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Biomedical subjects

H Haapasalo

Publications and source records attributed to H Haapasalo.

At least 19 recordsLinked to original sources

Knee injuries in leisure-time physical activities: a prospective one-year follow-up of a Finnish population cohort.

This prospective one-year follow-up study compared the risks of knee injuries in various commuting and lifestyle activities as well as in recreational and competitive sports in a 15 to 74-year-old Finnish population cohort. A cohort of 3657 persons was randomly selected from the nationwide population register of Finland. Ninety-two percent of them accepted to participate (n = 3363). The subjects were interviewed by telephone three times during the one-year follow-up. The recorded data included all physical activities that lasted 15 minutes or more, and all injuries that were sustained during these activities. Fifteen percent (n = 321) of all reported injuries affected the knee. The individual risk of knee injury per 1000 exposure hours was low in commuting activities (cycling, walking), 0.06 (95 % CI 0.04 to 0.09) and in lifestyle activities (gardening, hunting, fishing, home repair etc.), 0.04 (0.03 - 0.06). In recreational and competitive sports, the knee injury risk was almost ten times higher, 0.44 (0.39 - 0.50). For commuting activities (p = 0.046) and for recreational and competitive sports (p < 0.001), there was a decreasing injury rate with age. In lifestyle activities (p = 0.038), in turn, there was an increasing trend of injuries with aging. In commuting activities (hazard ratio, HR 5.99, 95 % CI 1.40 to 25.6), the risk of knee injury was significantly higher in women than in men. In conclusion, the knee injury risk per exposure hours is almost ten times lower in commuting and lifestyle activities compared to recreational and competitive sports. The knee injury risk is especially high in the age group of 15 to 25 years, especially in various team sports and ball games. At population level, however, widely practiced low-to-moderate intensity activities with relatively low injury risk per exposure hours produce a large absolute number of knee injuries.

Adolescent↗

Expression of transmembrane carbonic anhydrases IX and XII in ovarian tumours.

AIMS: Carbonic anhydrase (CA) isozymes IX and XII have been suggested to play a role in oncogenic processes. The aim of the present study was to investigate CA IX and XII expression in patients with ovarian tumours. METHODS AND RESULTS: A series of ovarian tumours was immunostained for CA IX and XII and the results were correlated with histopathological and clinical parameters. Most cases of borderline mucinous cystadenomas, mucinous cystadenocarcinomas and serous cystadenocarcinomas were moderately or strongly positive for CA IX. In malignant tumours, the staining was most prominent in hypoxic regions. Expression of CA XII was detected in all tumour categories, although the mean staining intensity was weaker than for CA IX in all groups except for clear cell carcinomas. CONCLUSIONS: The wide expression of CA IX and XII in ovarian tumours suggests that these isozymes could represent potential targets in ovarian cancer therapy. The expression pattern of CA IX suggests that it could also serve as a useful histopathological marker protein for hypoxia in malignant ovarian tumours.

Antigens, Neoplasm↗

Amplification of the epidermal growth factor receptor in astrocytic tumours by chromogenic in situ hybridization: association with clinicopathological features and patient survival.

Chromogenic in situ hybridization (CISH) was used to detect amplification of the epidermal growth factor receptor (EGFR) gene in tissue microarrays of tumours derived from 287 patients with grade II-IV diffuse astrocytomas. Amplification was found in 32% of the tumours with a highly significant association with histological grade (4% in grade II, 21% in grade III and 39% in grade IV; P < 0.001). Amplification of the EGFR gene was more common in primary than in secondary glioblastomas (41%vs. 16%, P = 0.033). Overexpression of EGFR mRNA and protein (wild-type and vIII variant) was found to correlate with EGFR gene amplification (P = 0.028, P = 0.035 and P = 0.014 respectively), but wild-type EGFR protein was also frequently overexpressed in tumours without EGFR gene amplification. Patients with older age (P < 0.001) and tumours with lack of p53 overexpression (P = 0.03) and higher apoptosis rate (P < 0.001) had significantly more EGFR gene amplifications than their counterparts. No such correlation with apoptosis was found in glioblastomas. The survival of patients with EGFR gene-amplified grade III tumours was significantly shorter than in those with grade III non-amplified tumours (P = 0.03). No such difference was noted in glioblastomas (grade IV tumours). Our data verify the central role of EGFR in the pathobiology of astrocytic tumours, and highlight the advantages of CISH as a simple and practical assay to screen for EGFR gene amplification in astrocytic tumours.

Adolescent↗

Ultrarapid Ki-67 immunostaining in frozen section interpretation of gliomas.

BACKGROUND: Astrocytic tumours, the most common gliomas, are often classified intraoperatively using standard morphological staining. The final diagnosis and grading of gliomas on paraffin wax sections is often assisted by Ki-67 immunohistochemistry, but standard immunostaining protocols take too long to be used intraoperatively. AIMS: To investigate a new rapid Ki-67 immunohistochemical test for its use in an intraoperative setting. METHODS: The new Ki-67 immunostaining (Ultrarapid-Ki67) method on frozen sections can be carried out in 10 minutes. Thirty four pilocytic and diffuse astrocytomas were immunostained by rapid Ki-67 and results were compared with corresponding MIB-1 staining, histological grading, and prognosis. RESULTS: The staining protocol was practical to perform and the results were morphologically and quantitatively indistinguishable from those after immunostaining with MIB-1, an antibody recognising Ki-67 in paraffin wax embedded tissue. A comparison of Ultrarapid-Ki67 and MIB-1 immunostaining of paraffin wax sections showed almost identical quantitative correlation in astrocytic gliomas (r = 0.916; p<0.001). The Ultrarapid-Ki67 indices (percentage of positive cells) of low grade (I/II) astrocytomas ranged from 0% to 6.1%, whereas those of representative high grade (III/IV) tumours were significantly higher (range, 5.6-45%; p<0.001). The best prognostic cutoff point for Ultrarapid-Ki67 was 7.5%, which divided diffuse grade II-IV astrocytomas into significantly differing subsets (p = 0.0008). CONCLUSION: Ultrarapid-Ki67 immunostaining is a useful adjunct to morphological diagnosis and grading of astrocytic tumours, and as a fast test (approximately 10 minutes for staining plus three to four minutes for scoring), it could be used in routine intraoperative diagnosis of gliomas and other neoplastic diseases.

Adolescent↗

No GIST-type c-kit gain of function mutations in neuroblastic tumours.

AIMS: Neuroblastic tumours (NTs) have been shown to respond to imatinib treatment in vivo and in vitro, possibly via inactivating the c-kit receptor. The purpose of this study was to identify gastrointestinal stromal tumour (GIST)-type c-kit gene associated mutations in exons 9, 11, 13, and 17 in NTs to recognise a subset of tumours that would probably respond to imatinib treatment. METHODS: Expression of the c-kit protein was detected immunohistochemically in a total of 37 archival paraffin wax embedded NTs using polyclonal rabbit antihuman c-kit antibody. After immunohistochemistry, c-kit gene associated chromosomal mutations in all cases of NT were detected with denaturing high performance liquid chromatography (HPLC). RESULTS: Denaturing HLPC analysis did not reveal GIST-type mutations in four immunohistochemically detected c-kit positive or in 33 c-kit negative NTs. CONCLUSIONS: c-kit receptor expression and GIST-type c-kit gene mutations are rare events in NTs. Oncogenic activation of c-kit in NTs presumably differs from that of GISTs, which may influence their responsiveness to imatinib treatment. Whether c-kit has an essential role in the pathogenesis of NTs remains to be investigated.

Antineoplastic Agents↗

New methods for molecular diagnosis and demonstration of the (CCTG)n mutation in myotonic dystrophy type 2 (DM2).

Myotonic dystrophy types 1 and 2 are autosomal dominant, multisystemic disorders with many similarities in their clinical manifestations. Myotonic dystrophy type 1 is caused by a (CTG)n expansion in the 3' untranslated region of the DMPK gene in 19q13.3 and myotonic dystrophy type 2 by a (CCTG)n expansion in intron 1 of ZNF9 in 3q21.3. However, the clinical diagnosis of myotonic dystrophy type 2 is more complex than that of myotonic dystrophy type 1, and conventional molecular genetic methods used for diagnosing myotonic dystrophy type 1 are insufficient for myotonic dystrophy type 2. Herein we describe two in situ hybridization protocols for the myotonic dystrophy type 2 mutation detection. Chromogenic in situ hybridization was used to detect both the genomic expansion and the mutant transcripts in muscle biopsy sections. Chromogenic in situ hybridization can be used in routine myotonic dystrophy type 2 diagnostics. Fluorescence in situ hybridization on extended DNA fibers was used to directly visualize the myotonic dystrophy type 2 mutation and to estimate the repeat expansion sizes.

Adult↗

A novel frozen brain tissue array technique: immunohistochemical detection of neuronal paraneoplastic autoantibodies.

We introduce a modification of the tissue microarray technique in which several frozen brain tissue specimens are collected to a single frozen brain array block. In the present application, we use it for the detection of neuronal paraneoplastic anti-Hu autoantibodies. Representative samples from 15 different brain regions were collected according to a standard neuropathological autopsy protocol. Cryostat sections from each block were cut and conventionally stained. From representative areas, cylinder tissue samples from each specimen were punched and then arrayed into a recipient array block. Using the cryostat sections of this brain array, autoantibodies from seven anti-Hu-positive patient sera (confirmed by immunoblotting) were screened by immunohistochemistry. Neuronal architecture was well preserved and immunohistochemical staining was comparable to that of conventional cryostat sections. Because of the variable staining pattern in different brain areas, two anti-Hu-positive sera could be detected immunohistochemically by the one brain array. With the present array technique, it is possible to characterize the variable staining patterns of neuronal paraneoplastic autoantibodies in different locations of the human brain. The frozen brain array also allows the detection of RNA and DNA targets involved in neurological diseases.

Aged↗

Histopathological differences of myotonic dystrophy type 1 (DM1) and PROMM/DM2.

Muscle biopsy findings in DM2 have been reported to be similar to those in DM1. The authors used myosin heavy chain immunohistochemistry and enzyme histochemistry for fiber type differentiation on muscle biopsies. Their results show that DM2 patients display a subpopulation of type 2 nuclear clump and other very small fibers and, hence, preferential type 2 fiber atrophy in contrast to type 1 fiber atrophy in DM1 patients.

Adult↗

Cell cycle regulators (p21, p53, pRb) in oligodendrocytic tumors: a study by novel tumor microarray technique.

Using the novel tissue microarray technique, we studied immunohistochemical expression of cell cycle regulators p53, p21, pRb in 42 grade II oligodendrogliomas, 16 grade III anaplastic oligodendrogliomas, 10 primary and 4 recidive grade II oligoastrocytomas, 10 grade III oligoastrocytomas and 2 other grade II mixed gliomas. The p53 immunopositivity associated with malignant histology of the tumor (p = 0.01, Mann-Whitney test) and high pRb expression (p = 0.015). The p21 score associated strongly with histological grade (p < 0.001). The immunopositive tumors had a significantly higher rate of proliferation (p = 0.021). The p21 immunopositivity correlated positively with p53 immunopositivity: among the 33 p21 immunopositive tumors 30 (91%) were p53 immunopositive and only 3 were p53 immunonegative (p = 0.017). Patients with p21 immunonegative primary tumors had significantly better prognosis: among them 42 of the 46 (91%) survived, whereas only 18 of the 30 patients (60%) with p21 immunopositive primary tumors survived until the follow-up date (p = 0.0017). Statistical significance was reached in multivariate analysis as well (p = 0.01, exp(B) = 5.5). The pRb immunopositive tumors had higher proliferation rate than immunonegative tumors (p = 0.002). In multivariate variance analysis, comparing the effects of different regulatory proteins on cell proliferation, only the amount of pRb expression reached statistical significance (p = 0.004). In conclusion, the expression of p21 in oligodendrocytic tumors seems to be upregulated by p53 expression which rises with cell proliferation and malignancy as in attempt to halt cell cycle but seems to be overrun by other factors. The amount of p21 expression has independent prognostic significance and could be used in diagnosis to help the difficult evaluation of the malignancy potential of oligodendrogliomas and oligoastrocytomas.

Adolescent↗

Analysis of p53 tumor suppressor gene in families with multiple glioma patients.

The high incidence of gliomas in Li-Fraumeni families and the high frequency of somatic p53 mutations in sporadic glial tumors have raised the possibility that germline p53 mutations could play an important role in familial aggregation of gliomas. In the present study, 18 families with two or more gliomas were screened for germline p53 mutation. The families were identified through questionnaires sent to 369 consecutive glioma patients operated at Tampere University Hospital during 1983-1994. In these families, a family history of cancer was verified through the Finnish Cancer Registry. Interestingly, the questionnaires reveled only 15 of 57 cancers (index gliomas excluded) retrieved through the Cancer Registry. None of the 18 families fufilled the criteria for classic Li-Fraumeni syndrome. Immunostaining analysis of p53 protein accumulation suggested that alterations of the p53 gene are as common in familial as in sporadic gliomas. Sequencing analysis of exons 4-10 of the p53 gene revealed no germline mutations in any of the 18 families. Thus, although occasional glioma families carrying germline p53 mutations have been identified in earlier studies, systematic evaluation of familial glioma patients suggests that the p53 gene is not a common susceptibility gene in case of familial gliomas. The p53 tumor suppressor gene seems to have a similar role in the tumorigenesis of most familial and sporadic gliomas.

Adult↗

Inactivation of root canal medicaments by dentine, hydroxylapatite and bovine serum albumin.

AIM: This study examined and compared the inhibition of the antibacterial effect of saturated calcium hydroxide solution, chlorhexidine acetate and iodine potassium iodide by dentine, hydroxylapatite and bovine serum albumin. METHODOLOGY: Enterococcus faecalis strain A197A prepared to a suspension of 3 x 10(8) cells per ml in 0.5% peptone water was used. Fifty microL of saturated calcium hydroxide solution, 0.05% chlorhexidine acetate or 0.2/0.4% iodine potassium iodide were incubated at 37 degrees C with 28 mg dentine powder (DP), hydroxylapatite (HA) or bovine serum albumin (BSA) in 50 microL water for 1 h before adding 50 microL of the bacterial suspension. Samples for bacterial culturing were taken from the suspension 1 and 24 h after adding the bacteria. In further experiments, the amount of dentine was stepwise reduced from 28 mg 150 microL-1 to 2.8 mg 150 microL-1. RESULTS: Calcium hydroxide was totally inactivated by the presence of 28 mg of DP, HA or BSA. Chlorhexidine (0.05%) was strongly inhibited by BSA and slowed down by dentine. However, HA had little or no inhibitory effect on chlorhexidine. The antibacterial effect of 0.2/0.4% iodine potassium iodide on E. faecalis was totally inhibited by dentine (28 mg), but was practically unaffected by HA or BSA. A stepwise reduction of dentine from 28 mg 150 microL-1 to 2.8 mg 150 microL-1 was followed by a similar reduction of the inhibition of the antibacterial activity of chlorhexidine. Iodine potassium iodide was not inhibited at all with dentine amounts less than 28 mg. However, the effect of saturated calcium hydroxide solution was totally eliminated by dentine, in all four concentrations. CONCLUSION: Inhibition by dentine of the antibacterial activity of calcium hydroxide, chlorhexidine and iodine potassium iodide occurs by different mechanisms. Different components of dentine may be responsible for the inhibition of these three medicaments. Calcium hydroxide was particularly sensitive to inhibition by both inorganic and organic compounds.

Animals↗

Good maintenance of exercise-induced bone gain with decreased training of female tennis and squash players: a prospective 5-year follow-up study of young and old starters and controls.

This prospective 5-year follow-up study of 64 adult female racquet sports players and 27 controls assessed the changes in the playing-to-nonplaying arm bone mineral content (BMC) differences to answer three questions: (1) Are training-induced bone gains lost with decreased training? (2) Is the bone response to decreased training different if the playing career has been started before or at puberty rather than after it? (3) Are the possible bone changes related to the changes in training? The players were divided into two groups according to the starting age of their tennis or squash playing. The mean starting age was 10.5 years (SD, 2.2) among the players who had started training before or at menarche (young starters; n = 36) while 26.4 years (SD, 8.0) among those players who had begun training a minimum of 1 year after menarche (old starters; n = 28). At baseline of the 5-year follow-up, the mean age of the young starters was 21.6 years (SD, 7.6) and that of old starters was 39.4 years (SD, 10.5). During the follow-up, the young starters had reduced the average training frequency from 4.7 times a week (2.7) to 1.4 times a week (1.3) and the old starters from 4.0 times a week (1.4) to 2.0 times a week (1.4), respectively. The 5-year follow-up revealed that despite reduced training the exercise-induced bone gain was well maintained in both groups of players regardless of their clearly different starting age of activity and different amount of exercise-induced bone gain. The gain was still 1.3-2.2 times greater in favor of the young starters (at the follow-up, the dominant-to-nondominant arm BMC difference was 22% [8.4] in the humeral shaft of the young starters versus 10% [3.8] in the old starters, and 3.5% [2.4] in controls). In the players, changes in training were only weakly related to changes in the side-to-side BMC difference (r(s) = 0.05-0.34, all NS), and this was true even among the players who had stopped training completely a minimum 1 year before the follow-up. In conclusion, if controlled interventions will confirm our findings that an exercise-induced bone gain can be well maintained with decreased activity and that the maintenance of the bone gain is independent of the starting age of activity, exercise can be recommended for preventing osteoporosis and related fractures.

Adult↗

A controlled trial of the health benefits of regular walking on a golf course.

PURPOSE: To study the effects of regular walking during a golf game on various health and fitness indicators in middle-aged men. METHODS: Study subjects were 55 healthy male golfers aged 48 to 64 years who had been sedentary during the 7 months before the study, and 55 age-matched, similarly sedentary controls. During the 20-week study, those in the intervention group were encouraged to play golf two to three times a week; the controls were not. Measurements of body composition, cardiorespiratory performance, motor and musculoskeletal fitness, blood pressure, and serum lipid, glucose, and insulin levels were obtained at baseline and after the 20-week study. RESULTS: Walking during a golf game was a practical and safe form of physical activity with high adherence. It significantly increased aerobic performance and trunk muscle endurance, with a net difference (pretraining to posttraining change between the golfers and controls) of 36 seconds (95% confidence interval [CI]: 19 to 53 seconds, P < 0.001) for treadmill walking time and 13 seconds (95% CI: 2 to 24 seconds, P = 0.02) for static back extension. In addition, regular walking favorably affected body composition, including reductions in weight of 1.4 kg (95% CI: 0.6 to 2.1 kg, P < 0.001), in waist circumference of 2.2 cm (95% CI: 1.0 to 3.3 cm, P < 0.001), and in abdominal skin fold thickness of 2.2 cm (95% CI: 0.9 to 3.4 cm, P = 0.001). Golfers also had significantly greater increases in serum high-density lipoprotein (HDL) cholesterol levels and in the ratio of HDL cholesterol to total cholesterol. CONCLUSIONS: Regular walking had many positive effects on the health and fitness of sedentary middle-aged men. Walking during a golf game is characterized by high adherence and low risk of injury and is therefore a good form of health-enhancing physical activity.

Aged↗

Chromosome imbalances in familial gliomas detected by comparative genomic hybridization.

Familial occurrence of gliomas, in the absence of well-defined hereditary multisystem disorders, is reported occasionally. We describe 17 families that have been afflicted with two or more gliomas but do not raise suspicion of other inheritable syndromes. The families were identified among 369 consecutive glioma patients operated at the Tampere University Hospital during 1983-1994. We applied comparative genomic hybridization (CGH) analysis on 21 gliomas occurring in these 17 families. The most frequent genetic alterations, detected in over 20% of the tumors, were losses of 6q, 10, 4q, 9p and gains of 7, 19, 20q, 1p. We compared the chromosomal alterations detected in the familial gliomas to those reported previously on 209 sporadic gliomas in nine different CGH studies. In this comparison, the familial gliomas more often showed losses of chromosome arms 4q and 6q and gains of 1p and 22q. The most frequent losses (9/21 tumors) in the familial gliomas resided on chromosome arm 6q (P = 0.005, Fisher's exact test; with Bonferroni correction, P = 0.04). The loss of 6q was also the most common intrafamilial aberration, present in four separate gliomas belonging to two families. The minimal common area of loss on this chromosome resided at 6q14-16. In conclusion, we have found several characteristic aberrations by CGH in the familial gliomas and we present new chromosomal regions possibly involved in the familial predisposition to gliomas.

Adult↗

Genetic aberrations in sporadic and neurofibromatosis 2 (NF2)-associated schwannomas studied by comparative genomic hybridization (CGH).

BACKGROUND: Schwannomas occur sporadically or in association with neurofibromatosis 2 (NF2), an autosomal dominant disorder, which predisposes to multiple schwannomas, meningiomas and spinal ependymomas, with bilateral vestibular schwannomas as the classic hallmark. As NF2 and sporadic schwannomas differ in some respect in their clinical and biological behavior we evaluated whether there are any differences in the distribution of genetic aberrations between NF2 and sporadic schwannomas. Our interest was also to verify whether secondary genetic alterations besides the loss of 22q could be detected in schwannomas. METHODS: We investigated DNA copy number changes in 25 schwannomas (12 NF2 and 13 sporadic schwannomas) using the comparative genomic hybridization (CGH) technique. Some chromosomal regions were further studied by LOH or FISH analysis. FINDINGS: CGH detected genomic abnormalities in 15 of 25 schwannomas (60%). The most common alteration was loss on 22q, found in 32% (8/25) of schwannomas. No consistent changes were detected in other chromosomal regions. The overall number of genetic aberrations was similar in NF2 and in sporadic schwannomas. INTERPRETATION: Our results support the present view that loss of chromosome 22q harboring the NF2 gene plays a universal role in the pathogenesis of schwannomas without consistent involvement of other chromosomal regions.

Adolescent↗

Does childhood and adolescence provide a unique opportunity for exercise to strengthen the skeleton?

Osteoporosis is a major, and increasing, public health problem. In this review we examine the evidence that childhood physical activity is an important determinant of bone mineral in adult years, and as such, may help to prevent osteoporosis. Animal studies provide incontrovertible evidence that growing bone has a greater capacity to add new bone to the skeleton than does adult bone. Observational studies in children undertaking routine physical activity and cross-sectional athlete studies in young sportspeople both reveal that activity is positively associated with bone mineral density (BMD). Longitudinal studies in pre- and peripubertal gymnasts reveal BMD gains far in excess of those that can be achieved in adulthood. However, such studies permit only limited conclusions as they contain the potential for selection bias and can be confounded by other determinants of bone mineral (e.g. dietary and lifestyle factors). Thus, research comparing inter-individual playing-to-nonplaying arm differences in bone mineral (e.g., in racquet sports) have proven to be extremely useful. These studies suggest that the BMD differences are clearly greater when bone is subjected to mechanical loading prior to the end of puberty and longitudinal growth of the body (in women, before menarche) rather than after it. Tanner stage II and III appears to be the maturational stage when the association between exercise and BMD becomes manifest in most adolescents. Do conclusions drawn from athlete studies apply to the general population? Randomised intervention studies of physical activity and bone mineral accrual in normal children confirm that childhood activity is strongly associated with bone mineral accrual. Furthermore, some retired athlete studies and a detraining study suggest that adolescent bone gain may, at least partly, persist despite reduced adult physical activity. Mechanisms that may underlie the association between childhood physical activity and bone mineral accrual are outlined. Thus, it appears that physical activity during the most active period of maturity (with respect to longitudinal growth of the body) plays a vital role in optimising peak bone mass and that benefits may extend into adulthood.

Adult↗

Exercise-induced bone gain is due to enlargement in bone size without a change in volumetric bone density: a peripheral quantitative computed tomography study of the upper arms of male tennis players.

Bilateral bone characteristics of the humerus (proximal, shaft, and distal sites) and radius (shaft and distal sites) in 12 former Finnish national-level male tennis players (mean age 30 years) and their 12 age-, height-, and weight-matched controls were measured with peripheral quantitative computed tomography (pQCT). The pQCT variables analyzed were bone mineral content (BMC), total cross-sectional area of bone (Tot.Ar), cross-sectional area of the marrow cavity (M.Cav.Ar), cortical bone (Co.Ar) and trabecular bone (Tr.Ar), volumetric density of cortical (Co.Dn) and trabecular (Tr. Dn) bone, cortical wall thickness (Co.Wi.Th), bone strength index (BSI), and principal moments of inertia (I(min) and I(max)). In the players, significant side-to-side differences, in favor of the dominant (playing) arm, were found in BMC (ranging 14%-27%), Tot.Ar (16%-21%), Co.Ar (12%-32%), BSI (23%-37%), I(min) (33%-61%), and I(max) (27%-67%) at all measured bone sites, and in Co.Wi.Th. (5%-25%) at the humeral and radial shafts, and distal humerus. The side-to-side M.Cav.Ar difference was significant at the proximal humerus (19%) and radial shaft (29%). Concerning the players' Co.Dn and Tr.Dn, the only significant side-to-side difference was found in the Co.Dn of the distal humerus, with the playing arm showing a slightly smaller Co.Dn than the nonplaying arm (-2%). In controls, significant dominant-to-nondominant side differences were also found, but with the majority of the differences being rather small, and significantly lower than those of the players. In conclusion, despite the large side-to-side differences in BMC, the volumetric bone density (Co.Dn, Tr.Dn) was almost identical in the dominant and nondominant arms of the players and controls. Thus, the players' high playing-arm BMC was due to increases in the Tot.Ar, M.Cav.Ar, Co.Ar, and CW.Th. In other words, the playing arm's extra bone mineral, and thus increased bone strength, was mainly due to increased bone size and not due to a change in volumetric bone density. These upper arm results may not be generalized to the entire skeleton, but the finding may give new insight into conventional dual-energy X-ray absorptiometry (DXA)-based bone density measurements when interpreting the effects of exercise on bone.

Adult↗

Prognostic value of the expression of tumor suppressor genes p53, p21, p16 and prb, and Ki-67 labelling in high grade astrocytomas treated with radiotherapy.

Cumulative inactivation of tumor suppressor genes and/or amplification of oncogenes lead to progressively more malignant astrocytic tumors. We have analyzed the significance of tumor suppressor genes p53, p21, p16 and retinoblastoma protein (pRb) and proliferative activity for survival in 77 high grade astrocytic tumors. After operation, the patients--25 anaplastic astrocytomas (AA) and 52 glioblastomas (GBs)--were treated with similar radiotherapy. The expression of the suppressor genes and the proliferative activity were analyzed immunohistochemically. p53 immunopositivity was found in 44% of AAs and 46% of GBs. Tumors with aberrant p53 expression had lower proliferation indices than p53 immunonegative tumors. Neither p53 expression nor p21 immunonegativity (52% of AAs and 48% of GBs) correlated with survival. p16 immunostaining was negative in 16% of AAs and in 44% of GBs, and it correlated inversely with survival in both uni- and multivariate analyses. pRb immunostaining was negative only in 8% of both AAs and GBs and the absence of p16 and pRb were mutually exclusive. Ki-67 labelling index (LI) was significantly higher in GBs (26.8%) than in AAs (20.3%), and in multivariate analysis it was an independent prognostic factor for survival. In 48% of AAs Ki-67 LI exceeded 20% and this subset of AAs had similar prognosis as GB. In high grade astrocytic tumors p16 immunonegativity was an independent indicator of poor prognosis in addition to the previously established patient's age, histopathology and Ki-67 LI. Furthermore, there was a subset of AAs with a high proliferation rate (> 20%) in which the histopathological hallmarks of GB were lacking, but which had similarly dismal prognosis as GB.

Adult↗