Correction of venlafaxine- and duloxetine-induced transaminase elevations with desvenlafaxine in a patient with Gilbert's syndrome.

Recent reviews have questioned whether the serotonin-norepinephrine reuptake inhibitor (SNRI) desvenlafaxine succinate offers any practical clinical advantages over existing SNRIs. The following case is one instance where it appears that this SNRI offers unique safety and benefit. Presented is a case report of a patient with Gilbert's syndrome, longstanding social phobia, and more recent depressive disorder not otherwise specified, who was found to have elevated liver transaminases when prescribed both duloxetine and venlafaxine. The patient subsequently responded to desvenlafaxine but without liver abnormalities. In this patient with Gilbert's Syndrome, desvenlafaxine's lack of metabolism through the cytochrome P450 (CYP) 2D6 pathway may explain the avoidance of these abnormalities and thus suggests a possible therapeutic role for this SNRI in similarly susceptible patients.

Isolation of human oral keratinocyte progenitor/stem cells.

Progenitor/stem cell populations of epithelium are known to reside in the small-sized cell population. Our objective was to physically isolate and characterize an oral keratinocyte-enriched population of small-sized progenitor/stem cells. Primary human oral mucosal keratinocytes cultured in a chemically defined serum-free culture system, devoid of animal-derived feeder cells, were sorted by relative cell size and characterized by immunolabeling for beta1 integrin, nuclear transcription factor, peroxisome proliferator-activated receptor-gamma, and cell-cycle analysis. Sorted cells were distinguished as progenitor/stem cells by functional assays and their ability to regenerate an oral mucosal graft. Small-sized cells demonstrated the lowest expression of peroxisome proliferator-activated receptor-gamma, the highest colony-forming efficiency, a longer long-term proliferative potential, an enriched quiescent cell population, and the ability to regenerate an oral mucosal graft, implying that the small-sized cultured oral keratinocytes contained an enriched population of progenitor/stem cells.

Development of an oral mucosa equivalent using a porcine dermal matrix.

We evaluated the suitability of a porcine acellular dermal matrix for the development of a 3-dimensional oral mucosal equivalent using an ex vivo-produced oral mucosal equivalent (EVPOME). Oral keratinocytes were seeded in a submerged model, and then in an air-liquid interphase model, using Transwell® inserts. EVPOME showed good cell viability and increased glucose consumption over time. Histological evaluation showed that stratified differentiated epithelium had formed in all matrices.

Issues in the psychopharmacologic assessment and treatment of the orthodox Jewish patient.

As with members of other cultural and religious groups, patients within the Orthodox Jewish community present with their own distinct clinical psychiatric issues related to their unique beliefs and practices. This article reviews the existing literature and anecdotal experience on the psychopharmacologic assessment and treatment of Orthodox Jewish patients. Specific aspects examined include this group's perceived intense stigma in receiving treatment, the priority this community places on cognitive functioning, and how the influence of Jewish laws on marriage and sexual practices impacts one's treatment decisions. The relevance of Jewish dietary laws, the Sabbath, and the community's interest in alternative treatments are also discussed. The limited ethno-psychopharmacology research related to Orthodox Jewish psychiatric patients is reviewed. We conclude that understanding issues such as these is critical if one is going to work within this cultural system in order to successfully address their mental health issues. However, the dearth of controlled research in this community needs to be addressed to provide more effective treatment.

Biochemical indicators of implantation success of tissue-engineered oral mucosa.

Real-time (RT) determination of the health of in vitro tissue-engineered constructs prior to grafting is essential for prediction of success of the implanted tissue-engineered graft. In addition, the US Food and Drug Administration requires specific release criteria in RT prior to the release of tissue-engineered devices for human use. In principle, assessing the viability and functionality of the cellular component can be achieved by quantifying the secretion of growth factors and chemokines of tissue-engineered constructs. Ex vivo-produced oral mucosa equivalents (EVPOMEs) were fabricated under thermally stressed conditions at 43 °C for 24 h to create a functionally compromised EVPOME. We used microchannel enzyme-linked immunosorbent assay to evaluate the functionality of the cellular component, oral keratinocytes, of stressed and unstressed EVPOMEs by measuring the release of vascular endothelial growth factor (VEGF), interleukin-8 (IL-8), human ß-defensin 1 (hBD-1), and tissue inhibitor of metalloproteinase 1 and 2 (TIMP-1 and -2) into the spent medium, which was collected on the same day prior to graft implantation into severe combined immunodeficiency mice. Implanted EVPOMEs' histology on the seventh postimplantation day was used to correlate outcomes of grafting to secreted amounts of IL-8, hBD-1, VEGF, TIMP-1, and TIMP-2 from corresponding EVPOMEs. Our findings showed that significantly higher levels of IL-8, hBD-1, and TIMP-2 were secreted from controls than from thermally stressed EVPOMEs. We also found a direct correlation between secreted VEGF and IL-8 and blood vessel counts of implanted EVPOMEs. We concluded that measuring the constitutive release of these factors can be used as noninvasive predictors of healthy tissue-engineered EVPOMEs in RT, prior to their implantation.

Combining stimulants with monoamine oxidase inhibitors: a review of uses and one possible additional indication.

BACKGROUND: Among antidepressant augmentation strategies, the addition of a stimulant to a monoamine oxidase inhibitor (MAOI) has received little attention in the literature in recent years because of the diminished clinical use of the latter and concerns of precipitating a hypertensive crisis or other serious complication. Despite that fact, experienced clinicians continue to use this combination for a variety of indications after other options have failed. This article reviews these reported uses and presents a case suggesting another possible indication. METHOD: A MEDLINE search was conducted for articles published from 1962 to December 2003 using relevant search terms (psychostimulant, stimulant, amphetamine, dextroamphetamine, pemoline or methylphenidate, atomoxetine, bupropion, monoamine oxidase inhibitor, and selegiline). A manual search was conducted of cross-references and other relevant recent psychiatric sources (2000-2003). RESULTS: The described uses of the MAOI-stimulant combination have included treatment of refractory depression and the MAOI-related side effects of orthostatic hypotension and daytime sedation. No documented reports were found in the recent literature of hypertensive crises or fatalities occurring when the stimulant was cautiously added to the MAOI. Also presented here is another possible indication for this therapeutic regimen: treatment of attention-deficit/hyperactivity disorder in an adult patient whose major depression had uniquely responded to the MAOI tranylcypromine. CONCLUSION: As in other fields of medicine, potentially hazardous medication combinations are utilized in psychiatry after cautiously weighing the danger of the treatment against the morbidity and risk of not adequately addressing the illness. Particularly, as the potential arrival of the apparently safer transdermal selegiline may increase the use of MAOIs, we feel this combination deserves additional controlled study.

The role of pimozide in clinical psychiatry: a review.

Pimozide, a diphenylbutylpiperidine neuroleptic which is FDA-approved as a backup treatment for Gilles de la Tourette's syndrome, has been used abroad for many years as a treatment of schizophrenia and has been recently reported to be particularly effective in treating monosymptomatic hypochondriacal psychosis and delusional jealousy. Pimozide may also have a role in the treatment of negative schizophrenic symptoms, pain syndromes, and obsessive compulsive disorder. After reviewing the relevant clinical literature supporting these indications, the authors review preclinical studies that provide points of departure regarding biochemical mechanisms underlying this unique therapeutic profile.

Pimozide treatment of the negative schizophrenic syndrome: an open trial.

Reports over the last 20 years suggest that pimozide, a neuroleptic of the diphenylbutylpiperidine (DPBP) group, might be helpful in the treatment of negative symptoms of schizophrenia, which are considered less responsive to standard neuroleptics than are positive symptoms. Research suggests that neuroleptic drugs of the DPBP group possess a unique property--potent calcium channel antagonism--which could explain their ability to relieve negative symptoms. Earlier reports, however, used measures not specifically designed to assess the negative syndrome. The Positive and Negative Syndrome Scale (PANSS) was developed and standardized to measure the negative syndrome in schizophrenia. The authors used the PANSS to study the effects of pimozide in a 6-week, open clinical trial with 10 neuroleptic-resistant schizophrenic inpatients who had prominent deficit features. Negative but not positive symptoms improved significantly, suggesting that the drug might target the negative profile. The authors discuss possible pharmacologic mechanisms for pimozide's potentially distinct clinical properties.

Ultrasonography of the rotator cuff. Normal and pathologic anatomy.

Forty-eight patients with shoulder pain and 15 normal volunteers underwent rotator cuff imaging using high resolution real time ultrasound. The potential diagnostic value of sonography in detecting rotator cuff tears was evaluated by correlating ultrasound findings with surgical findings in 19 patients, 12 of whom also underwent preoperative arthrography. The preoperative ultrasound diagnosis was correct in 18 of the 19 patients undergoing surgery for possible rotator cuff tears. In the group of 12 surgical patients undergoing both preoperative arthrography and sonography, ultrasound correctly predicted the presence of a rotator cuff tear in 12 of 12 patients, while arthrography predicted cuff tears in only nine of 12. Good anatomic definition of the rotator cuff was obtained in both symptomatic and asymptomatic groups. The characteristic appearance of the normal and pathologic rotator cuff is described. Rotator cuff sonography promises to be a valuable new diagnostic tool for evaluating patients with suspected rotator cuff tears.

CT of pancreas transplantation.

Thirty-eight abdominal CT examinations obtained on 20 patients after pancreas transplantation were reviewed to determine the CT findings associated with pancreas transplantation and to assess the clinical utility of CT in this setting. Visualization of the transplanted pancreas was variable and was strongly influenced by adequacy of gastrointestinal opacification with contrast material. In four cases, linear high-density material was present within the graft, which, depending upon the surgical technique for handling exocrine secretions, represented either pancreaticojejunal stents or silicone within the pancreatic duct. Abdominal fluid collections were identified in 19 patients and were the most common complication identified by CT. Four of these collections were drained percutaneously. The major value of CT in pancreas transplantation is the identification and management of abdominal fluid collections in patients with abdominal pain and fever.

Manufacturing and characterization of 3-d hydroxyapatite bone tissue engineering scaffolds.

Internal architecture has a direct impact on the mechanical and biological behaviors of porous hydroxyapatite (HA) implants. However, traditional processing methods provide very minimal control in this regard. This paper reviews a novel processing technique developed in our laboratory for fabricating scaffolds with controlled internal architectures. The preliminary mechanical property and in vivo evaluation of these scaffolds are also presented.

Intrauterine aspiration of a large fetal ovarian cyst.

Most large series of neonatal ovarian cysts are limited to those diagnosed in the newborn period. Eight cases of fetal ovarian cysts diagnosed prenatally by ultrasound have been reported, only one of which was aspirated in utero. Reported is the youngest fetus to undergo in utero aspiration of an ovarian cyst to reduce the risk of secondary pulmonary hypoplasia.

Microfibrillar collagen hemostatic pledgets.

The use of topical microfibrillar collagen hemostatic agents is increasing in many areas of clinical surgery. We have developed a method of preparing the hemostatic agent by which a pledget is formed in a syringe. This gives it a firm consistency and allows easier handling and application and can be done at the operating room table.

Lymphangiography and ultrasound in management of lymphoceles.

Recent reports describe the efficacy of ultrasound in the diagnosis and management of lymphoceles. To assess the appropriate role of ultrasound and lymphangiography in the management of this entity, we reviewed our experience with 14 cases diagnosed as lymphoceles. Three patients had lymphangiography alone, 5 had lymphangiography and ultrasound, and 6 had ultrasound alone. Our analysis concludes that both diagnostic modalities have a role in management depending on the size of the lymphocele and the associated clinical setting.

Development and characterization of a tissue-engineered human oral mucosa equivalent produced in a serum-free culture system.

A problem maxillofacial surgeons face is a lack of sufficient autogenous oral mucosa for reconstruction of the oral cavity. Split-thickness or oral mucosa grafts require more than one surgical procedure and can result in donor site morbidity. Skin has disadvantages of adnexal structures and a different keratinization pattern than oral mucosa. In this study, we successfully assembled, ex vivo, a human oral mucosa equivalent, consisting of epidermal and dermal components, in a defined, essential-fatty-acid-deficient, serum-free culture medium without a feeder layer, that could be used for intra-oral grafting in humans. Autogenous oral keratinocytes were seeded onto a cadaveric dermis, AlloDerm. The oral mucosa equivalent was cultured at an air-liquid interface for 2 wks. The resulting equivalent had a well-stratified parakeratinized epithelial layer similar to native oral keratinized mucosa. Expression of differentiation markers, filaggrin and cytokeratin 10/13, suggested a premature keratinized state. The presence of proliferation markers, proliferating cell nuclear antigen (PCNA) and Ki-67, suggested a state of hyperproliferation. Fatty acid composition of the equivalent was similar to that of in vitro cultured oral keratinocytes but differed from the that of in vivo native tissue, showing a lower content of 18:2 and 20:4, and a higher content of 16:1 and 18:1 fatty acids, respectively. The keratinocytes of the equivalent appeared to be in a more active and proliferative state than native keratinized mucosa. The dynamic nature of the cell population on the oral mucosa equivalent may be beneficial for intra-oral grafting procedures and for transfection of the keratinocytes.

CT-generated porous hydroxyapatite orbital floor prosthesis as a prototype bioimplant.

Hydroxyapatite bioceramic was used for the manufacture of an orbital floor prosthesis from spiral CT data acquired transaxially at 1-mm beam collimation, pitch of 1, and 0.2-mm reconstruction intervals. CT data were converted to vector file format for subsequent prosthesis manufacture on a stereo-lithography machine. The orbital floor prosthesis was engrafted onto an acrylic model of the orbit as a qualitative indication of its overall accuracy. High anatomic accuracy was achieved, as determined by visual inspection. Cross-hatching of the vector file data allowed a porous internal architecture of the prosthesis. Refinements in chemical structure of the hydroxyapatite bioceramic are expected to enhance mechanical properties.

Ultrasound and computed tomographic evaluation of renal transplantation.

Ultrasound and computed tomography are very useful in the diagnosis of parenchymal and urologic abnormalities after renal transplantation. The increased use of Doppler duplex sonography will further enhance the role of ultrasound in the evaluation of patients with kidney transplants. Computed tomography is of particular value in the setting of suspected posttransplant malignancy. Both imaging techniques can be used to guide diagnostic and therapeutic interventional radiologic procedures.

Ultrasound and computed tomography in the evaluation of pancreatic transplantation.

Both ultrasound and computed tomography are useful imaging modalities in the evaluation of pancreatic transplants and their complications. Ultrasound and computed tomography are most valuable in the detection of peripancreatic fluid collections, although some parenchymal abnormalities can occasionally be detected. Directed diagnostic aspiration is useful in determining the etiology of peripancreatic and other peritoneal fluid collections. The role of percutaneous catheter drainage in the management of these complex patients is not yet clearly defined.