TP53 mutation analyses on breast carcinomas: a study of paraffin-embedded archival material.

The aim of this investigation was to examine the possibility of analysing TP53 mutations in archival paraffin-embedded material with the constant denaturant gel electrophoresis (CDGE) method. We extracted DNA from 193 archival primary breast carcinoma samples, diagnosed in 1981-83; further analysis was possible for 186 of these. TP53 mutations in exons 5-8 were detected with CDGE in 30 samples (16.1%) and 17 of these mutations were confirmed by sequencing. Immunohistochemistry demonstrated TP53 nuclear accumulation in 58 tumours (31%). A strong association between the presence of TP53 mutations and TP53 immunostaining was observed (P < 0.001). Our mutation and immunohistochemistry results are in agreement with other findings based on fresh tumour tissue. TP53 abnormalities were significantly related to high S-phase fraction, low oestrogen receptor (ER) content and high tumour grade. Survival of patients with TP53 abnormalities, in the group as a whole, did not differ from patients with normal TP53. Our study did, however, show that patients with abnormal TP53 had a significantly shorter post-recurrence survival (P = 0.005) than patients with normal TP53.     

The prevalence of headache with emphasis on tension-type headache in rural Tanzania: a community-based study

The aim of the study was to assess the prevalence of headache with special attention to tension-type headache (TTH) in a rural area in northern Tanzania. A door-to-door study was performed using a standardized and validated questionnaire. A total of 7412 participants were screened. The total headache prevalence during the past year was 12.1%; the overall 1-year prevalence of TTH was 7%; 5% reported episodic TTH and 0.4% chronic TTH. Borderline cases (International Headache Society code 2.3) were described in 1.6%. The prevalence of headache was highest in the 41–50-year-old group in women and in the 61+ age group in men. This is the first account of the prevalence of TTH in a rural Tanzanian population, and shows that headache in general and, more specifically, TTH are prevalent disorders that deserve attention. However, the prevalence of primary headache seems to be lower than in Western countries.     

The effects of manual therapy and exercise directed at the cervical spine on pain and pressure pain sensitivity in patients with myofascial temporomandibular disorders

Summary No studies have investigated the effects of the treatments directed at the cervical spine in patients with temporomandibular disorders (TMD). Our aim was to investigate the effects of joint mobilization and exercise directed at the cervical spine on pain intensity and pressure pain sensitivity in the muscles of mastication in patients with TMD. Nineteen patients (14 females), aged 19–57 years, with myofascial TMD were included. All patients received a total of 10 treatment session over a 5‐week period (twice per week). Treatment included manual therapy techniques and exercise directed at the cervical spine. Outcome measures included bilateral pressure pain threshold (PPT) levels over the masseter and temporalis muscles, active pain‐free mouth opening (mm) and pain (Visual Analogue Scale) and were all assessed pre‐intervention, 48 h after the last treatment (post‐intervention) and at 12‐week follow‐up period. Mixed‐model anovas were used to examine the effects of the intervention on each outcome measure. Within‐group effect sizes were calculated in order to assess clinical effect. The 2 × 3 mixed model anova revealed significant effect for time (F = 77·8; P < 0·001) but not for side (F = 0·2; P = 0·7) for changes in PPT over the masseter muscle and over the temporalis muscle (time: F = 66·8; P < 0·001; side: F = 0·07; P = 0·8). Post hoc revealed significant differences between pre‐intervention and both post‐intervention and follow‐up periods (P < 0·001) but not between post‐intervention and follow‐up period (P = 0·9) for both muscles. Within‐group effect sizes were large (d > 1·0) for both follow‐up periods in both muscles. The anova found a significant effect for time (F = 78·6; P < 0·001) for changes in pain intensity and active pain‐free mouth opening (F = 17·1; P < 0·001). Significant differences were found between pre‐intervention and both post‐intervention and follow‐up periods (P < 0·001) but not between the post‐intervention and follow‐up period (P > 0·7). Within‐group effect sizes were large (d > 0·8) for both post‐intervention and follow‐up periods. The application of treatment directed at the cervical spine may be beneficial in decreasing pain intensity, increasing PPTs over the masticatory muscles and an increasing pain‐free mouth opening in patients with myofascial TMD.     

Retinal vessel oxygen saturation in healthy individuals

Purpose. We measured oxygen saturation in retinal vessels of healthy eyes to determine the effects of age, sex, and cardiovascular parameters, as well as the reliability of the measurements and topographic differences. Methods. The Oxymap T1 retinal oximeter is based on a fundus camera. It simultaneously captures retinal images at two different wavelengths and estimates retinal vessel oxygen saturation. Mean saturation of main retinal arterioles and venules was measured in 120 healthy individuals aged 18-80 years (median 47 years). Of the 120 participants 44 (37%) were male (49 years) and 76 (63%) female (44 years). Results. Oxygen saturation was 92.2 ± 3.7% (mean ± SD) in retinal arterioles and 55.6 ± 6.3% in venules. No significant difference in oxygen saturation was found between left and right eyes. The inferotemporal quadrant had lower oxygen saturation in arterioles and venules (P < 0.0001). Arteriolar oxygen saturation was stable with age. Venular oxygen saturation in males decreased by 1.9 ± 0.6% (mean ± SEM) per 10 years of age (P = 0.003) and by 0.7 ± 0.4% in females (P = 0.068). Arteriovenous (AV) difference increased by 1.5 ± 0.5% per 10 years in males (P = 0.004) and 1.0 ± 0.4% (P = 0.007) in females. For every 10 mm Hg increase in ocular perfusion pressure, oxygen saturation in arterioles increased by 0.9 ± 0.4% (P = 0.024) and in venules by 1.2 ± 0.7% (P = 0.075). Conclusions. Retinal arteriolar oxygen saturation is stable in healthy individuals, while there is a significant decrease in venular oxygen saturation with age in males and a similar trend in females. AV difference increases significantly with age for both sexes. Our study provided normative data for spectrophotometric retinal oximetry in the Caucasian population.     

Autologous and allogeneic bone marrow transplantation for poor prognosis patients with B-cell chronic lymphocytic leukemia

Twenty patients with poor prognosis B-cell chronic lymphocytic leukemia (B-CLL) underwent uniform high-dose chemoradiotherapy followed by rescue with multiple monoclonal antibody-purged autologous bone marrow (BM) (12 patients) or T-cell-depleted allogeneic BM from HLA-identical siblings (8 patients) in a pilot study to assess the feasibility of BM transplantation (BMT) in this disease. All had poor prognosis disease by either staging, BM pattern, tumor doubling time criteria, or cytogenetics. All patients achieved remission criteria (defined as < or = 2 adenopathy, absence of splenomegaly, < or = 20% of the intertrabecular space involved on BM biopsy) before BMT. Despite the use of fludarabine, a median of three treatment regimens were required to achieve BMT eligibility. After BMT, all patients achieved complete hematologic engraftment. Toxicities were not significantly different between autologous versus allogeneic BMT. Two toxic deaths were observed. Of 19 evaluable patients, 17 clinical complete clinical remissions (89%) were observed, with 2 patients (1 allogeneic and 1 autologous) exhibiting persistent BM disease. Complete clinical remissions were documented at the phenotypic and molecular level for the majority of patients in whom dual fluorescence for CD5 and CD20 (15 of 15; 100%) and Ig gene rearrangements (11 of 14; 79%) were performed. Although long-term follow-up is needed to assess any potential impact on the disease-free and overall survival of these patients, this study shows the feasibility of using high-dose chemoradiotherapy and BMT in patients with poor prognosis B-CLL.     

Fractionated total-body irradiation and high-dose etoposide as a preparatory regimen for bone marrow transplantation for 94 patients with chronic myelogenous leukemia in chronic phase

Ninety-four consecutive patients with chronic myelogenous leukemia in first clinical chronic phase, median age of 34.0 years (range, 6.8 to 52.4 years), with a histocompatible sibling donor, were treated with fractionated total body irradiation (1,320 cGy) and high-dose etoposide (60 mg/kg) followed by allogeneic bone marrow transplantation (BMT). The median time from diagnosis to BMT was 7.0 months (range, 2.3 to 72.0 months). Sixty patients were treated before BMT with hydroxyurea alone, four patients with busulfan alone, one patient with interferon alone, and the other 29 patients were treated with various combinations of these drugs. Cumulative probabilities of overall survival, event- free survival, and relapse at 5 years were 73%, 64%, and 14%, respectively. The median follow-up time for surviving patients was 38 months, ranging from 12 to 88 months. By stepwise Cox regression analysis, significant prognostic variables were age at transplant, acute graft-versus-host disease > or = grade II, cytomegalovirus- associated interstitial pneumonitis, and years from diagnosis to BMT.     

Assessment of stool colour in community management of prolonged jaundice in infancy

Jaundice persisting beyond the first 2 wk of life is often regarded as an indication for investigation to exclude cholestatic liver disease. Most babies with prolonged jaundice have breast milk-related jaundice, which is a benign condition. Cholestatic liver disease is usually accompanied by pale stools and yellow or orange urine. A community programme was established to ascertain the incidence of prolonged jaundice and determine whether abnormal stool and urine colour could be used to assist primary care staff in referral decisions. Data were collected on normal stool and urine colour and used to devise a colour chart and information sheet for parents. Babies with prolonged jaundice were identified and referred for investigation. In all, 3661 babies were recruited into the study, of which 127 were jaundiced at 28 d of age. Of these, 125 were breastfed. The incidence of jaundice in breastfed babies at 28 d was 9.2% (95% CI 7.8%-11.0%) Abnormal liver function tests (LFTs) were common, but no baby had abnormal stool or urine colour and none was found to have liver disease. Jaundiced breastfed babies who are well are unlikely to have serious disease. Elevated LFTs are compatible with a diagnosis of breast milk-related jaundice. Prolonged jaundice in bottle-fed babies, and persistent pallor of stools or yellow/orange urine, are rare and merit immediate referral. Parents and professionals can be advised to report pale stools without generating a large number of unnecessary referrals. Further work is needed to determine whether a colour chart reduces the mean age of referral and treatment of infants with cholestatic liver disease.     

The Kheda malaria project: the case for environmental control

The Kheda project experience has shown that bio-environmentalcontrol of malaria is feasible, cost effective and ecologicallysound. It clearly brings out the need to consider health issuesat the planning stage of all developments. Bio-environmentalcontrol of malaria is suggested as the first line of attackfor the control of mosquitoes, malaria and other mosquito-bornediseases. Insecticides may be reserved for short-term use. Thiswill enable judicious and selective use of insecticides in solelyepidemic situations. The growing problem of resistance to insecticidesin mosquitoes as well as environmental pollution, can then besolved on a long term basis.