluded that the Cefadroxila 500 mg capsule was bioequivalent to the Cefamox 500 mg capsule, according to both the rate and extent of absorption.     

Normal exophthalmometric values in children

We used a Hertel exophthalmometer to measure the degree of ocular protrusion in 852 subjects who had no history of orbital trauma or disease, endocrine disease, severe myopia, buphthalmos, or craniofacial deformities. The subjects ranged in age from 3 to 10 years. No statistically significant difference was observed between boys and girls or between right and left eyes in each age group. The mean normal protrusion values ranged from 9.11 mm in the 3-year-old group to 11.67 mm in the 10-year-old group. The mean outer orbital margin distance ranged from 78.7 mm in the 3-year-old group to 89.1 mm in the 10-year-old group. The data obtained were tabulated to plot percentile distribution curves of normal exophthalmometric values and outer orbital margin distance in children. No subject had more than 2 mm of asymmetry between the eyes.     

Isolated lesion of the axillary nerve: surgical treatment and outcome in 12 cases

We report a series of 12 cases of isolated lesions of the axillary nerve treated surgically. We discuss the pathogenesis, clinical pattern, and surgical treatment of this lesion together with the results obtained.     

Distinction between endometrial and endocervical adenocarcinoma: an immunohistochemical study.

We investigated the possibility of distinguishing between primary endometrial and endocervical adenocarcinomas by using a panel of immunohistochemical stains, which included vimentin (VIM), carcinoembryonic antigen (CEA), epithelial membrane antigen (EMA), and cytokeratins 7 and 20 (CK7 and CK20). Twenty-nine endocervical adenocarcinomas (CCAs) and 30 endometrial adenocarcinomas (EMCAs) including cases with overlapping histologic features (CCAs with endometrioid differentiation [15/29] and EMCAs with mucinous differentiation [16/30]) were evaluated. Most EMCAs (29/30, 97%) were VIM positive, whereas only 2/29 (7%) CCAs were VIM positive. The great majority of EMCAs (28/30) and all 29 CCAs were CK7 positive, whereas all 30 EMCAs and 27/29 CCAs were negative for CK20. CEA positivity was more common in CCAs (18/29, 62%) than in EMCAs (8/30, 27%). EMA positivity was present in all 30 EMCAs and in 26 of 29 (90%) CCAs. We conclude that VIM and CEA are useful immunohistochemical markers in distinguishing EMCAs and CCAs, but CK7, CK20, and EMA are not useful in this distinction.     

Prostatic cancer therapy: comparison of external-beam radiation and I- 125 seed implantation treatment of stages B and C neoplasms

Of 179 patients with stage B or C adenocarcinoma of the prostate, 106 underwent iodine-125 seed-implant therapy (I-125 SI) and 73 received external-beam radiation therapy (EB). A retrospective analysis determined disease-free survival rate, local tumor control, and complication rate for each treatment group. The 5-year disease-free survival rates for SI-treated patients were 75% for stage B and 30% for stage C groups. Corresponding rates for EB-treated patients were 75% and 40%, respectively. The rate of local tumor control for stage B patients was 85% for SI-treated and 88% for EB-treated patients. The corresponding rates for stage C tumors were 75% for SI-treated and 92% for EB-treated patients. The rate of long-term complications in each group was approximately 10%. For stage B cancer of the prostate, I-125 SI treatment is an acceptable alternative to EB therapy; our data are inconclusive regarding stage C treatment, but EB therapy is preferred.     

Plasma hydroxy-metronidazole/metronidazole ratio can detect early changes in hepatic function in ethanol-induced liver injury

AIMS: To evaluate the usefulness of plasma hydroxy-metronidazole/metronidazole (OH-MET/MET) ratios as a dynamic liver function test in ethanol abusers with or without liver cirrhosis. METHODS: Metronidazole was administered intravenously for 20 min to healthy volunteers, and to patients with alcohol-induced, non-cirrhotic hepatopathy and liver cirrhosis. Plasma concentrations of metronidazole and hydroxy-metronidazole were measured by high performance liquid chromatography in samples collected 5, 10, 20 and 30 min after the metronidazole infusion. RESULTS: Patients with non-cirrhotic alcoholic hepatopathy had significantly elevated aminotransferase levels compared to healthy volunteers and Child A patients. Child-Pugh C patients had significantly prolonged prothrombin times when compared to healthy volunteers and patients with non-cirrhotic hepatopathy. Metronidazole metabolism, as measured by the OH-MET/MET ratio following the intravenous administration of 500 mg of the drug, was significantly impaired in all ethanol-abusing individuals, including patients with non-cirrhotic alcoholic hepatopathy. CONCLUSIONS: Metronidazole metabolism was impaired in ethanol abusers, even in the absence of liver cirrhosis, indicating that ethanol was capable of affecting liver function in the early stages of alcohol-induced liver disease.     

Mucinous endometrial epithelial proliferations: a morphologic spectrum of changes with diverse clinical significance.

BACKGROUND: Mucinous differentiation of the endometrium can occur in a spectrum of changes ranging from benign (metaplasia) to malignant (adenocarcinomas with mucinous differentiation). Mucinous proliferations with simple architecture are generally considered benign; however, more complex growth patterns have an uncertain biologic behavior, particularly when these changes are focal and/or are encountered in biopsy or curettage material. The disparity between the degree of cytologic atypia and the neoplastic potential makes their interpretation difficult in routine practice. We categorized and prospectively studied a series of these lesions based upon their degree of architectural complexity and correlated them with follow-up curettings and hysterectomies over a period of three years. METHODS: Mucinous proliferations of the endometrium were subdivided into three categories (A, B, or C) based upon increasing degrees of architectural complexity. Type A were mucin-containing epithelial cells, present singly or in small tufts, within architecturally benign glands or involving the endometrial surface. Type B proliferations were more complex, consisting of mucin-containing epithelial cells forming small pseudoglands with rigid, punched out spaces and no supporting stroma Conspicuous cytologic atypia or architectural features such as a filiform growth pattern characterized type C alterations. One hundred two curettings and 36 hysterectomies from 52 patients were reviewed. RESULTS: Patient's ages ranged from 39 to 71 years (median, 55 yr); 41 patients (80%) were over age 50. Twenty patients (40%) were receiving hormone replacement therapy. Nineteen type A, 17 type B, and 16 type C mucinous endometrial proliferations were analyzed. Excluding those cases in which a conventional coexisting precancerous lesion was also present in the initial endometrial sample, the percentages of endometrial carcinoma following a curettage diagnosis of types A to C, respectively, were 0, 64.7%, and 100%. Carcinomas following type B alterations were all well-differentiated and all were confined to the endometrium or inner third of the myometrium. CONCLUSION: Mucinous endometrial proliferations comprise a spectrum subdivisable into biologically meaningful subsets. A high percentage of type B alterations were found to have endometrial adenocarcinoma on follow-up; however, all were well-differentiated and showed either no or minimal invasion. This finding suggests that the absence of cytologic atypia in complex mucinous lesions identifies subsets of lesions at low concurrent risk for deeply invasive cancer. The presentation of type B lesions as predominantly microglandular surface lesions without co-existing atypical hyperplasias suggests that a subset of well-differentiated adenocarcinomas arise via neoplastic alterations in surface epithelium.     

Risk of iron overload and 'hemochromatosis allele(s)' in patients on maintenance hemodialysis

In the present study, we have evaluated the relationship between serum ferritin (SF) levels, 'hemochromatosis allele(s)', blood transfusions and iron parenteral administration in 69 hemodialysis patients. We demonstrated significantly higher SF levels in patients with hemochromatosis allele(s) (HA+) than in patients without hemochromatosis alleles (HA-). In addition, HA+ patients who had received blood transfusions up to 15 months prior to the study had SF levels even higher than those without blood transfusions. On the other hand, HA- patients had normal levels of SF, independent of blood transfusions. After intravenous administration of 1 g iron saccharate, SF levels were significantly higher only in HA+ transfused patients. In conclusion, our study demonstrated that HA+ patients are at a higher risk of iron overload and therefore the use of transfusional and/or parenteral iron should be strictly limited.