PubMed Health⌕ Search

Biomedical subjects

K Mattila

Publications and source records attributed to K Mattila.

At least 37 records · Page 2Linked to original sources

Presenilin mutations associated with Alzheimer disease cause defective intracellular trafficking of beta-catenin, a component of the presenilin protein complex.

The presenilin proteins are components of high-molecular-weight protein complexes in the endoplasmic reticulum and Golgi apparatus that also contain beta-catenin. We report here that presenilin mutations associated with familial Alzheimer disease (but not the non-pathogenic Glu318Gly polymorphism) alter the intracellular trafficking of beta-catenin after activation of the Wnt/beta-catenin signal transduction pathway. As with their effect on betaAPP processing, the effect of PS1 mutations on trafficking of beta-catenin arises from a dominant 'gain of aberrant function' activity. These results indicate that mistrafficking of selected presenilin ligands is a candidate mechanism for the genesis of Alzheimer disease associated with presenilin mutations, and that dysfunction in the presenilin-beta-catenin protein complexes is central to this process.

Alzheimer Disease↗

Intraosseous fat necrosis simulating septic arthritis and osteomyelitis in a patient with chronic pancreatitis.

A woman with a 20-year history of alcohol abuse and chronic pancreatitis developed an osteoarticular involvement of her right ankle in association with subcutaneous nodules. Histopathological examination of the tissue samples obtained during surgical revision of the ankle showed necrotic fat and connective tissue. Microbiological cultures remained negative. The patient was administered long-term antimicrobial treatment without any apparent benefit. Four months later, she died of pancreatic insufficiency and pneumonia. Postmortem examination showed numerous foci of intra-abdominal fat necrosis. Histopathological examination of the bone samples from the right ankle showed fat necrosis with lipophages. Based on these findings, we consider that the osteoarticular involvement in this patient was caused by intraosseous fat necrosis. This case reminds us of the importance of considering the possibility of this condition whenever a patient with chronic pancreatic disease develops sterile osteoarthritis.

Ankle Joint↗

Becoming a doctor--was it the wrong career choice?

The aim of the study was to investigate the social background of physicians, the reasons that influenced doctors to enter medicine, and the association between those reasons and satisfaction in career choice of young Finnish doctors. An extensive postal questionnaire was mailed to a random sample of 2632 young Finnish doctors in 1988 and to 2332 doctors in 1993. We found out that majority of the respondents reported that interest in people, a wide range of job opportunities, the fact that medicine is a highly-appreciated profession, and success at school had influenced their decision to enter medicine quite a lot or very much. In 1988, 8% and in 1993, 7% of the respondents reported that interest in people had not influenced their career choice at all or only slightly. More women than men were influenced quite a lot or very much by factors like interest in people, success at school and vocation, meaning the lifelong calling to physicians' profession. A total of 22% of respondents would not enter medicine again. Vocation, interest in people and wide range of job opportunities were significantly more rarely mentioned as an important career choice motive by these respondents. It seems that interest in human beings and vocation are important to would-be doctors, and also help them to get along in the physicians' profession. Medical schools should develop their curricula towards more humanistic medicine in order to maintain their students' interest in people.

Adult↗

The effect of prolonged doxycycline therapy on Chlamydia pneumoniae serological markers, coronary heart disease risk factors and forearm basal nitric oxide production.

Chronic Chlamydia pneumoniae infection, characterized by elevated levels of C. pneumoniae IgG and IgA antibodies and immunocomplexes, is associated with myocardial infarction and angiographically verified coronary heart disease. C. pneumoniae organisms have also been found in coronary atheromas, but not in healthy vessels. We investigated the effect of 4 months' doxycycline therapy on serological markers of C. pneumoniae infection and coronary risk factors. Thirty-four non-smoking men, aged 57.9 (+/- 5.2) years, who had mild hypertension or moderate hypercholesterolaemia and a previous coronary bypass, were randomly assigned to receive doxycycline or matching placebo for 4 months. Acetylsalicylic acid and beta-blocker were the only other medications allowed. Patients were examined physically and by laboratory tests; their basal nitric oxide production was determined by blood flow responses to intra-arterial monomethyl-L-arginine at baseline and at 2 and 4 months. The tests were also taken at 6 months after medication. At entry, the demographic, clinical, blood flow and laboratory measurements were similar in both groups, with the exception of fibrinogen and triglyceride levels, which were higher in the placebo group. No significant changes were found in any of the parameters during the treatment. Thus extended doxycycline therapy did not affect C. pneumoniae antibodies or coronary heart disease risk factors. We conclude that doxycycline monotherapy may not be sufficient to eradicate chronic C. pneumoniae infection.

Adult↗

Changes in the oral health of adolescents treated by the Finnish public dental services between the ages of 13 and 15 years.

Oral cavity health was monitored in 2422 young people aged 13-15 years attending four health centres in Finland between 1992 and 1995. Assessments were made in terms of DMF, D and CPITN indices at clinical examinations. Of those who had no carious teeth at the initial examination, 60% did not develop cavities during the whole period, whereas half of those who had at least two carious teeth at the initial examination developed at least three new carious teeth. The treatment time needed by the latter accounted for half of the total time expended by the researchers until the end of the period. Costs can be saved or new patients brought into the dental care system by reorganizing the treatment of the patients who suffer from abundant caries and by reducing the resources devoted to the treatment of healthy patients.

Adolescent↗

Chronic compartment syndrome of the quadriceps femoris muscle in athletes. Diagnosis, imaging and treatment with fasciotomy.

BACKGROUND AND AIMS: Chronic quadriceps femoris muscle compartment syndrome is described. MATERIAL AND METHODS: Over a 13 year period nine patients were diagnosed, treated surgically by fasciotomy and followed up at a referral center specialized in sports traumatology. There were four power lifters, three body builders, one endurance walker and one cyclist in the series. The use of anabolic steroids was admitted by four of the nine patients. The patients complained of gradually worsening pain on the anterolateral side of the thigh during training. Initially the pain appeared only at the end of the training session. As the syndrome became more severe, the pain began earlier during exercise and gradually became worse preventing maximal training. Skeletal radiographs and ultrasound examinations were normal, except in two patients, who had a positive echography finding with local atrophy. MRI examination confirmed the US diagnosis. RESULTS AND CONCLUSIONS: As conservative treatment did not provide relief of symptoms, a fasciotomy anterior to the iliotibial tract was performed bilaterally to seven patients and unilaterally to two patients. Biopsies from the atrophied sites showed muscle cell necrosis. All the patients recovered well after the surgery and were able return to their original level of sport. The only complication of surgery was a postoperative hematoma in one patient, which delayed the beginning of the training, but did not result in any persistent complaints.

Adult↗

How Estonian and Finnish primary care doctors rate their need for common drugs.

OBJECTIVE: To compare ratings of the necessity of drugs in the daily practice of experienced primary care doctors in Estonia and Finland to find out the differences and similarities in the therapeutic traditions of the two different societies. METHODS: A questionnaire was sent to all Estonian district doctors born in the 1940s and to all Finnish specialized general practitioners born in the 1940s, who then evaluated the necessity of the listed drugs on a visual analogue scale. The ratings, from 0 to 100, were entered into a computer, using a graphic tablet and a pressure sensitive pointer. RESULTS: The six most highly-evaluated drugs among the Estonian respondents were digoxin, glyceryl trinitrate, aspirin, calcium-channel blockers, beta-adrenoceptor blockers and frusemide; and among the Finnish general practitioners (GPs) were penicillin, insulin, glyceryl trinitrate, beta-adrenoceptor blockers, frusemide and angiotensin-converting enzyme (ACE) inhibitors. The ratings of 15 out of 33 drugs/drug groups were very similar both in Estonia and Finland. The biggest differences between the opinions of the Estonian and Finnish doctors appeared in the ratings regarding the necessity of antacids, cimetidine, insulin, sulphonylureas, reserpine. ACE inhibitors, oral contraceptives, penicillin, metronidazole, trimethoprim, indomethacin, phenobarbital and theophylline. CONCLUSION: The revealed differences are suggested to be related to the different health care systems (different task profiles of doctors, different pharmaceutical services), different education of doctors, different availability of drugs in the past and different prices, all of which influence therapeutic traditions.

Estonia↗

In vivo low density lipoprotein oxidation relates to coronary reactivity in young men.

OBJECTIVES: This study was undertaken to examine the relation of in vivo low density lipoprotein (LDL) oxidation and other lipid risk factors to coronary reactivity in normal subjects. BACKGROUND: Experimental studies have shown that oxidized LDL (ox-LDL) particles are injurious to the vascular wall by impairing its normal vasodilator function. METHODS: We used noninvasive positron emission tomographic (PET) imaging with intravenous dipyridamole to measure coronary flow reserve, a marker of coronary endothelial and smooth muscle function, in 30 healthy men (mean [+/-SD] age 34.4 +/- 3.2 years). As a marker of in vivo LDL oxidation, the autoantibody titer against ox-LDL was measured by the enzyme-linked immunosorbent assay method. RESULTS: Plasma levels of autoantibody titer against ox-LDL were inversely associated with coronary flow reserve (r = -0.42, p = 0.023). High LDL cholesterol levels (above median > 3.0 mmol/liter) were associated with a low coronary flow reserve only in subjects expressing simultaneously high levels of ox-LDL titer (above median). Subjects with simultaneously high levels of LDL cholesterol and ox-LDL titer had lower coronary flow reserve values than subjects in other groups (3.89 vs. > 5.0 in other groups, p = 0.066). CONCLUSIONS: These data provide evidence for the role of ox-LDL in affecting the coronary reactivity in vivo and support the concept that oxidative modification of LDL particles provides a mechanism by which high LDL concentrations exhibit injurious effects on the coronary vascular bed.

Adult↗

Ischial tuberosity apophysitis and avulsion among athletes.

Ischial tuberosity pain in athletes may be caused by several clinical entities, which include acute and old bony or periosteal avulsions and apophysitis. We studied the natural course of these injuries based on our clinical case series of fourteen patients with apophysitis and twenty-one with avulsion of the ischial tuberosity. Only patients with the diagnosis confirmed by X-ray finding were included. The clinical diagnostic criteria by ischial apophysitis consisted of gradually increasing functional and palpatory pain at the ischial tuberosity without any major trauma at the beginning of the symptoms. Typically there was asymmetry on plain radiographs of the ischial tuberosities in apophysitis; the involved apophyseal area became sclerotic, wider than the non-symptomatic apophysis, osteoporotic patches developed and the lower margin of the ischial tuberosity became irregular. The patients with avulsion reported an acute trauma at the beginning of the symptoms and an avulsion fragment was immediately after injury or later seen in plain radiographs. The mean age of the patients with apophysitis (14.1 yrs) was lower than that of the subjects with avulsions (18.9 yrs). Apophysitis of the ischial tuberosity usually healed well without complications. Avulsions often caused more prolonged pain with referral pain to the posterior parts of the thigh which often required operative interventions. A small bony or periosteal avulsion sometimes grew to a pseudotumor calcification. We recommend conservative treatment as the primary treatment modality for both ischial tuberosity apophysitis and avulsion fractures.

Adolescent↗

Solution structure of nodularin. An inhibitor of serine/threonine-specific protein phosphatases.

The three-dimensional solution structure of nodularin was studied by NMR and molecular dynamics simulations. The conformation in water was determined from the distance and dihedral data by distance geometry and refined by iterative relaxation matrix analysis. The cyclic backbone adopts a well defined conformation but the remote parts of the side chains of arginine as well as the amino acid derivative Adda have a large spatial dispersion. For the unusual amino acids the partial charges were calculated and nodularin was subjected to molecular dynamic simulations in water. A good agreement was found between experimental and computational data with hydrogen bonds, solvent accessibility, molecular motion, and conformational exchange. The three-dimensional structure resembles very closely that of microcystin-LR in the chemically equivalent segment. Therefore, it is expected that the binding of both microcystins and nodularins to serine/threonine-specific protein phosphatases is similar on an atomic level.

Enzyme Inhibitors↗

Conformational analysis of a toxic peptide from Trimeresurus wagleri which blocks the nicotinic acetylcholine receptor.

The 22-residue toxic peptide (WTX1) from the venom of the Southeast Asian snake Trimeresurus wagleri has multiple sites of action, but its lethal effect has been attributed to blocking the postsynaptic acetylcholine receptor at the neuromuscular junction. The 3-dimensional structure of WTX1 was studied using 2-dimensional nuclear magnetic resonance spectroscopy, circular dichroism, and computer simulations. In aqueous solution, WTX1 was shown to have extended and flexible "tails" defined by a short, rigid disulfide-bonded loop. The flexible regions can undergo structural rearrangement when moved from an aqueous to a less polar environment and may contribute to its effectiveness at different receptor sites. By substituting Gly or Phe for His at position 10, significant effects on the disulfide bond formation and, thereby, the activity of the peptide were observed. These results suggest that even subtle differences in single residues can have profound effects on the dynamics of folding, disulfide bond formation, and activity of this toxic peptide.

Amino Acid Sequence↗

Where should special attention be paid in undergraduate medical education? Two surveys among Finnish physicians.

The study focuses on Finnish doctors' views of their undergraduate medical education. In 1988, a study (Junior Physician 88 Study) involving all the doctors registered during the years 1977-1986 in Finland (n = 5208) was carried out. A questionnaire was sent to a random sample of 2632 doctors, and after two mailings 1745 questionnaires (66.3%) were returned. A total of 1334 gave at least one answer to the question: 'Where should special attention be paid in undergraduate medical education?' Five years later, in 1993, another study (Physician 93 Study) involving all medical doctors registered in Finland during the years 1982-1991 (n = 4671) was carried out. The same questionnaire was sent to a random sample of 2332 doctors, and after two reminders 1818 questionnaires (78.0%) were returned, and 1228 doctors also answered the open-ended question. Content analysis was used to analyse the answers qualitatively and quantitatively. About 90% of the answers could be classified into two main categories: practical skills and evaluation of subjects. The most common proposal for the improvement of undergraduate medical education was that the practical skills needed in general practice should be taught. More education in administration and health economics was also desired. Respondents said that preclinical and clinical studies should be more closely integrated. In answers to the open question, the course in public health was strongly criticized for being too theoretical. Learning of the core knowledge for medical practice was considered essential.

Clinical Competence↗