Functional genetic variants in the vesicular monoamine transporter 1 modulate emotion processing.

Emotional behavior is in part heritable and often disrupted in psychopathology. Identification of specific genetic variants that drive this heritability may provide important new insight into molecular and neurobiological mechanisms involved in emotionality. Our results demonstrate that the presynaptic vesicular monoamine transporter 1 (VMAT1) Thr136Ile (rs1390938) polymorphism is functional in vitro, with the Ile allele leading to increased monoamine transport into presynaptic vesicles. Moreover, we show that the Thr136Ile variant predicts differential responses in emotional brain circuits consistent with its effects in vitro. Lastly, deep sequencing of bipolar disorder (BPD) patients and controls identified several rare novel VMAT1 variants. The variant Phe84Ser was only present in individuals with BPD and leads to marked increase monoamine transport in vitro. Taken together, our data show that VMAT1 polymorphisms influence monoamine signaling, the functional response of emotional brain circuits and risk for psychopathology.

VMAT1 deletion causes neuronal loss in the hippocampus and neurocognitive deficits in spatial discrimination.

Vesicular monoamine transporters (VMAT) are involved in presynaptic storage and release of neurotransmitters. While it was thought initially that only VMAT2 is brain expressed and VMAT1 is present only in the periphery, recent data have challenged the exclusive expression of VMAT2 in the brain. To further elucidate the role of VMAT1 brain expression and its potential role in neuropsychiatric disorders, we have investigated mice lacking VMAT1. Comparison of wildtype and knock-out (KO) mice using qPCR and immunohistochemistry documents the expression of VMAT1 in the brain. Deletion of VMAT1 leads to increased hippocampal apoptosis and reduced neurogenesis as assessed by caspase-3-labeling and 5-bromo-deoxy-uridine-labeling. Behavioral data show that mice lacking VMAT1 have neurocognitive deficits. VMAT2 expression is not altered in VMAT1 KO mice, suggesting a distinct role of VMAT1. Our data support VMAT1 brain expression and suggest that VMAT1 plays a key role in survival of hippocampal neurons and thus might contribute to neurocognitive deficits observed in neuropsychiatric disorders.

Hearing loss with cochlear modiolar defects and large vestibular aqueducts.

OBJECTIVE: Defects of the cochlear modiolus have been found to be associated with most cases of large vestibular aqueduct. The clinical significance of these modiolar defects has not been studied previously. The purpose of this article is to correlate clinical (functional) parameters, such as hearing outcomes, with the severity of the radiographic findings in these dysplastic inner ears. STUDY DESIGN: The study design was a retrospective chart review, supplemented with telephone interviews and clinic visits. SETTING: The study was conducted at an academic, tertiary care center. PATIENTS: Thirty consecutive patients with large vestibular aqueducts participated. RESULTS: Scores of modiolar deficiencies yielded inconsistent correlations with hearing loss. Vestibular aqueduct morphology and thickness correlated very strongly with the severity of hearing loss. CONCLUSIONS: These observations support the hypothesis that large vestibular aqueduct-related hearing loss may be caused by transmission of subarachnoid pressure forces into the inner ear. However, the thickness and morphology of the vestibular aqueduct may simply be markers for more subtle cochlear dysplasia manifest by modiolar deficiency.

Intramuscular atropine sulfate in children: comparison of injection sites.

In children undergoing inhaled induction of anesthesia with halothane who suffer bradycardia, submental glossal injection of atropine may result in more rapid onset of vagolysis than traditional intramuscular sites. We compared the intervals between injection and onset of heart rate acceleration (tHR increases) after intramuscular injection of atropine into the deltoid, vastus lateralis, and glossa in children between 1 mo and 10 yr of age scheduled for elective surgery. The tHR increases was determined by measuring the interval between atropine injection and the time point at which the slope of the heart rate curve initially became positive. To ensure that the drug had taken effect before surgical stimulation, heart rate observation was continued until it increased at least 5% above baseline with evidence of continuing acceleration. Anesthesia was induced in all subjects by mask with nitrous oxide and halothane. After tracheal intubation, constant inspired concentrations of the anesthetics were administered for 3 min. While heart rate was monitored, atropine (0.02 mg/kg) was injected into one of the three sites. Each patient's end-tidal anesthetic concentrations were recorded, and minimum alveolar anesthetic concentrations (MAC) were subsequently calculated and adjusted for age. The tHR increases was recorded and averaged for each group. The study groups did not differ by age, weight, end-tidal anesthetic concentrations, age-adjusted MAC, or heart rate at the time atropine was administered. After submental glossal injection (n = 11), tHR increases increase was fastest (3.0 +/- 1.1 min) and was significantly faster than that found with deltoid injection (n = 16; 4.4 +/- 1.1 min) or vastus lateralis injection (n = 8; 6.4 +/- 2.4 min) (P < 0.05 compared with both). The tHR increases also differed significantly between the deltoid and the vastus lateralis (P < 0.05). We conclude that submental glossal injection of atropine results in a more rapid onset of vagolysis than injection at traditional intramuscular sites.

Vascular leiomyoma of the superior turbinate: first reported case.

BACKGROUND: Vascular leiomyoma is an uncommon smooth muscle tumor rarely found in the head and neck area. We report the first case arising for the superior turbinate of the nasal cavity. METHODS: A case presentation, treatment, and review of the literature are discussed. RESULTS: Twenty-one months after embolization and surgical resection, the patient is doing well, without evidence or recurrence. CONCLUSIONS: Vascular leiomyoma is a rare benign tumor of the nasal cavity, and surgical excision yields high cure rates.

Transforming growth factor beta 1 improves wound healing and random flap survival in normal and irradiated rats.

OBJECTIVES: To evaluate the effect of chronic irradiation on wound healing and random flap survival (FV), and the effect of transforming growth factor beta 1 (TGF-beta 1) in this setting using an animal model. DESIGN: A randomized, controlled study with four groups of rats to study the effect of irradiation 4 months before surgical intervention. The effect of TGF-beta 1 on FV and wound healing also was evaluated in the irradiated and nonirradiated groups. SUBJECTS: Ninety-five rats were available for evaluation. Group 1 (n = 10) was the control; group 2 (n = 28) received TGF-beta 1; group 3 (n = 28) received radiation therapy; and group 4 (n = 29) received radiation therapy and TGF-beta 1. INTERVENTION: The irradiated groups received 15 Gy to their dorsal skin. Four months later all received McFarlane skin flaps. Groups 2 and 4 received topical TGF-beta 1, 4 micrograms, to the bed of the flap; groups 1 and 3 received saline. On postoperative day 7 all rats were evaluated for tensile strength and FV, and histologic staining with hematoxylin-eosin for collagen and TGF-beta 1 was done. The slides were evaluated in a "blinded" fashion. RESULTS: Irradiation decreased tensile strength and FV, but not to a notable degree. Transforming growth factor beta 1 improved tensile strength in the irradiated (P = .04, Student's t test) and nonirradiated groups (P = .05, Student's t test). Transforming growth factor beta 1 also improved FV in all groups, but significantly in the irradiation plus TGF-beta 1 group (P = .001, Student's t test). The TGF-beta 1 group had the most mature collagen present at the wound edge. No qualitative difference was seen in the immunohistochemical staining for the four groups. CONCLUSIONS: Transforming growth factor beta 1 improves wound healing and random FV in radiated and nonirradiated rat skin. Further study is needed to determine the radiation dose necessary to create an "impaired wound-healing model" in rats, and the optimum dose of TGF-beta 1 in this setting.

CT of the temporal bone: findings after mastoidectomy, ossicular reconstruction, and cochlear implantation.

Because of its superior visualization of bone detail, compared with that of MR imaging, CT commonly is used in patients who have had otomastoid or other forms of temporal bone surgery. The already complex anatomy of the temporal bone is distorted by the combination of surgical procedures and preexisting abnormalities, making proper identification of the postoperative imaging studies difficult. The purpose of this essay is to familiarize radiologists with the more common neurootologic surgical procedures and the expected postoperative findings in patients who have had this type of surgery. Special emphasis is placed on the indications for the procedure and the distinguishing features associated with each procedure.