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Biomedical subjects

B Bertram

Publications and source records attributed to B Bertram.

At least 19 recordsLinked to original sources
PubMed2002

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↗
PubMed2000

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↗
PubMed2000

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↗
PubMed1999

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↗
PubMed1998

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↗
PubMed1998

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↗
PubMed1997

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↗
PubMed1997

[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↗
PubMed1997

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↗
PubMed1997

Malformations in cochlear implant patients.

OBJECTIVE: To report on cochlear implantation in children with bony inner ear malformations. PATIENTS: 30 children with bony inner ear malformations who have received cochlear implants. INTERVENTIONS: High-resolution spiral computed tomography is used to identify malformations. Magnetic resonance imaging is used to detect the presence of an acoustic nerve and determine the integrity of the auditory pathway and central nervous system structures. Both imaging techniques may be used intraoperatively, as well as facial nerve monitoring and electrical auditory brainstem response monitoring. Three-dimensional reconstructions are helpful in preoperative planning. Large vestibular aqueducts and vestibular malformations can be successfully managed. RESULTS: Postoperative results have been encouraging, although children with malformations tend to occupy the lower third of rehabilitation results of all children with implants.

Child↗
PubMed1997

Stress experienced by parents of children with cochlear implants compared with parents of deaf children and hearing children.

OBJECTIVE: To compare the stress experienced by parents of children with cochlear implants with that experienced by parents of deaf children and hearing children. STUDY DESIGN: The Parenting Stress Index and problem-oriented interviews were used with the parents of these three groups of children. RESULTS: Parents of deaf children were found to experience greater levels of stress than parents in the other two groups. CONCLUSION: Parents of children with cochlear implants experience about the same level of stress as parents of hearing children.

Child↗
PubMed1997

Preliminary conversation with the parents before cochlear implantation.

OBJECTIVE: To provide parents of hearing-impaired children about to undergo cochlear implantation with an opportunity to discuss their expectations and the pedagogical implications of surgery. SETTING: Parents and children participate in discussions at the medical center where the cochlear implantation will take place. PATIENTS: More than 700 children and their parents have participated. OUTCOMES: Parents of congenitally deaf children differ somewhat in their expectations and behavior from the parents of postlingually deafened children.

Child, Preschool↗