Intratemporal facial nerve transfer with direct coaptation to the hypoglossal nerve.

OBJECTIVE: To evaluate functional recovery after facial-hypoglossal nerve transfer with direct coaptation of the intratemporal part of the facial nerve. STUDY DESIGN: Retrospective study. SETTING: University-based tertiary referral center. PATIENTS: Nine patients who underwent facial-hypoglossal transfer surgery between 2001 and 2006 to treat a unilateral complete facial nerve palsy. INTERVENTION: The facial nerve is mobilized in the temporal bone, transsected at the second genu, transferred and directly coaptated to a partially incised hypoglossal nerve. MAIN OUTCOME MEASURES: The House-Brackmann grading system was used to evaluate facial nerve reinnervation. Tongue atrophy and movements were documented. Quality of life related to facial function was assessed using the validated Facial Disability Index. RESULTS: A House-Brackmann Grade III (86%) was achieved in six patients, and Grade IV (14%) in one patient with an average follow-up of 22 months (range, 12-48 mo). Two patients had a follow-up of less than 12 months after surgery, and reinnervation was still in progress. In none of the patients who were operated on was tongue atrophy or impaired movement observed. Postoperative Facial Disability Index scores (mean, 71.8 +/- standard deviation [SD] 10.6) for physical functioning and social functioning (mean, 85.7 +/- SD 9.8) were increased for all patients when compared with preoperative scores (mean, 28.6 +/- SD 9.0; mean, 37.7 +/- SD 14.4, respectively). CONCLUSION: The facial-hypoglossal nerve transfer with direct coaptation of the intratemporal part of the facial nerve offers good functional results with low lingual morbidity and improved quality of life. The technique is straightforward, relatively simple, and should be considered as first option for reanimation of traumatic facial nerve lesions.     

The role of mast cells and histamine in leukocyte-endothelium interactions in four rat strains

 The objective of the present study was to determine the role of mast cells and histamine in leukocyte-endothelium interactions in mesenteric venules of four rat strains: Brown Norway, Lewis, Sprague-Dawley and Wistar. Intravital microscopy showed that the mast cell stabilizer cromoglycate (5 mg/kg i.v. just before exteriorization of the mesentery) did not affect the baseline level and velocity of leukocyte rolling in any of the four strains. This finding is in agreement with the observation that cromoglycate pretreatment only slightly influenced mast cell degranulation in all strains except the Brown Norway. After mast cell stabilization, only in Sprague-Dawley did topical administration of histamine (10^–4 M) result in a significant increase in the level of leukocyte rolling and a decrease in the rolling velocity compared with the time control. Histamine induced leukocyte adhesion only in the Brown Norway strain. In conclusion, the hypothesis presented in other studies, that degranulation of mast cells, and more specifically the release of histamine, is of major importance for the induction of leukocyte-endothelium interactions in rat mesenteric venules is not generally applicable; the present study shows a clear strain dependency. Received: 18 July 1997 / Received after revision: 17 November 1997 / Accepted: 13 March 1998     

Search for intracranial aneurysm susceptibility gene(s) using Finnish families

Background

Cerebrovascular disease is the third leading cause of death in the United States, and about one-fourth of cerebrovascular deaths are attributed to ruptured intracranial aneurysms (IA). Epidemiological evidence suggests that IAs cluster in families, and are therefore probably genetic. Identification of individuals at risk for developing IAs by genetic tests will allow concentration of diagnostic imaging on high-risk individuals. We used model-free linkage analysis based on allele sharing with a two-stage design for a genome-wide scan to identify chromosomal regions that may harbor IA loci.

Methods

We previously estimated sibling relative risk in the Finnish population at between 9 and 16, and proceeded with a genome-wide scan for loci predisposing to IA. In 85 Finnish families with two or more affected members, 48 affected sibling pairs (ASPs) were available for our genetic study. Power calculations indicated that 48 ASPs were adequate to identify chromosomal regions likely to harbor predisposing genes and that a liberal stage I lod score threshold of 0.8 provided a reasonable balance between detection of false positive regions and failure to detect real loci with moderate effect.

Results

Seven chromosomal regions exceeded the stage I lod score threshold of 0.8 and five exceeded 1.0. The most significant region, on chromosome 19q, had a maximum multipoint lod score (MLS) of 2.6.

Conclusions

Our study provides evidence for the locations of genes predisposing to IA. Further studies are necessary to elucidate the genes and their role in the pathophysiology of IA, and to design genetic tests.     

Psychiatric issues in the management of patients with HIV infection.

Approximately 1 million persons are now infected with human immunodeficiency virus (HIV) in the United States. Evidence exists that psychiatric disorders are common in patients with HIV and that these patients may not receive optimal care because their psychiatric disorders are a barrier to medical care, communication with clinicians, and adherence to medical recommendations. We describe herein a complex case seen at The Johns Hopkins Hospital with several psychiatric conditions that are common in our HIV clinic population. We describe the collaborative treatment of the patient by a multidisciplinary team including both medical and mental health practitioners. We briefly describe a coherent diagnostic and treatment approach to patients in HIV clinics and the supporting rationale from the literature. We discuss the need for comprehensive evaluation, a multidisciplinary treatment team, and therapeutic optimism.     

Computer-assisted medication review for asthmatic patients as a basis for intervention Constructing and validating an algorithmic computer instrument in pharmacy practice

OBJECTIVE: To construct and validate a computer instrument that identifies asthma patients receiving--theoretically--suboptimal drug therapy in community pharmacies, by the use of patient medication records. This selection enables the pharmacist to assist these patients in using medicines appropriately. METHODS: According to Dutch asthma guidelines which describe a stepwise approach and in order to define correct profiles for the use at each level of these guidelines, the optimum use of drugs in the different levels in asthma treatment was expressed in defined daily doses (DDDs) per pharmacological drug-group during a period of one year. An algorithmic computer instrument was developed to select patients with medication use deviant from these profiles. By using nine different selection profiles, the computer instrument stratified patients according to the medication records filed in the pharmacy computer. Patient medication records in four community pharmacies were investigated to validate the selection profiles as indicators for theoretically suboptimal drug use by asthma patients. The validation was performed by comparing the professional judgement of participating pharmacists with the selections made by the computer. MAIN OUTCOME MEASURE: Positive predictive value and negative predictive value of the selection made by algorithmic computer instrument. Rate of false-positive results. RESULTS: The computer instrument identified asthma patients using theoretically suboptimal drug therapy with approximately 95% predictive value compared with the professional judgement of the pharmacists. The rate of false-positive results was 5%. CONCLUSION: The results of the algorithmic computer instrument and the professional judgement of the pharmacists are in close agreement. The instrument will be utilised in further research in the IPMP study (Interventions on the principle of Pulmonary Medication Profiles) investigating the role of Dutch community pharmacists in counselling patients who are at risk of suboptimal drug use in the treatment of their asthma.     

Biology‐Driven Gene‐Gene Interaction Analysis of Age‐Related Cataract in the eMERGE Network

Bioinformatics approaches to examine gene‐gene models provide a means to discover interactions between multiple genes that underlie complex disease. Extensive computational demands and adjusting for multiple testing make uncovering genetic interactions a challenge. Here, we address these issues using our knowledge‐driven filtering method, Biofilter, to identify putative single nucleotide polymorphism (SNP) interaction models for cataract susceptibility, thereby reducing the number of models for analysis. Models were evaluated in 3,377 European Americans (1,185 controls, 2,192 cases) from the Marshfield Clinic, a study site of the Electronic Medical Records and Genomics (eMERGE) Network, using logistic regression. All statistically significant models from the Marshfield Clinic were then evaluated in an independent dataset of 4,311 individuals (742 controls, 3,569 cases), using independent samples from additional study sites in the eMERGE Network: Mayo Clinic, Group Health/University of Washington, Vanderbilt University Medical Center, and Geisinger Health System. Eighty‐three SNP‐SNP models replicated in the independent dataset at likelihood ratio test P < 0.05. Among the most significant replicating models was rs12597188 (intron of CDH1)–rs11564445 (intron of CTNNB1). These genes are known to be involved in processes that include: cell‐to‐cell adhesion signaling, cell‐cell junction organization, and cell‐cell communication. Further Biofilter analysis of all replicating models revealed a number of common functions among the genes harboring the 83 replicating SNP‐SNP models, which included signal transduction and PI3K‐Akt signaling pathway. These findings demonstrate the utility of Biofilter as a biology‐driven method, applicable for any genome‐wide association study dataset.