Impedance detected abnormal bolus transit in patients with normal esophageal manometry. Sensitive indicator of esophageal functional abnormality?

SUMMARY: When used in combination with manometry, multichannel intraluminal impedance better characterizes the established manometric abnormalities into those with and without associated transit defects. However, the significance of the finding of normal manometry and abnormal impedance is not known. The objective of this study is to evaluate the clinical relevance of abnormal impedance associated with normal manometry during esophageal function testing in patients with a variety of esophageal symptoms. All patients referred for esophageal function testing during a 27-month period underwent combined multichannel intraluminal impedance and esophageal manometry studies including 10 liquid and 10 viscous swallows in supine position. From 576 patients with normal esophageal body manometry we identified 158 patients (27%) with abnormal impedance. The primary symptom in these 158 patients was compared to that in 146 consecutive patients with normal manometry and normal impedance selected from the original 576 patients. Abnormal bolus transit was found with viscous, liquid and both type swallows in 60%, 19% and 21% of the patients respectively. Of patients with abnormal bolus transit, 23% presented with dysphagia compared to 10% of normal transit patients (p = 0.0035). In conclusion, abnormal impedance even in patients with normal manometry may be a sensitive indicator of esophageal functional abnormality as represented by the symptom of dysphagia in these patients. Abnormal transit was more frequently identified with viscous than liquid swallows. Prospective studies to further clarify impedance detected transit defects in patients with normal manometry and the role of viscous swallows in diagnostic testing are warranted.

The free vascularized flap and the flap plate options: comparative results of reconstruction of lateral mandibular defects.

OBJECTIVES/HYPOTHESIS: Reconstruction of the mandible and oral cavity after segmental resection is a challenging surgical problem. Although osteocutaneous free flaps are generally accepted to be optimal for reconstruction of anterior defects, the need for bony reconstruction for a pure lateral mandibular defect remains controversial. STUDY DESIGN: A retrospective study. METHODS: A retrospective comparative study of short- and long-term outcomes of three different reconstruction techniques for lateral defects was performed. In total, 57 patients were included, of whom 27 had a plate and pedicled pectoralis major myocutaneous flap (PMMF group), 16 had a plate and free radial forearm flap (FRFF group), and 14 had an osteocutaneous free flap. Functionality, flap failure, and complications were scored. RESULTS: Plates had to be removed in 7 of the 27 patients in the PMMF group and 2 of the 16 in the FRFF group; none of the 14 osteocutaneous free flaps failed. The difference was of borderline statistical significance (P = .055). Longterm functional outcome revealed no statistically significant difference in oral deglutition (P = .76) or in facial contour (P = .36). Oral continence was significantly better in patients in the FRFF group (88%) as compared with the PMMF group (52%) or the osteocutaneous free flap group (43%) (P = .02). On the other hand, the results for speech favored the osteocutaneous free flap group; 13 of 14 patients (92.9%) had a normal score compared with 12 of 16 patients (75%) in the FRFF group and 17 of 27 (63%) in the PMMF group. However, this represented a borderline statistically significant result (P = .06). CONCLUSIONS: For lateral mandibular defects, the osteocutaneous free flap is reliable and durable in the long term. However, in a selected group of patients either of the two flap-plate options is a viable reconstructive option.

Use of image coregistration in salvage prostate brachytherapy.

PURPOSE: We describe a method of performing salvage prostate brachytherapy on patients whose initial implant was suboptimal. This technique uses an image correlation algorithm only previously used to fuse postimplant magnetic resonance and computed tomographic (CT) images. Here, the initial postimplant CT and the second preimplant volume study are coregistered to plan delivery of the salvage implant. MATERIALS AND METHODS: Two early-stage patients had salvage implants performed with this technique, in which only a limited number of sources were visible on the ultrasound images. The dosimetric results of the first implant were displayed on the preplan generated for the second procedure. The planned total dose then was visualized prior to salvage implant. RESULTS: The implants were performed without complication. Rectum and urethra doses remained acceptable. In each case, the improvement in coverage of the gland was dramatic (V80 coverage improved from 65.2% and 47.3% to 93.1% and 92.2%, respectively), precluding the need for further intervention. CONCLUSIONS: Coregistration of the postimplant CT scan to an ultrasound volume study can be quantifiably and reliably performed. The resulting image set can be used to guide needle placement during a second salvage implant to achieve much improved dosimetric coverage of the gland.

The free iliac crest and fibula flaps in vascularized oromandibular reconstruction: comparison and long-term evaluation.

BACKGROUND: A variety of free flaps have been successfully used for mandible reconstruction. This study compared the short- and long-term results of using the free iliac crest and fibula flaps. METHODS: We conducted a retrospective analysis of 117 patients who underwent mandibular reconstruction, 59 patients with iliac crest and 58 with free fibula. Accurate long-term functional assessment was possible in 31 cases in the iliac crest group and in 48 patients with fibular reconstruction. Anterior or combined anterolateral defects formed 72% and 64% in the iliac crest and fibula groups, respectively. The remainder were pure lateral defects. In both series, a skin paddle was included to provide either lining, skin cover, or both in 77% of the cases, whereas in 23% bone only was used. RESULTS: Complications included two perioperative deaths and three flap losses in the iliac crest group and five flap losses in the fibula group. Long-term functional and cosmetic assessment showed no statistically significant differences in oral continence (p > 0.9), speech (p = 0.57), and contour results (p = 0.80) between the two groups. However, oral deglutition was statistically significantly better in the fibula free flap group (p = 0.009). CONCLUSION: Although the fibula free flap is the flap of choice, the iliac crest is an excellent and reliable complementary flap for mandibular reconstruction.

A comparison of memory for and attitudes about alcohol, cigarette, and other product advertisements in college students.

The purpose of this study was to compare the attitude ratings and recall scores of cigarette, alcohol, automobile, deodorant, jeans, soft drink, athletic shoe, breakfast cereal, and fast food restaurant advertisements. Male and female college students rated the advertisements of these product groups on a number of traits--adventurous, eye-catching, appealing, informative, believable, good times, recreational, effectiveness, romantic, athletic, buy product, and honesty. Drawing on their everyday experience, the students also were asked to recall as much about the advertisements from these product groups as they could. The results revealed that the rating and recall scores of the alcohol advertisements were significantly higher than those for the cigarette advertisements and among the highest of all of the advertisement groups. The female recall scores generally were significantly higher than the male recall scores. In contrast to the cigarette advertisements, the high scores of the alcohol advertisements were interpreted to be due in part to the wider distribution alcohol advertising has had. That alcohol advertising ranked among the highest of all of the advertising groups indicates that college students view alcohol advertising very favorably.

Differential modulation of CYP2E1 activity by cAMP-dependent protein kinase upon Ser129 replacement.

Many toxic compounds are activated by cytochrome P450 (CYP) 2E1 to reactive metabolites, which represents a potential hazard for cellular homeostasis. Therefore knowledge about CYP2E1 regulation could be of great biological importance. It has been shown that CYP2E1 is controlled transcriptionally and post-translationally by phosphorylation. In the present study we investigated the role of serine-129 (Ser129) in the protein kinase A (PKA) recognition sequence motif Arg-Arg-Phe-Ser129. To gain further insights into the possible relevance of Ser129 for CYP2E1 function, Ser129 was replaced by alanine (Ala) or glycine (Gly) by site-directed mutations of the cDNA coding for CYP2E1. The mutant cDNAs were transfected into Chinese hamster lung fibroblast V79 cells. Despite the mutation in the PKA phosphorylation motif, all strains produced catalytically active CYP2E1. However, there was a marked change in the substrate preference: The Gly129-containing strains hydroxylated p-nitrophenol (PNP) to a markedly higher extent than the wild-type cDNA-containing cells, while they demethylated N-nitrosodimethylamine (NDMA) to a markedly lower extent than the wild-type cells. All the strains activated NDMA to mutagenic products. Treatment with the membrane-permeating cAMP derivative db-cAMP reduced markedly both the PNP hydroxylase and the NDMA demethylase activities as well as the mutation frequency induced by NDMA in the Ser129-containing strain. This decrease in activity was not accompanied by a decrease in CYP2E1 content. In addition, the catalytic activities of CYP2E1 were decreased in microsomes from rat hepatocytes treated with db-cAMP. Also in this case, the decrease in activities was not accompanied by a decrease in enzyme protein. These findings argue that involvement of Ser129 and its phosphorylation is not in determining CYP2E1 protein level, but rather in controlling its catalytic activity. In contrast, in the strains containing Ala129 or Gly129, treatment with db-cAMP caused a marked increase in both PNP hydroxylase and NDMA demethylase. In these strains a similar db-cAMP-mediated increase was also observed in the mutation frequency, resulting from the treatment with the promutagen NDMA, which is activated by CYP2E1. Our results show that CYP2E1 in V79 cells responds in two separate ways to db-cAMP exposure depending on the amino acid residue present in the PKA recognition sequence. The enzyme is committed to a negative regulation by db-cAMP if Ser129 is the target amino acid for PKA, leading to a decrease in the metabolic activation to mutagenic and carcinogenic species. On the other hand, Ala129 or Gly129 substitution directed CYP2E1 toward a positive regulation by increasing its catalytic activities and metabolic activation to mutagenic intermediates in the presence of db-cAMP. We also obtained evidence that cAMP-mediated downregulation of wild-type (Ser129) CYP2E1 was not accompanied by its destruction but instead by its stabilization, which shows that Ser129 is not involved in CYP2E1 degradation but dictates requirements for its specific activities.

Oromandibular reconstruction with the fibular free flap. Analysis of 50 consecutive flaps.

OBJECTIVE: To evaluate the results and functional outcome associated with fibular free flap reconstruction of orofacial and mandibular defects. DESIGN: We conducted a retrospective analysis of 50 consecutive fibular free flaps during a 3-year period. Forty patients were available for follow-up, which ranged from 4 to 39 months. SETTING: Academic tertiary care referral medical center. PATIENTS: Fifty consecutive mandibular reconstructions using the fibular free flap were performed on 47 patients. Thirty-five patients (74%) underwent primary reconstruction. Sixty-six percent of the mandibular defects were anterior or combined anterolateral types; the remainder were pure lateral defects. In 38 patients (81%), a skin paddle was included with the flap to provide either a mucosal lining or skin cover, whereas in only 9 patients (19%), bone was used alone. MAIN OUTCOME MEASURES: Factors reflecting functional properties and processes as well as complications of the upper aerodigestive tract were evaluated clinically and radiographically. RESULTS: Four flaps required reexploration as emergencies, and none were successfully salvaged (8.5% failure). Three patients underwent further free vascularized fibula transfer with 1 failure. During follow-up, swallowing was normal in 25 patients (64%), oral continence was normal or almost normal in 26 patients (67%), and speech was normal or easily intelligible in 35 patients (90%). Aesthetic results were excellent or acceptable in 37 patients (95%). CONCLUSIONS: Our results reveal that the vascularized fibular free flap is very suitable with an excellent success rate for reconstructing both the composite or simple long-spanned mandibular defect. The overlying skin island is reliable and provides lining or coverage for intraoral and extraoral defects. Superior functional cosmetic results are expected in the majority of patients, while donor site morbidity is minimal.

Fenestrated fontan procedure: evolution of technique and occurrence of paradoxical embolism.

The Fenestrated Fontan procedure (FFP) has improved outcome in high risk patients. The technique is evolving, however, and complications are not fully known. Over a 3-year period 13 patients (mean age 35 +/- 29 months) underwent an FFP in our institution. In the first two patients the fenestration had to be created because of high right atrial pressure and low cardiac output; in 11 patients the FFP was planned. In three patients the sutures for the adjustable fenestration were crossing the defect. In 10 patients, purse-string sutures were placed around but not across the defect. Because large fenestrations were created in 11 patients (8-12 mm) Glenn shunts were performed to improve arterial saturation. The postoperative course was relatively uneventful, with chest tubes being removed 1-8 days (mean 4 +/- 3 days) postoperatively and the hospital stay ranging from 7 to 27 days (mean 14 +/- 6 days). One patient had bleeding and another had a mediastinal abscess. The first patient died (7.6%) because of hemodynamic instability due to prolonged cardiopulmonary bypass from the creation and enlargement of the fenestration. One patient had a paradoxical cerebral embolism from clots that formed on the sutures crossing the fenestration. Because of this problem the remaining patients were placed on salicylates while awaiting closure of their fenestration. All 12 patients had their fenestrations closed, performed under local anesthesia in 9, at mediastinal abscess drainage in 1, and spontaneously in 2. We conclude that creation of large fenestrations in combination with Glenn shunts and the use of adjustable fenestrations are viable modifications of the FFP. The use of purse-string sutures around the fenestration and antiplatelet drugs can probably minimize the occurrence of paradoxical embolism.

Balamuthia mandrillaris meningoencephalitis presenting with acute hydrocephalus.

The leptomyxid amoeba Balamuthia mandrillaris, previously believed to be a harmless soil-inhabiting organism, is now known to be a rare but consistently lethal cause of meningoencephalitis in humans. We report a case of amebic meningoencephalitis caused by B. mandrillaris which presented as a febrile illness with acute hydrocephalus.

Delayed posttraumatic tamponade.

Delayed cardiac tamponade is a rare phenomenon with two primary causes: delayed hemorrhage after an acute injury or delayed pericarditis with effusion. We present a case of cardiac tamponade 4 weeks after injury, with findings compatible with delayed hemorrhage and pericarditis. Our case emphasizes the need for follow-up of patients with penetrating chest trauma for several months after injury; echocardiography should be used if symptoms of tamponade appear.

Use of a national data base to assess perioperative risk, morbidity, mortality, and cost savings in coronary artery bypass grafting.

To show the usefulness of the Society of Thoracic Surgeons (STS) National Database in providing clinical and cost-related outcome data, we studied 297 consecutive patients who had isolated coronary artery bypass grafting (CABG) and who were assigned to either a "fast track" or traditional track. The observed overall mortality rate was 2.7%. The predicted mortality based on preoperative risk factors was 4.7%. Before the initiation of a "fast-track" protocol and critical pathways, the average length of stay was 8.2 days and the average cost of uncomplicated isolated CABG was $18,476. The length of postoperative stay and the cost decreased to 6.0 days and $12,427, respectively, with the application of a fast-track protocol (when appropriate) and critical pathways without affecting clinical outcomes. Use of the STS National Database provided rapid and reassessing evidence that survival and quality of care were not compromised with implementation of a cost-saving fast-track protocol and critical pathways.

Analysis of lysophophatidylcholine-induced endothelial dysfunction.

Endothelial dysfunction caused by the early atherosclerotic process or by endothelial exposure to atherogenic lipids, including lysophosphatidylcholine (lysoPC), is characterized by a selective impairment of responses mediated by the pertussis toxin-sensitive Gi-2 protein. Experiments were performed to analyze the mechanisms underlying this effect. Bradykinin (BK: Gi-2 protein-independent), serotonin (5-HT: Gi-2 protein-dependent), or direct activation of the G(i-2)-protein by mastoparan increased the release of endothelium-derived nitric oxide (EDNO) from porcine arterial endothelial cells (EC). LysoPC decreased the release of EDNO caused by 5-HT, but did not affect the response to BK or mastoparan. LysoPC did not increase production of superoxide radicals detected by lucigenin-enhanced chemiluminescence. Western blot analysis showed no difference in the level of immunoreactive Gi alpha-2 between control and lysoPC-treated cells. Activation of the Gi-2 protein by serotonergic or alpha 2-adrenoceptor stimulation decreased the pertussis toxin-catalyzed ADP-ribosylation of Gi alpha-2 protein in membranes from control but not lysoPC-treated cells. However, direct activation of the Gi-2 protein by mastoparan inhibited the ADP-ribosylation in membranes from control and lysoPC-treated cells. The toxin-catalyzed reaction was reduced in lysoPC-treated cells or lysoPC-treated membranes. LysoPC reduced the ability of endothelin to increase GTP gamma S binding to the Gi-2 protein but did not affect the activity of mastoparan. These results suggest that lysoPC inhibits a pertussis toxin-sensitive signaling pathway in EC by an effect consistent with receptor:Gi-2-protein uncoupling.

Frequency of Bolton tooth-size discrepancies among orthodontic patients.

The purpose of this study was to determine the percentage of orthodontic patients who present with an interarch tooth-size discrepancy likely to affect treatment planning or results. The Bolton tooth-size discrepancies of 157 patients accepted for treatment in an orthodontic residency program were evaluated for the frequency and the magnitude of deviation from Bolton's mean. Discrepancies outside of 2 SD were considered as potentially significant with regard to treatment planning and treatment results. Although the mean of the sample was nearly identical to that of Bolton's, the range and standard deviation varied considerably with a large percentage of the orthodontic patients having discrepancies outside of Bolton's 2 SD. With such a high frequency of significant discrepancies it would seem prudent to routinely perform a tooth-size analysis and incorporate the findings into orthodontic treatment planning.

The free flap and plate in oromandibular reconstruction: long-term review and indications.

The purpose of this study was to define the role of reconstruction plates as bone replacement in oromandibular reconstruction. From 1987 through 1991, 71 consecutive oral cancer patients underwent composite resection and reconstruction and were entered into one of two studies. In the first study of 31 patients, 15 underwent oromandibular reconstruction using a radial forearm osteocutaneous flap, while the remainder (16) received a radial forearm fasciocutaneous flap together with a mandibular reconstruction plate. The second study involved 40 subsequent patients, all receiving the latter form of reconstruction. Twenty-one of the plates were stainless steel, and the remaining 19 were of the titanium hollow screw (THORP) type. We followed the patients prospectively. We defined success as a reconstruction that we did not have to remove. Additionally, since the patients had limited life expectancy, we developed the idea of days of life lost and incorporated it into our definition of a successful outcome. Vascularized autogenous bone proved to be more successful than metallic plates used alone in terms both of reconstruction survival and of minimizing days of life lost. The overall success rate of mandibular plate reconstruction was 78.9 percent, but analysis by defect type revealed a failure rate of 35 percent when the defects were anterior and only 5 percent when they were lateral. THORP plates demonstrated a trend towards more durability. We would now recommend plate reconstruction only in lateral defects in patients with a poor prognosis.

Evidence against a role for serine 129 in determining murine cytochrome P450 Cyp2e-1 protein levels.

The cytochrome P450 CYP2E subfamily plays a central role in drug and carcinogen metabolism. The cellular content of this protein is regulated at both the transcriptional and posttranslational levels. CYP2E1 is degraded by both rapid and slow acting proteolytic systems. In the presence of a substrate, CYP2E1 becomes stabilized, and the contribution of the rapid actinig proteolytic pathway to its destruction decreases. It has been suggested that phosphorylation at serine 129 acts as a switch to initiate the fast acting degradative pathway. Phosphorylation at serine 129 has also been suggested to be the point at which hormones, such as insulin, exert actions on the stability of this protein. In order to investigate the role of phosphorylation in determining murine Cyp2e-1 levels, serine 129 was changed by site-directed mutagenesis to amino acids that could not be phosphorylated and the recombinant proteins expressed in COS 7 cells. Replacement of serine 129 with alanine and glycine does not lead to Cyp2e-1 accumulation. In the presence of insulin, although Cyp2e-1 levels increase slightly, specific stabilization of the wild-type protein relative to the two mutant forms is not observed. These observations provide evidence that insulin can act by stabilization of Cyp2e-1 protein but suggest that the phosphorylation of serine 129 is not the molecular basis of stabilization observed.

Recognition and management of accessory mitral tissue causing severe subaortic stenosis.

Failure to recognize the presence of accessory mitral tissue causing subaortic stenosis can lead to not only the performance of inappropriate operations, but the persistence and recurrence of obstruction or even death. Over a 12-month period, we treated 2 children with severe subaortic stenosis caused by accessory mitral tissue. In 1 patient, who was 4 years old, the echocardiogram showed the accessory mitral tissue to be attached to the anterior mitral leaflet and ballooning into the subaortic area. The other patient, as a newborn, underwent simultaneous repair of a complete canal defect and coarctation. Two years later, the patient was seen because of syncopal episodes, progressive mitral insufficiency, and subaortic stenosis thought to be caused by anterior displacement of the anterior mitral leaflet. Mitral valvuloplasty and a conal enlargement procedure were planned. Intraoperatively, after the mitral valvuloplasty had been done, the subaortic stenosis was found to be due to a tight subaortic ring formed by accessory mitral tissue located at the septum and its fibrous extension to the anterior mitral leaflet. In both patients, excision of the accessory mitral and fibrous tissues resulted in a wide-open subaortic area. Both patients had an uneventful hospital course, and follow-up echocardiography showed no noteworthy residual left ventricular outflow gradient. We believe that increased awareness and sophisticated echocardiographic techniques should lead to an increased recognition of accessory mitral tissue causing subaortic stenosis. Simple resection of the accessory mitral tissue and its secondary fibrous tissues can be curative.

Classification problems of U.S. Air Force spatial disorientation accidents, 1989-91.

Spatial disorientation (SD) continues to contribute to a fairly constant proportion of military aircraft accidents. The U.S. Air Force (USAF) fielded a new accident investigation reporting form in July 1989, which for the first time specified Type I SD, Type II SD, and Type III SD as possible causes of aircraft accidents. Of a total of 91 major accidents that occurred over the 2-year period beginning in October 1989, SD was rated as contributing significantly to 13 (14%). Coding for SD on accident investigation reporting forms was not consistent, however. Individual flight surgeons differed in their approaches to coding accidents as SD-related; other differences were noted between flight surgeons and pilots, and additional procedural differences resulted in inconsistent reporting over time. There is a consensus that SD represents a major problem in military aviation, but a scientific approach to this important problem would be facilitated if agreement could be reached on definitional and semantic issues.