Heikki Hiekkanen

Efficacy of prednisolone in children hospitalized for recurrent wheezing

Data on the efficacy of corticosteroids on respiratory picornavirus‐induced wheezing are limited. To determine whether prednisolone is effective in rhinovirus‐ or enterovirus‐induced recurrent wheezing, we conducted a controlled trial comparing oral prednisolone (2 mg/kg/day in three divided doses for 3 days) with placebo in hospitalized wheezing children and studied post hoc virus‐specific efficacy in early wheezing (<3 episodes, reported elsewhere) and in recurrent wheezing (≥3 episodes). Virus‐negative children where excluded. Our primary endpoint was the time until children were ready for discharge. Secondary endpoints included oxygen saturation and exhaled nitric oxide during hospitalization, duration of symptoms, blood eosinophil count, and impulse oscillometry 2 wk after discharge, and occurrence of relapses during the following 2 months. Virus‐specific effects were analyzed with interaction analysis in a multivariate regression model. During the study period, 661 patients were hospitalized, 293 randomized, and 59 were accepted in this analysis (mean age 2.6 yr, s.d. 1.3). Prednisolone did not significantly decrease the time until ready for discharge in all patients (prednisolone vs. placebo, medians, 18 vs. 24 h, p = 0.11). However, prednisolone decreased the time until ready for discharge in children with picornavirus infection (respectively, 12 vs. 24 h, p = 0.0022) and more specifically, in children with enterovirus infection (6 vs. 35 h, p = 0.0007). In the secondary endpoints, prednisolone decreased the duration of cough and dyspnea in rhinovirus‐affected children (p = 0.033 for both). Prospectively designed clinical trial is needed to test the hypothesis that prednisolone reduces symptoms in picornavirus‐affected wheezing children.

Major lower extremity amputation in elderly patients with peripheral arterial disease: incidence and survival rates

Background and aims: The methods of treating peripheral arterial disease (PAD) have changed and become more prophylactic. This study describes and analyzes 1) the incidence rates of major lower extremity amputation (LEA) due to PAD, 2) occurrence of re-amputation, and 3) the survival of amputees and factors predicting survival. Methods: The series consisted of 210 patients (mean age 76.6, SD 10.7 yrs, 45.2% men) who underwent their first, i.e. index, major leg amputation because of PAD, in 1998–2002, in the city of Turku, Finland, population 175,000. Results: Theage-and gender-standardized incidence rate of combined above-knee and below-knee amputations was 24.1/100,000 person-years during 1998–2002. Thirty-four per cent of amputees underwent repetitive amputation. One-month mortality was 21% (n=45), one-year mortality 52% (n=109) and overall mortality 80% (n=168). Cardiovascular diseases predicted equally well 31-day, one-year, and overall mortality in age- and gender-adjusted analysis. Multiple co-morbidities (p=0.023) and unilateral above-knee amputations (p=0.047) were significant predictors for overall mortality in age- and gender-adjusted analysis. Cardiovascular diseases remained a significant predictor for 31-day and overall mortality in multivariate analysis (p=0.008 and p=0.015, respectively). Amputated patients’ previous vascular procedures did not have any effect on mortality in the Cox model. Most revascularizations were performed less than six months before the index/first major LEA. Conclusion: Major LEAs seem to have been done late, and mainly for pain relief in the end-stage of patients with peripheral arterial disease.

Group IIA phospholipase A2 as a prognostic marker in prostate cancer: relevance to clinicopathological variables and disease-specific mortality

Group IIA Phospholipase A2 (PLA2‐IIA), a key enzyme in arachidonic acid and eicosanoid metabolism, participates in a variety of inflammatory processes but possibly also plays a role in tumor progression in vivo. Our aim was to determine the mRNA and protein expression of PLA2‐IIA during prostate cancer progression in localized and metastatic prostate tumors. We evaluated the prognostic significance of PLA2‐IIA expression in biochemical recurrence, clinical recurrence and disease‐specific survival after surgical treatment. The expression of PLA2‐IIA was examined by immunohistochemistry and chromogenic in situ hybridization in tissue microarrays of radical prostatectomy specimens and advanced/metastatic carcinomas. The expression data were analyzed in conjunction with clinical follow‐up information and clinicopathological variables. The mRNA and protein expression of PLA2‐IIA was significantly increased in Gleason pattern grade 2–4 carcinomas compared with benign prostate (p‐values 0.042–0.001). In metastases, the expression was significantly lower than in local cancers (p=0.001). The PLA2‐IIA expression correlated positively with Ki‐67 and α‐methylacyl CoA racemase (AMACR) expression. The prognostic evaluation revealed decreased PLA2‐IIA protein expression among patients who had died of prostate cancer. In conclusion, PLA2‐IIA expression is increased in carcinoma when compared with benign prostate. However, metastatic carcinoma showed decreased expression of PLA2‐IIA when compared with primary carcinomas. PLA2‐IIA may serve as a marker for highly proliferating, possibly poorly differentiated prostate carcinomas. The protein expression of PLA2‐IIA may be diminished in patients who consequently die of prostate cancer.

The effect of hospital operative volume, residual tumor and first-line chemotherapy on survival of ovarian cancer — A prospective nation-wide study in Finland

OBJECTIVE Our recent prospective, nation-wide study indicated better surgical outcome in ovarian cancer patients operated at university hospitals compared to other hospitals. Here we report how this is reflected in 5-year cancer-specific survival (CSS). METHODS Detailed 5-year follow-up data were obtained on 275 patients by using a special questionnaire, and the data were verified from the Finnish Cancer Registry data. The hospitals were categorized to university and other hospitals and by the number of operations performed in 1999 (<10, 10-20, or >20 operations). Data were analyzed using the Coxs proportional hazards regression analysis. RESULTS The study population covered 90% of the epithelial ovarian cancer patients operated in 1999, in Finland. Eighty-two percent of the patients received platinum-based chemotherapy. The percentage of patients treated with a platinum-taxane combination was higher in university hospitals (63% vs. 49%, P=0.037). The 5-year CSS was 56% and the median disease-free survival (DFS) was 33 months. In multivariate analysis prognostic factors for CSS were stage (P=0.0027), residual tumor (P=0.0001), and primary chemotherapy (P<0.0001). Hospital operative volume was associated with residual tumor (P=0.027). When hospital operative volume increased with ten patients per year, the odds ratio for no residual disease was 1.203 (95% CI 1.022-1.417). CONCLUSION FIGO stage, residual tumor, and primary chemotherapy are significant prognostic factors for ovarian cancer. Hospital volume is associated with residual tumor. The results favor performance of ovarian cancer surgery in hospitals with higher operative volumes.

Regulation of prostate cell collagen receptors by malignant transformation

Cell adhesion receptors, including the integrin‐type collagen receptors (α1β1, α2β1, α10β1 and α11β1) participate in cancer progression and invasion. Quantitative RT‐PCR indicated that all 4 receptors are abundantly expressed in sarcoma‐derived cell lines, whereas most carcinoma‐derived cells express α1β1 and α2β1 only. This was surprising because α11β1 has been connected previously to the progression of lung adenocarcinomas. To test the hypothesis that α11 expression may not persist in cultured cancer cells we analyzed fresh tissue samples of 104 total prostatectomies, keeping in mind that prostate cancer cell lines showed negligible α11 mRNA levels. In prostate α2 expression was significantly lower in poorly differentiated carcinomas when compared to benign lesions (p = 0.0331). In immunohistochemistry the protein levels of α2 integrin decreased significantly (p = 0.0001) and the protein levels of α11 subunit increased significantly (p = 0.029) with the increasing grade of carcinoma. Thus α11β1 may replace α2β1 during tumor progression. Our observations support the idea that α11β1 may be expressed in tumors but the corresponding cell lines may lose the expression of this integrin. Previous studies have shown that in cell culture androgen receptor (AR) controls α2β1 expression. We measured AR mRNA levels and the number of AR positive nuclei in the prostate samples and the results showed a significant correlation between α2β1 and AR. Androgen receptors may control the mechanisms regulating integrin expression in prostate.

Force production and EMG activity of neck muscles in adolescent headache.

Purpose. This study compared the maximal force, EMG/force ratio and co-activation characteristics of the neck-shoulder muscles between 30 adolescents with migraine-type headache, 29 with tension-type headache, and 30 headache-free controls. Method. Force was measured with surface electromyography (EMG) from the cervical erector spinae (CES), the sternocleidomastoid (SCM) and trapezius muscles during the maximal isometric neck flexion, neck extension and shoulder flexion. Results. Girls with migraine-type headache had higher EMG/force ratios between the EMG of the left agonist SCM muscle and the corresponding maximal neck flexion (p = 0.030) and neck rotation force to the right side (p = 0.024) than the girls with tension-type headache. Migrainous girls had more co-activation of right antagonist CES muscle during maximal neck flexion force than the girls without headache (p = 0.015). Neck force production showed no significant differences between girls. Girls with tension-type headache displayed lower left shoulder flexion force than girls with migraine-type headache (p = 0.005) or with no headache (p = 0.005). In boys, no significant differences were observed. Conclusions. Girls with tension-type headache and migraine-type headache have differences in neuromuscular function in the neck-shoulder muscles. The data amplify our knowledge of the neck-shoulder muscle dysfunction in adolescent headache, and may encourage the use of specific rehabilitation methods in the management of different types of headache.

Atopic characteristics of wheezing children and responses to prednisolone

We wanted to test the hypothesis that the efficacy of systemic corticosteroid is associated with atopic characteristics in wheezing children.

Neck flexor muscle fatigue in adolescents with headache – An electromyographic study

Background: Muscular disorders of the neck region may be of importance for the etiology of tension‐type headache. However, in adolescents, there are no data on the association between neck muscle fatigue and headache.

Neck muscles cross‐sectional area in adolescents with and without headache – MRI study

Background: Cervical musculature may play an important role in the genesis of tension‐type headache. However, there are no reports on a possible association between the morphometrical features of the neck flexion and extension muscles and adolescence headache.