PINK1 mutations in sporadic early-onset Parkinson's disease.

Pathogenic PINK1 mutations have been described in PARK6-linked Parkinson's disease (PD) patients of Asian origin. However, data on the frequency of PINK1 mutations in sporadic early-onset Parkinson's disease (EOPD) Asian patients are lacking. The objectives of this study were to report the frequency of PINK1 mutations of sporadic EOPD in an Asian cohort comprising of ethnic Chinese, Malays, and Indians, and to highlight a PINK1-positive patient who presented with restless legs symptoms. Eighty consecutive sporadic EOPD patients from the movement disorder clinics of two major tertiary institutions in the country were included. We performed sequence analysis of all the coding and exon-intron junctions of the PINK1 using specific primer sets. In addition, we genotyped polymorphisms detected from the analysis in a group of sporadic PD patients and controls. Three different mutations (two homozygous nonsense and one heterozygous missense) in the putative kinase domain were found in three patients, giving a 3.7% frequency of PINK1 mutations in our EOPD cohort. All the mutations were absent in 200 healthy controls. One patient with a novel homozygous nonsense PINK1 mutation presented unusually with restless legs symptoms. Separately, analysis of the frequency of four PINK1 polymorphisms in a group of sporadic PD and controls did not reveal any significant differences. We highlight a 3.7% frequency of PINK1 mutations in an Asian cohort (ethnic Chinese, Malay, and Indian) of EOPD. The phenotypic spectrum associated with PINK1-positive patients may be wider than previously reported. Polymorphisms of PINK1 do not appear to modulate risk of PD in our population.     

Risk factors for oral hairy leukoplakia in HIV-infected adults of Brazil

BACKGROUND: Oral hairy leukoplakia (OHL) may be an indicator of the progression of Human Immunodeficiency Virus (HIV)-induced immuno-depression, and the evaluation of risk factors leading to OHL is important in the management of these HIV-infected patients. However, there are few studies that analyze risk factors leading to OHL in the Brazilian population. The aim of this case-control study is to present data about prevalence rates and risk factors leading to OHL in a sample of HIV-infected adults in Brazil. METHODS: This case-control study included 111 HIV-infected patients treated at a clinic for sexually transmitted diseases and HIV. In the initial examinations with dentists, variables were collected from all patients. Diagnosis of OHL was performed in accordance with the International Classification System and cytological features. The Fisher and the chi-squared tests were used for statistical analysis. The proportional prevalence and odds ratio were estimated. RESULTS: Outcome presented a positive, statistically significant association among the presence of OHL and viral load of 3000 copies/mul or greater (P = 0.0001; odds ratio (OR) = 5.8), presence of oral candidiasis (P = 0.0000; OR = 11.1), previous use of fluconazole (P = 0.0000; OR = 24.6), and use of systemic acyclovir (P = 0.032; OR = 4.3). Antiretroviral medication presented a negative, statistically significant association with the presence of OHL (P = 0.002; OR = 8.4). CONCLUSIONS: Prevalence of OHL was 28.8%. Viral load, oral candidiasis, previous use of fluconazole, and systemic acyclovir were determined to be risk factors for OHL. Antiretroviral medication proved to be protective against the development of OHL.     

Familial risk assessment for early-onset coronary heart disease.

PURPOSE: We examined the performance of a familial risk assessment method that stratifies risk for early-onset coronary heart disease by considering the number of relatives with coronary disease, degree of relationship, lineage, and age at diagnosis. METHODS: By using data from the HealthStyles 2003 survey, we assessed the associations between familial risk and early-onset coronary heart disease, diabetes, hypercholesterolemia, hypertension, and obesity. By using area under the curve statistics, we evaluated the discriminatory ability of various risk assessment models. RESULTS: Of 4,035 respondents, 60% were female and 72% were white, with a mean age of 48.8 years. After adjustment for demographics, strong and moderate risk were significantly associated with approximately a five- and twofold risk of early-onset coronary disease, respectively. After adjustment for demographics and personal history of cardiovascular disease, strong familial risk was also significantly associated with diabetes, hypercholesterolemia, hypertension, and obesity. A risk assessment model that included familial risk, demographics, and personal history of diabetes, hypercholesterolemia, hypertension, and obesity was most optimal with an area under the curve statistic of 87.2% CONCLUSIONS: Familial risk assessment can stratify risk for early-onset coronary heart disease. Several conditions associated with increased familial risk can be prevented. These results have important implications for risk assessment and risk-reducing interventions.     

Outpatient microsurgical reversal of tubal sterilization by a combined approach of laparoscopy and minilaparotomy.

A prospective study of 17 cases of microsurgical reversal of tubal sterilization by a combined approach of laparoscopy and minilaparotomy was performed. Inclusion criteria included age less than 43; weight less than ideal body weight plus 20%; documentation of ovulation; 2 cm of proximal oviduct on hysterosalpingography; and a normal semen analysis or postcoital test. A comparison group of the 5 cases of sterilization reversal performed by a standard inpatient technique during the same period was analyzed. The study technique was performed on an outpatient basis in 15 of the 17 cases, 12 patients (71%) conceived 13 intrauterine pregnancies, one ectopic pregnancy occurred, and total patient costs and time until return to work were significantly less with the study versus standard technique.     

Rapid change in height and body proportions of Maya American children

Maya families from Guatemala migrated to the United States in record numbers from the late 1970s to the early 1990s. Births to Maya immigrant women have created a sizable number of Maya American children. The height and sitting height of 5 to 12 years children (n = 431) were measured in 1999 and 2000. Leg length was estimated and the sitting height ratio was calculated. These data were compared with a sample of Maya children living in Guatemala measured in 1998 (n = 1,347). Maya American children are currently 11.54 cm taller and 6.83 cm longer‐legged, on average, than Maya children living in Guatemala. Consequently, the Maya Americans have a significantly lower average sitting height ratio (i.e., relatively longer legs in proportion to length of the head and trunk) than do the Maya in Guatemala. These results add support to the hypothesis that both the height and body proportions of human populations are sensitive indicators of the quality of the environment for growth. Am. J. Hum. Biol. 14:753–761, 2002. © 2002 Wiley‐Liss, Inc.     

Multiple sclerosis patients have reduced HLA class II-restricted cytotoxic responses specific for both measles and herpes virus

It has been previously demonstrated that the generation of measles virus (MV)-specific cytotoxicity (CTL) is reduced in patients with multiple sclerosis (MS). By contrast, CTL specific for influenza virus (FLU) and mumps virus is normal. It is uncertain if reduced CTL is limited to MV in MS patients, or if reduced CTL may be found to other viruses as well. Since MV-specific CTL is predominantly restricted by HLA class II molecules, while FLU-specific and mumps-specific CTL have large HLA class I-restricted components, reduced MV-specific CTL may reflect a broader reduction in HLA class II-restricted CTL in patients with MS. To examine this question we studied the generation of CTL specific for herpes simplex virus type I (HSV). HSV-specific CTL, like MV-specific CTL is predominantly restricted by HLA class II molecules. We found that patients with MS had reduced generation of CTL to both MV and HSV. Most, but not all patients who had reduced generation of CTL to one virus also had a similar impairment with respect to the second virus. Some patients, however, had a reduction in the generation of CTL only to MV or to HSV. These findings extend our earlier observations regarding reduced MV-specific CTL in patients with MS to a second HLA class II-restricted virus, HSV. Such a reduction may reflect discrete impairments in immune function to separate viruses, possibly those that are associated with viral persistence, or may reflect a more generalized defect in HLA class II-restricted CTL.     

Development of a placental cell culture system for studying the control of mouse placental lactogen II secretion

Fetal placental tissue from 11 days pregnant mice was dissociated in collagenase and DNase solution and then separated on a 40 per cent Percoll gradient. Trophoblast cells banded at a density of 1.05 g/ml. When cultured on rat tail collagen, these cells formed colonies of mono- and binucleate cells varying in size from 40 to 70 microns. At the time of plating, about 13 per cent of the trophoblast cells secreted mouse placental lactogen II (mPL-II) as determined by reverse haemolytic plaque assay. The ratio of mPL-II-producing cells increased significantly in culture and reached 63 per cent after 48 h. The secretion of mPL-II increased continuously during six days of culture, whereas the total protein release was highest after the first day, declined the second day and then remained relatively constant for the last four days of culture. The DNA content of the cells did not change significantly during the six-day period. When the trophoblast cells were incubated with insulin (1 ng/ml to 5 micrograms/ml), a modest but significant reduction in mPL-II secretion was observed. No change in the mPL-II secretion was seen when epidermal growth factor was administered to the culture in concentrations from 1 ng/ml to 10 micrograms/ml. It is concluded that this in vitro culture system is suitable for studying both mPL-II secretion and the differentiation of mPL-II-producing cells.