Biomedical subjects

H Johansson

Publications and source records attributed to H Johansson.

At least 19 recordsLinked to original sources

PubMed1992

Effects of parathyroid hormone on cyclic AMP-formation and cytoplasmic free Ca2+ in the osteosarcoma cell line UMR 106-01.

The effects of parathyroid hormone (PTH) on cytoplasmic free Ca2+ (Cai2+) and cAMP-formation were investigated in the rat osteosarcoma cell line UMR 106-01. In fura-2 loaded adherent single cells bPTH 1-34 (10 nM - 1 microM) induced a rapid transient increase in Cai2+ in 11% of the studied cells. In fura-2 tracings from UMR 106-01 cells in suspension, bPTH 1-34 (0.1 microM) induced a transient increase in Cai2+ in 20% of the experiments. The transient increase in Cai2+ seen in suspensions of cells was not abolished by addition of EGTA (2.5 mM) prior to challenge with PTH, suggesting that the increase in Cai2+ was derived from intracellular stores. A marked rapid increase in cAMP-formation was observed in all experiments with cells in suspension, also in the experiments where PTH did not affect Cai2+. These data show that PTH causes a release of Ca2+ from intracellular stores in a small percentage of osteosarcoma UMR 106-01 cells, and that PTH is capable of inducing an increase in cAMP-formation without affecting Cai2+ in osteoblasts.

Animals↗

PubMed1992

Prognostic factors and natural history in lymph node-negative breast cancer patients.

The prognostic significance of clinical and histological factors as well as hormone receptors was analyzed in a population of 3,064 lymph node-negative breast cancer patients operated in the Stockholm region between 1976 and 1988. None of these patients received systemic adjuvant treatment. Multivariate analysis showed that only histological tumor size, number of examined axillary lymph nodes, and progesterone receptors were independent prognostic factors in terms of recurrence-free interval. An individual risk of recurrence was calculated taking into account these three factors to discriminate between three groups of patients with a risk of less than 15%, 15-25%, and more than 25% of recurrence at 5 years. Similar results were obtained taking into account only the first two factors. The prognostic information added by the knowledge of progesterone receptors only changed the recurrence rate in approximately 3%. This study showed that conventional prognostic factors permit the identification of high risk lymph node-negative breast cancer patients. Results obtained by the use of new more sophisticated factors should be compared with those obtained analyzing strong conventional prognostic factors.

Breast Neoplasms↗

PubMed1992

Cardiovascular mortality in a randomized trial of adjuvant radiation therapy versus surgery alone in primary breast cancer.

One concern with adjuvant radiation therapy for early breast cancer is the potential risk of increasing intercurrent mortality due to radiation-induced damage of the myocardium. The paper presents an analysis of long-term survival among 960 patients with primary breast cancer included in a randomized trial of pre- or postoperative radiation therapy (45 Gy/5 weeks) versus surgery alone. All patients were treated with a modified radical mastectomy. The mean follow-up was 16 years (range: 13-19 years). During the entire follow-up period there was an overall survival difference in favor of the irradiated patients that was of borderline significance (p = 0.09). There was no increase in intercurrent mortality due to any cause. However, when the results were analyzed according to estimated doses of radiation to the myocardium, the subset of patients who received the highest doses, that is, those treated with tangential 60Co fields for left-sided tumors, were found to have a significantly increased risk of death due to ischemic heart disease compared to the surgical controls (relative hazard: 3.2, p less than 0.05). No such increase was observed among the patients who received less radiation to the myocardium, that is, whose chest wall and internal mammary nodes were treated with electrons or those with right-sided tumors, irrespective of the treatment technique. It is concluded that cardiovascular mortality associated with radiation therapy for early breast cancer is correlated with the biological dose of radiation to the heart and the irradiated volume. All of the following factors are thus important: laterality of the tumor, portal arrangements, radiation energy, fractionation, and total dose. The study illustrates that an increased cardiovascular mortality can be avoided by the use of appropriate techniques and avoidance of excessive treatment.

Adult↗

PubMed1992

Histological and clinical features of non-familial primary parathyroid hyperplasia.

Relations between histopathological characteristics and clinical data were retrospectively investigated in patients with sporadic primary hyperparathyroidism due to hyperplasia. The study comprised 100 patients with chief cell hyperplasia and nine with hyperplasia of the water-clear cell type operated on during the period of 1959-1989. The chief cell hyperplasia was associated with a renal stone disorder as the predominant symptom in 41 patients, psychiatric/neuromuscular manifestations in 26 patients, while 23 patients were apparently asymptomatic. The remaining ten patients had miscellaneous symptoms. Patients with renal stones were more frequently of the male sex and generally had lower serum calcium values and less marked increments in total parathyroid glandular weights than patients with other symptoms or those who were overtly asymptomatic. Two main morphological patterns, diffuse and nodular hyperplasia, were encountered in chief cell hyperplasia. Diffuse hyperplasia was usually found in moderately enlarged glands, with a less variable size and morphology. It was also more prevalent among young patients having moderate hypercalcaemia and either recurrent renal stones or neuromuscular/psychiatric symptoms. The glands affected by nodular hyperplasia were asymmetric in size with a variable cellular arrangement and a high proportion of oxyphil cells. Nodular hyperplasia was irrespective of symptoms more frequent in the elderly patients. Water-clear cell hyperplasia was not encountered during the last decade of the study and until then it was an occasional finding in patients with marked hypercalcaemia. In this histological entity the glands were greatly and asymmetrically enlarged.

Adult↗

PubMed1992

Competing risks determining event-free survival in early breast cancer.

To evaluate the natural history of a disease and the effects of therapeutic interventions, it is important to determine which are the causes of treatment failure and to assess the extent to which each cause contributes to the total failure rate. The paper presents a new biostatistical technique to decompose the total event-free survival of a diseased population into cause-specific failure rates. The technique was based on a competing risk approach thereby avoiding biases related to assumptions of independence between different types of event. Such assumptions are inherent in the conventional Kaplan-Meier or actuarial methods. The competing risk method was used to analyse the pattern of failure among 2,850 pre- and postmenopausal patients with early-stage breast cancer and the results were compared to those obtained using conventional methods. The following events were analysed: loco-regional recurrence, distant metastasis, contralateral breast cancer, other new primary malignancies, and intercurrent deaths. The rate of new primary malignancies was found to be significantly higher in post- than in premenopausal patients (6% vs 3% at 10 years). In low-risk, node-negative postmenopausal patients the incidence of recurrences from breast cancer were found to be no greater than other types of events. This observation highlights the significance of the effect of different adjuvant therapies not only on the disease itself but also on the risk of second primary malignancies and other intercurrent diseases. In general, it was found that the conventional statistical methods tended to overestimate the event-specific rates. In conclusion, the method based on competing risks permits an unbiased analysis of all types of events determining the total event-free survival. It is thus useful for the description of the natural history of breast cancer as well as other diseases.

Aged↗

PubMed1992

Randomized trial of adjuvant tamoxifen in node negative postmenopausal breast cancer. Stockholm Breast Cancer Study Group.

The paper presents long-term results of a randomized trial of adjuvant tamoxifen (40 mg daily for 2 or 5 years) versus surgery alone including 1,347 postmenopausal patients with histologically negative axillary nodes and a tumour diameter less than or equal to 30 mm. Data on the estrogen receptor status of the primary tumour were available in 1,136 patients (84%). At a median follow-up of 7 years (range 1.7-13.0 years) there was a significant prolongation of the recurrence-free survival among those allocated to tamoxifen (p less than 0.01), significantly fewer deaths due to breast cancer (p = 0.02) and a trend towards improved overall survival (p = 0.11). The treatment benefit was restricted to patients with ER-positive tumours. There was no significant reduction of breast cancer recurrences in the tamoxifen group among patients whose tumours were classified as ER-negative. The results support and extend previous studies in showing a long-term benefit of tamoxifen in postmenopausal breast cancer patients with node-negative, estrogen receptor positive disease.

Breast Neoplasms↗

PubMed1992

Multiple endocrine adenopathy.

The syndromes of multiple endocrine adenopathy (MEA) have associated endocrine abnormalities that are similar to the clinical syndromes based in the same hyperfunctions of parathyroid, pancreatic islets, thyroid C-cell and chromaffin tissue seen in sporadic cases. The natural history, histopathology and management of these problems when they occur in the hereditary MEA syndromes differ in significant and instructive ways over the isolated disorders. These differences and similarities of MEA adenopathies were discussed at an international conference, with the suggestion that the MEA syndromes afford opportunity to investigate regulation and control of pathogenesis in surgical endocrinological syndromes.

Adult↗

PubMed1992

Prognostic significance of immunohistochemical c-erbB-2 proto-oncogene expression and nuclear DNA content in human breast cancer.

Immunoreactivity of the c-erbB-2 proto-oncogene product and nuclear DNA content were assessed in specimens from 211 breast cancer patients with a mean follow-up of 16 years (range 13-19 years). A routine immunoperoxidase technique was used and cytometrical DNA assessments were performed on cytodiagnostically identified tumour nuclei, using image analysis. C-erbB-2 cell membrane staining was observed in 29% of the cases and was found to be related to tumour size (P = 0.02), histopathological grade (P = 0.02) and nuclear DNA content (P < 0.01). In univariate analysis immunohistochemical c-erbB-2 expression was of prognostic significance among node-positive patients (P = 0.02), but not among women with node-negative disease. This prognostic ability was reduced by multivariate analysis and was no longer significant. In contrast, nuclear DNA content was significantly related to distant recurrence-free survival even in multivariate analysis after adjustment for nodal status and tumour size (P < 0.01). In conclusion, the findings of the present study indicate that c-erbB-2 expression is of limited prognostic value in a subgroup of patients, whereas nuclear DNA content seems to provide significant prognostic information even in node-negative patients.

Adult↗

PubMed1992

Mechanical performance, level of continuous contraction and muscle pain symptoms in home care personnel.

The interrelationships between reported complaints, clinical status, mechanical performance and EMG pattern of the shoulder flexors and the knee extensors, respectively, during maximum dynamic contractions were investigated. A group of 97 randomly selected women employed in the home care service participated. Those who reported complaints had more clinical findings, such as reduced mobility, tender points and muscle tightness, than non-complainers. The level of muscle activity during the passive part of the contraction cycle was significantly higher in the shoulder flexors than in the knee extensors. Subjects without reported complaints who had been employed for more than ten years had a significantly lower activity level in the shoulder muscles than subjects without complaints who had been employed for a shorter time. We suggest that a high muscle tension level between contractions might precede muscle pain. A cluster analysis including sociodemographic, clinical and physiological variables revealed different subgroups, which points to the need to investigate the work situation in a multivariate way.

Adult↗

PubMed1991

Bradykinin induces formation of inositol phosphates and causes an increase in cytoplasmic Ca2+ in the osteoblastic cell line MC3T3-E1.

Recordings of fura-2 fluorescence from single osteoblastic MC3T3-E1 cells showed that bradykinin (BK, 1 microM) induced a rapid increase in cytoplasmic free Ca2+ (Cai2+, from 114 +/- 13 to 239 +/- 17 nM, mean +/- SEM). Following this initial transient (less than 1 minute) increase there was a second slow increase in Cai2+ (from 117 +/- 11 to 151 +/- 12 nM). Incubation in buffer with no Ca2+ did not affect the first rapid BK-induced increase in Cai2+ but eliminated the second slow increase. Addition of indomethacin or hydrocortisone to the incubation buffer did not inhibit the effect of BK on Cai2+. BK caused a dose-dependent initial rapid increase in Cai2+ with threshold at 1 nM and a maximal effect (241 +/- 30% of basal Cai2+ concentration) at 0.1 microM. The B1 BK receptor agonist des-Arg9-BK (1 microM) caused only a small increase in Cai2+ in MC3T3-E1 cells (from 101 +/- 20 to 140 +/- 4 nM). BK dose and time dependently stimulated the formation of inositol phosphates in MC3T3-E1 cells with EC50 at 2.4 nM and a significant increase in inositol trisphosphate already seen after 15 s. The Ca2+ ionophore ionomycin induced a rapid increase in Cai2+ and prostaglandin E2 (PGE2) formation in MC3T3-E1 cells. Forskolin (10-30 microM) increased cyclic AMP accumulation but did not affect Cai2+ or PGE2 formation. Depletion of extracellular Ca2+ significantly reduced (but did not abolish) BK-induced PGE2 formation. The initial action of BK on Cai2+ is probably due to an inositol-(1,4,5)-trisphosphate-mediated rapid release of Ca2+ from intracellular stores in osteoblasts and is followed by an influx of extracellular Ca2+. The effect is due to B2 BK receptor occupancy and is not secondary to the prostaglandin synthesis. The BK-induced breakdown of phosphatidylinositol-(4,5)-bisphosphate with a subsequent increase in Cai2+ may be involved in BK-induced prostaglandin formation in osteoblasts.

Animals↗

PubMed1991

Influence from stretch-sensitive receptors in the collateral ligaments of the knee joint on the gamma-muscle-spindle systems of flexor and extensor muscles.

In lightly alpha-chloralose anaesthetized cats, activity was recorded simultaneously from 2-4 primary muscle spindle afferents from triceps surae and/or posterior biceps and semitendinosus muscles. Increased tension in medial or lateral collateral ligament was found to evoke changes in the responses of the primary spindle afferents to sinusoidal stretching of their parent muscles. It is concluded that these changes were due to reflex actions of stretch/tension-sensitive receptors in the collateral ligaments on fusimotor neurones. Thus, receptor afferents from the collateral ligaments may contribute to the regulation of the activity in the gamma-motor-muscle-spindle system, and thereby also be of importance for the control of muscular stiffness and knee joint stability.

Animals↗

PubMed1991

Pathophysiological mechanisms involved in genesis and spread of muscular tension in occupational muscle pain and in chronic musculoskeletal pain syndromes: a hypothesis.

This paper introduces a pathophysiological model for the cause of muscular tension and pain in occupational pain syndromes and chronic muskuloskeletal pain syndromes, which also might clarify why these conditions have a tendency to perpetuate themselves and spread from one muscle to another. The model can briefly be described as follows. Metabolites produced by (static) muscle contractions stimulate group III and IV muscle afferents, which activate gamma-motoneurones projecting to both homonymous and heteronymous muscles. The gamma-motoneurones influence the stretch sensitivity and discharges of secondary and primary spindle afferents. Increased activity in the primary muscle spindle afferents enhances the muscle stiffness, which leads to further production of metabolites in both homo- and heteronymous muscles. Increased activity in secondary spindle afferents, which project back to the gamma system, constitutes a 'built in' second positive feedback loop which may perpetuate the condition with less 'support' from activity in group III and IV muscle afferents.

Afferent Pathways↗

PubMed1991

Surgical treatment of endocrine pancreatic lesions in MEN-1.

The surgical treatment of endocrine pancreatic lesion in the multiple endocrine neoplasia syndrome type 1 (MEN-1) has remained a controversial issue. Histologic studies have revealed that the pancreatic lesions generally consist of numerous microadenomas, spread throughout the pancreas, together with occasional larger tumors. The patients may also harbor multiple, mainly gastrin secreting, duodenal microadenomas. A total pancreatectomy/duodenectomy should theoretically be needed for cure, but has not been recommended due to the associated mortality and morbidity, considering also the favorable prognosis of most MEN-1 patients. When pancreatic involvement in MEN-1 is biochemically diagnosed efforts should be made to localize the lesions by computed tomography, angiography and, in some patients, also transhepatic portal vein catheterization and venous sampling (PTP). Hypergastrinemia and the Zollinger-Ellison syndrome (ZES) generally constitute two-thirds of the clinically detected pancreatic lesions in MEN-1. Surgery may be undertaken in ZES-MEN-1 patients with focal lesions visualized by radiology or PTP in order to minimize the risk of malignant development in a gross tumor. Patients with insulin excess and hypoglucemia as well as the rare vipoma patient may, even in the absence of radiologically visualized tumors, be subjected to exploration, and these patients are usually found to harbor one or several gross tumors. The more frequent clinically silent, mainly PP-producing tumors should be removed when visualized by radiology. However, indications for surgery also have to emphasize an unusually malignant behavior in certain kindreds and patients may thus have to be explored when only biochemical data indicate the presence of pancreatic lesions. Pancreatic operations in MEN-1 should generally include a corpus and tail resection, together with enucleation of lesions in the pancreatic head, and in addition to that a careful duodenal exploration. Intraoperative ultrasound examination appears to be of considerable value by its ability to reveal also smaller lesions which may escape palpation.

Humans↗

PubMed1991

Abdominal surgery in patients with midgut carcinoid tumors.

In patients with midgut carcinoid tumors a curative, radical tumor removal should be attempted when possible. As these tumors are generally malignant, irrespective of size, the radical surgery implies that intestinal resection for excision of a primary tumor should be combined with an extended mesenteric resection. When the patients present with the carcinoid syndrome the disease is, with few exceptions, too advanced for curative surgery. However, surgery often has to be performed also in patients with the advanced carcinoids. Patients with more extensive disease may thus benefit from surgical debulking of large mesenteric or hepatic metastases. Moreover, when the patients present with abdominal symptoms it is important to exclude a threatening major abdominal complication, such as intestinal obstruction or ischemia. As these complications may cause malnutrition and deterioration, it is important to treat them properly, sometimes by repeated surgery.

Carcinoid Tumor↗

PubMed1991

Hodgkin's disease in northern Sweden 1971-1981. I. A histopathological reevaluation of 223 cases.

A histopathological reexamination was made of diagnostic material in 223 patients with Hodgkin's disease (HD) collected between 1971 and 1981. The diagnosis of HD was considered to be incorrect in 90 cases (40%). Change of diagnosis to non-Hodgkin's lymphoma was made in 56 cases, of which 23 were high-grade and 26 were low-grade lymphomas (7 not determined), and to angioimmunoblastic lymphadenopathy in 10 cases. These discrepancies were considered to be due mainly to progress in the understanding and classification of malignant lymphomas, which stresses the importance of review of histologic material in retrospective studies on Hodgkin's disease.

Follow-Up Studies↗

PubMed1991

Hodgkin's disease in northern Sweden 1971-1981. II. A retrospective analysis of prognostic factors.

Factors relevant for prognosis were retrospectively studied in a series of 133 morphologically reviewed patients with Hodgkin's disease collected between 1971 and 1981. For the whole material complete remission rate was 74% and 5-year survival was 62%. These seemingly rather poor results could be explained by a high mean age (48 years) in this relatively unselected material, in combination with a very unfavourable outcome for the elderly patients. In a multivariate analysis of prognostic factors age of the patient turned out to be the only independent factor with a significant bearing on the prognosis.

Adolescent↗

PubMed1991

Hodgkin's disease in northern Sweden 1971-1981. III. The clinical and prognostic impact of age.

A retrospective material of 133 patients with Hodgkin's disease treated between 1971 and 1981 was analysed. In part II of this study it was shown that the prognosis was closely associated with age of the patient. In this part some clinical factors, including therapy, were compared between 66 patients less than 50 years of age and 67 patients 50 years or more. The groups differed mainly in the outcome of primary chemotherapy. Older patients with Hodgkin's disease were particularly vulnerable to chemotherapy, probably as an effect of the disease itself.

Adolescent↗

PubMed1991

DNA ploidy pattern of parathyroid parenchymal cells in renal secondary hyperparathyroidism with relapse.

The nuclei of parathyroid parenchymal cells, analyzed using image cytometry (ICM), in relapsing and non-relapsing secondary hyperparathyroidism due to uremia, showed a DNA-distribution pattern of diploid type. Nevertheless, some differences were observed within the groups, as regards the concept of 'scattered cells' in ICM DNA histograms. The relative incidence of 'scattered cells' was particularly high in the histograms from parathyroid glands with nodular hyperplasia and in those from parathyroid parenchyma grafted into the skeletal musculature. In these two kinds of parathyroid specimens, the 'scattered cells' were both of chief-cell and oxyphil-cell types. In contrast, 'scattered cells' were not so conspicuous when parenchymal cells of glands with diffuse hyperplasia were analyzed. As there is some clinical and histopathological evidence that the cells in both nodular-hyperplastic and autografted parathyroid parenchyma have increased growth potential, it is hypothesized that the relative incidence of the 'scattered cells' in the ICM DNA histograms indicates an increased proliferative activity.

Adult↗