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Biomedical subjects

J Thomsen

Publications and source records attributed to J Thomsen.

At least 55 records · Page 3Linked to original sources

Acoustic neuroma/vestibular schwannoma growth: past, present and future.

The growth of vestibular schwannoma (VS) was investigated in a series of 123 patients with 127 tumors in the period 1973 1993. The material was reanalysed and updated 3 years later in 1996. By termination of the first observation period (mean 3.4 years), 94 tumors (74%) exhibited measurable growth, 23 tumors (18%) no measurable growth and 10 tumors (8%) negative growth. By the end of the extended observation period (mean 3.8 years), tumor growth was observed in 104 tumors (82%), no tumor growth in 15 tumors (12%) and negative growth in eight tumors (6%). Several growth patterns were noticed: however, these were not static as the growth patterns of the tumors changed during the extended observation period. Accordingly, the expected growth figures by the end of this century (mean observation period approximately 4 years) will probably be: growth in 111 tumors (87%), no growth in 10 tumors (8%) and negative growth in six tumors (5%). The results indicate that neither the present study nor the previously published studies on tumor growth reflect the natural history of VS, but they only provide information on tumor growth, growth rates and growth patterns during a given observation period.

Adolescent↗

A morphometric analysis of nucleoli in cultured carcinoma cells of the human thyroid.

Cells from 7 patients operated on for thyroid cancer were investigated. Samples of cells from the carcinoma and from the normal thyroid tissue were cultured with and without TSH stimulation. For light microscopy, serial sections of cells were cut and the size of nucleoli was measured and the number of nucleoli per cell counted. At the electron microscopic level the number and the volume of the fibrillar centres (FC) were estimated taking the Swiss cheese effect into account. The areal densities of FC, the fibrillar and granular component in nucleoli were determined by point counting. The results indicate that the malignant transformation has no influence on the size of the FC, but the observed numbers as well as the total area of FC are larger in cancer cells than in the normal thyroid epithelial cells. The nucleolar density of the fibrillar component is larger and that of the granular component is smaller in thyroid carcinoma cells than in non-malignant thyroid epithelial cells (p = 0.0001). Thus simple morphometry at the electron microscopic level might be helpful to discriminate between thyroid epithelial cells and thyroid carcinoma cells in culture.

Carcinoma↗

Aryl hydrocarbon (Ah) nonresponsiveness in estrogen receptor-negative MDA-MB-231 cells is associated with expression of a variant arnt protein.

Several studies have reported a correlation between expression of the estrogen receptor (ER) and aryl hydrocarbon (Ah) responsiveness in human breast cancer cell lines. MDA-MB-231 cells are ER-negative and Ah-nonresponsive; however, initial studies showed that 2,3,7,8-tetrachlorodibenzo-p-dioxin induced CYP1A1 mRNA levels (5.8-fold) and chloramphenicol acetyltransferase activity (2.6-fold) in high passage (Hp, >50 passages) cells transiently transfected with an Ah-responsive plasmid. In contrast, no induction responses were observed in low passage (Lp, <20 passages) cells. The Ah responsiveness of Hp compared to Lp MDA-MB-231 cells was associated with a >2-fold increased expression of the Ah receptor in Hp cells. Further analysis revealed that the apparent molecular weight of the Ah receptor mRNA transcript and immunoreactive protein were comparable in Lp MDA-MB-231 and Ah-responsive human HepG2 cells. In contrast, RT-PCR analysis of the Ah receptor nuclear translocator (Arnt) protein showed that HepG2 cells expressed the expected 2.6-kb transcript, whereas a 1.3-kb transcript was the major product in MDA-MB-231 cells. Western blot analysis confirmed that HepG2 cells primarily expressed a 97-kDa wild-type form of Arnt, whereas a dominant 36-kDa variant was expressed in MDA-MB-231 cells. Complete sequence analysis of the variant form of Arnt revealed a major deletion of the C-terminal region of the protein (aa 330 to 789). Like HepG2 cells, the wild-type 2.6-kb transcript was detected in ER-positive (Ah-responsive) MCF-7 cells, whereas the low-molecular-weight variant Arnt was dominant in ER-negative MDA-MB-231, MDA-MB-435, and Adriamycin-resistant MCF-7 cells. These results suggest that expression of this protein may be useful as a prognostic factor in breast cancer.

Amino Acid Sequence↗

Antibiotic treatment of children with secretory otitis media. Amoxicillin-clavulanate is superior to penicillin V in a double-blind randomized study.

OBJECTIVE: To compare the effect of 2 different antimicrobial agents in the treatment of secretory otitis media (SOM). DESIGN: Prospective, double-blind, randomized study. PATIENTS: From a pool of 1450 children (aged 1-10 years) with SOM, defined by tympanometry as having type B or C2 tympanograms, 429 with SOM of at least 3 months' duration were included in the trial. After exclusion of 69 patients, the remaining 360 were evenly distributed among 4 treatment groups: penicillin V (Primcillin) for 14 and 28 days, and amoxicillin and clavulanate potassium in combination (Spektramox) for 14 and 28 days. Criteria for improvement was a change in tympanometric findings to type C1 or type A. RESULTS: The success rates were in favor of amoxicillin-clavulanate treatment for 28 days (P < .001) (rates for respective 14- and 28-day groups: penicillin V, 23% and 19%; amoxicillin-clavulanate, 31% and 44%). Antimicrobial therapy was more efficient (P < .001) in unilateral vs bilateral disease. CONCLUSION: Antibiotic treatment improves the middle ear status in patients with SOM, and amoxicillin-clavulanate provides superior improvement to penicillin V.

Acoustic Impedance Tests↗

Translabyrinthine vestibular schwannoma surgery: postoperative tinnitus and cochlear nerve integrity.

Cochlear neurectomy as a surgical treatment for tinnitus is known to be only partially successful in many conditions. Translabyrinthine surgery for acoustic neuromas may be performed using a dissection technique which preserves an 'anterior curtain' which helps to protect the facial nerve. The cochlear nerve may be retained within this tissue though it can be cut during the dissection. To assess whether its integrity affects tinnitus the video recordings of 117 patients undergoing this operation were reviewed to grade the likelihood of the cochlear nerve having been retained intact. A postal questionnaire, with a response rate of 83%, was used to assess tinnitus. Patients who had a probable or definite nerve section had significantly lower postoperative tinnitus severity. The same relationship was found when patients were matched for tumour size and preoperative tinnitus. This procedure could act as a model for the effect of cochlear neurectomy on tinnitus associated with acoustic neuromas in a prospective trial.

Adult↗

Thallium chloride 201Tl combined with single photon emission computed tomography (SPECT) in the evaluation of vestibular schwannoma growth.

Thallium chloride 201Tl combined with SPECT was performed in a series of 29 patients with neuroradiological evidence of vestibular schwannoma (VS). The relative tumor uptake (U) and relative tumor concentration (C) of the radiotracer 201Tl was determined, and the cerebellum served as a reference. The relative tracer concentration and uptake were correlated to tumor volume determined by gadolinium DTPA enhanced MR, to prediagnostic duration of symptoms, to tumor vascularity expressed by the average number of intratumoral vessels using the endothelial marker CD31, and to the proliferative activity in the tumors expressed by positive staining with the monoclonal antibody MIB-1 for Ki-67. A positive 201TI enhancement was detected in 17 tumors (n = 17). Tumors U and C were statistically unrelated to tumor volume (p = 0.236 and p = 0.439). SPECT demonstrated all tumors > 0.8 cm3, but it had its limitation as a diagnostic modality of small intracanalicular tumors, when compared with gadolinium DTPA enhanced MR. Relating U and C in all tumors (n = 29) and the prospectively registered data on the prediagnostic duration of symptoms, a statistical significance was found (p = 0.012 and p = 0.015). No statistically significant correlation was observed between U and C and the proliferative activity of the tumors expressed by positive staining with the monoclonal antibody MIB-1 for Ki-67 (p = 0.063 and p = 0.086). A statistically significant correlation was noted between C and U in the operated group (n = 12) and tumor vascularity expressed by the average number of the intratumoral vessels (p = 0.003 and p = 0.014). SPECT was found to be superior to MR in determining VS growth potentials as it expresses tumor vascularity, which is essential for tumor growth. It seems that we now have an in vivo functional radiological modality capable of providing data on VS vascularity and determination of growth potential in the individual tumor. A high radioactive tracer uptake in the tumor corresponded to high tumor vascularity, indicating a high growth rate and vice versa.

Adult↗

Increase of diagnosed vestibular schwannoma in Denmark.

The incidence of acoustic neuroma/vestibular schwannoma (VS) in Denmark, with a population of approximately 5 million inhabitants was estimated in 3 periods: June 1976-June 1983, July 1983-June 1990 and July 1990-December 1995. The incidence of tumors increased from 7.8 tumors per million per year in the first period to 9.5 tumors per million per year in the second period. The figure of 12 tumors per million per year is established in the third period. A significant increase of the newly diagnosed intracanalicular and small tumors, with an extracanalicular extension of 1-10 mm was observed in the third period compared with the first 2 periods. Correspondingly a decrease in the newly diagnosed giant tumors was noted in the last 2 periods compared with the first period.

Denmark↗

Squamous cell carcinoma of the oral cavity: the results of the surgical and non-surgical therapeutic modalities in a consecutive series of 156 patients treated in Copenhagen county.

A retrospective study on patients, treated for intraoral squamous cell carcinoma in Copenhagen county, is reported. The material included 156 patients, 66 females and 90 males. Age at diagnosis varied between 35 and 95 years with a mean of 65 years. Mean age of females/males was 70/62 years. Twelve therapeutic modalities were performed; surgery, radiotherapy, chemotherapy and different combinations of these. Three and five years crude survival were 43% and 37%. Three and five years crude survival rates were 70% and 61% for patients in stage I, 39% and 32% for patients in stage II, 29% and 16% for patients in stage III and 19% and 17% for patients in stage IV. The results are similar to those achieved in other centers. Since no significant improvement has been noted in patient survival during the last 5-6 decades and since the therapeutic morbidity has not always been acceptable to the patients, other therapeutic principles such as the so-called minimal invasive therapy should be considered in future treatment of intraoral cancer.

Aged↗

Microfluorometric kinetic analysis of cathepsin B activity in single human thyroid follicular epithelial cells using image analysis and continuous monitoring.

The activity of a cysteine proteinase, cathepsin B (EC 3.4.22.1), was determined in unfixed single human thyroid follicular epithelial cells at room temperature using an image analysis system. The formation of the reaction product was monitored every minute by measuring the increasing fluorescence intensity of emitted light from a Schiff-base product formed by the substrate N-CBZ-ala-arg-arg-4-methoxy-2-naphthylamide and the coupling agent 5-nitrosalicylaldehyde. Non-specific fluorescent signals were eliminated by adjusting the video signal to zero using leupeptin, a specific inhibitor of cathepsins B, H and L. The enzyme activity was expressed as fluorescence intensity versus time. After a mean lag period of 5 min (range 4-8 min, n = 4), the enzyme activity increased linearly lasting on average 5 min (range 3-8 min), followed by a marked decrease in reaction rate for 3 min (range 1-4 min), and another linear increase for 11 min (range 8-14 min). The second linear part of the curve was not as steep as the first one. The reaction velocity recorded in individual granules resulted either in a biphasic curve or straight line, suggesting the presence of two distinct organelle compartments with differences in membrane permeability. It is concluded that human thyroid follicular epithelial cells in culture exhibit cathepsin B activity which can be monitored continuously by videomicrofluorometry without interference from non-specific fluorescence.

Cathepsin B↗

[Teleradiology: use of multimedia PC for access to electronic patient records and teleconsultation].

A PC-platform is presented using internet technology on Ethernet (local) or ISDN (external) for access to digital hospital infrastructures comprising electronic multimedia patient records integrating information systems of all clinical departments. In addition, a videoconferencing system is implemented for teleconsulting, and a document camera allows transmission of analogue data. In combination with the multimedia-PC. Ethernet as well as ISDN offer satisfying performance for transmission of medical data including images. In 20 cases, visualisation of the electronic patient record, an average CT with report and 58 GIFF Images', or transfer of an ACR-NEMA file from CT, took seconds (Ethernet) or up to 3.5 minutes (ISDN - 58 CT images and report).

Computer Communication Networks↗

Endolymphatic sac surgery: why we do not do it. The non-specific effect of sac surgery.

Three of the present authors described a trial in 1981 which showed that cortical mastoidectomy was as effective as an endolymphatic sac shunt in controlling vertigo in patients with Ménière's disease both on a short-term as well as a long-term basis. The hearing was not influenced by the treatment and any change was considered to be the result of time, rather than the effect of the surgery. Upon perusal of the literature only two other studies exist resembling our study, and they both reached the same conclusion, that sac surgery is at best non-specific and at worst of no value. None of the numerous other studies published have convinced the authors that sac decompression is specific in nature. We have also looked at ECoG as a means of proving the specificity of sac operations and come to the same conclusion that the existing information is conflicting and confusing, and cannot be used to prove anything about sac surgery. The present conclusion is therefore that in treating patients with Ménière's disease anything goes, even sac surgery.

Audiometry, Evoked Response↗

Nerve growth factor receptor expression in heterotransplanted vestibular schwannoma in athymic nude mice.

Nerve growth factor (NGF) has the potential to induce cellular differentiation in various neoplastic and non-neoplastic cell lines. The purpose of the present study was to determine by immunohistochemistry: the presence/distribution of nerve growth factor receptor (NGFr), cellular proliferation expressed by Ki-67, and intratumoral vascularization visualized by the endothelial marker CD 31, in a series of 61 human vestibular schwannoma heterotransplants in athymic nude mice. The immunohistochemical results were correlated to the observed macroscopic growth in 22 heterotransplants (36%) with obvious macroscopic growth, versus 39 heterotransplants (64%), that were stationary or regressed. The positive immunoreactivity to NGFr, number of Ki-67 positive nuclei and number of intratumoral vessels were significantly higher in the 22 (36%) growing heterotransplants than in the 39 heterotransplants (64%), which were stationary or regressed (p < 0.00005, p = 0.046, p < 0.00001). NGFr was statistically related to the vascularity of the heterotransplants expressed by CD 31 (p<0.00001). No significant relation was observed between NGFr and the proliferation, as estimated by Ki-67. The results revealed that the macroscopic growth of VS in athymic nude mice was associated with strong positive expression of NGFr, high cellular proliferation expressed by Ki-67 and vivid neovascularization expressed by CD 31. The possible clinical applicability of the achieved results is discussed.

Animals↗

Growth of vestibular schwannomas: in situ model employing the monoclonal antibody Ki-67 and DNA flow cytometry.

Vestibular schwannoma (VS) growth potentials were studied in an in situ model, in which the cycling cellular fraction was determined immunohistochemically by applying the mouse monoclonal Ki-67 antibody, and the tumor ploidy was estimated by DNA flow cytometry in a consecutive series of 124 VSs. The tumors were classified according to the average number of positively stained nuclei in 10 high-power fields into three groups: 28 highly (> 10), 33 moderately (> 5-10) and 63 low proliferating (< or = 5). The intratumoral proliferative variation was studied in 10 tumors. Only slight variation in the number of the positively stained nuclei were observed. Six of seven tumors removed because of macroscopically documented growth by computed tomography (CAT) scan were moderately or highly proliferative. Proliferation of VS was correlated to prospectively registered clinical data. A statistically significant relation was found between VS proliferation and the prediagnostic duration of symptoms (p = 0.0001). The proliferative status was unrelated to age, sex, and tumor size. Flow-cytometric determination of DNA index of the 124 tumors revealed 12 tetraploid (DNA index = 2), 110 diploid (DNA) index = 1) and two nondiploid tumors. A statistically significant relation was noted between tumor ploidy and proliferation status expressed by Ki-67 (p = 0.024). The tetraploid tumors showed significantly lower proliferation compared with the diploid tumors. Tumor ploidy was statistically unrelated to age, sex, tumor size, and duration of symptoms. The results of this study provide a link between the immunohistochemical, flow cytometric findings, and clinical data, which could probably be relevant in identifying patients at risk for rapid tumor growth and tumor recurrences, because a rapid test for cell proliferation is now available.

Adult↗

Amino acid residues 721-729 are required for full factor VIII activity.

Recombinant two-chain factor VIII, from which the B domain had been deleted, was expressed in Chinese hamster ovary cells. In addition to the major product, three minor factor VIII forms were isolated. The A2 domains generated by thrombin cleavage showed different electrophoretic mobilities. Peptide mapping of the A2 domains showed that two of the factor VIII forms had the expected C-terminus of the heavy chain at Arg740 [FVIII-(1-740)] and that the other factor VIII forms had C-termini at Tyr729 [FVIII-(1-729)] or Glu720 [FVIII-(1-720)]. The major FVIII-(1-740) form, FVIII-(1-729), and FVIII-(1-720) contained sulfated tyrosine residues at Tyr718, Tyr719 and Tyr723. The minor FVIII-(1-740) form was shown to lack sulfation at these positions. The specific clotting activity was approximately 1 x 10(4) U/mg for FVIII-(1-740) (both forms) and FVIII-(1-729), but twofold lower for FVIII-(1-720). A time study of thrombin activation showed that FVIII-(1-720) was activated slower than FVIII-(1-740), FVIII-(1-729) and plasma-derived factor VIII. Partially sulfated FVIII-(1-740) was activated at the same rate as the fully sulfated FVIII-(1-740). The equilibrium dissociation constant for binding of factor VIII to inactivated immobilized thrombin was the same for all factor VIII forms, showing that the slower activation of FVIII-(1-720) was not due to a lower affinity for the anion-binding exosite in thrombin.

Amino Acid Sequence↗

Halogenated aromatic hydrocarbon-induced suppression of the plaque-forming cell response in B6C3F1 splenocytes cultured with allogenic mouse serum: Ah receptor structure activity relationships.

The immunosuppressive effects of halogenated aromatic hydrocarbons (HAHs) were investigated in B6C3F1 female mice and in mouse splenocytes cultured with allogenic mouse serum using the Mishell-Dutton model for in vitro immunization to trinitrophenyl-lipopolysaccharide (TNP-LPS). Exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), 2,3,4,7,8-pentachlorodibenzofuran (PeCDF), 1,2,3,7,8-PeCDF, 1,3,6,8-tetrachlorodibenzofuran (TCDF), 3,3',4,4',5-pentachlorobiphenyl (pentaCB), or 3,3',4,4',5,5'-hexaCB resulted in a dose-dependent suppression of the splenic plaque-forming cell (PFC) response both in vivo and in vitro. The effective dose required to decrease 50% (ED50) of the response to 2,3,7,8-TCDD, 2,3,4,7,8-PeCDF, 1,2,3,7,8-PeCDF, 1,3,6,8-TCDF, 3,3',4,4',5-pentaCB, or 3,3',4,4',5,5'-hexaCB in vivo was 14.1, 5.5, 1695, 34,800, 21, and 19 nmol/kg, respectively, and in vitro was 7.0, 10.6, 149, 2325, 9.1 and 9.1 nM, respectively. There was an excellent rank order and linear correlation between the in vivo versus in vitro activities for these HAHs (r < 0.99) and the relative immunosuppressive potencies of these compounds paralleled their binding affinities for the aryl hydrocarbon (Ah) receptor. These results show that splenocytes cultured with allogenic mouse serum is an Ah-responsive in vitro assay which can be used for quantitating the immunosuppressive effects of HAHs.

Analysis of Variance↗

Acoustic neuroma (vestibular schwannoma): growth and surgical and nonsurgical consequences of the wait-and-see policy.

A prospective study of the consequences of the wait-and-see policy in in patients with neuroradiologic diagnostic evidence of having vestibular schwannoma was conducted in a series of 123 patients (127 tumors) over a 20-year period, from 1973 to 1993. The mean follow-up period was 3.4 years, mean annual growth rate was 3.2 mm/year, mean annual volume growth rate was 0.72 ml/year, and mean annual relative growth rate was 41%. Tumor growth was observed in 90 (74%) patients (94 tumors), no growth was seen in 23 (18%) patients (23 tumors), and negative tumor growth was seen in 10 (8%) patients (10 tumors). Surgery due to tumor growth was performed in 35 (28%) patients (35 tumors), 7 (6%) patients (7 tumors) were treated with gamma-radiation and/or shunt insertion, 7 (6%) patients died of brain stem herniation induced by tumor compression, 9 (7%) patients died of non-tumor-related causes, 28 patients were classified as candidates for hearing preservation surgery, and 21 (75%) patients lost their candidacy during the observation period due to tumor growth and/or deterioration of hearing. The results may limit indications for allocation of patients with vestibular schwannoma to the wait-and-see group.

Adolescent↗