Search PubMed⌕ Search

Biomedical subjects

J Ahlgren

Publications and source records attributed to J Ahlgren.

At least 19 recordsLinked to original sources

Cyclin A as a marker for prognosis and chemotherapy response in advanced breast cancer.

We wanted to study cyclin A as a marker for prognosis and chemotherapy response. A total of 283 women with metastatic breast cancer were initially enrolled in a randomised multicentre trial comparing docetaxel to sequential methotrexate-fluorouracil (MF) in advanced breast cancer after anthracycline failure. Paraffin-embedded blocks of the primary tumour were available for 96 patients (34%). The proportion of cells expressing cyclin A was determined by immunohistochemistry using a mouse monoclonal antibody to human cyclin A. Response evaluation was performed according to WHO recommendations. The median cyclin A positivity of tumour cells was 14.5% (range 1.2-45.0). Cyclin A correlated statistically significantly to all other tested proliferation markers (mitotic count, histological grade and Ki-67). A high cyclin A correlated significantly to a shorter time to first relapse, risk ratio (RR) 1.94 (95% CI 1.24-3.03) and survival from diagnosis, RR 2.49 (95% CI 1.45-4.29), cutoff point for high/low proliferation group 10.5%. Cyclin A did not correlate to chemotherapy response or survival after anthracycline, docetaxel or MF therapy. Of all tumour biological factors tested (mitotic count, histological grade and Ki-67), cyclin A seemed to have the strongest prognostic value. Cyclin A is a good marker for tumour proliferation and prognosis in breast cancer. In the present study, cyclin A did not predict chemotherapy response.

Antineoplastic Combined Chemotherapy Protocols↗

Phase II study of capecitabine in combination with paclitaxel in patients with anthracycline-pretreated advanced/metastatic breast cancer.

The addition of oral capecitabine to docetaxel improves response rate, time to progression (TTP) and overall survival in anthracycline-pretreated metastatic breast cancer (MBC). This phase II study evaluates the efficacy and safety of a 21-day cycle of oral capecitabine (1000 mg m(-2) twice daily, days 1-14) plus i.v. paclitaxel (175 mg m(-2), day 1) in anthracycline-pretreated advanced/MBC. In all, 73 patients were enrolled at 13 Swedish and Spanish centres. The objective response rate was 52% (95% confidence interval (CI): 40-63%) in the intent-to-treat population, including complete responses in 11%. Disease was stabilised in a further 29%. The median time to disease progression (TTP) was 8.1 months and the median overall survival was 16.5 months. The combination was generally well tolerated with a predictable safety profile. The most common treatment-related nonhaematological adverse events were hand-foot syndrome (42%), alopecia (30%) and diarrhoea (26%). The only treatment-related Grade 3/4 adverse events occurring in >5% of patients were alopecia (22%) and hand-foot syndrome (11%). Grade 3/4 neutropenia and lymphocytopenia were reported in 12 and 14% of patients, respectively. Capecitabine plus paclitaxel is highly active with a favourable safety profile in anthracycline-pretreated MBC.

Adolescent↗

Angiogenesis in invasive breast carcinoma--a prospective study of tumour heterogeneity.

Assessment of angiogenesis has been reported to be an independent prognostic factor in breast cancer, while other studies have been negative. This study prospectively investigates the degree of intratumoral microvessel heterogeneity and the possible influence on the results. From 21 invasive breast cancers six 4 micro sections were cut. Sections (n=126) were stained immunohistochemically with a CD31 monoclonal antibody (JC70). In each section, three areas with the most intense neovascularisation (hot spots) were identified and the microvessel density (MVD) was obtained by counting vessels at 200x magnification. The variation between sections contributed more to the total variance than variation between different tumours: 45.0 and 37.3%, respectively, according to a nested ANOVA analysis. Paired comparisons of two sections at a time from the same tumour showed a concordance in 59.0% (95% Confidence Interval (CI): (55.3-62.8)) with reference to a tentative cut-off level. Our study demonstrates that assessment of MVD in hot spots is questionable to measure angiogenesis due to the considerable intratumoral heterogeneity.

Adult↗

Five-node biopsy of the axilla: an alternative to axillary dissection of levels I-II in operable breast cancer.

BACKGROUND: Axillary clearance of patients with early breast cancer is accompanied by a high risk of arm morbidity. Less invasive ways to establish the axillary nodal status are therefore of interest, especially in women with low risk of nodal metastases. METHODS: Four hundred and fifteen breast cancer patients (clinical stage T(0-3) N(0-1) M(0)) were operated in the axilla with a five-node biopsy followed in the same operation by a further dissection of levels I-II of the axilla in order to evaluate the accuracy of the five-node node biopsy compared with level I-II dissection. RESULTS: In all patients the sensitivity of the five-node biopsy was 97.3% with a negative predictive value of 98.5% and a negative likelihood ratio of 0.027. Among cases detected by screening (n=204) and those clinically detected (n=197) the sensitivity of the five-node biopsy was 95.8% and 97.9% respectively, with negative predictive values of 98.7% and 98.0% and negative likelihood ratios of 0.042 and 0.021 respectively. CONCLUSION: Five-node biopsy of the axilla has good accuracy for correctly staging the axilla in both clinically and screening-detected cases. Five-node biopsy is an alternative to axillary clearance and sentinel node biopsy in patients with operable breast cancer.

Aged↗

Enzymatic mutation detection method evaluated for detection of p53 mutations in cDNA from breast cancers.

BACKGROUND: Rapid, reproducible, and easily run methods with high sensitivity and specificity are required for mutation screening of clinical samples. We evaluated the Enzymatic Mutation Detection (EMD(TM)) method by analysis of archival cDNA from 203 breast cancer patients and comparison with results of cDNA-based sequencing of the tumor suppressor gene p53. METHODS: The EMD technology uses the T4 endonuclease VII, which cleaves double-stranded DNA at sites where a DNA mismatch is present because of mispairing or an insertion/deletion of nucleotides. The EMD analyses were carried out by dividing the p53 gene into two overlapping fragments that were analyzed separately. After PCR amplification, the fragments were hybridized with wild-type p53 and subsequently exposed to the EMD enzyme. Cleavage products were analyzed and scored using an ALF(TM) automated DNA sequencer and ALFwin Fragment Analyzer software (VER: 1.02). RESULTS: The EMD technique had sensitivities of 45% and 64% and specificities of 83% and 84% for the two fragments, respectively. Patients with EMD-positive, wild-type p53 tumors had a survival similar to that of patients with EMD-negative, wild-type p53 tumors. Node-positive patients with p53 mutated tumors according to sequencing had a statistically significantly worse overall survival than those with p53 wild-type tumors (P = 0.016), whereas this difference in survival was not detected when p53 status was determined with EMD (P = 0.47). CONCLUSIONS: EMD had insufficient sensitivity for consideration in screening for the p53 gene in this archival material. Sequencing must still be considered as the standard procedure.

Breast Neoplasms↗

Omitting axillary surgery for low-risk breast cancer patients--a Swedish prospective cohort study.

The effects of mammography screening are a decrease in the sizes of tumours and a shift in stage. Very few small breast cancers (< or = 10 mm) have lymph node metastases when screening-detected, the rate being as low as 7%. Axillary clearance is not necessary for all such small tumours. A Swedish prospective cohort study, scheduled for 1500 patients, is being launched, where axillary surgery is omitted for screening-detected breast cancers of < or = 10 mm showing Elston grade I or II/and/or S-phase < or = 10%. Axillary surgery, with the associated disadvantages, will not be performed in 970 women out of 1000 expecting an axillary recurrence rate of 3%. Nordic breast cancer centres are welcome to join the study, which has already recruited around 500 patients.

Adult↗

Can axillary dissection be avoided by improved molecular biological diagnosis?

Axillary dissection is presently a routine staging procedure in the management of breast cancer. The use of adjuvant systemic treatment is largely based on the diagnosis of axillary metastases. Routine axillary dissection leads to acute and chronic side-effects in a large proportion of patients. The sentinel node technique is presently explored with the aim of decreasing the need for standard axillary dissection. A complementary way forward is to analyse the primary breast cancer for molecular markers with prognostic significance with reference to the risk for metastatic capacity and thereby obtain a 'biological staging' and identify those patients in need of systemic adjuvant therapy. A large number of molecular biological factors have been shown to have prognostic significance in breast cancer e.g. c-erbB-2, p53, uPA, PAI-I and VEGF. This article reviews the expression of these and other factors in the primary breast cancers in relation to the risk for axillary and systemic metastatic disease, with the long-term aim of excluding routine axillary dissection.

Axilla↗

Cross-comparison of two quality of life instruments used in a randomized study of combination chemotherapy in advanced breast cancer.

Twenty-six patients from a randomized study of combination chemotherapy in advanced breast cancer were included in a cross-comparison between two quality of life instruments: a categorical linear analogue scale (C-LASA) based on the instrument of Priestman and Baum and a Swedish instrument developed by Glimelius et al. Quality of life was assessed on day 1 and day 10 of each chemotherapy cycle and the instruments were compared using correlation and kappa analysis. For the physical dimension, the mean correlation coefficient on day 1 was 0.89 and the kappa coefficient was 0.62; and on day 10 the correlation coefficient was 0.83 and the kappa coefficient 0.62. For the emotional dimension the correlation and kappa coefficients were 0.89 and 0.71 and 0.89 and 0.61 on days 1 and 10, respectively. The corresponding values for the global dimension were 0.76 and 0.56 and 0.80 and 0.57 on days 1 and 10, respectively. A correlation was also demonstrated over time. The instruments gave similar measurements of quality of life for chemotherapy-treated patients with advanced breast cancer, but the feasibility of the C-LASA instrument was better.

Adult↗

Effects of buccal shields on the maxillary dentoalveolar structures and the midpalatal suture--histologic and biometric studies in rabbits.

The mechanism of the buccal shields with regard to regulating the transversal relationship of the maxillary dental arch is uncertain. The periosteal pull theory, growth at the midpalatal suture and changes in equilibrium have all been proposed as explanatory factors. The aim of the study was to investigate the transversal development of the dental arch and the osseous remodeling at the lateral surfaces of the maxillary alveolar process and in the midpalatal suture after stretching the bucca (cheek) with buccal shields in the vestibulum. Ten New Zealand white male rabbits 12 weeks old were used. The animals were divided into two groups (control and experimental). Initial and final impression had been taken from the two groups and plaster models were made using biometric analysis in all animals of each group. Transversal measurements were taken of the distances between the maxillary right and left teeth. Tetracycline hydrochloride and Alizarin complexone were used to label the mineralizing tissues. After the animals had been killed, the biopsies from the midpalatal suture, the alveolar wall, and the periosteum were studied under a microscope. The results from the biometric analysis showed maxillary dental arch expansion in the two groups that was significantly larger in the experimental group. Microscopically, the growth at the midpalatal suture was also significantly larger in the experimental group, while no significant differences were found at the maxillary alveolar bone in the two groups. The conclusions drawn from this study are that the vestibular buccal shields bring about an increased expansion of the maxillary dental arch and increased growth at the midpalatal suture. No increased bone deposition was found at the buccal dentoalveolar wall, inducing doubts as to the accuracy of the periosteal pull theory for widening of the dental arch.

Activator Appliances↗

EMG studies of lip and cheek activity in sucking habits.

Pronounced lip and mentalis (perioral) muscle activity was developed during thumb and dummy sucking. Cheek (Buccinator) activity was less evident, showing light to moderate activity. Lip and cheek activity was more noticeable during dummy sucking than thumb sucking. Sucking water through a straw and swallowing produced similar functional patterns to thumb sucking: strong lip and mentalis activity but comparatively low buccinator activity. Activity at rest in perioral muscles was pronounced among thumb and dummy suckers, while buccinator activity was negligible. Lip and cheek activity was substantially less, both at rest and during sucking, in a control group of children who were not thumb suckers.

Adolescent↗

Jaw-closing muscles: electromyographic activity of human subjects with reduced periodontal support.

The aim of this study was to compare the electromyographic (EMG) activity of jaw-closing muscles of individuals with normal and reduced periodontal bone support. Fourteen adult subjects with more than 24 remaining teeth and low levels of periodontal inflammation, were selected for the study. Subjects of the control group had 90% of the periodontal bone support left, while other subjects presented a reduction of 52% of the original periodontal bone. Chewing experiments were performed using silicone tablets, carrots and white bread. The EMG of masseter and anterior temporal muscles was performed bilaterally, using bipolar surface electrodes, and the EMG amplitude was full wave rectified, integrated and the area extension under the curve was used to access muscle activity. The results of the chewing experiments did not show any statistically significant difference in the EMG activity of the study groups, irrespective of the chewing stuff. The height of periodontal bone support did not seem to influence the electroactivity of jaw-closing muscles, indicating that reduced periodontal support might equally be able to withstand masticatory loads. Hence, individuals with reduced periodontal bone support revealed a similar EMG activity compared to subjects with normal periodontal bone support.

Alveolar Bone Loss↗

Prediction of axillary lymph node metastases in a screened breast cancer population. South-East Sweden Breast Cancer Group.

To define a subgroup of patients, in whom axillary dissection could be omitted, we analysed the frequency of pathologically confirmed lymph node metastases depending on tumour size, hormonal receptors, DNA ploidy, S-phase fraction (SPF), and clinical nodal status among 1,145 patients with stage I-II breast cancer from an area with ongoing screening. Clinical nodal status and tumour size were strongly correlated to pathological nodal status. Also SPF > 10% was strongly correlated to node positivity in univariate analysis. In multivariate analysis there was still a significant correlation among cases with tumour size < or = 20 mm. In conclusion, patients with clinically negative nodal status, and tumour size < or = 20 mm and < or = 10 mm had pathologically positive nodes in 25% and 15% of cases respectively. The addition of SPF did not lower these figures significantly since small tumours with high SPF are few.

Adult↗

Three-stage activator treatment of a severe skeletal Class II, open bite malocclusion.

Activator therapy for a severe Class II, Division 1 malocclusion with open bite malocclusion is described. The treatment was performed in three stages: one, "early-early," at the age of 5 to 6 years; one "early," between 9 and 11 years; this was followed by 2 years of retention with a maxillary retainer. The patient continued to be observed further over a 3-year period. The final records show a normal, stable occlusion, and good facial balance.

Activator Appliances↗

A ten-year evaluation of the quality of orthodontic treatment.

A 10-year evaluation of the quality of orthodontic treatment at the Department of Orthodontics, School of Dentistry in Malmö, University of Lund, showed that in approximately 3 cases out of 4 (73%) successful results were noted in the malocclusions under treatment. In approximately half the cases the ideal treatment goal, normal occlusion, was achieved. The treatment was unsuccessful in 12% and in a large group of patients (15%) the treatment was discontinued due to lack of motivation or compliance. More accurate study and documentation of subjective need of treatment (motivation, cooperation and social sufficiency) would improve the quality of orthodontic care and make it more efficient. Some sort of penalty due to distinct lack of patient cooperation might improve orthodontic care. Root resorption occurred frequently during orthodontic treatment with multiband fixed appliances, but the apical shortening was small and without clinical significance.

Adolescent↗

Muscle response to the oral-screen activator. An EMG study of the masseter, buccinator, and mentalis muscles.

The myofunctional changes that occur during orthodontic treatment with functional appliances constructed with vestibular screen elements, such as buccal shields and lip pads, have not been sufficiently investigated. The aim of this study was to examine electromyographically the response of the masseter, buccinator and mentalis muscles to the oral-screen activator (OSAC), which is a conventional activator constructed with buccal shields and lip pads. The material consisted of 10 children, with Angle Class II, division 1 malocclusion and narrow dental arches (mean age 10.7 years), treated at the Department of Orthodontics, School of Dentistry, Malmö, Sweden. The group had a mean overjet of 8.5 mm, and a mean ANB angle of 6 degrees. Six out of the 10 cases had incompetent lips at relaxed lip position. The construction bite of the OSAC was taken with the anterior teeth in edge-to-edge position. The recording procedure included the following positions: (a) postural position of the mandible with lips relaxed and lips closed; (b) clenching; (c) swallowing saliva; and (d) spatula exercise. EMG recordings were made after 1, 2, and 3 months of appliance treatment. Differences between means were tested with a two-way analysis of variance (ANOVA). The results showed that during postural position with lips closed there was a statistically significant increase in mentalis EMG with the oral-screen activator in place. The buccinator and masseter muscles showed no EMG activity during rest with or without the appliance in the mouth. During clenching we found no statistically significant difference in masseter EMG with or without the appliance in place. During swallowing saliva a statistically significant decrease was recorded in mentalis EMG with the oral-screen activator in the mouth, while buccinator activities remained the same with and without the appliance. The masseter activity, on the other hand, increased significantly with the activator in place. During spatula exercise mentalis and buccinator were highly activated. The conclusions drawn from this study are that the oral screen activator (OSAC) increased masseter activity during swallowing, but it remained unchanged during clenching. Lip pads increase mentalis activity during lip closure, but reduce mentalis hyperactivity during swallowing. The buccinator activity was insignificant and buccal shields did not change that activity. Spatula exercise stimulates both mentalis and buccinator activity.

Acrylic Resins↗

Continuous infusion 5-fluorouracil plus weekly cisplatin for pancreatic carcinoma. A Mid-Atlantic Oncology Program study.

Fifty-six previously untreated patients with biopsy-proven, locally advanced or metastatic and measurable adenocarcinoma of the pancreas were treated with the combination of a protracted intravenous infusion of 5-fluorouracil (5-FU) and low dose weekly bolus cisplatin administered continuously for 10 weeks followed by a 2-week rest period. The objective response rate was 16% with two patients (4%) achieving a complete response (confidence intervals, 8% to 29%). The median survival time for all treated patients was 5.8 months; however, 26% of all patients were alive at 1 year. Both median survival time and the proportion alive at 1 year exceed that of prior reports involving large patient groups, possibly due to better patient selection.

Adenocarcinoma↗