Alloantibodies against low-frequency human platelet antigens do not account for a significant proportion of cases of fetomaternal alloimmune thrombocytopenia: evidence from 1054 cases

BACKGROUND: Maternal alloantibodies against the five common human platelet antigen (HPA) systems (HPA-1 to -3, -5, and -15) are found in only 20% of cases referred for fetal and neonatal thrombocytopenia (FMAIT) investigations. The question asked was whether mismatches for the remaining 11 low-frequency HPAs (HPA-4 and -6bw to -17bw) might in part explain the remaining 80% of cases.
STUDY DESIGN AND METHODS: A total of 1054 paternal DNA samples from referred FMAIT cases (among which 223 cases where antibodies against a common HPA were found) were genotyped for 11 low-frequency HPAs as well as a recently discovered polymorphism ( ITGA2B -C2320T). The initial genotyping was carried out by TaqMan and potential heterozygotes were confirmed by DNA sequencing. Clinical and serologic data were collected for each case with a heterozygote father.
RESULTS: In total, eight heterozygous fathers were identified: four for HPA-6w, one each for HPA-10w and -11w, and two for HPA-12w. Maternal antibodies against the corresponding antigen were identified in four of the eight cases. In two of these cases, antibodies against HPA-1a and HPA-1b were also found.
CONCLUSION: It was concluded that the minor alleles of HPA-4 and -6bw to -17bw are exceptionally rare in the Caucasian population and therefore do not explain the large number of FMAIT referrals which test negative for the common HPA antibodies.     

Neurocognitive functioning in children with type-1 diabetes with and without episodes of severe hypoglycaemia

Previous studies have shown that recurrent severe hypoglycaemia can cause long-term cognitive impairment in children with type-1 diabetes, but the results are controversial, possibly due to the heterogeneity of samples and lack of comprehensive neuropsychological assessments of children. The aim of this study was to assess the effects of diabetes and severe hypoglycaemia on the neurocognitive functioning of children with a standardized, wide age-range neuropsychological test battery designed for the assessment of children. Eleven children with diabetes and a history of severe hypoglycaemia, 10 children with diabetes without a history of severe hypoglycaemia, and 10 healthy control children (a total of 31 children: 14 males and 17 females, age range 5 years 6 months to 11 years 11 months, mean 9 years 4 months, SD 1 year 11 months) were studied using the Wechsler Intelligence Scale for Children-Revised (WISC-R) and the NEPSY, a Developmental Neuropsychological Assessment. The NEPSY assessed development in attention and executive functions, language, sensorimotor functions, visuospatial processing, and learning and memory. Children with a history of severe hypoglycaemia had more neuropsychological impairments, more learning difficulties (as reported by parents), and needed more part-time special education than those in the other groups. Significant differences were found in verbal short-term memory and phonological processing. Results suggest that severe hypoglycaemia is a risk factor for learning due to deficits in auditory-verbal functioning.     

Spotlight on naturally absorbable osteofixation devices

The practice of using implants is growing day by day, and more foreign materials are being inserted for various indications. The field of implantology thus deserves intensive research and careful evaluation of results. Solutions to overcome current problems and risks are necessary. It has taken a long time to arrive at where we are now. Bioabsorbable devices were explored in the 1960s for surgical bone fixation. Failures were followed by changes in ways of thinking and innovations. Improvements in the strength properties and biocompatibility were achieved. Bioabsorbable polymeric materials such as high-molecular-weight polymers were used and also reinforced with other material or, more recently, by self-reinforcement to produce small yet strong devices. New generations of implants include those that contain bioactive substances such as antibiotics and growth factors. Developments in bioabsorbable materials continue to accommodate the new way of thinking brought about by the emergence of the field of tissue engineering. Surgeons, conversely, are also inventing new surgical techniques and methods to exploit the plastic and bioabsorbability properties of these materials for the better future of our patients. Such a multidisciplinary approach that involves surgeons and materials scientists should help to find solutions to the current limitations of these devices.     

Improvement in undergraduate medical education: a 10-year follow-up in Finland

Several studies have revealed that undergraduate medical education does not adequately prepare students for their work as physicians. There have been attempts to solve this problem in curriculum reforms in medical faculties. In this article, Finnish physicians' opinions on their undergraduate medical education are analysed. In 1988, a postal questionnaire was mailed to 2632 physicians registered during 1977-86, and altogether 1745 questionnaires were returned (66.3%). A follow-up study was done in 1998, and a questionnaire was sent to 2529 physicians who graduated between 1987 and 1996; 1822 questionnaires were returned (73.1%). Half of the respondents considered undergraduate education to correspond well with the requisite diagnostic skills and hospital doctors' work in general. In older and more traditional medical faculties (Helsinki, Oulu and Turku) education in primary healthcare work was considered insufficient. Also, more than 80% of the respondents felt they received too little teaching in administrative work. They reported that both traditional and younger, community-oriented faculties (Kuopio and Tampere) had considerably improved their education, especially in primary healthcare, during the 10-year follow-up. However, there were still clear differences between the education in the respective types of faculty as evaluated by their graduates. There is still room for improvements in undergraduate medical education, the better to meet the real needs of practising physicians in different fields of health care.     

BDNF regulates the expression of fragile X mental retardation protein mRNA in the hippocampus

Both fragile X mental retardation protein (FMRP) and brain-derived neurotrophic factor (BDNF) are implicated in the maturation of neurons and in the higher cognitive functions. We have investigated whether FMRP and BDNF are reciprocally regulated in neurons. Exposure of cultured hippocampal neurons to BDNF, but not to NT-3, reduced FMR1 mRNA levels to 84.8% of control at 4 h and the levels were back to baseline by 24 h or 4 days. Furthermore, expression of FMR1 mRNA was reduced (82.4% of control) in vivo in the hippocampus of transgenic mice overexpressing TrkB receptors, and a small but significant (5.1%) decrease was also detected in FMRP protein levels. In contrast, the expression patterns of BDNF and TrkB mRNAs were not altered in FMRP-deficient mice compared to wild-type mice. Our data provide evidence that BDNF via TrkB signaling decreases FMRP expression and suggest a role for FMRP in BDNF-induced synaptic plasticity.     

Probiotic effects on faecal inflammatory markers and on faecal IgA in food allergic atopic eczema/dermatitis syndrome infants

Probiotic bacteria are proposed to alleviate intestinal inflammation in infants with atopic eczema/dermatitis syndrome (AEDS) and food allergy. In such infants we investigated effects of probiotic bacteria on faecal IgA, and on the intestinal inflammation markers tumour necrosis factor-alpha (TNF-alpha), alpha1-antitrypsin (AT), and eosinophil cationic protein (ECP). A total of 230 infants with AEDS and suspected cow's milk allergy (CMA) received in a randomized double-blinded manner, concomitant with elimination diet, Lactobacillus GG (LGG), a mixture of four probiotic strains (MIX), or placebo for 4 wk. Four weeks after treatment, CMA was diagnosed with a double-blind placebo-controlled milk challenge. Faecal samples of 102 infants, randomly chosen for analysis, were collected before treatment, after 4-wk treatment, and on the first day of milk challenge. After treatment, IgA levels tended to be higher in probiotic groups than in the placebo group (LGG vs. placebo, p=0.064; MIX vs. placebo, p=0.064), and AT decreased in the LGG group, but not in other treatment groups. After challenge in IgE-associated CMA infants, faecal IgA was higher for LGG than for placebo (p=0.014), and TNF-alpha was lower for LGG than for placebo, but non-significantly (p=0.111). In conclusion, 4-wk treatment with LGG may alleviate intestinal inflammation in infants with AEDS and CMA.     

Lack of effect of hormonal treatment and smoking on cytokeratin expression in buccal mucosa

Differences in cytokeratin expression of clinically normal buccal mucosa were studied in 50 healthy women by indirect immunofluorescence staining with monoclonal antibodies. The subjects were divided into four groups: control group (N= 18), smokers (N=8), oral contraceptive users (N=8) and smokers receiving oral contraceptives (N=16). Our findings indicate that cytokeratin expression in non-cornified stratified epithelium is not influenced by smoking or oestradiol/progesterone treatment. Only cytokeratin No. 19 showed variable patterns of expression but the differences could not be ascribed to smoking or contraceptives. Cytokeratin No. 19 gave a positive reaction in the basal and suprabasal layers in 34 subjects (68%). In 9 (18%) specimens, the staining was positive in the basal cells and showed a positive heterogeneous cytoplasmic reaction in the suprabasal cells. Interestingly, cytokeratin No. 7 was recognized in all epithelial cells except the basal cells. Our results suggest that changes in the serum oestradiol levels do not affect the cytokeratin pattern in buccal mucosa.