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Biomedical subjects

E Alhava

Publications and source records attributed to E Alhava.

At least 73 records · Page 4Linked to original sources

Does vitamin D strengthen the increase in femoral neck BMD in osteoporotic women treated with estrogen?

The long-term effects on bone of estrogen therapy (HRT) combined with vitamin D3 supplementation were evaluated and compared with the effects of HRT without vitamin D3 supplementation in a 4-year prospective, partly randomized study among 60 osteoporotic women (mean age 55.4 years; range 49.7-59.4 years). The women studied were a subgroup of the population-based Kuopio Osteoporosis Risk Factor and Prevention Study (OSTPRE) (n = 13,100). The bone mineral densities (BMD) of the lumbar spine and femoral neck were determined by dual-energy X-ray absorptiometry (DXA) in 3236 perimenopausal women. Those 106 women with baseline BMD more than 2 SDs less than the mean value in this population, either at the lumbar spine (BMD < 0.826 g/cm2) and/or femoral neck (BMD < 0.684 g/cm2), were offered treatment for osteoporosis. After exclusions, 60 women were included in the analyses. Group allocation was: HRT (estradiol valerate (2 mg) plus cyproterone acetage, 1 mg, sequentially: ClimenR) (n = 21); HRT + Vit D: Climen + vitamin D3 (cholecalciferol, 300 IU/day, no intake during June-August) (n = 23); controls: 16 women who refused all treatment served as a non-randomized control group. In the HRT group, the highly significant increase in lumbar BMD was 5.4%, 5.3%, 4.7% and 4.0% after 1, 2, 3 and 4 years of treatment, respectively, all compared with the baseline values and with the control group. The increase in femoral neck BMD was statistically insignificant (1.4%, 2.2%, 1.9% and 2.1%, respectively; p > 0.05). In the HRT + Vit D group, the lumbar BMD increased by 3.7%, 4.9%, 4.9% and 4.9% (p < 0.001), whereas the 5.8% increase in femoral neck BMD reached significance at 4 years (p < 0.01) when compared with the control group as well as with the baseline values. However, there were no statistically significant differences in lumbar or femoral BMD changes between the two HRT groups. In conclusion, estrogen can substantially increase lumbar bone mass in patients with postmenopausal osteoporosis. In addition, the combination of HRT and vitamin D3 may increase femoral neck BMD in osteoporotic women more than estrogen alone.

Androgen Antagonists↗

Clinical relevance of p53 index and expression of proliferating cell nuclear antigen and Ki-67 in gastric cancer.

The prognostic value of the immunohistochemical expression of p53 protein, proliferating-cell nuclear antigen (PCNA) and Ki-67 antigen was evaluated in a series of 116 stage I-II gastric cancer patients. The staining for p53 protein (staining frequency and intensity) in malignant cells was expressed as a p53 index. Similarly, the staining frequency and intensity for PCNA and Ki-67 were evaluated. The p53 index was independent of the stage and differentiation grade, but significantly related to DNA ploidy, S-phase fraction and mitotic activity. A high p53 index was a sign of inferior survival, compared to a low or intermediate index. p53-negative tumours were also associated with poor survival. In a multivariate analysis, only the depth of tumour infiltration and the presence of nodal metastases were independent prognostic factors in stage I-II gastric cancer. PCNA expression and Ki-67 antigen expression were not related to the stage, ploidy, proliferative activity or p53 expression, and they had no impact on survival. The results indicate that p53 protein expression may be of prognostic significance in gastric cancer, while PCNA and Ki-67 antigen expression have no predictive value.

Adult↗

Expression of CD44 and variant proteins in human colorectal cancer and its relevance for prognosis.

BACKGROUND: CD44 is a cell adhesion molecule often expressed in the form of various splice variants. The role of standard CD44 isoform (CD44s) and its variants in colorectal carcinogenesis is partly conflicting. Therefore, we compared the expression of CD44s (hermes-3) and its splice variants (v3 and v6) with traditional prognostic factors in 194 colorectal cancer patients treated at Kuopio University Hospital and followed up for a mean of 14 years. METHODS: Formalin-fixed, paraffin-embedded tissue sections from 194 patients with colorectal carcinoma were examined immunohistochemically to detect the expression of different forms of CD44. The hypothesis that CD44s, CD44v3, and CD44v6 expression intensities and distribution in cancer cells correlated with survival was tested with the log-rank test, hazard ratios, and their confidence intervals. RESULTS: In high-grade tumours CD44s and CD44v6 expression intensities and CD44s percentages were stronger than in low-grade tumours. CD44v6, CD44v3, and CD44s expression intensities in tumour epithelium were also stronger in Dukes C and D tumours than in A and B tumours. In the univariate survival analysis patients with strong CD44s, CD44v3, and CD44v6 expression intensities in tumour epithelium had lower cancer-related survival than the patients who had weak CD44s, CD44v3, and CD44v6 expression intensities. Recurrence-free survival was also shorter in patients with intense signals for CD44v3 and CD44v6 in tumour epithelium. In the multivariate analysis the CD44v6 expression intensity in tumour epithelium predicted independently both cancer-related and recurrence-free survival in T1-4N0-3M0 and T1-3N0M0 cases. In addition, the CD44v3 expression intensity in tumour epithelium was a significant predictor of RFS in T1-3N0M0 cases. CONCLUSIONS: These results strongly suggest that the CD44 splice variants v6 and v3 have prognostic significance in colorectal cancer.

Adult↗

Azaserine-induced rat pancreas tumor model with transplantable cultured cells.

The purpose of this study was to describe the inoculation technique and patterns of growth as well as to characterize typical histological features of Lewis rat subcutaneous and intrapancreatic tumors, induced by inoculation of cultured pancreatic cancer cells (DSL-6A/C1). Subcutaneous inoculation of cultured cells produced a solid tumor that was a locally invasive, well- to moderately differentiated ductal adenocarcinoma. Tumor take was 100% in animals 5 weeks of age; tumor growth was consistent and predictable and a tumor volume of approximately 1 cm3 was reached in 8 weeks. After intrapancreatic transplantation the tumors showed the same histological features as subcutaneous tumors. During inoculation carcinoma cells easily spread around the injected area, and after 2 weeks both pancreatic tumors and superficially infiltrating carcinomas were found in the liver and spleen and around the peritoneum. Tumor take was 60% and tumor growth was somewhat indefinite and unpredictable in the pancreas. However, by reducing the injected carcinoma cell volume and solving the technical problems, 100% tumor take was achieved. The tumor volume reached 2 mm3 during 2 weeks and larger tumors showed a tendency for invasion. According to our results, subcutaneous as well as intrapancreatic tumor induction with cultured cells offers a model for pancreatic cancer studies.

Adenocarcinoma↗

Subchondral bone remodeling increases in early experimental osteoarthrosis in young beagle dogs.

We evaluated subchondral bone remodeling and structure in the condyles of the femur and the patellar surface of the femur in early experimental osteoarthrosis of young female beagle dogs. 14 littermate (twin) dogs were divided into operation (n 7) and control groups (n 7). The dogs in the operation group underwent surgically a 30 degrees valgus angulation of the right tibia to induce osteoarthrotic articular cartilage lesions in the knee (stifle) joint. 7 months postoperatively, bone samples were harvested from both condyles and the patellar surface of the femur and evaluated by histomorphometry of subchondral bone. Cartilage samples from the same areas were taken for histology. In the operated dogs, subchondral bone remodeling increased strikingly in the patellar surface of the femur; osteoid thickness and osteoblast surface/bone surface increased up to 42% and 94% (p < 0.05), as compared to controls. Total and active erosion depths increased by 14% and 30% in the same area (p < 0.05). However, in bone structural parameters no significant difference could be observed between the groups. In the medial condyle of the femur, the trabecular number decreased in operated dogs, as compared to controls (p < 0.05). The lateral condyle of the femur in operated animals did not differ from controls in the parameters tested. In the operated dogs, histology from cartilage samples showed initial osteoarthrotic changes in the patellar surface and the medial condyle of the femur. Histologic changes were greatest in the patellar surface of the femur, as assessed by the Mankin scores. At the very onset of osteoarthrosis, subchondral bone remodeling increases, but the bone structural changes are indistinct. It seems that in this osteoarthrosis model, cartilage lesions precede major subchondral changes in the structure of the bone.

Animals↗

Bone density at the proximal femur after total hip arthroplasty.

Recent developments in dual xray absorptiometry have made it possible to quantify bone mineral density changes adjacent to total hip arthroplasty. Even small changes in local bone mass that are not visible with conventional radiographs can be detected using dual xray absorptiometry. Commonly there is a loss of 10% to 45% of the periprosthetic bone mass during the first years after total hip arthroplasty. Recent studies have suggested that this bone loss is not necessarily progressive and some degree of restoration of bone density around implants may occur. Current data suggest that there is active bone remodeling in the proximal femur in response to prosthetic implantation. Such response differs between different stem designs and type of fixation.

Absorptiometry, Photon↗

Nuclear morphometry as a predictor of disease outcome in gastric cancer.

Nuclear morphometric features including nuclear area (NA), nuclear perimeter (PE), their variation (SDNA, SDPE), and mean largest and smallest nuclear diameters (Dmax, Dmin) were examined in 116 patients with stage I-II gastric adenocarcinoma. Morphometric measurements were compared with tumour differentiation, depth of invasion (pT), lymph node status (pN), and Lauren classification. All morphonuclear features were significantly larger in the intestinal type than in the diffuse type of cancer. None of the morphometric variables was related to TNM status or tumour size. Nuclear area and perimeter and their variation were closely related to survival in univariate analysis, patients with small and regular nuclei surviving longer. In the multivariate analysis, pT, pN, perineural invasion, and the standard deviation of nuclear perimeter (SDPE) were independent predictors of survival. Nuclear morphometry is a quantitative, objective, and highly reproducible method of revealing malignant features in several neoplasms. The results of the present study suggest that nuclear morphometric data may help in defining prognosis in gastric cancer.

Adenocarcinoma↗

Prognostic value of tumour-infiltrating lymphocytes (TILs) in colorectal cancer.

Clinical follow-up data of 276 colorectal adenocarcinoma patients treated in Kuopio University Hospital between 1976 and 1986 and followed up for a mean of 14 years were analysed. The clinical findings were correlated with tumour-infiltrating lymphocytes (TILs) and with histological and quantitative factors including nuclear parameters and volume-corrected mitotic index. In univariate survival analysis, TNM classification, Dukes' stage, histological grade, and TILs were significant predictors of survival. TNM classification, Dukes' stage, and TILs also predicted recurrence-free survival. In multivariate analysis, TILs were an independent prognostic factor of survival in all cases, as well as in patients with T1-4N0-3M0 and T1-4N1-3M1. TILs also independently predicted recurrence-free survival. TILs can provide important prognostic information in colorectal cancer to be used in evaluating for adjuvant therapy in different tumour stages.

Adenocarcinoma↗

Vitamin D and HRT: no benefit additional to that of HRT alone in prevention of bone loss in early postmenopausal women. A 2.5-year randomized placebo-controlled study.

The study was designed to examine the effect of hormone replacement therapy (HRT) and low-dose bone loss in non-osteoporotic early postmenopausal women and to determine whether Vit D supplementation can give additional benefit to an already optimized estrogen regimen. The effects of HRT and Vit D on bone mineral density (BMD) were studied in postmenopausal women in a 2.5-year randomized placebo-controlled study. The study population was a subgroup of the Kuopio Osteoporosis Risk Factor and Prevention Study (OSTPRE) (n = 13100). A total of 464 early postmenopausal women were randomized to four groups: (1) HRT (a sequential combination of 2 mg estradiol valerate and 1 mg cyproterone acetate (E2Val/CPA); (2) vitamin D3 (cholecalciferol, 300 IU/day); (3) HRT + Vit D; and (4) placebo (calcium lactate; 93 mg Ca2+/day). Lumbar (L1-4) and femoral neck BMD were determined by dual-energy X-ray absorptiometry before and after 2.5 years of treatment. After 2.5 years, lumbar BMD had increased by 1.8% in the HRT group (p > 0.001) and by 1.4% in the HRT + Vit D group (p = 0.002), whereas lumbar BMD had decreased by 3.5% (p < 0.001) in the Vit D group and by 3.7% (p < 0.001) in the placebo group. The loss of femoral neck BMD was lower in the HRT (-0.3%) and the HRT + Vit D (0.9%) groups compared with the Vit D (-2.4%) and the placebo groups (-3.7%). This study confirms the beneficial effect of HRT on BMD. It also shows that low-dose vitamin D supplementation has only a minor effect in the prevention of osteoporosis in non-osteoporotic early postmenopausal women and does not give any benefit additional to that of HRT alone.

Anthropometry↗

The effect of dobutamine infusion on splanchnic blood flow and oxygen transport in patients with acute pancreatitis.

OBJECTIVES: To measure the blood flow distribution and oxygen transport in pancreatitis and to evaluate the regional effects of increased systemic blood flow. DESIGN: Nonrandomized controlled trial. SETTING: A general intensive care unit in a tertiary care center. PATIENTS: 10 patients with pancreatitis requiring mechanical ventilation were studied after fluid resuscitation, and for the response to dobutamine, the patients served as their own controls. For the baseline, 11 patients scheduled for elective abdominal surgery served as a control group. INTERVENTIONS: Systemic and regional hemodynamics were measured after fluid resuscitation to predefined hemodynamic endpoints. In patients with pancreatitis, the measurement was repeated after cardiac output had been increased by at least 25% by dobutamine. MEASUREMENTS AND RESULTS: Hepatosplanchnic blood flow was estimated using regional catheterization and the dye dilution method. In patients with pancreatitis, the cardiac index did not differ from that of the control group (3.9 +/- 0.8 vs 4.1 +/- 0.71.min-1.m-2;NS). Accordingly, there was no difference in the splanchnic blood flow (1.1 +/- 0.4 vs 1.2 +/- 0.51.min-1.m-2;NS). Systemic and splanchnic oxygen consumption was increased in patients with pancreatitis (179 +/- 25 vs 147 +/- 27 ml.min-1.m-2, p < 0.05 and 68 +/- 15 vs 49 +/- 19 ml.min-1.m-2, p < 0.05), and systemic and splanchnic oxygen extraction was higher (0.34 +/- 0.08 vs 23 +/- 0.05, p < 0.01 and 0.46 +/- 0.18 vs 0.28 +/- 0.08, p < 0.05, respectively). Dobutamine had inconsistent effects on splanchnic blood flow: in individual patients, splanchnic blood flow even decreased substantially. CONCLUSIONS: In severe pancreatitis, oxygen consumption is increased in the splanchnic region; increased splanchnic oxygen demand is not always met by adequately increased blood flow. Increasing the systemic blood flow with dobutamine does not improve perfusion in the splanchnic bed.

Acute Disease↗

Associations of early premenopausal fractures with subsequent fractures vary by sites and mechanisms of fractures.

In a retrospective population-based study we assessed whether and how self-reported former fractures sustained at the ages of 20-34 are associated with subsequent fractures sustained at the ages of 35-57. The 12,162 women who responded to fracture questions of the baseline postal enquiry (in 1989) of the Kuopio Osteoporosis Study, Finland formed the study population. They reported 589 former and 2092 subsequent fractures. The hazard ratio (HR), with 95% confidence interval (CI), of a subsequent fracture was 1.9 (1.6-2.3) in women with the history of a former fracture compared with women without such a history. A former low-energy wrist fracture was related to subsequent low-energy wrist [HR = 3.7 (2.0-6.8)] and high-energy nonwrist [HR = 2.4 (1.3-4.4)] fractures, whereas former high-energy nonwrist fractures were related only to subsequent high-energy nonwrist [HR = 2.8 (1.9-4.1)] but not to low-energy wrist [HR = 0.7 (0.3-1.8)] fractures. The analysis of bone mineral density (BMD) data of a subsample of premenopausal women who underwent dual x-ray absorptiometry (DXA) during 1989-91 revealed that those with a wrist fracture due to a fall on the same level at the age of 20-34 recorded 6.5% lower spinal (P = 0.140) and 10.5% lower femoral (P = 0.026) BMD than nonfractured women, whereas the corresponding differences for women with a former nonwrist fracture due to high-energy trauma were -1.8% (P = 0.721) and -2.4% (P = 0. 616), respectively. Our results suggest that an early premenopausal, low-energy wrist fracture is an indicator of low peak BMD which predisposes to subsequent fractures in general, whereas early high-energy fractures are mainly indicators of other and more specific extraskeletal factors which mainly predispose to same types of subsequent fractures only.

Absorptiometry, Photon↗

Systemic and regional effects of experimental gradual splanchnic ischemia.

PURPOSE: We evaluated the effects of gradual intestinal ischemia on systemic and regional haemodynamics and oxygen transport. MATERIALS AND METHODS: Superior mesenteric artery (SMA) blood flow was decreased by 40%, 70%, and 100% for 60-minute periods and thereafter released in 12 pigs. Hemodynamic changes were monitored continuously, and the intestinal perfusion was evaluated by changes in portal vein-arterial lactate gradient, intramucosal pH, tonometric Pco2, tonometric-portal vein Pco2 gradient, and regional oxygen extraction. RESULTS: Local signs of intestinal hypoperfusion developed during the SMA occlusion. Intramucosal pH and portal vein pH decreased from 7.18 +/- 0.04 to 6.81 +/- 0.04 (P < .01) and from 7.36 +/- 0.01 to 7.25 +/- 0.03 (P < .05), respectively. Intramucosal Pco2 and tonometric-portal vein Pco2 gradient increased from 12.4 +/- 1.3 to 21.2 +/- 1.8 kPa (P < .01) and from 6.0 +/ 1.3 to 14.0 +/- 1.9 kPa (P < .05), respectively. Portal vein-arterial lactate gradient and splanchnic oxygen extraction increased from 0.02 +/- 0.07 to 2.32 +/- 0.47 mmol/L (P < .01) and from 0.44 +/- 0.03 to 0.60 +/- 0.03 (P < .05), respectively. Systemic changes observed during the SMA occlusion were reduction of cardiac index (161 +/- 12 to 114 +/- 8 mL/min/kg, P < .01) and pulmonary capillary wedge pressure (4 +/- 1 to 3 +/- 1 mm Hg) and increase in heart rate (124 +/- 5 to 173 +/- 11 beats/ min, P < .01) and mean arterial pressure (79 +/- 3 to 104 +/- 5 mm Hg, P > .01). Systemic oxygen extraction increased (P > .05), arterial pH increased (P < .05), and arterial lactate decreased (P < .01) during the SMA occlusion. Splanchnic ischemia defined as an increase in portal vein-arterial lactate gradient above mean +2 SD of the baseline occurred at 93 +/- 15 minutes corresponding 70% SMA occlusion. CONCLUSION: We conclude that signs of tissue hypoperfusion started to develop at 70% SMA occlusion and that regional tissue hypoperfusion in the splanchnic region may develop without any systemic signs of oxygen supply/demand mismatch.

Hemodynamics↗

The importance of fluorescence distribution and kinetics of ALA-induced PpIX in the bladder in photodynamic therapy.

Photodynamic therapy (PDT) is a new anticancer technique directed at the selective destruction of neoplastic tissue. Aminolevulinic acid (ALA), a precursor in the biosynthesis of home, induces the production of the endogenous photosensitizer protoporphyrin IX (PpIX). In this study the fluorescence distribution of ALA-induced PpIX was investigated in the rat bladder wall by fluorescence microscopy. The fluorescence studies showed that PpIX concentrates in bladder mucosa and that the highest fluorescence levels are achieved after four hours of 300 mg/kg ALA administration. A clear trend in difference between mucosa and muscularis layers was found in all samples taken after 1, 2, 4 and 6 hours of ALA administration. Our results suggest that to get the highest PpIX fluorescence intensity in bladder mucosa it is best to use 300 mg/kg ALA administration. Four hours is the time point when the highest difference in fluorescence between mucosa and muscularis is reached.

Aminolevulinic Acid↗

Lactose intolerance associated with fractures of weight-bearing bones in Finnish women aged 38-57 years.

Lactose intolerance (LI) often results in decreased calcium intake. To test if long-term low intake of calcium affects bone strength, we examined fracture risks related to LI in women aged 38-57 years. The 11,619 Finnish women aged 47-56 years who responded to the baseline postal inquiry of the Kuopio Osteoporosis Risk Factor and Prevention Study in 1989 formed the study population. In all, 896 women reported LI and 1299 women reported a fracture in 1980-1989. Current intake of dairy calcium was lower in women with LI (570 mg/d) than in the other women (850 mg/d) (p < 0.0001). The fracture risk in general was slightly elevated in women with LI compared with the other women, with an odds ratio (OR) (95% CI) of 1.33 (1.09-1.62). However, the fractures at the three most common sites (wrist, ankle, and rib) were not related to LI. In contrast, fractures at the tibia and metatarsal were strongly related to LI with ORs of 3.31 (1.51-7.24) and 2.84 (1.47-5.50), respectively. The adjusted OR for nonankle lower body fractures combined was 2.15 (1.53-3.04), whereas that for all upper body fractures combined was 1.15 (0.88-1.54). The 10 women with LI and a tibial or metatarsal fracture showed a 19% lower femoral BMD than all the other women in the densitometry subsample of 3222 women (p < 0.001). Long-term premenopausal calcium deficiency differentially affects bones with weight-bearing nonankle bones being at the greatest risk of suffering reduced strength.

Adult↗

Protoporphyrin-IX distribution and photodynamic effect in rat oesophagus after aminolaevulinic acid administration.

BACKGROUND: Photodynamic therapy (PDT) is a method for local and selective tumour destruction achieved by the action of light on a photosensitizing drug. METHODS: We investigated the distribution of 5-amino-laevulinic acid (ALA)-induced protoporphyrin-IX fluorescence in rat oesophagus by fluorescence microscopic examination and then studied the effects of PDT. RESULTS: The highest level of fluorescence was achieved in the mucosa after 4 h of 300 mg/kg ALA administration. A clear difference in fluorescence between mucosa and muscularis was found in all samples except those taken 24 h after ALA administration. PDT with ALA caused destruction of the mucosal and, partly, submucosal layers of the oesophagus without damaging the muscularis layer. CONCLUSIONS: According to our results with microscopic fluorescence kinetics and the preliminary results of PDT, selective destruction of the superficial layer of the rat oesophagus is achieved with PDT after ALA administration.

Aminolevulinic Acid↗

Microangiopathy in acute acalculous cholecystitis.

BACKGROUND: Acute acalculous cholecystitis is a well recognized complication of many acute illnesses. Ischaemia of the gallbladder seems to have an important role in its pathogenesis. METHODS: Microangiography was performed in 15 gallbladders immediately after cholecystectomy by infusing 10 per cent barium sulphate into the specimen. Five patients had symptomatic gallstone disease, five had acute gallstone-associated cholecystitis and five had acalculous cholecystitis. Sections for histological examination were taken from adjacent sides of the microangiography section. Filling of the vessels by contrast medium was compared with histological findings. RESULTS: Microangiography of the gallbladder in acute gallstone-associated cholecystitis showed strongly dilated arterioles and regular filling of the capillary network, whereas in acalculous cholecystitis the capillary filling was poor and irregular. CONCLUSION: Disturbed microcirculation may play an important role in the pathogenesis of acute acalculous cholecystitis.

Adult↗