Polymyalgia rheumatica following influenza vaccination.
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Biomedical subjects
Publications and source records attributed to C Perez.
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Immunocytochemical, biochemical, and molecular genetic studies indicate that apolipoprotein E (apoE) plays an important role in the process of amyloidogenesis-beta. However, there is still no clear translation of these data into the pathogenesis of amyloidosis-beta. Previous studies demonstrated sodium dodecyl sulfate (SDS)-resistant binding of apoE to the main component of Alzheimer's amyloid-A beta and modulation of A beta aggregation by apoE in vitro. To more closely characterize apoE-A beta interactions, we have studied the binding of thrombolytic fragments of apoE3 to A beta in vitro by using SDS-polyacrylamide gel electrophoresis and intrinsic fluorescence quenching. Here we demonstrate that SDS-resistant binding of A beta is mediated by the receptor-binding, N-terminal domain of apoE3. Under native conditions, both the N- and C-terminal domains of apoE3 bind A beta; however, the former does so with higher affinity. We propose that the modulation of A beta binding to the N-terminal domain of apoE is a potential therapeutic target for the treatment of amyloidosis-beta.
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Eosinophilic panniculitis is characterized by a prominent infiltration of subcutaneous fat with eosinophils. We report a case of Fasciola hepatica infection presenting with eosinophilic panniculitis successfully treated with bithionol. To our knowledge, this is the first report of recurrent eosinophilic panniculitis associated with Fasciola hepatica infection.
Hypoglycemic activity-guided fractionation together with chemical analysis led to the isolation of one guaianolide (lactucin-8-O-methylacrylate) from the chloroform extract of the dried fruits of Parmentiera edulis. Identification was based on spectroscopic methods. The compounds lowers blood sugar levels after administration to alloxan-diabetic mice.
Hypoglycemic activity-guided fractionation together with chemical analysis led to the isolation of one flavone (5, 7,3'-trihydroxy-3,6,4'-trimethoxyflavone) from the chloroform extract of the leaves of Brikkellia veronicaefolia. Identification was based on spectroscopic methods. The isolated flavone was tested for hypoglycemic activity in normal and alloxan-diabetic CD1 mice (25-30 g) were administered in doses of 10, 25 and 50 mg/kg body weight. The blood glucose levels were determined before and 1.5, 3, 4.5 and 24 hours after drug administration. The results showed that the flavone produces a significant hypoglycemic effect in normal as well as in diabetic mice. Comparison was made between the action of the flavone and a known hypoglycemic drug as tolbutamide (50 mg/kg). The flavone was found to be slow and less effective than tolbutamide.
New acetylcholinesterase inhibitors were synthetized via a lipase-mediated regioselective amidation using Candida antarctica lipase B as a biocatalyst in the key step. The new compounds have two different structural fragments: a N-benzylpiperidine moiety to anchor the enzyme active site and a dicarboxylic aminoacid to act as a biological carrier. Some analogues of N-benzylpiperazine were also synthesised and studied but they did not display AChE inhibitor activity. A preliminary structure activity relationship study was performed employing some computational techniques as similarity indices and electrostatic potential maps.
Glanzmann thrombasthenia is a rare platelet disorder inherited as an autosomal recessive trait. Abnormal uterine bleeding is a common problem in women with the disease. Medical management may not always be effective and further treatment may be necessary. Two women underwent endometrial ablation with a continuous-flow circulating hydrothermal ablator. After follow-up of 12 and 18 months, both women remained without abnormal uterine bleeding.
The Boston Diagnostic Aphasia Examination Battery (BDAE) is one of the most widely used aphasia tests worldwide. Information about general population performance, however, is limited. This paper analyzes the effects of gender, age, socioeconomic status (SES), academic achievement, and occupation on the BDAE Spanish version. The BDAE was administered to a randomized sample of 156 occupationally active 19-60-year-old participants (75 male and 81 female) from two SES groups. Gender and age had a significant effect on some reading and writing subtests. Body-part naming and mechanics of writing scores were significantly decreased in the low SES group. Education had a significant impact over most of the BDAE subtests. A stepwise regression model showed that academic achievement was best able to predict the variance in BDAE scores with a low (< 15%) to modest (> 17%) but significant capability (F MANOVA p < .01). A factor analysis disclosed 7 factors that explained 67% of the total variance.
OBJECTIVE: This study reports the results of treating floor-of-mouth cancer with five different treatment modalities with long-term follow-up. STUDY DESIGN: Retrospective study of 280 patients with floor-of-mouth cancer treated in the Department of Otolaryngology-Head and Neck Surgery at Washington University Medical School (St. Louis, MO) from 1960 to 1994. METHODS: Patients with biopsy-proven squamous cell carcinoma of the floor of mouth who were previously untreated were treated with curative intent by one of five modalities and were all eligible for 5-year follow-up. The treatment modalities included local resection alone, composite resection alone (with neck dissection), radiation therapy alone, local resection with radiation therapy, and composite resection with radiation therapy. Multiple diagnostic, treatment, and follow-up parameters were studied using standard statistical analysis to determine statistical significance. RESULTS: The overall 5-year disease-specific survival (DSS) was 56% with death due to tumor in 44% of patients. The 5-year cumulative disease-specific survival (CDSS) was 0.61 (Kaplan-Meier probability) with a mean of 8.3 years and a median of 9.7 years. The DSS by treatment modality included local resection (76%), composite resection (63%), radiation therapy (43%), local resection with radiation therapy (61%), and composite resection with radiation therapy (55%). Overall, there was no significant difference in DSS by treatment modality. Recurrence at the primary site (41%) was the most common site of treatment failure. Nineteen percent of patients had recurrence in the neck. Eighty-eight percent of initial recurrences occurred within 60 months after the onset of treatment. Metastasis to a distant site occurred in 30% of patients. Twenty percent of these patients had second primary cancers, and 53% of these patients died of their second primary cancers. CONCLUSIONS: Significantly improved 5-year DSS was seen in the patients with clear margins, early clinical tumor stage, and negative nodes. Significantly decreased 5-year survival was seen in the patients with involved margins, advanced clinical tumor stage, positive nodes, and tumor recurrence. Patients with no clinically positive nodes (cNO) can be observed safely for regional nodal disease and subsequent positive nodes can be treated as they occur with no adverse affect on survival. Because of high recurrence rates at the primary site and neck, and an increased rate of both distant metastasis and the development of second primary cancers, patients should be monitored closely for a minimum of at least 5 years.
OBJECTIVE: Cocaine toxicity frequently manifests as seizures and status epilepticus. Frequently, dextrose is administered to patients with cocaine-induced seizures. The objective of this study was to examine the effect of pre-existing hyperglycemia on cocaine neurotoxicity and death in mice. METHODS: Swiss albino mice received intraperitoneal dextrose at a dose of 1 g/kg (12.5%) (hyperglycemic group, n = 98). The euglycemic group (n = 98) received an equal volume of 0.9% saline. After 60 minutes, all the animals received intraperitoneal cocaine at a dose of 90 mg/kg. The times to onset of ataxia, seizure, and death were recorded in seconds. Times to events were compared using a Kaplan-Meier method and results were compared using the logrank test. The overall percentage outcomes were compared using chi-square. RESULTS: The ataxia rates (hyperglycemic 97%, euglycemic 97%, chi(2) = 0, p = 1), seizure rates (hyperglycemic 85%, euglycemic 82%, chi(2) = 0.292, p = 0.589), and survival rates (hyperglycemic 62%, euglycemic 51%, chi(2) = 0.2514, p = 0.113) were similar between the groups. The survival following a seizure was significantly higher in the hyperglycemic group (hyperglycemic 57%, euglycemic 41%, chi(2) = 4.439, p = 0.035). The median ataxia time was earlier in the hyperglycemic group (190 sec) than in the euglycemic group (166 sec) (p = 0.031). Seizures occurred no earlier in the hyperglycemic group (331 sec) than in the euglycemic group (342 sec) (p = 0.207). Survival times were not different for the hyperglycemic group (9,133 sec) and the euglycemic group (7,593 sec) (p = 0.394). Survival times following seizures were not different for the hyperglycemic group (8,095 sec) and the euglycemic group (5,816 sec) (p = 0.0752). CONCLUSIONS: In mice with pre-existing hyperglycemia, ataxia occurred earlier and survival following cocaine-induced seizures was longer than for euglycemic mice. No significant difference in the overall percentage of seizures and death was detected. Pre-existing hyperglycemia had minimal effect on worsening cocaine toxicity in mice.
PURPOSE: Stage IV-S neuroblastoma is a metastatic disease associated with spontaneous regression and good survival, but 10% to 20% of infants die from early complications. The purpose of this study was to evaluate outcome and prognostic factors in infants with stage IV-S neuroblastoma treated prospectively with supportive care only or, in symptomatic patients, with low-dose cytotoxic therapy. PATIENTS AND METHODS: Eighty eligible infants were studied for response and survival with supportive care or, for symptomatic patients, cyclophosphamide 5 mg/kg/d for 5 days with or without hepatic radiation of 4.5 Gy over 3 days. Staging was reviewed centrally, and MYCN gene copy number, Shimada histopathologic classification, serum ferritin levels, and bone marrow immunocytology were determined. RESULTS: Stage IV-S and International Neuroblastoma Staging System stage 4S were 98% concordant. MYCN was not amplified in any of the tumors tested (n = 58), and Shimada histopathologic classification was favorable in 96% (n = 68/71). The 5-year event-free survival (EFS) rate for all infants was 86% and the survival rate was 92%. Supportive care was the only treatment provided for 44 (55%) of 80 infants, and their 5-year survival rate was 100%, compared with 81% survival for those requiring cytotoxic therapy for symptoms (P =.005). Five of six deaths were in infants younger than 2 months of age at diagnosis and were due to complications of extensive abdominal involvement with respiratory compromise or disseminated intravascular coagulation. Although age </= 3 months at diagnosis was significant for EFS (P =. 043), it was less significant for survival (P =.077). The only other significant factor predictive for improved survival was favorable Shimada histopathologic classification. Sites of metastatic involvement (liver, skin, or bone marrow) and surgical resection of the primary tumor were not significant for survival. CONCLUSION: This study confirms the favorable biologic features and excellent survival of infants with stage IV-S neuroblastoma with minimal therapy. Infants younger than 2 months old at diagnosis with rapidly progressive abdominal disease may benefit from earlier and more intensive treatment.
PURPOSE: A prospective Children's Cancer Group study, CCG-3881, has been completed to determine if a more accurate prediction of prognosis by biologic features can identify subgroups of infants with stage IV neuroblastoma (NBL) who require differing intensities of treatment. PATIENTS AND METHODS: One hundred thirty-four infants were registered from June 1989 to August 1995, with a median follow-up of 47.1 months (range, 0 to 88 months). The biologic factors examined were tumor MYCN copy number, Shimada histopathologic classification, serum ferritin, and bone marrow immunocytology (sensitivity, one tumor cell per 10(5) bone marrow cells). Patients treated on CCG-3881 (n = 116) received four-drug chemotherapy for 9 months (cisplatin, cyclophosphamide, doxorubicin, and etoposide), with surgery and local radiation to residual disease. After January 1991, all subsequent infants with tumor MYCN amplification (n = 18) were transferred after one cycle of therapy to the high-risk CCG-3891 protocol (open January 1991 to April 1996) for more intensive treatment. RESULTS: The 3-year event-free survival (EFS) and overall survival (mean +/- SD) for the 134 infants were 63% +/- 5% and 71% +/- 5%, respectively. Patients whose tumors were without MYCN amplification had a 93% +/- 4% 3-year EFS, whereas those with amplified MYCN had a 10% +/- 7% 3-year EFS (P <. 0001). Each of the other biologic features studied had prognostic significance in univariate analysis but not after stratifying by MYCN copy number. CONCLUSION: Infants less than 1 year of age at diagnosis with stage IV NBL have a much improved outcome compared with children >/= 1 year of age. Nonamplified MYCN tumors identify a group of infants with a 93% +/- 4% EFS, whereas amplified MYCN copy number clearly identifies patients who are unlikely to survive despite intensive chemotherapy.
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Our 10-year translational study of the oral premalignant lesion (OPL) model has advanced the basic understanding of carcinogenesis. Although retinoids have established activity in this model, a substantial percentage of our OPL patients progress to cancer, especially after treatment is stopped. On the basis of our 10-year OPL study, we have developed the first comprehensive tool for assessing cancer risk of OPL patients. This cancer risk assessment tool incorporates medical/demographic variables, epidemiological factors, and cellular and molecular biomarkers. Between 1988 and 1991, 70 advanced OPL patients were enrolled in a chemoprevention trial of induction with high dose isotretinoin (1.5 mg/kg/day for 3 months) followed by 9 months of maintenance treatment with either low dose isotretinoin (0.5 mg/kg/day) or beta-carotene (30 mg/d; total treatment duration, 1 year). We assessed the relationship between cancer risk factors and time to cancer development by means of exploratory data analysis, logrank test, Cox proportional hazard model, and recursive partitioning. With a median follow-up of 7 years, 22 of our 70 patients (31.4%) developed cancers in the upper aerodigestive tract following treatment. The overall cancer incidence was 5.7% per year. The most predictive factors of cancer risk are OPL histology, cancer history, and three of the five biomarkers we assessed (chromosomal polysomy, p53 protein expression, and loss of heterozygosity at chromosome 3p or 9p). In the multivariable Cox model, histology (P = 0.0003) and the combined biomarker score of chromosomal polysomy, p53, and loss of heterozygosity (P = 0.0008) are the strongest predictors for cancer development. Retinoic acid receptor beta and micronuclei were not associated with increased cancer risk. We have demonstrated a successful strategy of comprehensive cancer risk assessment in OPL patients. Combining conventional medical/demographic variables and a panel of three biomarkers can identify high risk patients in our sample. This result will need to be validated by future studies. With the identification of high risk individuals, more efficient chemoprevention trials and molecular targeting studies can be designed.
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The aqueous extract of the bark of Raphanus sativus was tested for its antiurolithiatic and diuretic activity. The urolithiasis was experimentally induced by implantation of zinc disc in the urinary bladder of rats. Significant decrease in the weight of stones was observed after treatment in animals which received aqueous extract in comparison with control groups. This extract showed an increase in the 24 h urine volume as compared to the control.