Multivariate analysis of psychomotor development in congenital hypothyroidism

In the Finnish programme of screening for congenital hypothyroidism (CHT), thyroid replacement therapy is started very early (at a median age of 6 days). Our experience with the first 50 patients detected by this programme confirms that clinically relevant mental retardation is avoided by early therapy. But some intrauterine damage is inevitable and its degree correlates with the severity of the CHT. Age at the start of therapy, in our narrow range, did not appear to influence the outcome, as we found only a paradoxical positive correlation between the two. Our results suggest that thyroid hormone is transferred from the mother to her hypothyroid child during delivery.     

Bone age at birth; method and effect of hypothyroidism

Bone maturity at birth (or during the neonatal period) can be estimated from the ossified distal femoral epiphyses (FE). In congenital hypothyroidism (CHT) bone maturation is retarded and neonatal bone age reflects the severity of prenatal thyroid failure. In our reference group of 111 healthy infants, the size of these epiphyses depended not only on the age but also on body size. Thus, if bone age is estimated from the size of an epiphysis, the size of the infant is a potential confounder. This problem was avoided by estimating the maturation lag from the difference between the observed and predicted heights of FE (FEHs). Models for predicting FEH were constructed from data from the reference group by multiple linear regression and confirmed in a separate group of 37 healthy infants. In 52 hypothyroid newborns both FEH and FEH lag correlated with serum thyroxine concentration, indicating that FEH can be used as a measure of bone maturation in a population that is fairly homogeneous for (postmenstrual) age and size. Otherwise FEH lag is a better indicator.     

Overexpression of p53 and long-term survival in colon carcinoma.

Survival analysis of 144 histologically confirmed cases of colon carcinoma diagnosed in a 12 year period (1971-82) at the Tampere University Hospital was performed to test the hypothesis that p53 overexpression is associated with a poor clinical outcome. Immunohistochemical staining of paraffin-embedded sections using a polyclonal antibody CM-1 against p53 protein was performed to identify aberrant expression of the p53 tumour-suppressor gene. Sixty-nine per cent of the tumours (100/144) showed overexpression of the p53 protein. The prevalence of p53 overexpression was independent of age and sex of the patient and subsite of the tumour, but was slightly, although not statistically significantly, higher in advanced than in localised tumours. Overexpression was associated with a higher S-phase fraction. Some indication of a larger proportion of aneuploid tumours among those with overexpression was also observed, although this finding did not reach statistical significance. Significantly reduced patient survival for tumours with p53 overexpression was found. Patients with p53-overexpressing tumours had a corrected 5 year survival rate of 37% compared with 58% among patients whose tumours had normal expression of p53. The corresponding 10 year rates were 34% and 54%. In the multivariate analysis using a Cox model, the survival difference was independent of age and sex of the patient, as well as of subsite and stage of the tumour. Furthermore, the effect of p53 overexpression remained after controlling for flow cytometric parameters in an analysis of a subset of tumours. Thus, p53 overexpression appears to be a useful prognostic indicator in colon carcinoma.     

Enhancement of the circulating antibody secreting cell response in human diarrhea by a human Lactobacillus strain.

Human Lactobacillus sp strain GG (Lactobacillus GG) administered during acute rotavirus diarrhea has been shown to promote clinical recovery. To elucidate the immune mechanisms behind such a favorable outcome, the ELISPOT (solid phase enzyme-linked immunospot) assay of Ig- and specific antibody-secreting cells among circulating lymphocytes was used, giving indirect evidence of the immunologic events in the gut. After rehydration, 39 children with acute rotavirus diarrhea, mean age 16 (SD 6) mo, randomly received either a Lactobacillus GG fermented milk product (study group) or a pasteurized yogurt (placebo group). The duration of diarrhea was significantly shorter in the study group than in the placebo group [mean 1.1 (SD 0.6) versus 2.5 (SD 1.4)d, p = 0.001]. Lactobacillus GG therapy was associated with a significantly enhanced nonspecific humoral response during the acute phase of the infection, reflected in the IgG, IgA, and IgM Ig-secreting cell numbers. At convalescence, 90% of the study group versus 46% of the placebo group had developed an IgA specific antibody-secreting cell response to rotavirus (p = 0.006). The results indicate that Lactobacillus GG promotes recovery from rotavirus diarrhea via augmentation of the local immune defense. Furthermore, specific IgA response to rotavirus is endorsed, which is possibly relevant in protection against reinfections.     

Local immune response in patients with cow milk allergy: follow-up of patients retaining allergy or becoming tolerant.

To assist in identifying factors that determine the clinical outcome of cow milk allergy, we subjected to rechallenge 37 patients with a history of cow milk allergy, mean (+/- SD) age 27.6 +/- 7.1 months, after a follow-up of 13.5 +/- 5.1 months with a milk-free diet. A solid-phase enzyme-linked immunoassay was used to assess the total number of immunoglobulin-secreting and specific antibody-secreting cells among peripheral blood lymphocytes primed during provocation by milk antigens, giving indirect evidence of local immune response in the gut. Patients with persistent cow milk allergy (n = 13) had milder reactions at rechallenge than they had shown at the time of diagnosis. Numbers of immunoglobulin-secreting cells in these patients increased significantly from a geometric mean (95% confidence interval) in the IgA class of 1570 (1009, 2445) to 2984 (1941, 4583) IgA-secreting cells/10(6) cells, in the IgG class of 1445 (1067, 1959) to 2740 (1698, 4425) IgG-secreting cells/10(6) cells, and in the IgM class of 842 (534, 1325) to 2235 (1429, 3495) IgM-secreting cells/10(6) cells. By contrast, in patients (n = 24) who had acquired cow milk tolerance, the number of immunoglobulin-secreting cells did not increase during provocation. The total number of IgA-secreting cells before rechallenge was significantly higher than it had been before the initial challenge. The patients who acquired cow milk tolerance also had specific antibody-secreting cells of IgA isotype before the second challenge. These results indicate that in cow milk allergy the ability to mount a local immune response against cow milk antigens, particularly in the IgA class, is related to the suppression of clinical sensitivity.     

Pneumococcal bacteriology after pneumococcal otitis media with special reference to pneumococcal antigens

Fifty-four ears with evidence of pneumococcus (Pn) in the first acute otitis media (AOM) in 38 infants and with prolongation or recurrence of the MEF during the follow-up were observed for 7-22 months for the presence of Pn by culture or of pneumococcal antigen (Pn-ag) by counterimmunoelectrophoresis or latex agglutination methods in their MEFs. During the first three 1-month observation periods, Pn and/or Pn-ags were detected in 24% to 9% of these ears, always of the initial type/group. Later on new Pn types/groups appeared also. In two of the 9 MEFs persisting for greater than or equal to 3 months, initial Pn-ag, with culturable Pn, was repeatedly found but not for longer than 5 months. Of the 12 ears resulting in secretory otitis media (SOM) only one showed initial Pn-ag (and Pn) in the MEF of SOM. Pneumococcal type/group pattern associated with prolongation or recurrence of infection did not differ from that of initial AOM. In another series of 151 SOM ears in 97 children, Pn-ags were detected in 7 MEFs. Four of them grew Pn, each of the corresponding group. Our studies suggest that the persistence of Pn-ags in the middle ear after AOM is limited and their occurrence in the MEFs of SOM is rare. Thus, the role of the persistence of Pn-ags in prolonged, recurrent or secretory otitis media seems questionable.     

Expression of intermediate filaments in ovarian and uterine tumors

We studied the expression of cytoskeletal intermediate filaments in different types of ovarian and uterine sarcomas and carcinomas. In both uterine and ovarian leiomyosarcomas, in endometrial stromal sarcomas, and also in ovarian sarcomas, most tumor cells appeared to be positive for desmin, the muscle type of intermediate filament protein. In most of the tumors, vimentin was present only in some neoplastic cells and in the vascular endothelia. Interestingly, both uterine and ovarian malignant mixed mesodermal tumors appeared to express several types of intermediate filaments, most of the stromal cells being positive for vimentin or desmin, and the epithelial component expressing keratin. The results show that most of the sarcomatous tumors of the ovary and uterus express mainly muscle type of intermediate filament protein. The results also demonstrate the ability of cells of mesodermal origin to express epithelial cytoskeleton markers--cytokeratins.     

Employment security and health

OBJECTIVE: To study the relation of contractual and perceived employment security to employee health. DESIGN: Cross sectional survey. SETTING: Municipal sector employees in eight Finnish towns. PARTICIPANTS: 5981 employees with a permanent contract and 2786 employees with a non-permanent contract (2194 fixed term contract, 682 government subsidised contract). OUTCOME MEASURES: Poor self rated health, chronic disease, and psychological distress. RESULTS: Compared with permanent employees, fixed term men and women had better self rated health (men odds ratio 0.70; 95% confidence intervals 0.50 to 0.98, women 0.70 (0.60 to 0.82) and less chronic disease (men 0.69; 0.52 to 0.91; women 0.89; 0.79 to 1.02), but women had more psychological distress (1.26; 1.09 to 1.45). The only difference between subsidised employees and permanent employees was the high level of psychological distress in women (1.35; 1.09 to 1.68). Low perceived employment security was associated with poor health across all three indicators. The association of low perceived security with psychological distress was significantly stronger in permanent employees than among fixed term and subsidised employees, indicating that perceived security is more important for mental health among employees with a permanent contract. CONCLUSIONS: Contractual security and perceived security of employment are differently associated with health. It is therefore important to distinguish between these aspects of employment security in studies of labour market status and health. Such studies will also need to control for health selection, which is unlikely to operate in the same way among permanent and non-permanent employees.