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Biomedical subjects

B Bertram

Publications and source records attributed to B Bertram.

At least 19 recordsLinked to original sources

[Paediatric cochlear implantation in the first year of life: preliminary results].

BACKGROUND: The success of cochlear implants in children was followed by a stepwise reduction in age at time of surgery. As a result of newborn hearing-screening (NHS) and the reliable audiologic diagnostic procedure, the question is raised as to whether an implantation before the age of 1 year is effective and safe in terms of surgery and rehabilitation. METHOD AND PATIENTS: This retrospective study included 27 children implanted before the age of 1 year (Gr. 1) and 89 children implanted between the age of 1 and 2 years (Gr. 2). Patient related data were analysed for individual history, surgery, rehabilitation and speech understanding. RESULTS: The incidence of complications was not increased in Gr. 1. The fitting of a speech processor was effective and uneventful in all children. The development of hearing and speech understanding showed better results after 2 years in Gr. 1. This development is more obvious for absolute age and not to rehabilitation time. CONCLUSION: In order to achieve an optimal timing for the development of speech understanding, cochlear implantation should be performed before the age of 2 years. This study revealed no additional risks for children in Gr. 1, but the development of speech understanding was better. As a consequence, cochlear implantation should be considered for very young children with an identified bilateral profound hearing loss.

Cochlear Implantation↗

[Pediatric cost-benefit analysis].

BACKGROUND: The aim of this study was to explore the cost-benefit-ratio of pediatric cochlear implantation for congenitally deaf and prelingually deafened children compared to children with hearing aids. The payers' perspective was chosen as this is the most relevant for cost discussions. The study should verify the hypothesis that educational and associated full costs increase with the age at implantation and that these can be below costs for children with hearing aids. METHODS: Children implanted at different ages (group 1: 0 - 1.9 yr., group 2: 2 - 3.9 yr., group 3: 4 - 6.9 yr.) were compared with deaf children using hearing aids (group 4). Payers were sick funds and public authorities, the first paying for medical and indirect costs, the latter paying for education. Educational settings were used as measure for benefit. All costs related to the hearing deficiency were included up to the age of 16 years (end of primary education) based on 1999 costs. RESULTS: Discounted medical and indirect costs for a pediatric cochlear implant user varied between DM 112,000 (53,300 US dollars) and DM 91,000 (43,300 US dollars) depending on the age at implantation. Costs for a hearing aid user added up to DM 36,000 (17,100 US dollars). These costs were paid by the sick funds. Costs for education varied between DM 159,000 (75,700 US dollars) for group 1 and DM 257,000 (122,400 US dollars) for group 3 compared to DM 277,000 (131,900 US dollars) for hearing aid users. These differences are mainly based on the use of mainstream schools. Total costs for sick funds and public authorities ad up to DM 271,000 (129,000 US dollars), DM 334,000 (159,000 US dollars) and DM 348,000 (165,700 US dollars), respectively, for the three age groups of implanted children compared to DM 313,000 (148,600 US dollars) for hearing aid users. CONCLUSION: This study supports the view that pediatric cochlear implantation provides positive cost-benefit ratios compared to hearing aid users depending on the age at implantation. From a societal/payer perspective implantation of prelingually deafened children is especially recommended for children under the age of 2 years. Implantation between ages 2 and 3,9 can be recommended from an educational perspective. Implantation at ages >7 years must be based on individual decisions considering psychosocial environment, speech and language status and type of communication.

Adolescent↗

[Glaucoma in practices of ophthalmologists].

The aim of this study is to describe the prevalence of glaucoma among patients of office-based ophthalmologists on the basis of accounting data. The data can be taken from the so-called Patient-physician-panel for morbidity analysis (ADT panel) that has been developed by the Central Research Institute of Ambulatory Health Care in Germany. In this panel, the treatment data of patients treated by selected office-based physicians in North Rhine and Brandenburg are included. In both regions, 30 ophthalmologists were involved in the survey. The two random samples that have been performed, include the treatment data of nearly 55,000 patients from North-Rhine and of 58,000 patients from Brandenburg. The treatment prevalence of glaucoma with established diagnosis amounts to about 12% of the ophthalmologic patients in North Rhine and to about 13% in Brandenburg. If these figures are secondarily related to the total number of persons older than 39 years who are insured via social health insurance funds in these regions, the rates are 2.8 or 2.9% respectively. The majority of patients suffering from glaucoma (including suspected cases and exclusion diagnoses) underwent tonometry and it can be assumed that most of the patients received medical treatment. With the help of the morbidity panel, glaucoma patients with established diagnosis can be distinguished from those patients for whom this diagnosis has only been excluded and from cases where the suspicion remained unconfirmed. The standardised treatment prevalence of glaucoma almost amounts to the same rate in both regions. Ophthalmologists should use the additional specifications of the ICD-10 code more often (especially for cases of suspicion and exclusion). This would also lead to a higher significance of the ICD-10 terms indicated.

Adult↗

Induction of DNA breaks and apoptosis in crosslink-hypersensitive V79 cells by the cytostatic drug beta-D-glucosyl-ifosfamide mustard.

To study molecular aspects of cytotoxicity of the anticancer drug beta-D-glucose-ifosfamide mustard we investigated the potential of the agent to induce apoptosis and DNA breakage. Since beta-D-glucose-ifosfamide mustard generates DNA interstrand crosslinks, we used as an in vitro model system a pair of isogenic Chinese hamster V79 cells differing in their sensitivity to crosslinking agents. CL-V5B cells are dramatically more sensitive (30-fold based on D(10) values) to the cytotoxic effects of beta-D-glucose-ifosfamide mustard as compared to parental V79B cells. After 48 h of pulse-treatment with the agent, sensitive cells but not the resistant parental line undergo apoptosis and necrosis, with apoptosis being the predominant form of cell death (70 and 20% of apoptosis and necrosis, respectively). Apoptosis increased as a function of dose and was accompanied by induction of DNA double-strand breaks in the hypersensitive cells. Furthermore, a strong decline in the level of Bcl-2 protein and activation of caspases-3, -8 and -9 were observed. The resistant parental cells were refractory to all these parameters. Bcl-2 decline in the sensitive cells preceded apoptosis, and transfection-mediated overexpression of Bcl-2 protected at least in part from apoptosis. From the data we hypothesize that non-repaired crosslinks induced by beta-D-glucose-ifosfamide mustard are transformed into double-strand breaks which trigger apoptosis via a Bcl-2 dependent pathway.

Animals↗

Biodegradability of antineoplastic compounds in screening tests: influence of glucosidation and of stereochemistry.

Some pharmaceuticals such as antineoplastics are carcinogenic, mutagenic, teratogenic and fetotoxic. Antineoplastics and their metabolites are excreted by patients into waste water. In laboratory testing the frequently used isomeric anti-tumour agents cyclophosphamide (CP) and ifosfamide (IF) were shown to be not biodegradable. They are not eliminated in municipal sewage treatment plants and therefore detected in their effluents. Structural related compounds are beta-D-glucosylisophosphoramidmustard (beta-D-Glc-IPM; INN = glufosfamide) and beta-L-glucosylisophosphoramidmustard (beta-L-Glc-IPM). beta-L-Glc-IPM has no antineoplastic effects whereas beta-D-Glc-IPM is active against tumours. In contrast to IF and CP and almost all other investigated antineoplastics beta-D-Glc-IPM is inherently biodegradable. Improved biodegradability of beta-D-Glc-IPM compared to IF shows that reducing the impact of pharmaceuticals on the aquatic environment is feasible by changing the chemical structure of a given compound exerting a similar mode of action and therapeutic activity. Stereochemistry may be crucial for pharmaceutical activity of the compounds as well as for its biodegradability in the environment.

Antineoplastic Agents↗

Mechanistic aspects of the cytotoxic activity of glufosfamide, a new tumour therapeutic agent.

Beta-D-glucosyl-ifosfamide mustard (D 19575, glc-IPM, INN = glufosfamide) is a new agent for cancer chemotherapy. Its mode of action, which is only partly understood, was investigated at the DNA level. In the breast carcinoma cell line MCF7 glufosfamide inhibited both the synthesis of DNA and protein in a dose-dependent manner, as shown by the decreased incorporation of [3H-methyl]-thymidine into DNA and [14C]-methionine into protein of these cells. Treatment of MCF7 cells with 50 microM glufosfamide was sufficient to trigger poly(ADP-ribose) polymerase (PARP) activation, as revealed by immunofluorescence analysis. Both CHO-9 cells, which are O6-methylguanine-DNA methyltransferase (MGMT)-deficient, and an isogenic derivative, which has a high level of MGMT, showed the same cytotoxic response to beta-D-glc-IPM, indicating that the O6 position of guanine is not the critical target for cytotoxicity. By contrast, a sharp decrease in survival of cross-link repair deficient CL-V5 B cells was observed already at concentrations of 0.1 mM beta-D-glc-IPM, whereas the wild-type V79 cells showed a 90% reduction in survival only after treatment with 0.5 mM of this compound. The therapeutically inactive beta-L-enantiomer of glufosfamide also showed genotoxic effects in the same assays but at much higher doses. This was probably due to small amounts of ifosfamide mustard formed under the conditions of incubation. The results indicate that the DNA crosslinks are the most critical cytotoxic lesions induced by beta-D-glc-IPM.

Animals↗

Cochlear implantation in children under the age of two: the MHH experience with the CLARION cochlear implant. Medizinische Hochschule Hannover.

This paper examines reports on the selection criteria, the surgical procedure, and the postoperative performance for children under the age of 2 implanted with the CLARION Multi-Strategy Cochlear Implant (1.2 device). Eighteen children have been implanted since 1996 with a mean age at implantation of 18 months (range 11 to 23 months). All children were selected by means of a standardized preoperative diagnostic protocol. The surgical procedure used in older children was modified depending on the head and mastoid size, skull thickness, and recurrent otitis media. Auditory perception was tested prior to as well as 3, 6, 12, and 18 months following implantation by means of a standardized age-adapted test protocol. The electrode array was inserted without difficulty in all cases, with no complications to date. On average, auditory performance improved over time up to 18 months after implantation. Closed-set test scores increased by 25% to 55% in 18 months. Open-set test scores began to show improvement between 6 and 12 months postoperatively. Overall, our experience indicates that cochlear implantation in children under the age of 2 is relatively safe and reliable. The Clarion 1.2 device surgery can be performed without complications. Auditory performance results support the effectiveness of early implantation.

Cochlear Implantation↗

Transport of the new chemotherapeutic agent beta-D-glucosylisophosphoramide mustard (D-19575) into tumor cells is mediated by the Na+-D-glucose cotransporter SAAT1.

For beta-D-glucosylisophosphoramide mustard (beta-D-Glc-IPM), a new alkylating drug in which isophosphoramide mustard is stabilized, a higher selectivity and lower myelotoxicity was observed than for the currently used cytostatic ifosfamide. Because beta-D-Glc-IPM is hydrophilic and does not diffuse passively through the lipid bilayer, we investigated whether a transporter may be involved in the cellular uptake. A variety of cloned Na+-sugar cotransporters were expressed in Xenopus oocytes, and uptake measurements were performed. By tracer uptake and electrical measurements it was found that beta-D-Glc-IPM was transported by the low-affinity Na+-D-glucose cotransporter SAAT1, which had been cloned from pig and is also expressed in humans. At membrane potentials between -50 and -150 mV, a 10-fold higher substrate affinity (Km approximately 0.25 mM) and a 10-fold lower Vmax value were estimated for beta-D-Glc-IPM transport than for the transport of D-glucose or methyl-alpha-D-glucopyranoside (AMG). Transport of beta-D-Glc-IPM and glucose by SAAT1 is apparently performed by the same mechanism because similar sodium dependence, dependence on membrane potential, electrogenicity, and phlorizin inhibition were determined for beta-D-Glc-IPM, D-glucose, and AMG. Transcription of human SAAT1 was demonstrated in various human carcinomas and tumor cell lines. In one of these, the human carcinoma cell line T84, phlorizin inhibitable uptake of beta-D-Glc-IPM was demonstrated with substrate saturation and an apparent Km of 0.4 mM. The data suggest that the Na+-D-glucose cotransporter SAAT1 transports beta-D-Glc-IPM into human tumor cells and may accumulate the drug in the cells. They provide an example for drug targeting by employing a plasma membrane transporter.

Animals↗

Pediatric cochlear implantation in cochlear malformations.

OBJECTIVE: This study aimed to present relevant information about pediatric cochlear implantation in malformed cochleas based on the experience gathered with 12 implanted children. STUDY DESIGN: A retrospective analysis was performed. SETTING: All patients were diagnosed and implanted at the Medical University of Hannover. Medical check-ups were performed regularly. The rehabilitation concept was developed by the Cochlear Implant Center of Hannover. PATIENTS: All children were female and were between 2 and 13 years of age at the time of implantation, with the average age being 4 years and 2 months. Only patients who were younger than 14 years of age and implanted between September 1992 and October 1995 were evaluated. INTERVENTION: Diagnostic computed tomographic scans including three-dimensional reconstructions and magnetic resonance imaging images were performed. In all cases, Nucleus devices (Mini 22 or 20 + 2) were implanted. Medical University of Hannover standard surgical technique was used, although in most cases, facial nerve monitoring and electrically evoked auditory brain stem responses were additionally recorded. Total or partial obliteration of the middle ear had occurred in two cases. An anteroposterior approach was used four times. The implantation was followed by the standard rehabilitation procedure for children. RESULTS: No serious complications occurred. All children responded to acoustic stimuli and showed improvement in their speech production. However, one autistic child performed poorly, and for another child suffering from a CHARGE syndrome, results still are pending. CONCLUSIONS: Given suitable preconditions, cochlear implantation is feasible with an acceptable risk of complications. Implantation appears to be beneficial in most cases with cochlear malformations provided that eighth nerve and cochlear lumen are present.

Adolescent↗

Chemopreventive effects of S-(N,N-diethyldithiocarbamoyl)-N-acetyl-L-cysteine against benzo[a]pyrene.

The putative antimutagenic/anticarcinogenic organosulfur compound, S-(N,N-diethyldithiocarbamoyl)-N-acetyl-L-cysteine (AC-DDTC), has been demonstrated to inhibit the metabolic activation and the genotoxicity of N-nitrosodiethylamine. We have investigated the chemopreventive activity of AC-DDTC against benzo[a]pyrene (B[a]P) in the Salmonella typhimurium bacterial mutation assay, in the chromosome aberration assay using Chinese hamster lung fibroblast (CHL), and in the mouse micronucleus assay in bone marrow cells. In the bacterial mutation assay, AC-DDTC produced a concentration dependent decrease in the number of mutant colonies induced by B[a]P. The chromosome damaging responses of B[a]P in CHL cells were abolished by the treatment of AC-DDTC, approximately to the level of the control. In the in vivo mouse bone marrow micronucleus test, pretreatment of AC-DDTC 1 h prior to B[a]P reduced the frequency of micronucleated polychromatic erythrocytes. The inhibitory effects were statistically significant and dose-dependent. Our results demonstrate that AC-DDTC, one of the mixed disulfide model compounds of disulfiram, prevents the mutagenic effects of B[a]P.

Acetylcysteine↗

[Prevalence of patients with diabetes mellitus without and with retinopathy in an ophthalmology practice].

OBJECTIVE: In a prospective study 10,000 consecutive patients were interviewed and examined in a German ophthalmology practice to evaluate the prevalence of diabetes mellitus and diabetic retinopathy. PATIENTS: Out of all patients 496 (4.96%) suffered from diabetes. In most patients (488:230 male, 258 female; mean age: 66 +/- 15 years) a clinical workup including demographic data and binocular ophthalmoscopy was performed. RESULTS: Diabetic retinopathy (DR) was present in 130 (26.6%) of the 488 diabetic patients. Subgroup analysis showed a higher prevalence of diabetic retinopathy in patients with insulin therapy (85 of 149; 57%) to those treated with oral antidiabetics (37 of 198; 19%) or diet only (8 of 141; 6%). The prevalence was significantly correlated with the duration of diabetes in the groups treated with insulin (P < 0.01) and with oral antidiabetic drugs (P < 0.001). Mild or moderate non-proliferative DR was found in 93 patients (19%), severe non-proliferative DR in 23 patients (4.7%) and proliferative DR in 14 of 488 patients (2.9%; 13 with insulin-dependent diabetes). Clinically significant diabetic macular edema was identified in 41 patients (8.4%). In 48 (9.8%) laser coagulation had already been performed: 13 cases with panretinal scatter, 18 with a focal coagulation, 17 cases with both. CONCLUSIONS: The prevalence of diabetes mellitus in a German ophthalmological referral practice is similar to the total prevalence in Germany (4.9%). Diabetic retinopathy was found in fewer patients than reported in the Wisconsin Epidemiologic Study and other recent studies in other countries. The data in this study showed that regular screening of all diabetic patients is mandatory.

Adolescent↗

Morphologic changes of the macula in a patient with Purtscher's retinopathy.

Purtscher's retinopathy is a rare complication after trauma to the chest or bone fractures. We report about a patient, which we examined 6 months after a serious car accident. Visual acuity was 20/20 in both eyes. Examination with the Amsler grid revealed a paracentral scotoma in the left eye. In the fluorescein angiography of the left eye performed with a scanning laser ophthalmoscope we found capillary dropout, which corresponded well to the scotoma. Measured by digital image analysis, the area of the foveal avascular zone was eccentrically enlarged by a factor of 4. The mean perifoveal intercapillary area was also enlarged in the corresponding quadrant. This reflects that focal capillary dropout may result in scotoma rather than in a decrease in visual acuity as reported in other diseases.

Adult↗