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Biomedical subjects

R Johansson

Publications and source records attributed to R Johansson.

At least 73 records · Page 4Linked to original sources

p53 expression and cell proliferation as prognostic factors in laryngeal squamous cell carcinoma.

PURPOSE: To investigate the prognostic significance of p53 expression and proliferation markers in primary laryngeal squamous cell carcinoma. PATIENTS AND METHODS: Primary tumors for analyses were obtained from 103 patients, with complete follow-up data. All patients were treated between the years 1975 and 1990. The expression of p53 was analyzed with monoclonal D07 antibody and proliferative activity with Ki-67 (MIB-1) and PCNA (monoclonal 19A2) antibodies. Volume corrected mitotic (M/V) index and histological grade were determined in hematoxylin and cosin-stained slides. RESULTS: Sixty-eight percent of the tumors overexpressed p53. During a median follow-up of 62 months, 41 (40%) of patients relapsed. In univariate analysis site of the primary tumor, stage, p53 expression, histologic grade, and M/V index were significant predictors of disease-free survival. In multivariate analysis, only M/V index was a statistically significant predictor of disease-free survival. Overall survival was significantly better for those overexpressing p53 (10-year cumulative survival rate 68% v 44%, P = .004). In multivariate analysis, M/ V index (P = .02), p53 (P = .02), and stage (P = .007) were statistically significant predictors of overall survival. When this analysis includes stratification according to the type of treatment received, M/V index (P = .007), stage (P = .0002), and p53 (P = .006) were even more significant predictors of overall survival. No association between p53 status and proliferative activity was found. CONCLUSION: Overexpression of p53 is associated with favorable disease-free and overall survival in laryngeal squamous cell carcinoma. It may also have an independent prognostic value in laryngeal cancer. M/V index, p53 overexpression, and stage predict with significant accuracy the 10-year overall survival.

Adult↗

Blood flow-independent accumulation of cisplatin in the guinea pig cochlea.

Considerable interindividual variability in the ototoxic effect of cisplatin has become the unpredictable dose-limiting factor in its use as curative as well as palliative therapy. The drug accumulates in highly vascular areas in the cochlea, causing dose-related hair cell loss. The purpose of this study was to assess blood flow-dependent aspects of cisplatin absorption in the cochlea in order to better understand factors that may influence cisplatin-induced ototoxicity. The effect of reduced cochlear blood flow on the ototoxic action of cisplatin was studied in guinea pigs. Before cisplatin administration the cochlear vasculature in each animal was unilaterally pre-constricted, by the application of 2% epinephrine to the round window. A 20-30% reduction in cochlear blood flow, assessed by laser Doppler flowmetry, was maintained before and after intravenous infusion of 0.1% cisplatin. Cisplatin infusion affected cochlear blood flow but not vessel conductivity. The cochlear blood flow decrease, maintained by local epinephrine application to the round window during cisplatin infusion, did not alter the cisplatin-induced hearing loss. In addition, the concentration of free cisplatin in scala tympani perilymph did not differ between epinephrine-treated and non-treated ears. Our results indicate that cisplatin transport into the cochlea is not an energy-dependent process in the lateral wall vasculature.

Animals↗

Radiotherapy enhanced ototoxicity of cisplatin in children.

We reviewed and re-examined 31 children (6 months-14 years at the time of diagnosis), who had been treated for a neoplasm in Turku University Central Hospital between 1989 and 1994. The children were divided into 3 groups according to the site of the neoplasm and the type of therapy. Group I included 13 children, operated on for an intracranial tumor and received postoperative radio- and cisplatin-based chemotherapy. Group II included 14 children operated on for intracranial tumors and treated with radiotherapy, but not given chemotherapy. Group III included 4 children suffering from extracranial malignancies and they had received chemotherapy including cisplatin. The children in Group I had significantly worse hearing thresholds in the middle- and high-frequency range than children in Groups II and III. In a precise analysis of the different factors, no single dose of cisplatin, inner ear irradiation dose or totally to the central nervous system (CNS) received irradiation dose correlated to the detected hearing loss. However, multiple linear correlation analyses suggest a combined effect of radiotherapy plus cisplatin resulting in a high frequency hearing loss. This is in accordance with earlier random case reports, and supports the idea that radiotherapy should be considered cautiously in children treated with cisplatin for intracranial malignancies.

Adolescent↗

Open phase II study of high-dose toremifene as first-line therapy for advanced breast cancer.

In an open phase II study conducted in Finland and Latvia, 73 postmenopausal women were treated with 240 mg of toremifene (Fareston) as first-line therapy for advanced breast cancer. Among the 56 patients evaluable for responses, 59% achieved objective responses [complete response (CR) plus partial response (PR)], 29% showed no change (NC), and 12% had progressive disease (PD). When all treated patients were included, the objective response rate was 47%. Several very long durations of responses up to 86 months and survival durations up to 95 months were observed. In assessable patients, the best objective response rates were seen in those with soft-tissue (74%) and visceral (60%) disease. In 54% of patients with very large inoperable primary cancers, a PR was achieved. Half of patients reported side effects, about 60% of which were mild; 30%, moderate; and 5%, severe. Based on response rate and safety, high-dose toremifene is useful as first-line therapy for advanced breast cancer.

Adult↗

Hypermethylation of calcitonin gene regulatory sequences in human breast cancer as revealed by genomic sequencing.

DNA methylation has been studied intensively during the past years in order to elucidate its role in the regulation of gene expression, gene imprinting and cancer progression. Earlier studies have shown that a general genomic under-methylation is associated with chronic lymphocytic leukemia and metastatic prostate cancer. Site-specific methylation changes, as revealed by the use of methylation-sensitive restriction enzymes, have been reported to occur in the promotor region of the calcitonin gene in chronic myeloid leukemia as it progresses from the chronic phase to blast crisis, in non-Hodgkin's lymphoid neoplasms and in non-lymphocytic leukemia. We have now explored possible methylation changes associated with benign and malignant breast tumors. Two approaches were employed: (i) chemical determination of general genomic methylation status and (ii) base-specific analysis of the methylation changes in the promoter of the calcitonin gene with the aid of genomic sequencing. The results did not reveal any changes of total DNA 5-methylcytosine content in ductal carcinoma of breast in comparison with benign tumors. There was a small, yet significant, increase in 5-methylcytosine content in lobular carcinoma. Genomic sequencing of the promoter region of the calcitonin gene, however, revealed a striking hypermethylation at or around the transcription start site of the gene in ductal carcinomas. In benign tumors and lobular carcinomas, this region was either entirely unmethylated or only slightly methylated. The latter changes may reflect a regional hypermethylation of the short arm of chromosome 11, which harbors, in addition to the calcitonin gene, a number of putative or established tumor-suppressor genes. Our results demonstrate that genomic sequencing in its present form can be used for a reliable and precise DNA methylation analysis of primary human tumors.

5-Methylcytosine↗

A new method for analysis of atrial activation during chronic atrial fibrillation in man.

To further clarify the mechanisms maintaining chronic atrial fibrillation (CAF), a method identifying preferable activation patterns of the atria during fibrillation, by time averaging of multiple discrete excitation vectors, was developed. Repeated recordings, each of 56 atrial bipolar electrograms simultaneously acquired during 8 s, were made at multiple sites in the right atrial free wall and the left atrial appendage in 16 patients with CAF using a 2.17 x 3.54 cm electrode array. The local activation times (LAT's) in each recording were estimated as the median activation time at the respective measurement point. By calculating the time difference between the LAT's at adjacent measurement points in two spatial dimensions, a direction vector was created for each activation wave passing each set of measurement points, a total of 42 sets. By time averaging of the individual direction vectors (typically n = 55) at each set of measurement points, preferable activation patterns were determined. Three types of activation patterns were found: 1) inconsistent activation (n = 5), 2) consistent activation with preferential propagation directions (n = 7) and 3) consistent activation with impulses originating from a localizable site within the recording area (n = 4). All activation patterns were reproducible and the two latter patterns were proven significant using statistical tests. We conclude that this new method is useful in further clarification of the mechanisms involved in the maintenance of atrial fibrillation.

Aged↗

Local anaesthesia and propofol-fentanyl sedation for carotid artery surgery.

BACKGROUND: In patients undergoing carotid artery surgery with local anaesthesia (LA), a sedative/analgesic pharmacological supplement is appropriate in most cases in order to provide comfort. This adjunct should not preclude continuous clinical neurological monitoring. The aim was to investigate if a combination of fentanyl and propofol to supplement LA would provide comfort for the patient, allow continuous clinical neurological monitoring and absence of difficulties for the anaesthetist, and good conditions for surgery, including insertion of a shunt if this should become necessary. METHODS: During a 1-year period low doses of propofol and fentanyl were used to supplement LA in 36 cases of carotid artery surgery in 34 consecutive patients. A shunt was only used if neurological dysfunction occurred. Data on haemodynamics, pulmonary gas exchange, clinical neurological monitoring, and subjective opinions from patients, surgeons and anaesthetists were obtained. Morbidity within 30 days was documented. RESULTS: Conversion to general anaesthesia was undertaken in one patient, previously operated on the same artery, who became unconscious due to a stroke during manipulation of the artery before arteriotomy. No other adverse outcome was found within 30 days. In the remaining 35 cases the procedures were carried out under LA. Stump pressures below 50 mmHg were found in 17/35 cases. Intraoperative neurological dysfunction was detected in 10/35 cases (stump pressures between 23 and 60 mmHg). Shunting was easily performed, and rapidly relieved the neurologic symptoms in all these patients. Intraoperative respiratory and haemodynamic control was satisfactory. Ease of performance, including clinical neurological monitoring, was acknowledged by both anaesthetists and surgeons, and all 33 patients (35 operations) who were accessible for a postoperative interview stated that they would prefer the same regimen in the case of further surgery. CONCLUSION: The number of cases in this open, uncontrolled study does not permit an evaluation of this anaesthetic and sedative technique in terms of neurological and cardiac outcome. Thus, we simply want to inform about our positive experiences regarding patient acceptance and ease of performance in all relevant respects when fentanyl and propofol are used to supplement LA for carotid artery surgery.

Aged↗

The use of a water extract from the bark of Choerospondias axillaris in the treatment of second degree burns.

Burns are common in Vietnam, and because of economic constraints and limited resources for the import of appropriate treatments, the health authorities are obliged to rely on traditional herbal remedies. It is therefore essential to evaluate current drugs, one of which is the water extract of the bark of the tree Choerospondias axillaris. It has been used for many years in the Vietnam-Sweden hospital at Uong Bi in northern Vietnam. We assessed the efficacy of the remedy in an open, randomised controlled clinical trial, in which 20 patients with second degree burns were treated with the extract of the Choerospondias axillaris and 19 with saline gauze. The mean healing time was significantly shorter for patients treated with Choerospondias axillaris (11 days) compared with patients treated with saline gauze (17 days) (p < 0.01), and the number of wound infections was significantly lower in the Choerospondias axillaris group (7/20 compared with 16/19, p = 0.003). The bark extract was easy to apply and additional wound care was not usually necessary, while the treatment with saline gauze was laborious for both patients and staff and was much more expensive. The extract from Choerospondias axillaris is a convenient treatment for second degree burns in both children and adults.

Adolescent↗

Auditory feedback regulation of perturbed stance in stroke patients.

The effect of auditory input on impaired postural control perturbations was evaluated in two groups of stroke patients participating in a rehabilitation programme after a recent (< 12 months) and single episode of stroke, or less recent (> 12 months), and multiple episodes of stroke. Auditory input took the form of feedback signals generated by the forces actuated by the feet on a force platform in response to the patient's postural movements. Vibratory stimuli applied to the calf muscles induced sudden perturbations which the patients had to counteract to maintain an upright stance. The effect of auditory feedback in facilitating the maintenance of stance was measured in terms of sagittal torque variance (body sway) recorded on a force platform. In the presence of auditory feedback, body torque variance in response to perturbed posture was significantly reduced in the recent stroke group, whereas in the less recent stroke group the auditory feedback did not prove effective. Moreover, learning seems essential to utilize the auditory feedback.

Acoustic Stimulation↗

Radiation-induced changes in human brain metabolites as studied by 1H nuclear magnetic resonance spectroscopy in vivo.

PURPOSE: External radiation therapy for brain tumors exposes healthy areas of brain to considerable doses of radiation. This may cause cognitive and psychological impairment, which indicate neuronal dysfunction. 1H-magnetic resonance spectroscopy (MRS) was used to study brain metabolites in the adjacent regions 0.5-13 years after exposure to therapeutic irradiation. METHODS AND MATERIALS: Eight patients with irradiated brain tumors were examined by means of in vivo 1H-MRS using a point-resolved spectroscopy (PRESS) sequence with echo times of 60 or 270 ms. The metabolites were quantified by using brain water concentration as internal reference. The volume of interest (VOI) was positioned in irradiated brain areas excluding, however, scar and recurrent tumor. The respective radiation doses were measured based on radiation therapy plans, simulator films, and localization MR images. RESULTS: The concentration of the neuron-specific metabolite N-acetyl-L-aspartate (NAA) was 13.2 +/- 1.4 mmol/l in controls, whereas it was reduced in the brains of treated patients to 8.6 +/- 0.9 mmol/l (total radiation dose 59-62 Gy). Concentrations of creatine and choline-containing compounds were unchanged. The T2 of water was longer in irradiated than in unexposed brain areas. CONCLUSION: Therapeutic brain irradiation causes neuronal damage, which is reflected by reduction of N-acetyl-L-aspartate (NAA) concentrations. 1H-MRS could serve clinically as a means of evaluating adverse effects in the central nervous system, enabling intervention and rehabilitation.

Adult↗

Development of human precision grip. V. anticipatory and triggered grip actions during sudden loading.

When an object held by a precision gripis subjected to an abrupt vertical load perturbation, somatosensory input from the digits triggers an increase in grip force to restore an adequate safety margin, preventing frictional slips. In adults the response occurs after a latency of 60-80 ms. In the present study, children from 2 years old upward and adults grasped and lifted an object using a precision grip. Sudden, unpredicted increases in load force (tangential to the grip surfaces) were induced by the experimenter by dropping a small disc on to a receptacle attached to the object. The impact elicited a grip force response which in young children had a longer latency and a smaller amplitude than was seen in adults. The grip response latency gradually become shorter and its amplitude increased with increasing age, reaching adult values at 6-10 years. The muscle activity underlying the response could have several bursts. The adults showed one brisk response, appearing 40-50 ms after impact, in extrinsic and intrinsic hand muscles, while younger children also exhibited a short-latency burst, appearing about 20 ms after impact. It is suggested that the short-latency response was mediated via spinal pathways, and that these pathways are disengaged by supraspinal centers during development. In a predictable loading situation, when subjects dropped the disc themselves into the receptable using the contralateral hand, they changed strategy. Adults induced a well-timed anticipatory grip force increase prior to the impact that was scaled to the weight of the object. The youngest children did not time the force increase properly in relation to the impact. Yet, they could scale their anticipatory grip force increase with respect to the weight of the dropped disc. This suggests a well-developed capacity to use information about the weight of objects held by one hand to parameterize a programmed force output to the other hand.

Child↗

Galvanic vestibular stimulation for analysis of postural adaptation and stability.

Human postural dynamics was investigated in 12 normal subjects by means of a force platform recording body sway, induced by bipolar transmastoid galvanic stimulation of the vestibular nerve and labyrinth. The model adopted was that of an inverted segmented pendulum, the dynamics of postural control being assumed to be reflected in the stabilizing forces actuated by the feet as a result of complex muscular activity subject to state feedback of body sway and position. Time-series analysis demonstrates that a transfer function from stimulus to sway-force response with specific parameters can be identified. In addition, adaptation to the vestibular stimulus is demonstrated to exist, and we describe this phenomenon using quantification in terms of a postural adaptation time constant in the range of 40-50 s. The results suggest means to evaluate adaptive behavior and postural control in the erect human being which may be useful in the rehabilitation of individuals striving to regain upright stance.

Adaptation, Physiological↗

Discrimination of patients with acoustic neuroma and peripheral vestibular lesions with human posture dynamics.

A group of normal subjects (n = 17) was compared with groups of patients with a diagnosis of vestibular neuritis (n = 18), and acoustic neuromas (n = 35). Fisher linear discriminant analysis was applied to distinguish clusters of parameters characteristic for each disease. Hence it was possible to distinguish the vestibular neuritis patients from the normal group with statistical significance (p < 0.01). Also the patients with an acoustic neuroma could be distinguished from the normal subjects with statistical significance (p < 0.05).

Diagnosis, Differential↗

Postural control and vestibular function in patients selected for cochlear implantation.

Postural control and vestibular and eye motor function were evaluated in 7 postlingually deaf patients before cochlear implantation as vibration toward the calf muscles or galvanic electrical stimulation of the vestibular nerves perturbed stance. The patients were compared with 21 control subjects. Vibration-induced bodysway was increased in the patients compared to the normals. Galvanic stimulation induced a bodysway that was not significantly different from that of the control group suggesting that the patients selected for cochlear implantation, and with otherwise reduced postural control, are sensitive to electrical stimulation of the vestibular nerve. This finding may contribute with a complementary hypothesis to the causes of dizziness among cochlear implant patients.

Adult↗

Vestibular stimulation perturbs human stance also at higher frequencies.

The effect of primary vestibular disturbance on postural control was investigated in 11 normal subjects exposed to perturbation by bi-polar binaural galvanic stimulation of the vestibular nerve. The stimulus consisted of 30 s of sinusoidal galvanic stimulation at frequencies of 0.2, 0.3, 0.5, 1.0, 1.5, 2.0, 3.0 and 4.0 Hz, with a current of +/- 1 mA, the subject standing with open or closed eyes and the response evoked being recorded with a force platform. As compared with resting values, i.e. no stimuli, variance of lateral body sway was significantly greater at all frequencies tested in the closed eyes condition and at frequencies of 0.2, 0.5, 1.0, 3.0 and 4.0 Hz in the open eyes condition; using a high pass filter with a cut-off frequency of 0.1 Hz, variance of lateral body sway was significantly greater at frequencies 0.2, 0.3, 0.5, 1.0 and 2.0 Hz in the closed eyes condition and at frequencies 0.5 and 2.0 Hz in the open eyes condition. These findings suggest that in the lateral plane vestibular input affects and probably contributes to human postural control over a wider frequency range than suggested by findings in previous studies. Moreover, the visual contribution appears to enable the subject to suppress vestibular input causing lateral body sway only in the lower frequency range (here at 0.2 and 0.3 Hz). This evidence of vestibular contribution to postural control in the lateral plane is consistent with the response characteristics of the vestibulo-ocular reflex.

Adolescent↗