Treatment of nasopharyngeal stenosis by prosthetic hollow stents: Clinical experience in eight patients.

OBJECTIVE: A series of nasopharyngeal appliance designs is presented that represents our evolving experience over a 20-year period in the adjunctive use of prosthetic stents in the surgical correction of nasopharyngeal stenosis. DESIGN: Retrospective assessment of effectiveness of two nasopharyngeal stenosis hollow stent designs in a consecutive series of patients for relief of nasal obstructive symptoms. SETTING: Tertiary academic medical center, Craniofacial Program at Children's Hospital. PATIENTS: Four patients with nasopharyngeal stenosis were treated with a preoperatively fabricated stent made from a clasped palatal appliance onto which hollow acrylic conduits were extended through surgically re-created pharyngeal ports. A subsequent set of four patients with nasopharyngeal stenosis were treated with intraoperatively-fashioned silastic grommets, as opposed to palatal appliances. INTERVENTIONS: Postoperative intraoral stenting of nasopharyngeal ports. MAIN OUTCOME MEASURES: Maintenance of pharyngeal port opening after 1 year, improvement in nasal airway obstructive symptoms. RESULTS: The palatal appliance stents were less well tolerated and had a lower maintenance of port patency after device removal (4 of 8, 50%). The silastic grommets provided better retention into the ports and increased patient tolerance, as well as better 1-year port maintenance (6 of 8, 75%). CONCLUSIONS: The grommet stent appliance offers numerous advantages over a conventional dental-clasped appliance for prosthetic nasopharyngeal stenting, including obviation of extensive preoperative preparation, ease of insertion and removal, and exchange of air during the stenting period. Improved nasopharyngeal patency with this device may be due to greater patient tolerance and subsequent longer use.     

Is there a diurnal pattern in the clinical symptoms of HELLP syndrome?

OBJECTIVE: To determine if there is a diurnal pattern in the clinical symptoms of HELLP (Hemolysis, Elevated Liver enzymes, Low Platelets) syndrome. STUDY DESIGN: A retrospective study was performed in 134 pregnancies complicated by HELLP syndrome. The medical records were reviewed to describe each HELLP episode. Time of day was divided into three periods, day, evening, and night. The following parameters were categorized according to the time of day: onset of symptoms, consultation by the doctor, initial blood sampling, diagnosis and decrease of symptoms. Biochemical parameters at clinical presentation and consecutive changes within 24 h were recorded. RESULTS: In 65 pregnancies 77 HELLP episodes were well documented. Times of onset of symptoms and consultation by the doctor were significantly higher during the evening and night (p < 0.001), whereas times of diagnosis and decrease of symptoms occurred significantly more during the day (p < 0.001). In only 49.3% of the cases were diagnostic laboratory criteria met at clinical presentation. This was mainly due to platelet values in excess of 100 x 10(9)/l. Several hours later (median 8 h, range 2-23) the decrease in platelets occurred. CONCLUSIONS: A diurnal pattern exists in the clinical symptoms of HELLP syndrome that is characterized by an exacerbation during the night and recovery during the day. There is a considerable delay between the onset of symptoms and the fulfillment of diagnostic laboratory criteria.     

Hepatic gene downregulation following acute and subchronic exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin.

Chronic exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) has been shown to lead to the development of hepatotoxicity and carcinogenicity in the liver of female rats. In this study, we investigated hepatic gene downregulation in response to acute and subchronic TCDD exposure. We identified 61 probes which exhibited a downregulation of twofold or greater following subchronic (13 weeks) exposure to TCDD. Comparative analysis of the hepatic expression of these 61 probes was conducted with rats subchronically exposed to PeCDF, PCB126, PCB153, and a mixture of PCB126 and PCB153. PCB153 produced little or no alteration in these probes, while the binary mixture mimicked most closely the downregulation observed with TCDD. To discern if the repression of genes within this probe set occur as a primary response to TCDD exposure, we analyzed the early responsiveness of 11 genes at 6, 24, and 72 h following a single exposure to TCDD. We observed early repression of the 11 genes within this early time course, indicating that the repression of this subset of genes occurs as a primary response to TCDD exposure and not as a secondary response to 13 weeks of subchronic treatment. In addition, the gender, species, and AhR dependence of these responses were also investigated. Gender- and species-dependent repression was observed within this subset of genes. Furthermore, utilizing AhR knockout mice, we were able to determine the AhR-dependent downregulation of seven of 11 genes. Together these results assist efforts to understand the multitude of effects imposed by TCDD and AhR ligands on gene expression.     

Radioiodine therapy of Graves' hyperthyroidism in patients without pre-existing ophthalmopathy: can glucocorticoids prevent the development of new ophthalmopathy?

BACKGROUND: Radioiodine therapy (RIT) combined with glucocorticoids is an effective therapy for Graves' disease, but it is debatable whether glucocorticoids should be applied in patients without Graves' ophthalmopathy (GO). METHODS: The effect of 0.4 - 0.5 mg prednisone every second day over a period of 5 weeks after RIT was monitored over a follow-up period of at least 12 months after RIT. A questionnaire was sent to 186 consecutive patients without GO concerning eye symptoms after RIT. 148 patients (80 %) answered. If eye symptoms had occurred after RIT, additional clinical examination was carried out at our outpatient clinic. The primary endpoint was the absence or onset of GO within the first year after RIT. RESULTS: Within 12 months after RIT the examination confirmed GO in 5 out of 148 patients (3.4 %). In all cases the symptoms were transient. No adverse reaction to the use of prednisone after RIT was noted. CONCLUSIONS: The risk of new GO in the first year after RIT was low and the clinical course of GO was mild when RIT was combined with a low-dose glucocorticoid regimen. Preventive administration of glucocorticoids can therefore be recommended in patients with Graves' disease even without evident GO.     

Maximal inspiratory and expiratory pressure measurement in tracheotomised patients.

The present study compared four different sites and conditions for the measurement of maximal inspiratory pressure (MIP) and maximal expiratory pressure (MEP) in 38 spontaneous breathing tracheotomised patients. Of the patients, 28 had chronic obstructive pulmonary disease (COPD). The four different conditions were: 1) through a cuff inflated cannula (condition A); 2) through the mouth with a deflated cannula (condition B); 3) through the mouth with a phonetic uncuffed cannula (condition C); and 4) through the mouth after stoma closure (condition D). Five trials in each condition were performed using a standardised method. The measurement of both MIP and MEP differed significantly depending on the condition of measurement. MIP taken in condition A was significantly higher when compared with conditions B, C and D. MEP in condition A was significantly higher when compared with condition B and D. In condition A the highest frequency of the best measurement of MIP and MEP was observed at the fourth and fifth effort, respectively. The same results were obtained after the selection of only COPD patients. In conclusion, respiratory muscle assessment differs significantly depending on measurement condition. Measurement through inflated cannula tracheotomy yields higher values of both maximal inspiratory and maximal expiratory pressure.     

Rescue of the Cold Preserved Rat Liver by Hypothermic Oxygenated Machine Perfusion

The aim of the study was to investigate whether hypothermic oxygenated liver perfusion after cold liver preservation resuscitated metabolic parameters and whether this treatment had a benefit for liver viability upon reperfusion.
We preserved rat livers either by cold storage (UW) for 10 h, or by perfusion for 3 h (oxygenated modified UW) after 10 h cold storage. We assessed viability of livers after preservation and after ischemic rewarming + normothermic reperfusion ex vivo . Ten hour cold storage reduced mitochondrial cytochrome oxidase and metabolically depleted the livers. Oxygenated perfusion after cold storage resulted in uploaded cellular energy charge and oxidized mitochondrial cytochrome oxidase. Reperfusion after 10 h cold storage increased formation of superoxid anions, release of cytosolic LDH, lipid peroxidation, caspase activities and led to disruption of sinusoidal endothelial cells. In contrast, reperfusion after 10 h cold storage + 3 h hypothermic oxygenated perfusion resulted in no changes of lipid peroxidation, bile flow, energy charge, total glutathione, LDH release and of caspase activation, as compared to fresh resected livers.
This study demonstrates, that a metabolically depleted liver due to cold storage can be energy recharged by short-termed cold machine perfusion. The machine perfused graft exhibited improved viability and functional integrity.     

Costimulation and Autoimmune Diabetes in BB Rats

Costimulatory signals regulate T-cell activation. To investigate the role of costimulation in autoimmunity and transplantation, we studied the BB rat model of type 1 diabetes. Diabetes-prone BB (BBDP) rats spontaneously develop disease when 55–120 days of age. We observed that two anti-CD28 monoclonal antibodies (mAb) with different functional activities completely prevented diabetes in BBDP rats. Anti-CD154 mAb delayed diabetes, whereas treatment with CTLA4-Ig or anti-CD80 mAb accelerated disease. Anti-CD86 or anti-CD134L mAbs had no effect. Diabetes resistant BB (BBDR) rats are disease-free, but >95% of them develop diabetes after treatment with polyinosinic-polycytidylic acid and an mAb that depletes Treg cells. In the induced BBDR model, anti-CD154 mAb delayed onset of diabetes, whereas CTLA4-Ig, anti-CD134L or either of the anti-CD28 mAbs had little or no effect. In contrast, blockade of the CD134-CD134L pathway was highly effective for preventing autoimmune recurrence against syngeneic islet grafts in diabetic BBDR hosts. Blockade of the CD40-CD154 pathway was also effective, but less so. These data suggest that the effectiveness of costimulation blockade in the treatment of type 1 diabetes is dependent on both the costimulatory pathway targeted and the mechanism of induction, stage, intensity and duration of the pathogenic process.     

Denervation pattern of three mimic muscles in Bell's palsy.

OBJECTIVE: To explore the presence and grade of denervation in three mimic muscles in facial nerve palsy. METHODS: The frontalis, orbicularis oculi (OO), and mentalis muscles were explored in 54 patients with Bell's palsy, after 30 days from the beginning of symptoms. Concentric needle electromyography, including fibrillation detection, was performed in the three muscles on the affected side. Compound muscle action potentials (CMAP) were recorded on both sides and a CMAP ratio was calculated from each muscle. The House-Brackman scale was used to assess the initial clinical evaluation and the follow-up until recovery. RESULTS: Fibrillation was recorded in 32 patients on the 30th day after the onset and was present in 100% of mentalis and in 90% of frontalis, but in only 34% of OO, a statistically significant difference. The grade of fibrillation in OO was also statistically lower from those in the other two muscles. The 32 patients were grouped according to the presence (A) or not (B) of fibrillation in OO. In group A, CMAP ratios (affected/normal side) did not differ significantly among the three muscles. However, in group B they were significantly greater in OO and frontalis than in mentalis. In between-group comparison, group B muscles had significantly higher CMAP ratios, lower degree of fibrillation, and better functional recovery. CONCLUSION: In facial palsy, the presence and grade of fibrillation in OO are lower than in frontalis and mentalis muscles and prognosis is more favorable for the non-fibrillating OO group of patients.