PubMed Health⌕ Search

Biomedical subjects

L M Holbach

Publications and source records attributed to L M Holbach.

At least 19 recordsLinked to original sources
PubMed2006

Different genetic pathways in the development of periocular sebaceous gland carcinomas in presumptive Muir-Torre syndrome patients.

Periocular sebaceous gland carcinomas (SGCs) occur in the eyelids either sporadically or as a phenotypic feature of Muir-Torre syndrome (MTS). In knockout mice mismatch-repair (MMR) defects or inactivation of the fragile histidine triad (FHIT) gene are associated with MTS-like signs, including SGC. To dissect the genetic alterations associated with microsatellite instability (MSI) and inactivation of the FHIT gene, we studied nine periocular SGC specimens from MTS patients. Immunohistochemistry was performed for FHIT, MSH2, MLH1, and MSH6. We assessed MSI as well as loss of heterozygosity (LOH) at the FHIT locus with polymorphic markers and genomic multiplex PCR. Epigenetic silencing was detected by methylation-specific PCR (MSP) and combined bisulfite restriction analysis (COBRA). Our analyses identified two SGCs with FHIT positivity and high-grade MSI, and seven cases with loss of FHIT and microsatellite stability (MSS). MSI correlated with loss of MSH2 and MLH1 immunostaining. Loss-of-function mechanisms affecting the FHIT gene were identified as intragenic deletions eliminating the coding exons 5 and 6 on one hand, and complete biallelic methylation of the FHIT transcription regulatory region on the other hand. Germinal FHIT mutations as a predisposing factor for MTS were excluded in two index patients with cancer in three generations, including an FHIT-negative SGC. Our data suggest that either somatic inactivation of the FHIT gene associated with MSS or inactivation of the MMR system resulting in MSI contribute to the development of periocular SGCs in presumptive MTS.

Acid Anhydride Hydrolases↗
PubMed2006

Epigenetic silencing contributes to frequent loss of the fragile histidine triad tumour suppressor in basal cell carcinomas.

BACKGROUND: Extensive exposure to ultraviolet radiation is associated with genetic alterations in basal cell carcinomas (BCCs), which represent some 75% of skin cancers. OBJECTIVES: As recent data suggested the fragile histidine triad (FHIT) gene product to participate in DNA damage responses we wished to address whether functional deletion of this tumour suppressor participates in the development of BCC. Our study focused on epigenetic inactivation of the FHIT gene. METHODS: Paraffin-embedded specimens from 17 patients with BCC were available for methylation-specific polymerase chain reaction (MSP), combined bisulphite-dependent restriction analysis (COBRA) of the FHIT gene and immunohistochemistry of its product. RESULTS: We report for the first time that 100% of BCCs are negative for FHIT by immunostaining. Aberrant methylation of the FHIT promoter occurred in a significant portion of BCCs. MSP detected hypermethylation of the FHIT/FRA3B locus in nine of nine (100%) periocular BCCs and in six of eight (75%) BCCs from other body regions. COBRA yielded similar results, confirming that some 88% of the 17 BCCs analysed harbour epigenetic silencing of the FHIT gene. Loss of FHIT protein was demonstrated immunohistochemically, confirming that promoter hypermethylation correlated with loss of gene expression. CONCLUSIONS: We have identified epigenetic silencing of the FHIT tumour suppressor gene as a frequent inactivation mechanism which is likely to contribute to functional deficiencies in DNA damage response of BCCs.

Acid Anhydride Hydrolases↗
PubMed2005

Management of spontaneous enophthalmos due to silent sinus syndrome: a case report.

Silent sinus syndrome (SSS) is a rare disease exhibiting unilateral enophthalmos and hypoglobus. A 26-year-old white female presented with right side enophthalmos and hypoglobus. There was no history of previous trauma or maxillary sinus diseases. A CT scan showed an opacified right maxillary antrum with decreased volume and downward bowing of the right orbital floor. From clinical and radiological findings the diagnosis SSS was made. Biopsies were collected from the maxillary sinus for the exclusion of malignancy. Two months later orbital floor reconstruction was carried out. Before antrostomy of the affected maxillary sinus, a relative enophthalmos of 4mm was determined. Five days after antrostomy the value reduced to 2.3mm. During the following 2 months the enophthalmos remained constant. At the end of the operation for orbital floor reconstruction it was 0.1mm. Five days after surgery the relative enophthalmos increased to 0.8mm. The value remained constant during the following 3 months. Initial antrostomy of the affected maxillary sinus may lead to a relevant, spontaneous reduction of enophthalmos. After a minimum period of 2 months a re-evaluation should be made, if a reconstruction of the orbital floor is still necessary for the correction of the globe position.

Adult↗
PubMed2004

Hertel exophthalmometry versus computed tomography and optical 3D imaging for the determination of the globe position in zygomatic fractures.

It has been the aim of the present study, to introduce the combination of computed tomography and optical 3D imaging to exophthalmometry and to compare the resulting data to the classic Hertel method. Twenty patients without orbital pathology and 12 patients were included in the study, who were subjected to a preoperative computed tomography. Optical 3D images of the facial surface were assessed and Hertel exophthalmometry was carried out to determine protrusion. In patients with zygomatic fractures the assessment of optical 3D images and Hertel values was repeated 5 days after surgery. Preoperative axial CT slices and postoperative optical contours through the globes were superimposed and the change in protrusion was determined. The protrusion values assessed either by CT, Hertel exophthalmometry or optical 3D imaging for patients without orbital pathology did not show any statistically significant differences between each other. For zygomatic fractures, Hertel exophthalmometry revealed more pronounced protrusion data in four of five cases of a posterolaterally dislocated lateral orbital rim and a higher degree of enophthalmos in cases without dislocation of the lateral orbital rim than it could be proved in the CT slices. The differences between optical measurements and CT data were minimal in patients with zygomatic fractures. The combination of computed tomography as baseline measurement and optical 3D imaging for the follow-up examinations reveal more realistic data in cases of zygomatic fractures than Hertel measurements and should be preferred.

Adult↗
PubMed2004

Surgery for primary basal cell carcinoma including the eyelid margins with intraoperative frozen section control: comparative interventional study with a minimum clinical follow up of 5 years.

AIM: To assess recurrence of primary basal cell carcinoma (PBCC) including the eyelid margins after resection with or without intraoperative frozen section control (IFS). METHODS: Comparative non-randomised interventional study involving review of records of consecutive patients with histological diagnosis of PBCC including the eyelid margins, treated surgically at the University of Erlangen-Nürnberg between 1989 and 1998. Patients with a minimum clinical follow up of 5 years treated with (group I) or without (group II) IFS were compared. Postoperatively, permanent paraffin sections were available in all patients. RESULTS: 165 patients were available for study. There were 145 patients with a minimum of 5 years follow up. Of these, no tumour recurrences were observed in group I (n = 114) compared with three (9.7%) in group II (n = 31) (p = 0.002). CONCLUSIONS: Surgery for PBCC including the eyelid margins with IFS and immediate plastic reconstruction, as performed in the present study, is associated with better long term cure compared with surgery with clinical control.

Adult↗
PubMed2003

[Management of conjunctival malignant melanoma associated with primary acquired melanosis (PAM) using 0.02% mitomycin C eyedrops].

BACKGROUND: The therapy of malignant diseases of the conjunctiva with local chemotherapy is an extension of the therapeutic options in this field. We report on our experience in the therapy of malignant melanomas of the conjunctiva associated with primary acquired melanosis (PAM). METHODS AND PATIENTS: Between March 1998 and April 2001, 13 patients with malignant melanoma of the conjunctiva associated with PAM (6 female; 7 male; mean age 57+/-13 years) were treated with local chemotherapy. The tumor was classified as stage pT2 (pN0, pM0) in seven patients, stage pT3 (pN0, pM0) in three patients and in the remaining three patients the lid was involved in the malignant process (pT4, pN0, pM0). Local chemotherapy (mitomycin C 0.02% eyedrops 5 times a day) was applied after incisional biopsies in 2 cycles for 14 days with a 14-day break. In 4 patients a third cycle was included. RESULTS: Regression of the tumor was observed after completion of the therapy in all cases. Severe ocular or systemic secondary effects were not seen in our patients. Nine patients were without recurrence within the follow-up time. In three patients, a recurrence of the disease was observed. In these cases, the eyelid was involved in the process. CONCLUSION: Local chemotherapy with mitomycin C is a useful option in the treatment of malignant melanomas of the conjunctiva associated with PAM if the tumor stage is pT3 or less. From our point of view the combination with incisional biopsy is of great benefit. Prognosis of conjunctival malignant melanomas involving the lid margin (pT4) is poor.

Administration, Topical↗
PubMed2001

Persisting retinal ganglion cell axons in blind atrophic human eyes.

PURPOSE: To evaluate enucleated blind atrophic human eyes for the persistence of retinal ganglion cell axons. This might be of relevance for contact to an electronic prosthesis in the future. METHODS: A total of 2460 surgically enucleated eyes were studied in our ophthalmic pathology laboratory between 1981 and 1996. All eyes histopathologically classified as displaying ocular atrophy with shrinkage (axial length < or = 21 mm) and with an available optic nerve cross section without crush artifacts were selected. Only eyes of patients older than 18 years and without light perception prior to enucleation were analyzed (n = 57). Optic nerve fibers were counted under light microscopy in semithin optic nerve sections. RESULTS: Axons amounting to more than 5% of the mean axon count in normal eyes (> 57,950 axons) were detected in 24 (42%) of 57 optic nerves, and an axon count more than 10% of the mean normal count (> 115,900 axons) was found in 15 (26%) of 57 optic nerves. The retina was at least partially detached and disoriented in all 57 eyes. The inner nuclear layer was detectable in 46 (81%) of eyes, whereas the outer nuclear layer was present in 13 (23%) of 57 eyes; photoreceptors were detectable by light microscopy in only 3 eyes (5%). Intraocular calcification due to osseous metaplasia of the retinal pigment epithelium was present in 62% of the globes. CONCLUSION: Blind atrophic human eyes reveal persisting retinal ganglion cell axons. Whether direct electrical stimulation of these axons or their retinal ganglion cells has the potential to create visual information remains to be studied.

Adolescent↗
PubMed2001

Orbital lymphangioma with positive immunohistochemistry of lymphatic endothelial markers (vascular endothelial growth factor receptor 3 and podoplanin).

BACKGROUND: Existence of true orbital lymphangiomas has been questioned in recent years. Therefore an orbital lymphangioma was analyzed with two new specific markers of lymphatic endothelium. METHODS: Case-report with clinicopathological, immunohistochemical, and ultrastructural findings. A 25-year-old man presented with recurrent lower lid "hematomas" and a pea-sized tumor palpable in the left lower lid. Magnetic resonance imaging showed an inferonasally located orbital tumor which extended to the posterior pole of the eye. The highly vascularized tumor was excised by medial orbitotomy. RESULTS: Histopathologically, the mass consisted of large, erythrocyte-filled cavernous vessels without evidence of smooth muscle cells or pericytes surrounding them. Numerous lymph follicles and small arterioles were scattered between them. Immunohistochemically, endothelial cells lining the lumina of the cavernous vessels were partly positive for podoplanin and vascular endothelial growth factor receptor 3 (flt-4), two markers of lymphatic endothelium. These markers did not react with endothelial cells lining the arterioles. Ultrastructurally, cavernous vessels displayed features characteristic of lymphatic vessels, and the smaller vessels demonstrated signs of arterioles. CONCLUSION: Ultrastructural analysis and immunohistochemistry using two new markers of lymphatic endothelium suggest a lymphatic nature of large vessels in an orbital lymphangioma. A greater series of vascular orbital tumors must be studied with these new lymph endothelial markers to confirm the existence of true orbital lymphangiomas and to analyze different profiles of lymph endothelial marker expression.

Adult↗
PubMed2001

Primary intraosseous cavernous hemangioma of the orbit.

PURPOSE: Primary orbital intraosseous hemangioma is a rare, benign neoplasm presenting most frequently in patients in their fourth or fifth decade of life. We describe an elderly patient affected by this tumor. METHODS: Case report. RESULTS: A 75-year-old man presented with a slowly growing, bony mass in the left orbital rim inferolaterally. He had a history of nephrectomy because of a renal carcinoma. Computed tomography showed a bony lesion with internal radiating trabeculations. A biopsy was performed. Histopathologically, the tumor was an intraosseous cavernous hemangioma. CONCLUSION: Primary intraosseous cavernous hemangioma of the orbit may infrequently affect elderly patients. One indication for surgical removal of these tumors in the absence of visual disturbances is to rule out metastatic disease in patients with a history of malignancy.

Aged↗
PubMed2001

Silicone oil-associated optic nerve degeneration.

PURPOSE: To report the frequency and extent of silicone oil migration into the optic nerve during silicone oil endotamponade. METHODS: Histopathologic analysis of 74 eyes enucleated after silicone oil endotamponade. RESULTS: In 14 of 74 enucleated eyes (24%), optically empty vacuoles regarded as silicone oil vacuoles were observed in the retrolaminar optic nerve. In three eyes, silicone oil in the optic nerve was surrounded by a granulomatous inflammatory reaction. In serial cross sections, the vacuoles extended up to the line of surgical transsection (up to 9 mm) of the optic nerve and constituted up to 40% of the total cross-sectional area. CONCLUSIONS: After silicone oil endotamponade, silicone oil may replace a considerable amount of tissue of the retrolaminar optic nerve. A granulomatous inflammatory reaction surrounding silicone oil may add to optic nerve damage.

Eye Enucleation↗
PubMed2001

Orbital involvement in cherubism.

PURPOSE: To demonstrate the clinical, radiologic, and histopathologic features of a patient with orbital involvement in cherubism that prompted surgical treatment. DESIGN: Single interventional case report. INTERVENTION: Findings of the ophthalmic evaluation, computed tomography (CT) scans, intraoperative examination, and light microscopy of the specimens were analyzed. MAIN OUTCOME MEASURES: Globe displacement, orbital bony lesions detected on CT scans, histopathology, and postoperative results were assessed. RESULTS: A 27-year-old female was seen with a slowly progressive superonasal globe displacement and a temporal orbital mass bilaterally of 6 years' duration. She had a history of cherubism, but her cheeks and jaws had a normal appearance instead of the bilateral fullness of the lower half of the face typical of the disease. CT scans demonstrated multicystic bony lesions arising from the orbital floors bilaterally. The masses were excised using an anterior transcutaneous transseptal orbitotomy. Histopathology demonstrated numerous giant cells in a fibrovascular stroma, confirming the clinical diagnosis of cherubism. Postoperative recovery was complete. CONCLUSIONS: Orbital involvement in cherubism may develop beyond puberty, after stabilization or regression of the lesions in the jaws. Patients with cherubism should be routinely evaluated by an ophthalmologist.

Adult↗
PubMed2001

[Eyelid and facial injuries due to dog bites].

BACKGROUND: Head und neck injuries of children are mistly due to dog bite. PATIENTS AND METHODS: During the 10-year interval from 1990 to 2000 sixteen patients suffering from dog bite injuries were seen in our department. Age, gender, pattern of ocular and periocular wounds, surgical management and long-term damage were analyzed. RESULTS: Medial lower eyelid injuries with lacrimal duct involvement were most common. Ten victims were younger than four years. 87% of the dogs belonged to the family and friends of the patients. Two localized infections and no systemic infection were seen. CONCLUSION: Primate microsurgical wound repair leads to a satisfying functional, morphological, and esthetic long-term result.

Age Distribution↗
PubMed2001

[Conjunctival balloon cell nevi--light- and electronmicroscopic findings in 2 patients].

CASE REPORTS: Two 19-year-old patients presented with small nasal conjunctival tumors. Histologic examination revealed subepithelial tumors consisting of large cells with deeply basophilic, small, centrally-placed nuclei and abundant, slightly eosinophilic cytoplasm with microvesicles. Electron microscopy showed premelanosomes in some of the balloon cells. CONCLUSION: The balloon cell nevus is a rare variant of the conjunctival nevi. The characteristic intracellular microvesicles are probably degenerative remnants of premelanosomes.

Adult↗