Diagnosis of atrophic gastritis from a serum sample.

On the basis of the levels of serum pepsinogen I (S-PGI) and gastrin-17 (S-G-17) as well as Helicobacter pylori antibodies it is possible to establish with high sensitivity and specificity whether the patient has gastritis, whether the gastritis is atrophic or not and in which part of the stomach the atrophic changes are located. The tests enable the identification of patients whose risk of gastric cancer, consequences of vitamin B12 deficiency or peptic ulcer is increased considerably and who should therefore undergo gastroscopy. They also facilitate diagnosis of non-atrophic Helicobacter gastritis enabling treatment before endoscopy.

Serum levels of amidated gastrin-17 and pepsinogen I in atrophic gastritis: an observational case-control study.

BACKGROUND: Helicobacter pylori infection is often diagnosed with non-endoscopic methods, such as serology or breath or antigen stool tests. These tests provide information on the presence or absence of the H. pylori gastritis only. We investigated whether atrophic gastritis can be diagnosed and typed non-endoscopically if the serum levels of pepsinogen I (S-PGI) and gastrin-17 (S-G-17) are assayed in connection with H. pylori testing. METHODS: The present investigation is an observational case-control study comprising 100 selected dyspeptic outpatients with (cases) or without (controls) advanced (moderate or severe) atrophic gastritis. Before the blood tests, all patients underwent a diagnostic gastroscopy with multiple biopsies. The series of cases includes 56 patients. Eight had an advanced antrum limited atrophic gastritis, 13 had resected antrum (in two of whom the corpus mucosa in the stump was atrophic), and 30 had corpus-limited atrophic gastritis. Four patients had an advanced atrophic gastritis in both the antrum and corpus (multifocal atrophic gastritis), and the whole stomach was removed in one patient. Twenty of the 44 controls had a non-atrophic H. pylori gastritis. Both the antrum and corpus were normal and healthy in 24 patients. The S-PGI and S-G-17 were determined with EIA methods using monoclonal antibodies to PGI and amidated G-17. Postprandial S-G-17 (S-G-17prand) was measured 20 min after a protein-rich drink. The H. pylori antibodies were assayed with a polyclonal EIA method. RESULTS: A low S-PGI (<25 microg/l; an empirical cut-off with best discrimination) was found in 31 of 37 patients (84%) with and in 3 of 63 patients (5%) without corpus atrophy in the biopsy specimens. A low S-G-17prand (<5 pmol/l) was found in all 8 patients with H. pylori-associated antral atrophy and in 11 of 14 patients (79%) with resected antrum but in 3 of 20 control patients (15%) with H. pylori-related non-atrophic gastritis. Median and mean values of both S-G-17prand and S-PGI decreased with increasing grade of antral and corpus atrophy, respectively. Among all patients with atrophic gastritis (multifocal atrophic gastritis, or atrophic gastritis limited to antrum or corpus) or resected stomach, 50 of 56 patients (89%; Cl 95%: 81%-97%) had a low S-PGI and/or a low S-G-17prand with positive H. pylori serology. Such low values werc found in 3 of the 44 control patients (7%; CI 95%: 0%-14%). CONCLUSIONS: Low serum levels of G-17prand and PGI are conceivable biomarkers of atrophic antral and corpus gastritis, respectively. A low S-G-17prand is a sign of the multifocal or antrum-limited atrophic gastritis in patients infected with H. pylori.

Soluble and membrane-bound catechol-O-methyltransferase in normal and malignant mammary gland.

The levels of 26 kDa-soluble (S) and 30 kDa-membrane-bound (MB) catechol-O-methyltransferase (COMT) polypeptides were determined in paired samples from normal and neoplastic breast tissue of 32 patients with breast cancer. Immunohistochemical staining showed that the COMT reaction in normal mammary tissue was restricted to the epithelial cells in the ducti and lobuli, whereas in the tumors a strong reaction was also seen in the malignant cells. The amounts of COMT proteins in tumors could not be correlated with various clinical or pathological parameters. Quantitative immunoblotting analysis revealed that the total amount of COMT proteins in tumors was more than 50% higher than in respective normal samples in 26 out of 32 patients. Five cases showed less than a 50% difference and in one case less COMT was detected in the tumor. In most cases the amount of both S- and MB-COMT forms was increased. The average amount of total COMT was 178 +/- 57 pg/microg total protein in normal tissue and 566 +/- 94 pg/microg total protein in tumor. Respective values for S-COMT were 137 +/- 52 pg/microg total protein in normal tissue and 369 +/- 62 pg/microg total protein in tumor and for MB-COMT 41 +/- 10 and 197 +/- 41 pg/microg total protein, respectively. Analysis of COMT-specific transcripts suggested that the COMT enzyme level in tumors is determined in some cases by transcriptional and in some cases by post-transcriptional mechanisms.

Local heroes beat national champions: quality improvement in Finnish health care.

UNLABELLED: FINNISH HEALTH CARE: Although health care services in Finland are organized uniformly throughout the country, they, along with the application of total quality management (TQM)/continuous quality improvement (CQI), are the responsibility of municipalities. CASE 1: At the Helsinki City Health Organization, top management launched an organizationwide quality improvement (QI) initiative in 1993, entailing 150 CQI projects. Yet top and middle managers were not sufficiently dedicated to the initiative to provide adequate support to many of the quality projects. Only "islands of activity" were spotted. CASE 2: A physician in the pediatrics department of a hospital helped initiate CQI projects--for improvements in administration of x-rays for patients with antebrachium fractures, transport of samples to the microbiology laboratory, and admissions of patients with acute infectious disease. Successes led senior management in the hospital federation to issue a quality policy based on CQI management, showing the power of the good example. CASE 3: The first launch of CQI at the Helsinki University Central hospital was part of a management development project that did not have the full support of senior management and that, consequently, failed. A second initiative undertaken a year later, the quality council, was more successful. CASE 4: At a local center for social services and primary care, quality projects have strengthened the organization's team and network structures across two professional cultures. DISCUSSION: The four cases provide insight into the diffusion of TQM/QI and implementation strategies on the local level.

Delusional parasitosis in the elderly: a review and report of six cases from northern Finland.

A patient with delusional parasitosis has a strong conviction of being infested with parasites: for example, lice or worms. Such a patient is not satisfied with assurances or test results that no parasites are present, but is so convinced that he or she will go as far as to bring the parasites in "matchboxes" to a physician. Subjectively worried, the patient may try to pick the parasites out of the skin, causing cutaneous lesions and even ulcerations. The condition is classified as a delusional/paranoid disorder, somatic type according to DSM-III-R. Not much is known epidemiologically of this rare disorder, which usually affects older women who often are isolated socially. Therapy is regarded as difficult, and a wide variety of treatment methods have been attempted. In this article six female cases are presented, showing that a typical patient is an elderly woman who has suffered losses or is socially isolated. These patients lack deeper psychiatric insight into their problem, so they are mostly in the care of nonpsychiatric physicians. Treatment with a low dose of high-potency neuroleptics combined sometimes with antidepressants appears to be effective. Reducing social isolation is also important.

Endothelial Tie growth factor receptor provides antigenic marker for assessment of breast cancer angiogenesis.

Breast cancer prognosis has previously been linked to the degree of tumour vascularisation. In order to establish additional markers for tumour angiogenesis, we have used monoclonal antibodies against the endothelial Tie receptor tyrosine kinase to study the degree of vascularisation of breast carcinomas and the regulation of Tie expression in the vascular endothelial cells. Antibodies were used for Tie detection and the results were correlated with other prognostic markers. Of four monoclonal antibodies directed against different epitopes of the Tie extracellular domain, two reacted against Tie in unfixed histopathological sections of breast carcinomas. One of these antibodies (clone 7e8) was specific for the endothelial cells whereas the other (clone 10f11) also reacted with basement membranes and occasional carcinoma cells. When Tie expression was studied with the antibody clone 7e8, all 27 carcinomas, two in situ carcinomas, samples of histologically normal breast tissue (n = 16) or normal skin or lymph node tissue (n = 5) showed staining. Microvessel counts were higher in carcinomas (median 14; range 3-27) than in fibrodenomas (median 10; range 5-18) or histologically normal breast tissue (median 7; range 3-15, P = 0.0006). A similar result was obtained using antibodies against the CD31 (PECAM) antigen. Microvessel counts in 7e8 staining were not significantly associated with primary tumour size, axillary nodal status, histological grade or staining for oestrogen receptor, progesterone receptor, Ki-67 proliferation marker or p53 oncoprotein.

Coordinate-based mapping--a new method in health services research.

The Finnish national hospital discharge registers from 1985 and 1988 have been analysed by the National Board of Health. Results are provided for all the 21 Finnish hospital districts and central communal organizations. The small area variation phenomenon in hospital utilization cannot be explained by demographic or epidemiological factors. Rather, the variations seem to be largely due to organizational factors. The project aims to develop a data processing system capable of handling information on one million patients rapidly and economically, and show the results in an intelligible form as a table with standard headers or as a map illustration. Maps are superior to traditional statistical tables in demonstrating regional variations in health care utilization and in mortality. Maps based on small administrative units are useful for many purposes. These maps are, however, relatively 'noisy' due to substantial random variation. Coordinate-based mapping is a method to overcome some of these difficulties. It is based on linking hospital discharge and mortality data with exact address data. The method allows mapping independent of administrative boundaries. Several examples of coordinate-based maps are given. The method is used in Finland for annual analysis of hospital use.

Primary hereditary systemic amyloidosis (Meretoja's syndrome): clinical features and treatment by plastic surgery.

The characteristic, bloodhound-like appearance, which degenerates gradually, of patients with primary hereditary systemic amyloidosis, also called Meretoja's syndrome (MS), is attributable to amyloid degeneration of the craniofacial skin and peripheral facial nerves, but apparently also to amyloid deposits in the muscles; a finding not previously described. A material of five patients treated with plastic surgery is presented, and the peculiarities and differences of this rare disease in comparison with other peripheral neuropathies is discussed from a reconstructive viewpoint.

Mammographic patterns in twin pairs discordant for breast cancer.

As part of a case-control study of breast cancer in pairs of twins selected from the population-based Finnish Twin Cohort, mammograms of 30 pairs (seven monozygotic (MZ), 23 dizygotic (DZ] discordant for breast cancer were analysed. The mammographic pattern in the unaffected breast of the cancer case was compared with the pattern in the ipsilateral breast of the healthy twin (control). There were no differences for MZ pairs, while among DZ pairs the cancer case had a prominent parenchymal pattern significantly more often than the control, as assessed by two radiologists independently and blindly. Thus, there is a relationship between parenchymal pattern and risk of breast cancer even when the controls are the twin sisters of breast-cancer cases and are themselves at high risk. The overall similarity, despite disease discordance, in parenchymal pattern of the twins (more evident among MZ than DZ pairs) suggests a familial, possibly genetic influence on parenchymal pattern.

The predictive value of steroid hormone receptor analysis in breast, endometrial and ovarian cancer.

The predictive value of female sex steroid, estrogen and progesterone, receptor (ER and PR, respectively) assays in breast, endometrial and ovarian cancer is reviewed with emphasis on comparative aspects of these malignant tumors in relation to their hormone dependency. The endocrine etiology of these three tumor types seems to be at least partly different, and so is the expression of these receptors in normal and malignant tissues of the breast, endometrium and ovary. There is a tendency for decreased receptor concentrations and disappearance of these receptors in association with advancement of these malignancies. There is also a decrease in the presence and concentrations of ER and PR in relation to loss of differentiation in breast and endometrial cancer. Receptor analyses have an established position in the selection of patients with advanced breast cancer for endocrine treatment, and they give promise of a similar application in endometrial cancer and in endometrioid cancer of the ovary. It is not clear whether the disease-free interval is related to the presence or concentrations of ER or PR as such in the tumor tissue. There is better survival in breast cancer patients with receptor-positive tumors, which might be due to a response to endocrine treatment. The same seems to be true for patients with endometrial cancer. Future progress in the application of female sex steroid receptor analyses in breast, endometrial and ovarian cancer needs additional controlled clinical trials and more highly developed receptor assays.

Significance of estrogen and progesterone receptors, disease-free interval, and site of first metastasis on survival of breast cancer patients.

Estrogen and progesterone receptors (ER/PR) were measured in primary tumors and metastases of 397 breast cancer patients. Survival following mastectomy was significantly longer in patients with ER and PR positive tumors, as was survival after first recurrence. The prognostic value of ER and PR was compared with such clinical factors as disease-free interval (DFI) and the dominant site of first metastasis by Cox's regression analysis. With all the different therapy modalities long DFI was the best prognostic indicator. However, in the patient group treated with endocrine therapy, ER and PR positivity was the best prognostic indicator, suggesting that longer survival in receptor positive patients was related to the response to endocrine treatment.

Nandrolone decanoate added to tamoxifen in the treatment of advanced breast cancer.

Since 1980 we have been carrying out a prospective randomized trial comparing tamoxifen with the combination of tamoxifen plus nandrolone decanoate in advanced breast cancer. The tamoxifen dose is 30 mg daily and the nandrolone decanoate dose 100 mg i.m. once a week for four weeks and thereafter every other week. 98 post-menopausal patients have been evaluated for the response. The number of patients is 49 in both groups. The overall response rates (CR + PR) to tamoxifen and tamoxifen plus nandrolone decanoate were not significantly different; in the tamoxifen group the response rate was 49% and in the combination group 45%. The mean time to progression in tamoxifen group is over 13 months and in tamoxifen plus nandrolone decanoate group over 12 months. Our results do not suggest a synergistic effect from combining tamoxifen and nandrolone decanoate treatments. The response rates to tamoxifen at different sites of metastases were as follows: bones 47%, soft tissues 56%, and viscera 48%. The respective figures with the combination therapy were 36%, 64%, and 40%. Both treatments were well tolerated and in no patient was withdrawal of the therapy necessary. Mild virilization and hoarseness were experienced by all patients treated with nandrolone decanoate. Side-effects associated with tamoxifen were rare, although five patients experienced nausea and two had hot flushes.

Variation of estrogen and progesterone receptor status in breast cancer.

In a series of fifty breast cancer patients two estrogen and progesterone receptor assays were performed. In two simultaneous assays (tissue samples taken at the same time) disordant results in estrogen receptor, progesterone receptor and double receptor status were detected in 12%, 12% and 21% of cases respectively. In sequential assays (tissue samples taken with an interval between the samples) this variation was more pronounced, 24%, 36% and 36% respectively. The variation in simultaneous assays was similar between two samples of the same primary tumour as between samples from a primary tumour and a metastasis. In sequential assays there was no difference in the time between assays in concordant and discordant samples. The variation in receptor status is said to be due to the heterogeneity within the primary tumour.

Oestrogen and progesterone receptors and disease-free interval in primary breast cancer.

Oestrogen and progesterone receptor assays were performed in 286 women with primary breast cancer, and the patient group was followed up for a minimum of 24 months. Of the 263 patients belonging to clinical stages I-III and serving as the population used for calculation of disease-free interval only 1.9% received postoperative endocrine treatment and 6.5% chemotherapy. No significant relationship between the presence or concentrations of oestrogen or progesterone receptor and the disease-free interval was observed. It is therefore possible that the positive relationship between these variables reported in some investigations reflects an influence by adjuvant endocrine measures.

Correlation of estrogen and progesterone receptors and histological grade in human primary breast cancer.

The relationships between the presence of female sex steroid receptors and their concentrations, and the histological grade were investigated in primary breast carcinoma specimens from 151 patients. The concentrations of estrogen receptor were significantly lower in grade III tumours than in the more differentiated ones from pre- and post-menopausal patients, whereas the same was observed for progesterone receptor concentrations only between grades III and I in post-menopausal patients. Generally estrogen and progesterone receptor-positive, estrogen receptor rich tumours frequently belonged to well-differentiated tumour categories. Whereas most of the tumours belonging to grade III group were receptor-negative, approximately three fourths of receptor-negative tumours belonged to grade I and II categories. It is therefore suggested that estrogen receptor-negativity or low receptor concentrations and grade III histological appearance of breast carcinoma are independent risk indicators, and their concomitant use is recommended in designing treatment strategies for individual patients.

The desmoid tumor. III. A biochemical and genetic analysis.

We have carefully examined four patients with desmoid tumor (DT) and their 31 relatives. In three of four cases, biopsies of the DT demonstrated low yet significant amounts of estrogen but not progesterone receptors in the tumor cytosol. In the fourth case, where the receptors were not demonstrable, the affected patient was a menopausal woman and the receptors may have been blocked by endogenous estrogen. Fourteen of their 31 relatives demonstrated multiple minor bone malformations in x-ray screening of the skeleton. The inheritance of these malformations was compatible with an autosomal dominant trait with variable penetrance. These findings are compatible with our suggestion that the basic underlying cause for DT is an inherited defect in growth regulation of the connective tissue. When a trauma is superimposed on such an individual, a DT may result. The growth of the tumor is, however, controlled primarily by sex hormones, estrogen predominance over progesterone being inducive to tumor growth.