Suprathreshold Auditory Cortex Activation Visualized by Intrinsic Signal Optical Imaging

The suprathreshold tonotopic organization of rat and guineapig auditory cortex was investigated using intrinsic signaloptical imaging through a thinned skull. Optical imaging revealedthat suprathreshold pure sine wave tone stimulation (25–40dB) evoked activity over large cortical areas that were tonotopicallyorganized. Three-dimensional surface plots of the activatedareas revealed "patchy" auditory-evoked activity consistingof numerous local peaks and valleys building to a maximum. Subsequentdetailed electrophysiological mapping in the same subjects confirmedthe localization of auditory-evoked activity based on opticalimaging, including responses to a test frequency at corticalloci more than 2 octaves away from the threshold-defined isofrequencycontour. The success of this technique in visualizing auditorycortex functional organization at suprathreshold stimulus levelswill allow for future investigations of auditory cortex frequencyrepresentation. including representational plasticity inducedby a variety of experimental manipulations.     

Development of fluridil,a topical suppressor of the androgen receptor in androgenetic alopecia

Nonsteroidal antiandrogens (AA) cannot be topically used for androgenetic alopecia (AGA) because of systemic resorption. A new class of androgen receptor (AR) suppressors designed for safe topical treatment of AGA was synthesized from (3‐amino‐2‐hydroxy‐2‐methyl‐N‐(4‐nitro‐3‐trifluoromethyl)phenyl) propanamide (BP‐34), to contain perfluoroalkyl moieties. The trifluoromethyl derivative (fluridil) at 10 μM decreased expression of the AR in LNCaP human cells by 95%, its serum half‐life was 6 h; it decomposes hydrolytically to BP‐34 and trifluoroacetic acid. Acute intraperitoneal maximum tolerated dose (MTD) of fluridil in mice is 270–300 mg/kg/d and the subacute MTD is 450 mg/kg/d. The oral LD₅₀ in mice was 2,872 mg/kg in males, 2,232 mg/kg in females, and >2,500 mg/kg in rats. Fluridil solution in isopropanol was not cutaneously absorbed in rabbits, did not sensitize or show any phototoxic or photoallergic effects on guinea pig skin, and demonstrated no skin irritation potential in rabbits and humans. Fluridil solid induced only slight and reversible eye irritancy in rabbits and displayed no cytotoxicity to rabbit corneal fibroblasts in vitro. Fluridil demonstrated no significant mutagenicity potential by Ames method. In a double‐blind study, 43 males with AGA, Norwood grade II to Va, used topical 2% fluridil in isopropanol or the vehicle daily for 12 months. Anagens (growing hairs) increased in the fluridil group from 76% to 89%. All hematological and biochemistry values remained within normal range, including testosterone, which varied but seasonally. No fluridil or its decomposition product (BP‐34) was detected in serum. No adverse side effects were reported. Drug Dev. Res. 59:292–306, 2003. © 2003 Wiley‐Liss, Inc.     

Cancer Patterns in the Middle East Special Report from the Middle East Cancer Society

To update its cancer statistics, the newly established Middle East Cancer Society examined the cancer frequency patterns in Egypt and the Gaza Strip. The results revealed differing overall patterns. For men the highest frequencies were found for lymphoma, bladder cancer and cancers of the oral cavity and pharynx in Egypt, and for lung cancer, leukaemia and lymphoma in Gaza. For women, breast cancer had the highest frequency in both areas, followed by cancers of the oral cavity and pharynx in Egypt, and leukaemia and lymphoma in Gaza. The distribution of cancer occurrence by organ system also varied. In the light of the different ethnicities, lifestyles, socioeconomic levels and carcinogenic exposure among the countries of the Middle East, this kind of comparison can provide the background for more sophisticated approaches for discerning risk factors in cancer. We believe that further cooperation among participating countries will overcome the present limitations in data collection, registration and access.     

Susac syndrome.

OBJECTIVE: The objective of this study was to describe the clinical manifestations; radiographic, audiometric, and retinal fluorescein angiography findings; pathogenesis and treatment of Susac syndrome with review of the literature. STUDY DESIGN: We conducted a retrospective case review. SETTING: This study was conducted at a tertiary referral center. PATIENT: A 50-year-old woman presented with recurrent episodes of neurologic symptoms, bilateral sensorineural hearing loss, and silent retinal artery occlusion. INTERVENTIONS: The patient underwent complete evaluation, including magnetic resonance image studies, audiometric tests, and retinal fluorescein angiography. She was treated initially with corticosteroids and later with other immunosuppressive agents. RESULTS: The patient was initially diagnosed with left sudden sensorineural hearing loss. Despite comprehensive clinical and laboratory studies that did not reveal systemic disease, 3 weeks later, the patient developed vertigo, sensorineural hearing loss, and tinnitus in the opposite ear. The neurologic involvement and the bilateral audiologic manifestations raised the possibility of Susac syndrome. CONCLUSION: Susac syndrome is a rare disorder of unknown origin characterized by the triad of encephalopathy, fluctuating hearing loss, and visual loss resulting from microangiopathy of the brain, cochlea, and retina. The multiple organ involvement seen in Susac syndrome raises a differential diagnosis ranging from autoimmune disease, through systemic vasculitis, to multiple sclerosis. Otolaryngologists should be aware of this syndrome as a result of the vestibulocochlear manifestations and the multidisciplinary evaluation that is required.     

A benign congenital myopathy in an inbred Samaritan family.

We describe a novel form of myopathy in a mother and her two daughters from an inbred Samaritan family. The patients displayed severe neonatal hypotonia, lethargy and dysmorphic features. Motor milestones were delayed; however, the hypotonia and muscle weakness gradually improved during the first 2 years of life and independent walking was achieved by 18 months. The mother at the age of 23 years shows myopathic facies and minimal proximal weakness. Her intelligence is normal. Her muscle biopsy revealed central nuclei and disruption of the intermyofibrillary network with moth eaten and spiral fibers. Mutations in SMN, MTM1 and the myotonic dystrophy genes were excluded. We suggest this is a new benign form of congenital myopathy. Inheritance is probably autosomal recessive.     

The HOPA Gene Dodecamer Duplication Is Not a Significant Etiological Factor in Autism

A recent study has suggested that a dodecamer duplication in the HOPA gene in Xq13 may occur in a significant portion of male patients with autism. We have determined the incidence of this duplication in 202 patients from the South Carolina Autism Study. The incidence of the duplication was not significantly different between patients and controls. Three of the female patients inherited the duplication from nonautistic fathers. In addition, there was no systematic skewing of X inactivation in the female patients with the duplication, or in nonautistic mothers and sisters with the duplication. These findings suggest that the dodecamer duplication in the HOPA gene does not play a significant role in the etiology of autism.