Estimating phonation threshold pressure

Phonation threshold pressure (PTP) is the minimum subglottal pressure required to initiate vocal fold oscillation. Although potentially useful clinically, PTP is difficult to estimate noninvasively because of limitations to vocal motor control near the threshold of soft phonation. Previous investigators observed, for example, that trained subjects were unable to produce flat, consistent oral pressure peaks during/pae/syllable strings when they attempted to phonate as softly as possible (Verdolini-Marston, Titze, & Druker, 1990). The present study aimed to determine if nasal airflow or vowel context affected phonation threshold pressure as estimated from oral pressure (Smitheran & Hixon, 1981) in 5 untrained female speakers with normal velopharyngeal and voice function. Nasal airflow during /p/occlusion was observed for 3 of 5 participants when they attempted to phonate near threshold pressure. When the nose was occluded, nasal airflow was reduced or eliminated during /p/;however, individuals then evidenced compensatory changes in glottal adduction and/or respiratory effort that may be expected to alter PTP estimates. Results demonstrate the importance of monitoring nasal flow (or the flow zero point in undivided masks) when obtaining PTP measurements noninvasively. Results also highlight the need to pursue improved methods for noninvasive estimation of PTP.     

Pegylated peptides. V. Carboxy-terminal PEGylated analogs of growth hormone-releasing factor (GRF) display enhanced duration of biological activity in vivo

In the present study, human growth hormone-releasing factor (hGRF) and analogs were successfully pegylated at the carboxy-terminus using a novel solid- and solution-phase strategy. Following synthesis, these pegylated hGRF analogs were evaluated for in vitro and in vivo biological activity. Specifically, hGRF (1-29)-NH2, [Ala15]-hGRF (1-29)-NH2, [desNH2Tyr1, D-Ala2, Ala15]-hGRF(1-29)-NH2 and [His1, Val2, Gln8, Ala15, Leu27]-hGRF(1-32)-OH were each C-terminally extended using a Gly-Gly-Cys-NH2 spacer (previously demonstrated not to alter intrinsic biological activity), and then monopegylated via coupling to an activated dithiopyridyl-PEG reagent. PEG moieties of 750, 2000, 5000 or 10,000 molecular weight (MW) were examined to determine the effect of polymer weight on activity. Initial biological evaluations in vitro revealed that all C-terminally pegylated hGRF analogs retained high growth hormone (GH)-releasing potencies, regardless of the MW of PEG polymer employed. Two of these pegylated hGRF analogs, [desNH2Tyr1, D-Ala2, Ala15]-hGRF (1-29)-Gly-Gly-Cys(NH2)-S-Nle-PEG5000 and [His1, Val2, Gln8, Ala15, Leu27]-hGRF(1-32)-Gly-Cys(NH2)-S-Nle-PEG5000, were subsequently evaluated in both pig and mouse models and found to be highly potent (in vivo potency range = 12-55-fold that of native hGRF). Relative to their non-pegylated counterparts, these two pegylated hGRF analogs exhibited enhanced duration of activity.     

Mantle cell lymphoma: a clinicopathologic study of 80 cases

Mantle cell lymphoma (MCL) is a relatively uncommon yet distinct type of malignant lymphoma whose clinical and pathological characterization has been limited by the small numbers of cases published to date. We studied 80 cases of MCL seen at a single institution over 7 years to determine both clinical and pathological prognostic factors. The patients in this study were predominantly male (70%) and older (mean age, 63 years) and presented with advanced-stage disease (88%). Extranodal involvement was common. Median overall survival (OS) was 43 months. Except for performance status, prognosis was not significantly influenced by clinical prognostic factors. Histologically, MCL architecture was classified as diffuse (78%), nodular (16%), or mantle zone (6%); the OS among these groups was identical. Increased mitotic activity (>20 mitotic figures per 10 high power fields), blastic transformation, and peripheral blood involvement at diagnosis also predicted for a worse outcome, but bone marrow involvement did not. The presence or absence of a translocation t(11; 14) by cytogenetic analysis or a bcl-1 rearrangement by Southern analysis did not significantly predict outcome. In summary, this study of 80 cases of MCL highlights its distinctive clinicopathologic features and shows that increased mitotic activity, blastic morphology, and peripheral blood involvement at diagnosis are prognostically important factors.     

Renal gunshot wounds: methods of salvage and reconstruction

Over the past 14 years, 2079 patients have been seen at our institution with renal trauma. Of these, 84 sustained gunshot wounds (81 unilateral, 3 bilateral; a total of 87 renal units). We evaluated this group to characterize the nature of their injuries and establish a methodology for renal salvage and reconstruction. Preoperative radiographic staging was performed with excretory urography (IVP) or computed tomographic (CT) scanning. The injuries were classified into five categories: 16 contusions (18.4%), 12 minor lacerations (13.8%), 44 major lacerations (50.5%), six vascular injuries (6.9%), and nine combination laceration and vascular injury (10.3%). Most patients had multiple organ injuries, with 79 requiring associated surgical procedures (94%). The mean injury Severity Score (ISS) was 26.7 (range, 4-59). Based on radiographic and clinical staging criteria, 69 renal injuries were surgically explored (79.3%), and 12 patients underwent nephrectomy (13.8%). Forty-six renal units were reconstructed (66.6%) by various methods, including renorrhaphy, omental pedical flaps, mesh or peritoneal patch grafts, partial nephrectomy, and vascular repair. Overall, 75 renal units were salvaged (86.2%). Early renal vascular control was achieved in all patients who underwent renal exploration. Follow-up functional studies were done in 24 (28.5%): none had delayed nephrectomy or postinjury hypertension. Overall, 79 patients survived (94%); however, mortality was not related to renal injury. These findings suggest that aggressive radiographic staging coupled with early vascular control and careful selection of reconstructive techniques can ensure a high renal salvage rate in patients with renal gunshot injuries.     

Effect of race on outcome after kidney and kidney-pancreas transplantation in type 1 diabetic patients

OBJECTIVE: The racial impact on graft outcome is not well defined in diabetic recipients. The purpose of this study is to analyze our experience with kidney-alone (A) and kidney-pancreas (KP) transplantation in type 1 diabetic recipients and evaluate the impact of racial disparity on outcome. RESEARCH DESIGN AND METHODS: The records of 217 kidney transplants (118 KA, 99 KP) performed on type 1 diabetic patients between 1985 and 1995 at the Medical University of South Carolina and the University of Texas Medical Branch were reviewed. RESULTS: A total of 53 (31%) white patients and 15 (33%) black patients experienced at least one episode of biopsy-proven acute rejection of the renal graft (NS). Patient survival at 1, 2, and 5 years was similar in white (92, 87, 69%) and black (91, 91, 69%) patients (NS). Kidney graft survival at 1, 2, and 5 years in the KA group was 72, 62, and 42% in blacks, compared with 79, 76, and 53% in whites (NS). Kidney graft survival at 1, 2, and 5 years in the KP group was 92, 92, and 74% in blacks, compared with 83, 77, and 58% in whites (NS). Pancreas graft survival at 1, 2, and 5 years was 81, 81, and 81% in blacks, compared with 81, 75, and 62% in whites (NS). Cox regression analysis revealed that donor age > or = 40 years increased the risk of renal graft failure 6.2-fold (P = 0.0001), whereas the addition of a pancreas transplant to a kidney and a living-related transplant decreased the risk of failure of the kidney graft 0.2 (P = 0.005) and 0.1 times (P = 0.005). CONCLUSIONS: Our results suggest that when compared with whites, there may be a trend toward an improved kidney and pancreas graft outcome in blacks undergoing KP transplants. These findings suggest that diabetes may override the risk factors that account for the pronounced disparity in outcome observed between nondiabetic white and black recipients.     

Effect of n-3 fatty acids on VLDL production by hepatocytes is mediated through prostaglandins

The mechanism of the hypolipidemic effect of n-3 fatty acids was studied using isolated rat hepatocytes maintained in culture. EPA and DHA caused a significant reduction in the incorporation of 3[H]-leucine into apoB associated with the VLDL produced by hepatocytes in culture when compared to that in presence of palmitic acid. Presence of indomethacin, an inhibitor of cyclo-oxygenase reversed the effect of EPA on VLDL synthesis while diethyl carbamazine an inhibitor of lipoxygenase did not show any effect suggesting that the effect of EPA may be mediated through prostaglandins. This was further tested by invivo experiments where animals were fed fish oil containing diet with and without aspirin, which inhibits formation of prostaglandins. The incorporation of 3[H]-leucine into apo B and 14[C]-acetate into cholesterol of VLDL produced by hepatocytes from aspirin treated animals were significantly high. The reversal of the effect of n-3 fatty acids by agents which inhibit the formation of prostaglandin suggests that the n-3 fatty acids may exert their effect on VLDL production by liver cells through prostaglandins.