Effect of supervised and home exercise training on bone mineral density among breast cancer patients. A 12-month randomised controlled trial.

UNLABELLED: The ability of combined step aerobic- and circuit-training to prevent bone loss after breast cancer treatments was related to skeletal site and patients' menopausal status. Among premenopausal breast cancer survivors, a 12-month exercise intervention completely prevented bone loss at the femoral neck, whereas no exercise effect was seen at lumbar spine or at neither site in postmenopausal women. INTRODUCTION: The primary objective of this randomised clinical trial was to determine the preventive effect of supervised weight-bearing jumping exercises and circuit training on bone loss among breast cancer patients. METHODS: Of 573 breast cancer survivors aged 35-68 years randomly allocated into exercise or control group after adjuvant treatments, 498 (87%) were included in the final analysis. The 12-month exercise intervention comprised weekly supervised step aerobic- and circuit-exercises and similar home training. Bone mineral density (BMD) at lumbar spine and femoral neck were measured by dual-energy X-ray absorptiometry. Physical performance was assessed by 2-km walking and figure-8 running tests, and the amount of physical activity was estimated in metabolic equivalent-hours/week. RESULTS: In premenopausal women, bone loss at the femoral neck was prevented by exercise, the mean BMD changes being -0.2% among the trainees vs. -1.4% among the controls (p = 0.01). Lumbar bone loss could not be prevented (-1.9% vs. -2.2%). In postmenopausal women, no significant exercise-effect on BMD was found either at the lumbar spine (-1.6% vs. -2.1%) or femoral neck (-1.1% vs. -1.1%). CONCLUSIONS: This 12-month aerobic jumping and circuit training intervention completely prevented femoral neck bone loss in premenopausal breast cancer patients, whereas no effect on BMD was seen in postmenopausal women.

Effect of exercise on bone structural traits, physical performance and body composition in breast cancer patients--a 12-month RCT.

In this 12-month RCT, we examined whether aerobic impact exercise training (3x/week) could facilitate breast cancer survivors' recovery by enhancing their bone structural strength, physical performance and body composition. After the adjuvant chemo- and/ or radiotherapy, 86 patients were randomly assigned into the training or control group. Structural bone traits were assessed with pQCT at the tibia and with DXA at the femoral neck. Agility (figure-8 running), jump force and power (force platform), grip strength and cardiovascular fitness (2-km walk test) were also assessed. Training effects on outcome variables were estimated by two-way factorial ANCOVA using the study group and menopausal status as fixed factors. Bone structural strength was better maintained among the trainees. At the femoral neck, there was a small but significant 2% training effect in the bone mass distribution (p=0.05). At the tibial diaphysis, slight 1% to 2% training effects (p=0.03) in total cross-sectional area and bone structural strength were observed (p=0.03) among the postmenopausal trainees. Also, 3% to 4% training effects were observed in the figure-8 running time (p=0.03) and grip strength (p=0.01). In conclusion, vigorous aerobic impact exercise training has potential to maintain bone structural strength and improve physical performance among breast cancer survivors.

Early detection of colorectal cancer with faecal occult blood test screening.

BACKGROUND: Faecal occult blood test (FOBT) screening has been shown to decrease the incidence and mortality from colorectal cancer. This study compared the stage profile of patients with colorectal cancer diagnosed at the first FOBT screening round with that of an unscreened control group. METHODS: Subjects aged 60-64 years were allocated randomly to biennial FOBT screening (52 998 subjects) or a control group (53 002) in a Finnish prospective public health policy in 2004-2006. FOBT was performed with a guaiac test. At the end of 2007 the screened and control populations were linked to the Finnish Cancer Registry database, and the colonoscopic findings in the screen positives were analysed. RESULTS: Early-stage colorectal cancer was observed in 52 per cent of the FOBT-positive subjects, in 42.2 per cent of the total screened population and in 38 per cent of the control population (P = 0.191 for FOBT positives, P = 0.592 for total screened population). The prevalence of adenomas and colorectal cancer was 31.5 and 8.2 per cent respectively among the 806 subjects with a positive FOBT. Some 27.3 per cent of all colorectal tumours in the screened population were interval cancers. The tumour was located in the right colon in 28.9 per cent of the screened subjects and 22 per cent of controls (P = 0.255). CONCLUSION: Biennial FOBT screening improves detection of colorectal cancer at the first screening round, but the high percentage of interval cancers is a cause for concern.

Effectiveness of screening for colorectal cancer with a faecal occult-blood test, in Finland.

BACKGROUND: Screening for colorectal cancer (CRC) with guaiac-based faecal occult-blood test (FOBT) has been reported to reduce CRC mortality in randomised trials in the 1990s, but not in routine screening, so far. In Finland, a large randomised study on biennial FOB screening for CRC was gradually nested as part of the routine health services from 2004. We evaluate the effectiveness of screening as a public health policy in the largest population so far reported. METHODS: We randomly allocated (1:1) men and women aged 60-69 years to those invited for screening and those not invited (controls), between 2004 and 2012. This resulted in 180 210 subjects in the screening arm and 180 282 in the control arm. In 2012, the programme covered 43% of the target age population in Finland. RESULTS: The median follow-up time was 4.5 years (maximum 8.3 years), with a total of 1.6 million person-years. The CRC incidence rate ratio between the screening and control arm was 1.11 (95% CI 1.01 to 1.23). The mortality rate ratio from CRC between the screening and control arm was 1.04 (0.84 to 1.28), respectively. The CRC mortality risk ratio was 0.88 (0.66 to 1.16) and 1.33 (0.94 to 1.87) in males and females, respectively. CONCLUSIONS: We did not find any effect in a randomised health services study of FOBT screening on CRC mortality. The substantial effect difference between males and females is inconsistent with the evidence from randomised clinical trials and with the recommendations of several international organisations. Even if our findings are still inconclusive, they highlight the importance of randomised evaluation when new health policies are implemented. TRIAL REGISTRATION: 002_2010_august.

Rapid isolation of animal mitochondrial DNA by alkaline extraction.

A simple technique for rapid isolation of mitochondrial DNA (mtDNA) from animal cells is described. The method is based on the selective alkaline denaturation procedure of Birnboim and Doly [(1979) Nucleic Acids Res. 7, 1513-1523] and avoids the use of CsCl gradient centrifugation. The yield of mtDNA is comparable to that obtained by standard techniques. This DNA is sufficiently pure for restriction analysis and cloning of mtDNA fragments.

Recovery of the sutured facial nerve after removal of acoustic neuroma in patients with neurofibromatosis-2.

The authors compared the long-term recovery of sutured facial nerves after the removal of 8 neurofibromatosis-2 (NF2)-associated and 22 non-NF2 acoustic neuromas. The patients were from a series of 270 patients operated on for an acoustic neuroma between 1979 and 1989. The assessment was done with a modified House and Brackmann scale from video recordings. At least some facial movement or tone was achieved (Grade 5 or better) in all but three patients, but in none was the recovery excellent. The facial function, judged by the overall appearance in movement, recovered less in patients with NF2 (P = 0.048); a moderately good recovery (Grade 3 or better) was seen in one patient of eight with NF2, as compared with 13 of 22 with non-NF2. In conclusion, if the tumor cannot be peeled off easily from the facial nerve in patients with NF2, leaving a fragment of tumor behind is preferable to cutting and suturing the facial nerve.

Functional results of facial nerve suture after removal of acoustic neurinoma: analysis of 25 cases.

The facial nerve is sometimes severed during the removal of acoustic neurinomas, either intentionally to ensure complete removal, or unintentionally because of difficulties in identification. In such cases we have, if possible, sutured the nerve stumps microsurgically, either end to end or by use of an intervening nerve graft. We analyzed the outcome of 25 instances of facial nerve suturing in a series of 219 patients operated on for acoustic neurinoma from 1979 to 1987. The first signs of recovery appeared at an average of 12 months, and there was continued improvement for several years. Recovery was graded from 1 to 6. The anastomosis was successful in 24 of the 25 sutured nerves, in that at least some facial movement and tone were restored (Grade 5 or higher). In 11 of the 25 cases, facial appearance at rest and with movement was moderately good (Grade 2 or 3). A Grade 1 result, with no perceivable facial dysfunction, was never achieved. Typically, oral muscles showed the most improvement and frontal muscles the least. Facial appearance was better at rest than with movement, which was always complicated by some degree of synkinesis. Closure of the eye was so good in 13 of the 25 cases that neither tarsorrhaphy nor an eyelid spring was necessary. When the facial nerve is severed, intraoperative suture is recommended, because it provides a chance for moderately good restoration of facial appearance.

Interface between the facial nerve and large acoustic neurinomas. Immunohistochemical study of the cleavage plane in NF2 and non-NF2 cases.

In acoustic neurinoma surgery, the surgeon is required to find a cleavage plane between the facial nerve and the tumor, and with the aid of the operating microscope this is usually achieved by fine dissection. A histological specimen of the nerve-tumor interface is available only if the facial nerve was hopelessly adherent to the tumor (usually a large or giant neoplasm) and the surgeon decided to sever the nerve to obtain a complete removal. The authors have examined immunohistochemically the nerve-tumor interface of 20 such facial nerves (six cases of neurofibromatosis 2 (NF2) and 14 of non-NF2) in a series of 351 acoustic neurinomas. The largest extrameatal dimension of the 20 tumors ranged from 20 to 51 mm (median 39 mm). In all of these 20 instances the nerve-tumor contact area was at least partially devoid of a clear-cut histological cleavage plane. Where the facial nerve trunk was attached to the surface of the tumor, nerve fibers of the contact areas either abutted directly against tumor cells or nerve fibers were seen to penetrate into the tumor tissue. Frank embedding of nerve fibers was more frequent in NF2.

Inflammatory cell subpopulations in chronic otitis media. The Langerhans' cells.

Langerhans' cells (LCs) were studied in chronic otitis media by the immunoperoxidase technique and monoclonal antibodies. The LCs were a regular finding in ear canal skin, Shrapnell's membrane, thin and thick cholesteatoma epithelium, and open cavity skin; OKT6-positive cells were also found in smaller numbers in subepithelial connective tissue and lymphoid follicles, and in cuboidal secretory epithelium. The HLA-DR antibodies are less suitable for identification of LCs because many lymphoid cells express this antigen. Langerhans' cells form an important part of the immune defense system of the skin, which lacks the humoral secretory IgA defense mechanism of the mucous membranes. There is no proof that LCs are connected with the keratinization process and the possible reformation of cholesteatoma.

Treatment of labyrinthine fistula.

This cholesteatoma series comprises 84 ears, 81 of which had a labyrinthine fistula and 3 a horizontal semicircular canal opening that arose as a surgical complication. In 49 ears (58.3%), the operation was a primary one; in 35 ears (41.7%), it was a revision. Of all ears, 21 (25%) were deaf preoperatively. The fistula was located in the horizontal canal in 76 ears (90.4%). The matrix was removed in all these ears, and the fistula was covered with fibrin glue and fascia or periosteum. Hearing was preserved in all 57 ears in which matrix removal was carried out as the planned last stage. These included three ears in which the membranous canal was cut deliberately. Surgery that was performed against established rules caused deafness in three ears. Accidental opening of the horizontal canal caused no sensorineural loss in two ears as the fistulas were sealed immediately, while one ear in which the opening was not immediately recognized became deaf.

Preservation of hearing after removal of the membranous canal with a cholesteatoma.

Normal cochlear function was preserved in a patient after excision of the membranous canal from a huge fistula at revision surgery eight years after the primary procedure. A recurrent cholesteatoma had eroded the entire prominence of the horizontal canal and surrounded its membranous portion. The cholesteatoma, including the membranous canal, was removed in a one-stage procedure. The open ends of the bony canal were sealed with a fascia soaked in fibrin glue. After initial dizziness and severely reduced hearing, the patient quickly recovered, with normal bone conduction and a stable 30-dB hearing level by air conduction. The lumen of the membranous canal was patent, and only the ampullar end was atretic. Presumably, the fistula became separated from fluid spaces by formation of perilymphatic partitions and by collapse of the membranous labyrinth adjacent to the fistula.

Plasmin and fibronectin degradation in chronic secretory otitis media.

Mucoid effusions from 39 children with secretory otitis media, altogether 42 specimens, were analyzed for proteolytic activity using radial caseinolysis procedures, for fibronectin using a solid-phase enzyme immunoassay, and for fibronectin fragmentation using immunoblotting. All samples contained proteolytic activity, tentatively identified as plasmin on the basis of comigration with purified human plasmin in zymographic analysis. In 19 specimens the plasmin level exceeded 1 microgram/mg of protein; the highest value recorded was 18.7 micrograms/mg. Low levels of net plasminogen activator activity were found in 12 specimens and identified as urokinase according to comigration with the urokinase standard in zymography. Fibronectin was detected in all but one of the 42 specimens; in seven specimens the levels exceeded those in normal plasma, calculated per milligram of total protein. Extensive fragmentation of fibronectin was found in 19 specimens, correlating with high plasmin levels. The results are indicative of an ongoing proteolytic process in secretory otitis media and suggest that plasmin-caused degradation of the fibronectin-containing basement membrane and subsequent formation of granulation tissue may be involved in the development of adhesive middle ears.

Foreign body neonatal otitis media in infants.

HYPOTHESIS: An influx of amniotic fluid cellular content (AFCC) into the middle ears during birth may lead to the development of a chronic inflammatory process in the form of varying amounts of granulation tissue even if signs of otitis media are absent. This foreign body neonatal otitis media may predispose the child to recurrent otitis media. BACKGROUND: Foreign body neonatal otitis media caused by AFCC was described by Aschoff and elaborated by Wittmaack 100 years ago. Recent studies have shown how AFCC spreads to various middle ear compartments and causes histologic changes, the severity of which is related to the amount of AFCC. Specific elements become phagocytized after the first months of life but have caused the formation of inflammatory polyps and granulation tissue with round cell secretions in the meantime. METHODS: Ten temporal bones from the Temporal Bone Foundation, derived from infants aged 5 months to 1 year 11 months, were serially sectioned at 20 microm, saved at 0.2-mm intervals, numbered, and stained with hematoxylin and eosin. Every slide was studied for the presence, nature, and stage of pathologic tissue changes of the middle ear and the mastoid antrum. RESULTS: Pseudocystic granulation tissue was massive in the temporal bone of the 8-month-old child born through thick meconium. Severe changes were present in the temporal bones of two infants aged 5 months, one of which showed traces of AFCC. In the temporal bones of two older children, long-standing changes were minor, one of them still showed traces of AFCC. Fresh acute changes and long-standing histologic changes occurred side by side. CONCLUSIONS: Neonatal otitis media caused by AFCC can give rise to extensive granulation tissue and round cell secretion, which is likely to make the ear susceptible to infectious otitis media. Cumulative development of granulation tissue as a result of infection may lead to blockage of attic aeration and drainage pathways, causing irreversible adhesive otitis media. A data base should be formed of all neonates born through meconium-stained amniotic fluid to allow a comparison with those born through clear fluids. Surgery with the creation of auxiliary aeration pathways becomes advisable in the treatment of ears with massive development of granulation tissue.

Mucosal histochemistry in secretory otitis.

Mucosal biopsies were taken from 20 ears with secretory otitis media (glue ear) and histochemical stainings were made for comparison with data obtained from biochemical analysis of the fluids. Acid phosphatase, lactate dehydrogenase (LD), and malate dehydrogenase (MD), the activity of which in the ear fluids was 20 to 30 times higher than in serum, were found to appear as strong precipitates in the middle ear epithelium, particularly in the top layer. Alkaline phosphatase activity was only exceptionally seen in the epithelium but appeared in the capillaries and histiocytes. Nonspecific esterase appeared irregularly in the epithelium and regularly in histiocytes. The latter two had lower activities in ear fluids than in serum. Epithelial secretory cells and subepithelial glands and cysts showed strong alcian blue (AB)-positive staining. Positive material appeared also in the cytoplasm of the epithelial cells and in the intercellular substance. Distinct PAS-positive staining appeared in the columnar epithelium and particularly in the free mucus on top of the epithelium but was less promounced in the glandular structures and absent from the cysts.

Clinical results and complications of tympanostomy.

Tympanostomy tube treatment was used in 181 patients on 323 ears and a followup study was made as an average three years and two months later. Sixty-five percent of the ears had healed completely and in these the average tube treatment time had been 11.3 months. In 22% the tubes were still in position, the average time for treatment being 24.2 months. Five percent showed purulent discharge and recurrence of the glue ear was noted in 3%. A dry perforation developed in five patients. Cholesteatoma was seen in four ears but in only one of these it may have been related to the location of the tube at the posterior drum margin.

Immune complexes in middle ear fluid in chronic secretory otitis media.

Data on 87 patients (113 ears) with chronic secretory otitis media (SOM) are reported. The bacteriological analysis of the middle ear fluid (MEF) revealed Streptococcus pneumoniae in 7% of ears, Hemophilus influenzae in 9%, opportunistic bacteria in 20%, while 64% of the samples showed no growth. Free capsular polysaccharide pneumococcal antigens were found in 5% of the MEF samples using counterimmunoelectrophoresis (CIEP) with Omniserum containing 83 different pneumococcal polysaccharide types. Heating of the samples to disrupt the immune complexes increased the frequency of positive samples to 27%. These findings, together with the frequent occurrence of S pneumoniae and H influenzae in the nasopharynx, strongly support the opinion that chronic SOM in a considerable number of cases is an immune complex disease.

Comparative preoperative evaluation of eustachian tube function in pathological ears.

On 100 pathological ears with tympanic membrane perforation, eustachian tube functions was measured by using sonotubometry and the negative pressure equalization test in an attempt to compare these two methods. The pressure equalization test did not appear to be a reliable tool for preoperative clinical determination of tube function because sonotubometry showed tubal opening in 85% (myringoplasty group) and in 49% (radical surgery group) of patholoical ears, which were not able to equalize negative middle ear pressure at all during swallowing. The negative pressure equalization test is considered to be unphysiological and may produce a locking phenomenon of the tube. Even a small negative pressure can act like a valve, producing an obstruction that muscle activity of the tube is no longer able to overcome particularly when mucosal changes are present in the tubal orifice. Sonotubometry is a physiological test and as such gives a reliable picture of the opening of the tube during swallowing. Data on tympanic aeration postoperatively will be reported later.

Protein and cellular pattern of glue ear secretions.

Analysis of glue ear secretions showed that the total protein content was slightly higher than in serum and that in the effusion proteins appeared that were specific to the mucosal secretion. The cellular analysis of samples from 137 ears showed that lymphocytes and neutrophils predominated, and that monocytes and phagocytes appeared in most specimens. Eosinophils and mast cells were rare. Staining of bacteria in the smear was seen in one-third of the slides and the mucus strands were numerous. The cellular picture is in line with an infective etiology.

Lymphocyte morphology in mucoid middle ear effusions.

Cytologically, the mucoid middle ear effusions could be divided into a lymphocyte-monocyte type and a type where the granulocytes predominated. By alpha-naphthyl-acetate esterase (ANAE) staining procedure the T lymphocytes were found to make up the majority of lymphocytes in the first type, often accompanied by large numbers of ANAE-positive macrophages. In the second type the relative and particularly the absolute numbers of T cells were smaller. The T lymphocytes in aural effusions, distributed in agreement with their normal distribution in blood, could be the basis of possible delayed hypersensitivity immune mechanisms in the middle ear, but definite proof, either demonstrating receptor molecules directed to antigens or a specific response by T cells, is still lacking.

One-stage revision surgery for pediatric cholesteatoma: long-term results and comparison with primary surgery.

OBJECTIVE: Few studies report on revision surgery for pediatric cholesteatoma, even if most studies of primary surgery show high recurrence rates. We present independently evaluated long-term results of revision surgery and compare the results with those of primary surgery. METHODS: The series consisted of 42 consecutive pediatric (age <16 years) cholesteatoma revision operations in the Helsinki University ENT Department. The primary and revision surgery was non-staged, all mastoids were obliterated and the bony ear canals were reconstructed. The preoperative, surgical and annual control data were recorded in a database. The last control was independently performed (J.S.) with an average follow-up of 4.3 years and 87% attendance. RESULTS: The recurrence rate for revision operations was 38%. A retraction process developed in 38% of the ears and 67% of these retractions turned into active cholesteatomas. There was a non-significant difference for these figures as compared with primary surgery. Postoperative discharge and poor middle ear ventilation were associated with recurrence. The following factors showed significant differences between primary and revision surgery: increased number of bare facial nerve in the revision group, lower recurrence rate for experienced surgeons (as for both groups together) and improved hearing results for ears without recurrence in the revision group. CONCLUSIONS: Recurrent disease after revision surgery appears either in the attic or in the mesotympanum, or develops from a retraction pocket in a similar manner as was seen in patients receiving primary surgery. Recurrence is associated with discharging and poorly ventilated ears. Pediatric cholesteatoma surgery should be done or be supervised by experienced surgeons. The present operation methods result in many recurrences after primary and revision surgery. New surgical methods are needed to create additional aeration pathways to the epitympanum in order to improve middle ear aeration and to prevent some of the retractions.