Management of external penetrating injuries into the hypopharyngeal-cervical esophageal funnel

OBJECTIVE: To compare outcomes related to observation versus exploration for the hypopharynx and the cervical esophagus as the site of proven external penetrating injuries. METHODS: The records of 70 patients (47 with hypopharyngeal and 23 with cervical esophageal wounds) were retrospectively reviewed. RESULTS: No patient, observed or explored, who sustained a penetration into the hypopharynx above the level of the tips of the arytenoid cartilages of the larynx developed a complication. However, 22% of the patients with a hypopharyngeal injury below this level and 39% of patients with a cervical esophageal injury developed either a deep neck infection that required drainage or a postsurgical salivary fistula. CONCLUSIONS: Overall, the consequences of an external penetrating injury become more serious in the descending levels of the funnel formed by the hypopharynx and cervical esophagus. Injuries located in the upper portion of the hypopharynx can be routinely managed without surgical intervention. Neck exploration and adequate drainage of the deep neck spaces are, however, mandatory for all penetrating injuries into the cervical esophagus and most injuries into the lower portion of the hypopharynx.     

Contribution of serum protein association to discrepancy between the in vivo and in vitro UDS results for 6,7-dimethyl-2,4-di-1-pyrrolidinyl-7H-pyrrolo[2,3-d]pyrimidine (U-89843)

U-89843 has been shown to undergo biotransformation, both in vitro and in vivo, to form U-97924 as a major primary metabolite. U-89843 was found to be positive in an in vitro UDS mutagenesis screen conducted with primary rat hepatocytes in serum-free media. In contrast to in vitro results, no evidence of genetic toxicity of U-89843 was observed in rats in the in vivo/in vitro version of the UDS test with single oral doses up to 1400 mg/kg. The negative results may be related to more robust in vivo detoxification mechanisms or relatively lower exposure to reactive metabolites formed by bioactivation of U-89843 as compared to that observed in the serum-free in vitro hepatocyte test system. Further studies showed rat serum suppressed the in vitro metabolism of U-89843 as well as the formation of the corresponding hydroxylated metabolite, U-97924, the putative precursor of proposed reactive electrophilic metabolite. The measured in vivo systemic clearance of U-89843 (0.53 l/h/kg) in rats was about 1000-fold slower than the in vitro intrinsic clearance (606 l/h/kg) estimated by measuring the formation of U-97924 in rat liver microsomal incubations. Since U-89843 is extensively associated with serum proteins a poor extraction ratio into the liver may account for the slower biotransformation of U-89843 in vivo as compared to that exhibited in in vitro serum-free hepatocyte incubations. Addition of bovine serum albumin (1-40 mg/ml) to the in vitro UDS assay medium decreased the UDS mean net grains per nucleus response of U-89843. These results suggest that the effect of serum protein should be considered when comparing serum-free in vitro UDS and in vivo UDS results for highly serum protein bound compounds.     

Gastrulation initiation in Caenorhabditis elegans requires the function of gad-1, which encodes a protein with WD repeats

Although the role of dopamine dysfunction is well established in Parkinson's disease, the effect of nigrostriatal degeneration on motor performance during normal aging is less well understood. In this study, aged rhesus monkeys (25-27 years old) displayed significant impairments relative to young (3-5 years old) cohorts in motor function as assessed on a fine motor task and home cage activity. Additionally, the clinical motor function of aged monkeys was impaired relative to young monkeys as assessed on a clinical rating scale. Unbiased stereologic measurements of the substantia nigra revealed a significant age-related loss of tyrosine hydroxylase-immunoreactive (TH-ir; 50.3%) and dopamine transporter-immunoreactive (DAT-ir; 33.2%) nigral neurons. The monkeys performance on the fine motor task and on the clinical rating scale was correlated with TH-ir neuronal counts. The number of DAT-ir nigral neurons was correlated with activity and clinical rating scale scores. Our results suggest that age-related motor impairments in nonhuman primates are associated with spontaneous decreases in TH-ir and DAT-ir nigral cells. The correlation of motor deficits with the loss of TH-ir and DAT-ir nigral neurons suggests that aged nonhuman primates may provide a useful model for mimicking changes seen in human aging and early Parkinson's disease.     

The transverse nasal line: an embryonic fault line

The transverse nasal line has long been neglected and frequently overlooked. This narrow pink or hyperpigmented line or groove extends transversely between the upper two-thirds and the lower third of the nose. It is often hereditary and may be the locus of comedones and milia. Eighteen examples are reported by us, along with a possible embryological interpretation.