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Biomedical subjects

H Helin

Publications and source records attributed to H Helin.

At least 55 records · Page 3Linked to original sources

Loss of estrogen receptor in recurrent breast cancer is associated with poor response to endocrine therapy.

PURPOSE: Up to 30% to 40% of metastases from hormone receptor-positive primary breast cancer do not respond to endocrine therapy. We studied how often hormone receptor status changes between primary and recurrent tumors and whether such a change might explain unresponsiveness to endocrine therapy. PATIENTS AND METHODS: Primary breast cancer samples and matched asynchronous recurrences were studied from 50 patients who had not received any adjuvant therapy. Estrogen receptor (ER) and progesterone receptor (PR) status was determined immunohistochemically from histologically representative formalin-fixed paraffin-embedded tumor samples. ER status was ascertained by mRNA in situ hybridization. RESULTS: Thirty-five (70%) of 50 primary tumors were positive for ER and 30 (60%) for PR. Hormone receptor status of the recurrent tumor differed from that of the primary tumor in 18 cases (36%). Discordant cases were due to the loss of ER (n = 6), loss of PR (n = 6), or loss of both receptors (n = 6). Receptor-negative primary tumors were always accompanied by receptor-negative recurrences. Among 27 patients with ER-positive primary tumors, loss of ER was a significant predictor (P = .0085) of poor response to subsequent endocrine therapy. Only one of eight patients (12.5%) with lost ER expression responded to tamoxifen therapy, whereas the response rate was 74% (14 of 19) for patients whose recurrent tumors retained ER expression. CONCLUSION: Loss of ER expression in recurrent breast cancer should be considered as a cause for poor response to endocrine therapy in primarily ER-positive patients. We conclude that analysis of recurrent tumor samples may improve the predictive value of ER and PR assays.

Adult↗

Expression of peripheral-type benzodiazepine receptor and diazepam binding inhibitor in human astrocytomas: relationship to cell proliferation.

The expression of peripheral-type benzodiazepine receptor (PBR) and diazepam binding inhibitor (DBI) were studied in human astrocytic tumors using immunocytochemistry and in situ hybridization. Both PBR and DBI were prominently expressed in neoplastic cells, whereas in normal brain their amount was low or undetectable. Immunocytochemical double staining demonstrated that PBR and DBI were present in the same cells, suggesting that DBI may act in an autocrine manner in these cells. Analysis of 86 cases showed that PBR expression was statistically significantly associated with tumor malignancy grade (P = 0.004) and the proliferative index as determined by immunocytochemistry with the MIB-1 antibody (P = 0.004). Patients having tumors with high levels of PBR-immunoreactive cells had a shorter life expectancy than patients whose tumors showed lower PBR contents (P = 0.024). In conclusion, these results show that PBR expression is higher in neoplastic cells than in normal brain tissue. They also suggest that PBR immunocytochemistry might be useful in evaluating malignancy in brain tumors.

Adolescent↗

Corneal vascularization and opacification during long-term use of dipivefrin.

Dipivefrin hydrochloride is a lipophilic prodrug for epinephrine hydrochloride, allowing lower concentration of the drug to achieve the same intraocular pressure lowering effect and having also less harmful effects than epinephrine hydrochloride. However, harmful effects have been associated also with the use of dipivefrin and here we report of a case of corneal vascularization during long-term use of dipivefrin.

Blepharitis↗

Albumin excretion rate and its relation to kidney disease in non-insulin-dependent diabetes mellitus.

OBJECTIVE: To estimate the occurrence of increased albumin excretion rate (AER) and its significance as a marker of diabetic kidney disease in non-insulin-dependent diabetic subjects. DESIGN: Population-based, controlled cross-sectional study. SETTING: A primary health care centre in the city of Tampere, south-west Finland. SUBJECTS: Consecutive, recently diagnosed (n = 150) and long-term (n = 146) middle-aged non-insulin-dependent diabetic subjects. Matched non-diabetic control subjects (n = 150). MAIN OUTCOME MEASURES: Albumin excretion rate, fractional AER, microalbuminuria (AER 30-300 mg 24 h-1), clinical nephropathy (AER exceeding 300 mg 24 h-1) and kidney biopsy in diabetic subjects with an AER exceeding 100 mg 24 h-1. RESULTS: Mean (+/- standard deviation [SD]) 24-h AER was increased in recently diagnosed diabetic subjects, 54 (111) mg, and long-term diabetic subjects, 134 (479) mg, compared to non-diabetic control subjects, 16 (19) mg. The fractional AER was 7.5 (18.3) x 10(-6) in recent diabetic subjects, 53.1 (306.9) x 10(-6) in long-term diabetic subjects and 2.8 (3.7) x 10(-6) in non-diabetic control subjects. Microalbuminuria was found in 8% of non-diabetic subjects, in 29% of recent and in 27% of long-term diabetic subjects. The prevalence of clinical nephropathy was 7% in long-term and 4% in recent diabetic subjects, whilst no non-diabetic subject had nephropathy. In 12 of 16 eligible kidney biopsies, diabetic glomerulosclerosis was found, in four subjects the finding was normal. CONCLUSIONS: The AER is clearly increased in recent non-insulin-dependent diabetic subjects and further increased in diabetic subjects with a mean disease duration of 10 years. An increased AER in non-insulin-dependent diabetic subjects suggests diabetic kidney disease.

Adult↗

Isolated microscopic hematuria in patients with rheumatoid arthritis compared with age and sex matched controls. A population based study.

OBJECTIVE: To evaluate the prevalence and causes of isolated microscopic hematuria in patients with rheumatoid arthritis (RA). METHODS: An unselected population of 1018 patients with RA (810 women, 208 men) were studied prospectively (n = 604) or retrospectively (n = 414), and the results were compared with an age and sex matched control population (n = 457; 352 women, 105 men). Hematuria was defined as a positive dipstick result in 2 urine samples, and was regarded as isolated when no concomitant proteinuria was found (urine protein excretion < or = 0.15 g/24 h). To investigate the urological causes of isolated hematuria, urine cytology, renal ultrasound, and urethrocystoscopy were undertaken. Renal biopsy was performed when no urological lesions were found. RESULTS: There was no difference in the prevalence of isolated hematuria between patients with RA and controls (women 10 and 9%, men 5 and 6%, respectively; total 9% for both). Mild mesangial glomerulopathy was the most common renal biopsy finding in patients with RA with isolated hematuria, found in 13 of 15 adequate renal biopsy specimens. The cause of hematuria remained uncertain or unknown in 52% of the patients with RA and in 61% of controls. CONCLUSION: The prevalence of isolated microscopic hematuria was not significantly more frequent in patients with RA than in age and sex matched controls. This result was independent of the definition or grade of hematuria. Mesangial glomerulopathy was the most common renal biopsy finding in patients with RA with isolated hematuria.

Adult↗

[The detection of secondary amyloidosis in rheumatoid arthritis by aspiration biopsy of the subcutaneous fatty tissue].

81 rheumatoid arthritis patients were regularly and periodically examined in rheumatological department of Tartu University Clinic. Depending on the presence of amyloid in subcutaneous fat biopsies the patients were divided into two comparable groups: amyloid-positive (group 1 of 22 patients) and amyloid-negative (group 2 of 59 patients). Between the groups some differences were found: group 1 patients had more active and severe course of rheumatoid arthritis and higher level of rheumatoid factor and circulating immune complexes in the sera. Before biopsy secondary amyloidosis was diagnosed in 17.4% of the examines, biopsy of abdominal subcutaneous fat increased this rate to 27.2%. We could not ascertain any effect of previous treatment on secondary amyloidosis development except the connection with long-term use of corticosteroids. The analysis of 10379 autopsies showed that cases of RA with amyloidosis account for 30.9% of all amyloidosis cases. Multiple stepwise regression analysis determined predisposition factors to secondary amyloidosis as severity of locomotor system involvement, long-term use of corticosteroids, high level of rheumatoid factor and activity of rheumatoid process.

Abdomen↗

Sources of variation in the assessment of cell proliferation using proliferating cell nuclear antigen immunohistochemistry.

The reproducibility in quantitation of proliferation activity, determined using the monoclonal antibody 19A2 to proliferating cell nuclear antigen (PCNA), was tested in visual and computer-assisted analyses of brain tumor material. The PCNA labeling index was scored using count (PCNA-LI, visual and computer analyses) and area (PCNA-LIa, computer analysis) estimates of immunopositivity. The quality of immunostaining was the most important reason for variation in the assessment results. Other significant variation sources in the assessment were experience in selecting microscopic fields and distinguishing immunopositive nuclei from immunonegative ones. Computer-assisted analysis improved the reproducibility of quantitation between different observers (visual rPCNA-LI = 0.624 versus computer assisted rPCNA-LI = 0.904). Also, the use of PCNA-LIa improved the intraobserver and interobserver reproducibility in different stainings (observer 1:rPCNA-LI = 0.857 versus rPCNA-LIa = 0.874; observers 1 and 2: rPCNA-LI = 0.904 versus rPCNA-LIa = 0.927; observers 3 and 4: rPCNA-LI = 0.848 versus rPCNA-LIa = 0.906). PCNA-LIa by computerized image analysis improves accuracy in the evaluation of the granularly expressed PCNA level. Furthermore, the effect of tumor heterogeneity on the assessment results can be diminished with the computerized method because large tissue areas can be analyzed faster.

Astrocytoma↗

Renal biopsy findings and clinicopathologic correlations in nephropathia epidemica.

A series of 126 adult patients with a serologically confirmed diagnosis of nephropathia epidemica (NE) were studied during the acute phase of the disease. In 86 cases, renal biopsy was performed. The severity of renal failure correlated slightly with blood inflammatory parameters and the degree of hematuria but not with the amount of proteinuria. The degree of hematuria correlated inversely with the level of thrombocytopenia. The most common histopathologic lesion was acute tubulointerstitial nephritis. Interstitial edema and inflammatory cell infiltrations were most usually present, followed by tubular epithelial and luminal alterations. Slight glomerular mesangial changes were present in 25% of the biopsy specimens. Except for hemorrhage in the outer renal medulla, the histologic lesions were relatively mild and unspecific. Interstitial hemorrhage should remind a pathologist of the possibility of NE. Tubular, interstitial and glomerular histologic damage were but vascular lesions were not associated with the clinical severity of renal failure. Glomerular alterations did not relate to the amount of urine protein excretion. Correlations, however, were so weak that in clinical work renal biopsy is usually not indicated for determination of the severity of renal failure in NE. Intrinsic renal events are probably important in the development of renal failure in NE.

Acute Kidney Injury↗

Follow-up of patients positive in reticulin and gliadin antibody tests with normal small-bowel biopsy findings.

Twenty-five patients with positive serum reticulin or gliadin antibody titres and having normal small-bowel mucosal villous architecture were re-biopsied after a follow-up period of 1 to 7 years. Seven were found on control examination to have small-bowel villous atrophy. At the initial examination, when coeliac disease was 'excluded', they thus belonged to the entity latent coeliac disease. Morphometrically minor mucosal changes in the initial biopsy specimen, suggesting an ongoing process, were seen in only three of them. Especially the serum IgA-class reticulin antibody test was a good predictor of latent coeliac disease. This study implies that patients with so-called false-positive IgA-class reticulin or gliadin antibody test should be re-examined.

Adult↗

Frequency of amyloidosis in Estonian patients with rheumatoid arthritis.

Occurrence of secondary amyloidosis in hospitalized Estonian patients suffering from rheumatoid arthritis was studied using subcutaneous fat aspiration biopsies. Only 47 out of 59 samples included fat, and amyloidosis deposits were found in 11 of these (23%). The high frequency of amyloidosis may be due to selection of the most severe cases in the hospital.

Adipose Tissue↗

Amyloidosis--incidence and early risk factors in patients with rheumatoid arthritis.

In a 15-year follow-up examination, reactive secondary amyloidosis (RSA) was found by subcutaneous fat biopsy in six out of 74 still living patients (8.1%) of an original population of 102 with erosive and seropositive rheumatoid arthritis (RA). Five of the 24 deceased patients had had RSA. Thus the 15-year incidence of RSA in RA was at least 10.9% (11/102). To study early prognostic aspects of RSA, comparison was made of 14 entry variables and the initial treatment in the RSA group (n = 11) and the control group (n = 81) respectively. At onset (< or = 6 months) of RA only serum orosomucoid, but after three years morning stiffness, ESR, serum CRP and orosomucoid were significantly worse in patients whom later developed RSA. Three out of 48 patients treated with gold sodium thiomalate and seven out of 30 treated with chloroquine developed RSA (p = 0.04). It is concluded that continuously active disease was the risk factor underlying RSA. The role of early chloroquine therapy is discussed.

Adult↗

Aberrant p53 expression in astrocytic neoplasms of the brain: association with proliferation.

Aberrant expression of the p53 suppressor gene was evaluated in 102 cases of astrocytic neoplasms. Immunohistochemical staining with a monoclonal antibody (DO-7) and a polyclonal antibody (CM-1) to p53 protein (both wild type and mutant) on formalin-fixed paraffin sections showed a strong correlation with malignancy grade. The staining was positive in 49% of malignant neoplasms (grades III and IV) and in 19 to 29% of grade II astrocytomas, whereas none of the grade I tumors were positive. p53 expression was significantly associated with proliferation rate determined by immunohistochemical proliferating cell nuclear antigen (PCNA)-staining (median PCNA-labeling index (%): 4.22 (DO-7-positive) versus 1.18 (DO-7-negative), P < 0.0001; 4.02 (CM-1-positive) versus 1.18 (CM-1-negative), P < 0.001). Interestingly, in the glioblastoma group (n = 44), p53-positive tumors had higher proliferation indices, suggesting that histologically similar tumors could be divided into prognostically different subgroups by immunohistochemical demonstration of aberrant p53 expression.

Analysis of Variance↗

The expression of CEA, CA 19-9 and HMFG antigens in ovarian clear-cell and endometrioid carcinomas.

The tumour antigen expression of ovarian and endometrial endometrioid carcinomas, ovarian clear-cell carcinomas as well as endometrial and cervical clear-cell carcinomas were immunohistochemically compared. Of special interest were potential differences between the endometrioid and clear-cell carcinomas of the ovary. The expression of CEA and CA 19-9 tumour antigens in all these tumour types was heterogeneous, with 10-20% of the cases being positive for CEA and 40-75% being positive for CA 19-9. In contrast, HMFG IIIC 12, a monoclonal antibody originally directed against human milk fat globule (HMFG) membrane antigens, invariably detected a corresponding antigen on every case of these tumour types. Another HMFG antibody, SM IF 3, on the other hand, detected antigenic material on all clear-cell tumour types, but only rarely on endometrioid tumours of the ovary or endometrium. While HMFG IIIC 12 detects an antigen present on all ovarian, endometrial and mammary carcinomas, antibody SM IF 3 thus appears to be more restricted in its staining patterns. Our results with both of these antibodies indicate that ovarian clear-cell carcinomas and ovarian endometrioid carcinomas have antigenic differences, which provides further evidence that they belong to different tumour entities.

Adenocarcinoma↗

Proliferative activity of human uterine leiomyoma cells as measured by automatic image analysis.

Proliferative activity of uterine leiomyomas from premenopausal (n = 44) and postmenopausal (n = 12) women was investigated by automatic image analysis on frozen tissue sections using immunohistochemistry with anti-proliferating cell nuclear antigen antibody. The quantitative proliferation index (QPI) in premenopausal leiomyoma cells was significantly (p < 0.025) higher than that in leiomyomas in postmenopausal women. Leiomyomas proliferated most actively during the secretory phase. After the climacterium, leiomyomas showed no proliferative activity in the absence of hormone supply, while combined substitution with estrogen and progestagen considerably increased QPI.

Antibodies, Anti-Idiotypic↗

Prognostic significance of HER-2 oncoprotein expression in breast cancer: a 30-year follow-up.

PURPOSE: To study retrospectively the long-term prognostic significance of HER-2 oncoprotein expression in breast cancer (BC). PATIENTS AND METHODS: Two hundred nine consecutive female patients with invasive operable BC from a defined urban population were observed for a median of 30 years. Tissue expression of HER-2 oncoprotein was demonstrated by using an immunoperoxidase procedure. RESULTS: Fifty-five (26%) patients had cancer and a positive HER-2 oncoprotein stain reaction. They had significantly worse 10- and 25-year survival rates than those patients who had a negative stain reaction in their cancer (31% v 48% and 31% v 39%, respectively; P = .004). HER-2 expression was also associated with a poorer survival among patients who had axillary nodal metastases (P = .003; n = 104), but not among those patients who did not have metastases. HER-2 expression was related to the ductal histologic type, poor histologic grade, and high mitotic count, but not to tumor size, axillary nodal status, DNA ploidy, or S-phase fraction (SPF). In a multivariate analysis among patients with nodal metastases, HER-2 expression was an independent prognostic factor (P = .04) that predicted poor survival. However, if the entire series was entered onto the analysis, it did not emerge as an independent factor. CONCLUSIONS: HER-2 oncoprotein expression has long-term prognostic significance for predicting poor survival in BC, and it has an independent prognostic value among patients who presented with axillary nodal metastases. This result is contradictory to the argument that HER-2 expression is only a marker for drug resistance because the patients were not given adjuvant drug therapy.

Adult↗

Mesangial glomerulopathy in rheumatoid arthritis patients. Clinical follow-up and relation to antirheumatic therapy.

23 patients (16 women, 7 men) with rheumatoid arthritis (RA) and renal biopsy-proven mesangial glomerulopathy (MGP) were followed for 4-117 months (median 42) in order to evaluate the clinical course of their renal disease. Urinalysis was made, and 24-hour urine protein excretion and serum creatinine were determined. At the time of renal biopsy, the clinical renal findings of the patients were isolated hematuria (n = 10), isolated proteinuria (n = 6) and hematuria combined with proteinuria (n = 7). Hematuria persisted and renal function remained normal in all patients with isolated hematuria. A possible association between the presence of hematuria and the use of antirheumatic drugs was not established in this study. Proteinuria was clinically closely associated with the use of antirheumatic drugs in 9 out of 13 cases (6 with gold sodium thiomalate, 2 with D-penicillamine and 1 with auranofin) suggesting that antirheumatic drugs are important contributors to proteinuria in these patients. Renal function, although initially reduced in some patients, remained stable in all but 1 patient with IgA glomerulonephritis who developed the nephrotic syndrome and died of uremia. In conclusion, the clinical course of MGP in RA patients is benign in most patients. Moreover, this nephropathy may not represent a clinical entity. Proteinuria was related to antirheumatic drugs in most patients whereas microhematuria was constant even after stopping the antirheumatic drugs.

Adult↗