Studies in the diagnosis of breast disease (author's transl)]

The relative diagnostic accuracy of clinical examination, mammography, thermography and ultrasound was investigated in a comparative study. Mammography proved to be the most accurate diagnostic method, followed by clinical examination, thermography and ultrasound. Whereas in cases of advanced cancer (T2 to T4 tumour diameter greater than 2 cm) the correct diagnosis was made most reliably by clinical examination, mammography was superior to all other procedures in T1 tumours and in impalpable tumours. In our opinion thermography and ultrasound should be excluded for routine use or as a screening test because of the high false negative results. It is, however, noteworthy, that small intraparenchymal cysts can be detected and localized by ultrasound in a very high percentage of cases.     

Preoperative irradiation affects functional results after surgery for rectal cancer

PURPOSE: The Swedish Rectal Cancer Trial has unequivocally demonstrated that preoperative high-dose (5 × 5 Gy) radiotherapy reduces local failure rates and improves overall survival. This will have an impact on the primary treatment of rectal cancer. This study investigates the effect of preoperative high-dose radiotherapy on long-term bowel function in patients treated with anterior resection. METHODS: A questionnaire was answered by 92 percent (203/220) of patients who were included in the Swedish Rectal Cancer Trial and who were alive after a minimum of five years. Thirty-two patients were excluded, mainly because of postoperative stomas and dementia, which left 171 for analysis. RESULTS: Median bowel frequency per week was 20 in the irradiated group (n=84) and 10 in the surgery-alone group (n=87;P<0.001). Incontinence for loose stools (P<0.001), urgency (P<0.001), and emptying difficulties (P<0.05) were all more common after irradiation. Sensory functions such as discrimination between gas and stool and ability to safely release flatus did not, however, differ between groups. Thirty percent of the irradiated group stated that they had an impaired social life because of bowel dysfunction, compared with 10 percent of the surgery-alone group (P<0.01). CONCLUSIONS: The study indicates that high-dose radiotherapy influences long-term bowel function, thus emphasizing the need for finding predictive factors for local recurrence to exclude patients with a very high probability for cure with surgery alone and to use optimized radiation techniques.Supported by the Swedish Cancer Society (Grant 1921-B97-15XCC).Read at the meeting of The American Society of Colon and Rectal Surgeons, Philadelphia, Pennsylvania, June 22 to 26, 1997.     

Role of the innate immune system in host defence against bacterial infections: focus on the Toll-like receptors

The innate immunity plays a critical role in host protection against pathogens and it relies amongst others on pattern recognition receptors such as the Toll-like receptors (TLRs) and the nucleotide-binding oligomerization domains proteins (NOD-like receptors, NLRs) to alert the immune system of the presence of invading bacteria. Since their recent discovery less than a decade ago, both TLRs and NLRs have been shown to be crucial in host protection against microbial infections but also in homeostasis of the colonizing microflora. They recognize specific microbial ligands and with the use of distinct adaptor molecules, they activate different signalling pathways that in turns trigger subsequent inflammatory and immune responses that allows a immediate response towards bacterial infections and the initiation of the long-lasting adaptive immunity. In this review, we will focus on the role of the TLRs against bacterial infections in humans in contrast to mice that have been used extensively in experimental models of infections and discuss their role in controlling normal flora or nonpathogenic bacteria. We also highlight how bacteria can evade recognition by TLRs.     

Mental health problems and healthcare contacts in an urban and a rural area. Comparisons of two Swedish counties

Mental health problems are common in the general population. The aim of this study was to investigate differences in frequencies of self-reported psychiatric symptoms, harmful alcohol use and healthcare contacts, in an urban and a rural area in Sweden. Two samples of 10,441 (urban site) and 3538 (rural site) subjects, aged 20-64, responded to a questionnaire, covering demographic characteristics and self-report psychiatric instruments as well as contact with healthcare during the past 12 months. Psychiatric symptoms and symptoms of substance abuse were reported by 17% of the urban women compared with 13% of the rural women, and by 20% of the urban men compared with 15% of the rural men. This difference is mainly due to an uneven age distribution in the two populations and remains statistically significant only in the oldest age group (50-64 years). Symptoms of anxiety and depression occurred with similar frequencies in both samples. Harmful alcohol use was reported by 3.6% of the urban women, 1.5% of rural women, 11.8% of urban men and 8.6% of rural men. The urban sample had more often been in contact with medical services, 77% vs. 52%. Symptoms of anxiety and depression were equally common in the two samples. Harmful use of alcohol was more common in the urban sample, especially among women. Most obvious was the stronger inclination to seek help in the urban sample.     

Activity level and subjective knee function 15 years after anterior cruciate ligament injury: a prospective, longitudinal study of nonreconstructed patients

BACKGROUND: The activity level and subjective knee function after an anterior cruciate ligament (ACL) injury treated without reconstruction have not been well elucidated. HYPOTHESIS: Patients with ACL injury can achieve good knee function and satisfactory long-term activity level when treated by early activity modification combined with rehabilitation. STUDY DESIGN: Cohort study (prognosis); Level of evidence, 2. Materials and METHODS: One hundred patients with an acute total ACL injury were observed for 15 years. All patients initially underwent arthroscopic surgery and a rehabilitation program. They were advised to modify their activity level, especially by avoiding contact sports. Patients with recurrent giving-way episodes and/or secondary meniscal injuries that required fixation (n = 6) were subsequently excluded and underwent reconstruction (n = 22). Sixty-seven patients with unilateral nonreconstructed ACL injury remained at the 15-year follow-up. The Lysholm knee score, Tegner activity level, and a visual analog score for global knee function were recorded at regular intervals. At the final follow-up, patients were further evaluated with the Knee injury and Osteoarthritis Outcome Score (KOOS) and International Knee Documentation Committee (IKDC) subjective knee evaluation form. RESULTS: Forty patients resumed their preinjury activity level or higher within 3 years. The median activity level 15 years after injury had decreased from 7 to 4 according to Tegner activity scale (P < .001). The mean Lysholm knee score was 96 and 95, 1 and 3 years after injury, respectively, but declined to 86 after 15 years (P < .001). Forty-nine patients had good/excellent results, and 14 had fair (n = 6) or poor function (n = 8) at 15 years. Patients injured in contact sports scored lower in the quality of life sub-scale of KOOS than those injured in noncontact sports (P < .05). Thirteen of the 67 patients (19%) were reoperated with an arthroscopic procedure because of knee symptoms. CONCLUSION: Early activity modification and neuromuscular rehabilitation resulted in a good knee function and an acceptable activity level in the majority of the nonreconstructed patients. The decline in activity level of patients engaged in contact sports at the time of injury affected their subjective quality of life more than patients involved in noncontact sports.     

Recurrent superantigen exposure in vivo leads to highly suppressive CD4+CD25+ and CD4+CD25‐ T cells with anergic and suppressive genetic signatures

Staphylococcal enterotoxin B (SEB) activates T cells via non‐canonical signalling through the T cell receptor and is an established model for T cell unresponsiveness in vivo. In this study, we sought to characterize the suppressive qualities of SEB‐exposed CD4⁺ T cells and correlate this with genetic signatures of anergy and suppression. SEB‐exposed CD25⁺ and CD25^‐Vβ8⁺CD4⁺ T cells expressed forkhead box P3 (FoxP3) at levels comparable to naive CD25⁺ T regulatory cells and were enriched after exposure in vivo. Gene related to anergy in lymphocytes (GRAIL), an anergy‐related E3 ubiquitin ligase, was up‐regulated in the SEB‐exposed CD25⁺ and CD25^‐FoxP3⁺Vβ8⁺CD4⁺ T cells and FoxP3^‐CD25^‐Vβ8⁺CD4⁺ T cells, suggesting that GRAIL may be important for dominant and recessive tolerance. The SEB‐exposed FoxP3⁺GRAIL⁺ T cells were highly suppressive and non‐proliferative independent of CD25 expression level and via a glucocorticoid‐induced tumour necrosis factor R‐related protein‐independent mechanism, whereas naive T regulatory cells were non‐suppressive and partially proliferative with SEB activation in vitro. Lastly, adoptive transfer of conventional T cells revealed that induction of FoxP3⁺ regulatory cells is not operational in this model system. These data provide a novel paradigm for chronic non‐canonical T cell receptor engagement leading to highly suppressive FoxP3⁺GRAIL⁺CD4⁺ T cells.