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Biomedical subjects

Daniel J Lee

Publications and source records attributed to Daniel J Lee.

10 recordsLinked to original sources
PubMed2026

The 'Prostate Cancer Screening for People at Genetic Risk of Aggressive Disease' (PATROL) study.

BACKGROUND: Inherited (germline) pathogenic and likely pathogenic variants (gPVs) in key genes associated with increased risk of prostate cancer (PCa) now warrant more attentive PCa screening per National Comprehensive Cancer Network (NCCN) guidelines-e.g., BRCA2, HOXB13, ATM, BRCA1, MSH2, MSH6, CHEK2 and TP53. However, the optimal early detection strategy for gPV carriers, including use of age-adjusted PSA thresholds and prostate imaging may be refined. and as a means to investigate novel biomarkers. STUDY DESIGN: 'Prostate Cancer Screening for People at Genetic Risk of Aggressive Disease' (PATROL) is a multicentre, prospective early detection study for individuals at increased risk for PCa due to carrying a gPV in a PCa risk gene. ENDPOINTS: The primary endpoint is to determine the positive predictive value of pre-defined age-directed prostate-specific antigen (PSA) level thresholds and prostate-specific imaging, e.g., multiparametric magnetic resonance imaging (MRI) for clinically significant PCa on biopsy for individuals at risk of PCa due to a gPV. Exploratory endpoints include characterising clinicopathological characteristics of PCa and patient-reported outcomes. Biospecimens will be collected to evaluate emerging clinical and research biomarkers. PATIENTS AND METHODS: Key eligibility includes: individuals aged &#x2265;40&#x2009;years who carry a gPV in an eligible gene, who have no prior diagnosis of PCa, do not have another active malignancy, and provide informed consent. Study procedures include annual physical examination and PSA. Imaging with MRI is optional at baseline and recommended if the PSA level is above the protocol-recommended PSA level threshold. Participants will be offered prostate biopsy for any clinical concern, PSA level >1.0&#x2009;ng/mL if aged <50&#x2009;years; PSA level >1.5&#x2009;ng/mL if aged 50-59&#x2009;years; PSA level >2.0&#x2009;ng/mL if aged &#x2265;60&#x2009;years. If PCa is diagnosed, clinical care is determined by the participant and treating physician. If opting for active surveillance, study procedures will be collected annually for 10&#x2009;years or until definitive treatment. If definitive treatment, study procedures will be collected for an additional 1&#x2009;year. Long-term clinical outcomes will be collected annually until the study closes.

Humans↗
PubMed2006

Central auditory pathways mediating the rat middle ear muscle reflexes.

The middle ear muscle (MEM) reflexes function to protect the inner ear from intense acoustic stimuli and to reduce acoustic masking. Sound presented to the same side or to the opposite side activates the MEM reflex on both sides. The ascending limbs of these pathways must be the auditory nerve fibers originating in the cochlea and terminating in the cochlear nucleus, the first relay station for all ascending auditory information. The descending limbs project from the motoneurons in the brainstem to the MEMs on both sides, causing their contraction. Although the ascending and descending pathways are well described, the cochlear nucleus interneurons that mediate these reflex pathways have not been identified. In order to localize the MEM reflex interneurons, we developed a physiologically based reflex assay in the rat that can be used to determine the integrity of the reflex pathways after experimental manipulations. This assay monitored the change in tone levels and distortion product otoacoustic emissions within the ear canal in one ear during the presentation of a reflex-eliciting sound stimulus in the contralateral ear. Preliminary findings using surgical transection and focal lesioning of the auditory brainstem to interrupt the MEM reflexes suggest that MEM reflex interneurons are located in the ventral cochlear nucleus.

Acoustic Stimulation↗
PubMed2006

Microsatellite analysis of recurrent vestibular schwannoma (acoustic neuroma) following stereotactic radiosurgery.

HYPOTHESIS: Genetic and immunohistochemical studies may provide insight into the mechanisms of vestibular schwannoma (VS) recurrence following radiation therapy. BACKGROUND: Stereotactic radiation therapy is an increasingly common alternative to microsurgical resection for the primary management of sporadic VS. The molecular mechanisms associated with recurrent vestibular schwannoma (VS) following radiation therapy are not known. METHODS: Primary or irradiated VS tumors were fresh-frozen at the time of surgical resection and microdissected to undergo DNA extraction. Lymphocytic control DNA was isolated from blood obtained by venipuncture. Paired normal and tumor DNA specimens were analyzed for allelic loss by PCR amplification of polymorphic dinucleotide repeat sequences. Immunohistochemical studies were performed on paraffin-embedded, irradiated surgical specimens. RESULTS: Using 16 polymorphic microsatellite markers, 20 of 26 non-irradiated VS demonstrated loss of heterozygosity (LOH) in at least one locus of chromosome 22q. In contrast, none of the four irradiated recurrent VS demonstrated LOH on chromosome 22q (p = 0.008). No allelic loss was seen in either the primary or irradiated VS utilizing markers mapping to chromosome 10. Deletions on chromosome 10 are seen in both benign and higher-grade meningiomas and intracranial malignancies associated with radiotherapy. Immunohistochemical studies were performed to detect the protein product of the NF2 gene, merlin, in the four irradiated VS. NF2 staining was not observed. CONCLUSION: This study represents the first microsatellite and immunohistochemical analysis of recurrent VS following radiation therapy. Our preliminary observations suggest an alternative mechanism of NF2 inactivation that may correlate with radioresistance in VS.

Base Sequence↗
PubMed2006

Superior semicircular canal dehiscence presenting as postpartum vertigo.

OBJECTIVE: To describe the clinical and diagnostic features of superior semicircular canal dehiscence (SSCD) in patients with postpartum vertigo. STUDY DESIGN: Retrospective review, meta-analysis. SETTING: Tertiary neurotologic and audiologic center. PATIENTS: Two women who presented with a history of acute postpartum vertigo and SSCD confirmed on high-resolution computed tomography (CT) were included. Our meta-analysis of the surgical SSCD literature comprised a total of 43 patients. INTERVENTION: Patients with postpartum vertigo and SSCD underwent a complete medical evaluation, audiometric testing, CT imaging, magnetic resonance imaging studies, vestibular evoked myogenic potential testing, and laser Doppler vibrometer testing. Case 2 was managed with a middle fossa craniotomy and SSCD repair. RESULTS: The first patient presented with normal hearing and aural fullness, autophony, and sound sensitivity of the left ear. A 1-mm left-sided SSCD was seen on CT imaging. She is being managed conservatively. The second patient had left-sided conductive hearing loss with sound and pressure sensitivity. The contralateral ear was congenitally deaf. CT imaging revealed a 4-mm left-sided SSCD. Because of her disabling symptoms, the patient underwent a middle fossa craniotomy and superior canal plugging. Her vestibular symptoms resolved with improvement in hearing. Vestibular evoked myogenic potential and laser Doppler vibrometer testing in both cases were consistent with SSCD. CONCLUSION: This is the first description of patients with SSCD presenting after childbirth and should be included in the differential diagnosis of acute postpartum vertigo or disequilibrium. SSCD plugging can provide a stable repair with resolution of symptoms, reversal of diagnostic indicators, and hearing improvement.

Adult↗
PubMed2005

Effects of cytomegalovirus (CMV) related deafness on pediatric cochlear implant outcomes.

OBJECTIVE: Human cytomegalovirus (CMV) is a commonly recognized viral cause of perinatal sensorineural hearing loss. CMV-infected infants are also at risk for developmental neurological deficits. This retrospective study assesses the impact of CMV-induced deafness on pediatric cochlear implant outcomes. STUDY DESIGN AND SETTING: Thirteen patients from the Johns Hopkins pediatric cochlear implant database were identified with CMV-related deafness. A retrospective review of the medical records of the Johns Hopkins Hospital was performed. RESULTS: The mean age at implantation was 5.6 years. Follow-up audiometric data ranged from 6 to 48 months postoperatively. Mean speech perception scores were 4.5 (out of 6) following implantation. CONCLUSION: We have shown that cochlear implants can provide useful speech comprehension to patients with CMV-related deafness. Speech recognition scores were within the range established by our overall pediatric implant population. SIGNIFICANCE: This observation underscores the importance of a multidisciplinary rehabilitation program following implantation in these patients at risk for cognitive delay.

Antibodies, Viral↗
PubMed2003

Effects of congenital deafness in the cochlear nuclei of Shaker-2 mice: an ultrastructural analysis of synapse morphology in the endbulbs of Held.

It is well established that manipulation of the sensory environment can significantly alter central auditory system development. For example, congenitally deaf white cats exhibit synaptic alterations in the cochlear nucleus distinct from age-matched, normal hearing controls. The large, axosomatic endings of auditory nerve fibers, called endbulbs of Held, display reduced size and branching, loss of synaptic vesicles, and a hypertrophy of the associated postsynaptic densities on the target spherical bushy cells. Such alterations, however, could arise from the cat's genetic syndrome rather than from deafness. In order to examine further the role of hearing on synapse development, we have studied endbulbs of Held in the shaker-2 ( sh2 ) mouse. These mice carry a point mutation on chromosome 11, affecting myosin 15 and producing abnormally short stereocilia in hair cells of the inner ear. The homozygous mutant mice are born deaf and develop perpetual circling behavior, although receptor cells and primary neurons remain intact at least for the initial 100 days of postnatal life. Endbulbs of Held in 7-month old, deaf sh2 mice exhibited fewer synaptic vesicles in the presynaptic ending, the loss of intercellular cisternae, and a hypertrophy of associated postsynaptic densities. On average, postsynaptic density area for sh2 endbulbs was 0.23 +/- 0.19 microm(2) compared to 0.07 +/- 0.04 microm(2) ( p < 0.001) for age-matched, hearing littermates. These changes at the endbulb synapse in sh2 mice resemble those of the congenitally deaf white cat and are consistent with the idea that they represent a generalized response to deafness.

Animals↗
PubMed2003

Dehiscence of bone overlying the superior semicircular canal as a cause of an air-bone gap on audiometry: a case study.

Dehiscence of bone overlying the superior semicircular canal can result in a syndrome of vertigo and oscillopsia induced by loud noises or by maneuvers that change middle ear or intracranial pressure. Patients with this disorder can also experience a heightened sensitivity to bone-conducted sounds in the presence of normal middle ear function. High-resolution CT scans of the temporal bones demonstrate the dehiscence. The authors describe a patient with bilateral superior canal dehiscence who had bilateral low-frequency conductive hearing loss, normal middle ear function, intact acoustic reflexes, and intact vestibular-evoked myogenic potentials. These findings would not be expected on the basis of a middle ear cause of the conductive hearing loss. A high-resolution CT scan of the temporal bones in this patient revealed bilateral superior canal dehiscence. Normal acoustic immittance findings in the presence of conductive hearing loss should alert clinicians to the possibility of inner ear cause of an air-bone gap due to superior canal dehiscence.

Audiometry↗
PubMed2003

Clinical and histopathologic features of recurrent vestibular schwannoma (acoustic neuroma) after stereotactic radiosurgery.

OBJECTIVE: Stereotactic radiosurgery for vestibular schwannoma entails uncertain long-term risk of tumor recurrence and delayed cranial neuropathies. In addition, the underlying histopathologic changes to the tumor bed are not fully characterized. We seek to understand the clinical and histologic features of recurrent vestibular schwannoma after stereotactic radiation therapy. STUDY DESIGN: Retrospective review. SETTING: Tertiary referral center. PATIENTS: Four patients who underwent microsurgical resection of vestibular schwannoma after primary stereotactic radiation therapy. INTERVENTION: Patients were treated primarily with gamma knife radiosurgery or fractionated stereotactic radiotherapy followed by salvage microsurgery. Retrosigmoid craniotomy was used in all cases. MAIN OUTCOME MEASURES: Histopathologic review. Preoperative and postoperative facial nerve function was assessed with the House-Brackmann scale. RESULTS: We observed highly inconsistent radiation changes in the cerebellopontine angle and internal auditory canal. Fibrosis outside and within the tumor bed varied markedly, complicating microsurgical dissection. Light microscopy confirmed the presence of viable tumor in all cases. Histopathologic features were typical of vestibular schwannoma, and there was no significant scarring that could be attributed to radiation effect. CONCLUSIONS: The variable fibrosis in the cerebellopontine angle and lack of radiation changes seen histopathologically in irradiated vestibular schwannoma suggest that a uniform treatment effect was not achieved in these cases. Although all four patients with preoperative cranial neuropathies were found intraoperatively to have fibrosis in the cerebellopontine angle, excellent preservation of facial nerve anatomy and function was possible with salvage microsurgical resection. Additional analyses are needed to clarify the histopathologic and molecular characteristics associated with vestibular schwannoma growth after stereotactic radiation.

Aged↗
PubMedDate not supplied

Lipoma of the cerebellopontine angle.

Lipomas of the cerebellopontine angle (CPA) are unusual tumors that typically present with hearing loss, tinnitus, dizziness, and occasionally facial neuropathies. We describe the case of a healthy 42-year-old woman who presented with left-sided hearing loss and facial synkinesis. T1-weighted magnetic resonance imaging revealed an enhancing lesion of the left CPA with no signal on fat suppression sequences. Despite conservative therapy, the patient developed progressive hemifacial spasm, and a suboccipital craniotomy approach was used to debulk the tumor, which encased cranial nerves V, VII, VIII, IX, X, and XI. Surgical histopathology demonstrated mature adipocytes, consistent with lipoma. Two years after surgery, the patient remains free of facial nerve symptoms. Cerebellopontine angle lipomas are rare lesions of the skull base and are reliably diagnosed with T1-weighted and fat suppression magnetic resonance sequences, which we recommend in the routine radiologic workup of CPA tumors. Accurate preoperative diagnosis is crucial because most CPA lipomas should be managed conservatively. Partial surgical resection is indicated only to alleviate intractable cranial neuropathies or relieve brainstem compression.

Adult↗