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Biomedical subjects

H Johansson

Publications and source records attributed to H Johansson.

At least 109 records · Page 6Linked to original sources

Postoperative mortality in rectal cancer treated with or without preoperative radiotherapy: causes and risk factors.

Adjuvant preoperative radiotherapy in patients with rectal cancer improves local control and possibly overall survival. However, an increased postoperative mortality rate after radiotherapy has been observed in some trials. This study was based on 1399 patients in two randomized trials of radiotherapy. It reviewed the causes of death after operation and attempted to identify risk factors for postoperative mortality in patients with rectal cancer treated with or without high-dose (5 x 5 Gy) preoperative radiotherapy. The majority of deaths were from cardiovascular disease or infection. The risk of postoperative mortality was significantly increased in patients irradiated with a two-portal technique to a relatively large volume compared with those not given radiotherapy, but not in those irradiated with a four-portal technique to a limited volume. Age, sex, tumour stage and coexistent cardiovascular disease were independent risk factors for postoperative mortality. The risk of postoperative death in patients with rectal cancer is related to the preoperative radiotherapy technique.

Adenocarcinoma↗

X-ray microanalysis of elemental changes in human parathyroid glands in primary and secondary hyperparathyroidism.

The elemental composition of chief cells of parathyroid glands from patients with adenomatous primary hyperparathyroidism (HPT) and uremic secondary HPT was studied by X-ray microanalysis. Glands histologically deemed normal were used as controls. The analyses were also carried out on tissue specimens incubated in hypo-, normo- and hypercalcemic media (0.5, 1.25, and 3.0 mM calcium concentration). Analysis of chief cells from normal glands did not reveal any significant differences in ionic composition after exposure to the different calcium concentrations. In chief cells from adenomatous and uremic hyperplastic glands, elemental changes were noted. In comparison with specimens incubated in 1.25 mM calcium medium, cells in 0.5 mM calcium medium had a lower content of potassium and phosphorus. After stimulation with increasing extracellular concentration, an increase in the K/Na ratio was observed, due to a marked decrease of sodium and an increase of potassium; the calcium concentration was almost unchanged. Our findings indicate that in HPT an increase in serum calcium concentration might exert a stimulatory effect on the Na/K pump (sodium pump) and on the calcium-activated potassium channels. Either of these mechanisms might contribute to a lowering of cytoplasmic calcium. Our observations suggest that changes in ionic content of the parathyroid cells may be of importance for the stimulus secretion process in the cells.

Adult↗

A neural network approach to real-time spike discrimination during simultaneous recording from several multi-unit nerve filaments.

A multi-channel, real-time, unsupervised spike discriminator was developed in order to reconstruct single spike trains from several simultaneously recorded multi-unit nerve filaments. The program uses a Self Organising Map (SOM) algorithm for the classification of the spikes. In contrast to previous similar techniques, the described method is made for use on a PC, and the method may thus be implemented at relatively low cost. In order to test the accuracy of the program, a robustness test was performed, where noise with different RMS levels was superimposed on the spikes. Furthermore, the maximal classification rate was determined. The program is easy to use, since the only manual inputs needed are the voltage threshold for spike detection, and the number of units present in each recorded nerve filament.

Action Potentials↗

Detection of apoptotic cells and expression of Ki-67 antigen, Bcl-2, p53 oncoproteins in human parathyroid adenoma.

Presence of apoptotic cells and immunoreactivity to Ki-67, bcl-2 and p53 were studied in 20 cases of parathyroid adenoma. To determine apoptosis, the DNA nick end labeling method was used. 85% of the parathyroid adenomas were found to harbor apoptotic cells. All of the 20 adenomas contained Ki-67 immunoreactive cells. Proliferative activity was not more confined to nodular than to diffuse areas, but there was a highly significant difference in Ki-67 immunoreactivity between adenomatous tissue and the residual rim of normal tissue outside the adenoma. No Ki-67 immunoreactive cells were found in two normal parathyroid glands used as controls. All but one of the adenomas (95%) demonstrated immunoreactivity to bcl-2, but expression of p53 was detected in only a few adenomas (15%). There was a significant relationship between the adenoma weights and both Ki-67 and bcl-2. This study suggests that parathyroid adenomas contain cell populations with proliferative activity (clonal proliferation), but the weak immunoreactive expression of p53 combined with the relatively strong expression of bcl-2 might contribute to a slow glandular growth.

Adenoma↗

Graves' disease in children and adolescents. Late results of surgical treatment.

All children and adolescents with Graves' disease in the county of Uppsala (catchment area population 250,000) treated between 1970 and 1994 were evaluated in a retrospective study. The material comprised 31 patients with a mean age of 11 years (range 4-16), 29 (94%) of whom were girls, and four (13%) of the patients had Down's syndrome. Treatment was primarily conservative and surgery was considered if prolonged medical treatment failed. Lasting remission after antithyroid drug therapy (median 6.5 years; range 4.5-8 years) was noted in 6/31 patients (19%), three (10%) of whom subsequently developed hypothyroidism. Twenty-four of the remaining patients (77%) ultimately underwent subtotal (N = 20) or total thyroidectomy (N = 4) after experiencing one or more episodes of recurrent hyperthyroidism during medical treatment (median 6 years; range 0.5-11 years). After surgery one patient developed permanent hypocalcemia requiring low-dose vitamin D supplementation. During a postoperative follow-up period of 12.2 years ( median; range 1-17 years), there were two cases of recurrent thyrotoxicosis, 1 and 10 years after surgery. The results underline that gender and Down's syndrome are risk factors of juvenile Graves' disease and that the disorder often is difficult to control by long-term medical therapy. In such cases thyroid surgery offers a safe and prompt reversal of the thyrotoxicosis. A proportion of the patients may ultimately develop hypothyroidism, substantiating a need for long-term follow-up of persons afflicted with Graves' disease early in life.

Adolescent↗

Adjuvant tamoxifen therapy for early stage breast cancer and second primary malignancies. Stockholm Breast Cancer Study Group.

BACKGROUND: Tamoxifen is being increasingly used for the treatment of breast cancer and is undergoing study for the primary prevention of breast cancer. However, concerns have been raised that the drug may increase the incidence of new primary malignancies, such as endometrial, liver, and colorectal cancers. PURPOSE: Our goal was to assess the carcinogenic risks associated with long-term use of tamoxifen in women with early stage breast cancer. METHODS: The incidence of new primary cancers among 2729 women participants of the Stockholm Trial was determined at a median follow-up of 9 years. In this trial, after primary surgery, postmenopausal patients aged less than 71 years with unilateral invasive breast cancer were randomly allocated to receive either 2 years of adjuvant tamoxifen (40 mg daily) or no adjuvant endocrine therapy. Information on second cancers was obtained by retrospective linkage to the Swedish Cancer Registry. To increase statistical power, a joint analysis of the incidence of endometrial and gastrointestinal cancers was performed in the following three major studies in Scandinavia evaluating adjuvant tamoxifen therapy: the Stockholm Trial, the Danish Breast Cancer Group Trial, and the South-Swedish Trial. These studies included a total of 4914 patients with a median follow-up of 8-9 years. All P values were calculated from two-tailed tests of statistical significance. RESULTS: In the Stockholm Trial, there was a statistically significant (P = .008) reduction in the incidence of second primary cancers in the contralateral breast among the tamoxifen-treated patients. However, there was a nearly sixfold increase in endometrial cancers (P < .001) and a threefold increase in gastrointestinal cancers in the tamoxifen-treated patients. The results of the joint studies showed a statistically significant increase in endometrial cancers among the tamoxifen-treated patients (relative risk [RR] = 4.1; 95% confidence interval [CI] = 1.9-8.9). There was also an excess of gastrointestinal cancers associated with tamoxifen. Most of this excess involved colorectal cancers (RR = 1.9; 95% CI = 1.1-3.3) and stomach cancer (RR = 3.2; 95% CI = 0.9-11.7). There was no substantial increase in any other type of gastrointestinal cancer (e.g., liver cancer) among the tamoxifen-treated patients. CONCLUSION: The endometrium and gastrointestinal organs may be target sites for tamoxifen-induced carcinogenesis in humans. IMPLICATIONS: The increased incidence of colorectal and stomach cancers reported here should be regarded as tentative until supported by long-term data from a larger number of tamoxifen trials. Also, appropriate surveillance of cancer incidence is warranted for the protection of participants enrolled in current tamoxifen chemoprevention trials.

Aged↗

The Stockholm I trial of preoperative short term radiotherapy in operable rectal carcinoma. A prospective randomized trial. Stockholm Colorectal Cancer Study Group.

BACKGROUND: From 1980 to 1987, 849 patients with clinically resectable rectal adenocarcinoma were randomized into a controlled clinical trial to evaluate the role of preoperative radiotherapy. METHODS: Patients were given either 25 Gy during 5 to 7 days before surgery or underwent surgery alone. RESULTS: At a median follow-up time of 107 months (range, 62-144 months) the incidence of pelvic recurrence among 684 "curatively" operated patients was significantly lower among those who also received radiotherapy (P < 0.001) in all Dukes' stages. No significant difference was observed between the treatment groups with regard to frequency of distant metastases or overall survival. The time to local recurrence or distant metastasis and survival was significantly prolonged in the irradiated group. However, the postoperative mortality was 8% in the radiotherapy group compared with 2% in the surgery only group (P = 0.01). CONCLUSIONS: Preoperative short term radiotherapy reduced the incidence of pelvic recurrences and prolonged survival related to rectal cancer compared with surgery alone. The postoperative morbidity was significantly higher in the irradiated group.

Adult↗

Abdominoperineal resection and anterior resection in the treatment of rectal cancer: results in relation to adjuvant preoperative radiotherapy.

The outcome of patients with rectal cancer treated by abdominoperineal or anterior resection, with or without preoperative radiotherapy, was assessed to detect any differences attributable to the operative method and interactions between radiotherapy and type of surgery. The study was based on 1292 patients included in two consecutive controlled randomized trials of preoperative radiotherapy in operable rectal carcinoma. The outcome was not related to surgical method. Radiotherapy increased postoperative mortality and complications and reduced local and distant recurrence, but had no effect on overall survival. Effects of radiotherapy were similar irrespective of the type of surgery, except that the increase in postoperative mortality in irradiated patients was greater in those treated with abdominoperineal resection. Sphincter-saving procedures appear to have no adverse effects on outcome of rectal cancer, but the optimum use of radiotherapy is still to be defined.

Adult↗

Prognostic value of bcl-2 immunoreactivity in medullary thyroid carcinoma.

Bcl-2 expression has been evaluated immunocytochemically in a series of 33 medullary thyroid carcinomas (MTC) with long-term (mean, 10.3 years) follow-up. Twenty-six of 33 cases showed intense bcl-2 immunoreactivity in more than 25% neoplastic cells. Bcl-2 immunoreactivity did not correlate with several clinicopathologic parameters including sex and age of the patients, sporadic or familial disease, tumor size and stage, amount of amyloid stroma, and immunoreactivity for calcitonin, chromogranin A, proliferating cell nuclear antigen (PCNA), N-myc, and p53. Lack of bcl-2 immunoreactivity, however, correlated significantly (P = .0001) with a shorter survival. Indeed, the seven patients with tumors devoid of bcl-2 immunoreactivity all died of disease within 8 years from the diagnosis. In multivariate analysis, lack of bcl-2 immunoreactivity was an independent predictor of worse prognosis (P = .001 for disease-free survival and P = .0001 for overall survival). None of the other clinicopathologic variable investigated proved to be an independent prognostic parameter. It is concluded that down-regulation of bcl-2 expression in MTC may identify a subset of tumors with a more aggressive clinical course.

Adolescent↗

A method for analysis of encoding of stimulus separation in ensembles of afferents.

This paper describes a new method for the analysis of ensemble coding in populations of receptor afferents. The method is based on principal component analysis (PCA) combined with algorithms for calculation of stimulus separation (discrimination). It allows a quantification of the ability of ensembles of afferents to discriminate between stimuli of different intensity, and it can also be used to calculate to which extent each afferent in an ensemble contributes to the discrimination. Since the emphasis is put on discrimination of stimuli rather than on similarities between the representations of the stimulus in the ensemble response and the stimulus itself, it involves no implicit assumption about the unknown decoding mechanisms in the CNS. Examples of results obtained with analysis of and comparison of simultaneously recorded and pooled sequentially recorded populations of primary muscle spindle afferents are given. These results support some of the general arguments in favour of the ensemble coding theory, and indicate that the results of studies made on populations of simultaneously recorded receptor afferents may differ considerably from results obtained in studies on pooled sequentially recorded afferents. In contrast to when ensemble responses are based on parallel recordings, population responses constructed from sequential recordings will be distorted as a result of unavoidable temporal variations in physiological conditions.

Algorithms↗

Influences on the gamma-muscle-spindle system from contralateral muscle afferents stimulated by KCl and lactic acid.

The aim of the present study was to investigate whether increased concentrations of lactic acid and potassium chloride (KCl) in contralateral muscles can influence the sensitivity of primary and secondary muscle spindle afferents (MSAs) from ipsilateral extensor and flexor muscles. The experiments were performed on 7 cats anaesthetised with alpha-chloralose. Recordings were made simultaneously from 2-12 single MSAs from the triceps surae (GS) and/or the posterior biceps and semitendinosus muscles (PBSt). The mean rate of firing and the amplitude of a fitted sine curve of MSA responses to sinusoidal stretching of the receptor bearing muscles were determined. Responses of 42 primary MSAs (17 from PBSt and 25 from GS) were recorded. On 33 of these, clear-cut alterations in sinusoidal response were evoked by injection of 1 ml KCl (200-400 mM) or 1 ml lactic acid (20-50 mM) into the arterial supply of the contralateral GS or PBSt muscles. Six out of 8 secondary MSAs showed sizeable effects to increased intramuscular concentrations of KCl and/or lactic acid (3 from PBSt and 3 from GS). On both primary and secondary MSAs, from GS as well as from PBSt muscles, the large majority of effects were excitatory. All effects on secondary MSAs were compatible with reflex actions on static fusimotor neurones, whereas on primary MSAs different types of reflex responses were observed (i.e. pure static, pure dynamic and mixtures of static and dynamic fusimotor actions). Stimuli related alterations in MSA responses were completely abolished when the contralateral GS or PBSt nerves were anaesthetised.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Influences on the gamma-muscle spindle system from muscle afferents stimulated by increased intramuscular concentrations of bradykinin and 5-HT.

There is evidence that static muscular contractions induce a release of bradykinin (BK) in the working muscle, and that increased concentration of BK and 5-HT in a muscle increases the discharge rate of a subpopulation of group III and group IV muscular afferents. It is also known that activity in group III and IV muscle afferents may activate gamma-motoneurones to both homonymous and heteronymous muscles. The aim of the present study was to investigate whether increased concentration of BK and 5-HT in one muscle may influence the activity in primary and secondary muscle spindle afferents (MSAs) from the chemically affected muscle and from surrounding muscles, via fusimotor reflexes. The experiments were made on six cats anaesthetised with alpha-chloralose. The triceps surae (GS) and the posterior biceps and semitendinosus (PBSt) muscles were subjected to sinusoidal stretches. Simultaneous recordings of 2-11 MSAs from these muscles were made and the mean rate of firing and the modulation for each MSA were determined. Responses of 47 MSAs (26 PBSt and 21 GS) were recorded. The responsiveness of the MSAs to injections of BK (9-100 mg/ml, 0.5-1.0 ml) and 5-HT (25-150 mg/ml, 0.5-1.0 ml) was 89% and 83%, respectively, for injections into the arterial supply of the ipsilateral GS muscle, and 84% and 40% respectively for injections to the contralateral GS muscle. Of 10 secondarŁy MSAs, only one was unresponsive to BK injections, while several MSAs responded to both ipsilateral and contralateral BK injections.(ABSTRACT TRUNCATED AT 250 WORDS)

Afferent Pathways↗

Effects of L-DOPA on fusimotor control of triceps surae muscle spindles in the cat.

The experiments were performed on lightly alpha-chloralose anaesthetised and spinalized cats. Alterations in fusimotor activity were assessed by recordings from single spindle afferents (90 primary and 12 secondary) from the triceps surae muscle, before and after i.v. administration of L-beta-3,4-dihydroxyphenylalanine (L-DOPA). The effects of L-DOPA on fusimotor reflexes from ipsi- and contralateral hind limb afferents were investigated by using extensions of the intact contralateral hind limb and tonic stretches of the ipsilateral posterior biceps and semitendinosus muscles as reflex stimuli. Prior to injection of L-DOPA, a low reflex responsiveness was found to both the ipsi- and the contralateral stimulation. After administration of L-DOPA, the reflex responsiveness as well as the resting activity of the muscle spindle afferents were increased as a result of enhanced activity in mainly dynamic fusimotor neurones. The results indicate that changes in fusimotor activity elicited after administration of L-DOPA are caused by release of transmission in interneuronal pathways mediating ipsi- and contralateral reflexes to mainly dynamic fusimotor neurones. The possible role of monoaminergic descending control of fusimotor neurones in the regulation of muscle tone, tremor and rigidity is discussed.

Afferent Pathways↗

The role of the gamma-system for improving information transmission in populations of Ia afferents.

Ensemble coding of simple mechanical stimuli (small sinusoidal stretches) was studied in populations of simultaneously recorded primary muscle spindle afferents (MSAs). The experiments were made on 39 primary MSAs in chloralose anaesthetised cats. For the analyses we used a combination of principal component analysis and algorithms for quantification of stimulus discrimination. Ensembles of primary MSAs discriminated better between different muscle stretches than individuals, and showed a successive increase in discriminative ability with increasing ensemble size. The ensemble effect disappeared after cutting the ventral roots, indicating an important role for the fusimotor system in ensemble coding. Simultaneously recorded ensembles of MSAs showed significantly better discriminative ability than pooled sequentially recorded MSAs. This difference was abolished by the cutting of the ventral roots. It is hypothesised that, since the muscle spindles are connected to each other via secondary MSAs (projecting to gamma-motoneurones to other spindles), the fusimotor-muscle spindle system may constitute a neural network, in which each 'neuron' (i.e., each individual muscle spindle) is influenced by the activity in the whole network. In populations of pooled sequentially recorded MSAs, the connections would not exist. Thus, the population would lose its neural network quality, and the encoding ability of the population would decrease.

Afferent Pathways↗

High levodopa use in periodically time-clustered, Icelandic birth cohorts. A vestige of parkinsonism etiology? Europarkinson Preparatory Activity Research Group.

We evaluated levodopa use (LDU) by the Icelandic population focusing on: 1) annual gross levodopa (LD) sales from wholesalers to pharmacies for the period 1978-1990, using a reported method; 2) data from a prescription survey conducted from October 1st, 1990 to March 31st, 1991; and 3)raw and reported data on prevalences of Parkinson's disease (PD) in 1963 in this country. The standard for adjustments and reference population for LDU comparisons was the Swedish in 1984. Crude gross sales of LD in Iceland in 1990 and in Sweden in 1984 amounted to 1.67 and 1.35 DDD/1000 person days respectively. After respective adjustments for age, and for age and the infant mortality rates, taken as an indicator of health care quality, LDU in Iceland in 1990 was found to be 1.82 and 1.63 (95% CI 1.47-1.89) times that for Sweden. Prevalences of LD-prescription recipients in 1990-1991 and of PD in 1963 increased with age; however, those of drug users were higher than those of PD among the elderly. Higher-than-expected prevalences of PD and LD-prescription users (there being a partial overlap between these two categories) were found in periodically-clustered, one-year birth cohorts. These results support the notion that Iceland has a high LDU and suggest that this variation is due to a high prevalence of LD responsive disorders. Cohorts born after registered whooping cough outbreaks in Iceland may account for the magnitude and birth-related pattern of PD prevalences and LDU levels.

Adult↗

Immune-mediated complications in patients with myelodysplastic syndromes--clinical and cytogenetic features.

It has been recognized in recent years that some patients with myelodysplastic syndromes (MDS) develop immune-mediated complications (IMC), but little is known about the correlations to MDS-specific disease features. In a retrospective study of 82 MDS patients, we identified 10 (12%) with IMC (group A) and compared them to the remaining 72 cases (group B). Group A consisted of 5 patients with biopsy-verified skin vasculitis and 1 case each with temporal arteritis/polymyalgia rheumatica, necrotising panniculitis, Hashimoto's thyroiditis, autoimmune thrombocytopenia, and Sweet's syndrome. Survival times, sex ratio and distribution of MDS subtypes were similar in the two groups. The patients in group A were younger than those in group B (median 66 vs. 76 years, p < 0.01). Four patients (40%) in group A had a history of previous genotoxic therapy for malignant disorders. The bone marrow karyotype was evaluated in 62 patients. Clonal chromosomal abnormalities were found more frequently in Group A than in group B (8/9 vs. 26/53, p = 0.03), and complex karyotypes, i.e., three or more aberrations, were also observed to be more common in group A (3/9 vs. 8/53). The results indicate that IMC preferentially develop in patients with secondary MDS, in younger MDS cases, and in patients with cytogenetic abnormalities.

Adolescent↗

Influence of prior and subsequent pregnancy on breast cancer prognosis.

PURPOSE AND METHODS: The prognostic influence of pregnancies 5 years before (n = 173) and after (n = 50) breast cancer diagnosis was investigated in 2,119 women less than 50 years of age with a primary operable breast cancer. The main end point was distant metastasis. Univariate and multivariate analyses were performed using the Cox proportional hazards model. In the analyses of the effect of pregnancy after diagnosis of breast cancer, a Cox model with a time-dependent covariate was applied. RESULTS: Women with a pregnancy before diagnosis had slightly larger tumors than the control group. However, they did not differ with respect to nodal status and estrogen receptor (ER) status. There was no evidence that women with a pregnancy during the 5-year period preceding breast cancer diagnosis had a worse prognosis compared with women without pregnancy during the same period. Similarly, there was no evidence that women with a pregnancy after breast cancer diagnosis had a worse prognosis. CONCLUSION: The hormonal changes associated with pregnancy thus seem to have little, if any, influence on the prognosis of breast cancer. In the present study, at least, there was no indication of a worse prognosis. In fact, the relative hazard for women who became pregnant after diagnosis of breast cancer in comparison with women without a subsequent pregnancy was 0.48 (P = .14), which suggested a possible decreased risk of distant dissemination.

Adult↗