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Biomedical subjects

L A Orloff

Publications and source records attributed to L A Orloff.

18 recordsLinked to original sources

Long-term therapy for spasmodic dysphonia: acoustic and aerodynamic outcomes.

OBJECTIVE: To evaluate the long-term aerodynamic, acoustic, and electromyographic effects of serial botulinum toxin (BT) injections in patients with adductor spasmodic dysphonia. DESIGN: Two-year, nonrandomized, controlled, before-after study. SETTING: Ambulatory care clinic at a single academic medical center. PATIENTS: A convenience sample of 91 patients with adductor spasmodic dysphonia evaluated and treated during 2 years and 64 age- and sex-matched controls. INTERVENTIONS: Injections of BT into the thyroarytenoid muscles in conjunction with electromyographic evaluation and acoustic and aerodynamic evaluation before and after serial BT injections. MAIN OUTCOME MEASURES: Translaryngeal airflow, jitter, shimmer, signal-to-noise ratio, fundamental frequency, standard deviation of fundamental frequency, maximum phonation time, and inappropriate muscle activity by electromyography. RESULTS: Translaryngeal airflow, jitter, and shimmer improved significantly after serial BT treatments and showed sustained improvement over time. Fundamental frequency, standard deviation of fundamental frequency, and signal-to-noise ratio did not change significantly after BT treatment. Electromyographic data suggested decreased inappropriate muscle activity with repeated BT injections. CONCLUSION: Treatment with BT provides ongoing relief of voice perturbations in patients with adductor spasmodic dysphonia who undergo long-term cumulative therapy.

Adult↗

Methylene blue and sestamibi: complementary tools for localizing parathyroids.

OBJECTIVE: To determine the value and correlation between sestamibi scan and methylene blue staining for localization of parathyroid glands in patients with primary hyperparathyroidism. STUDY DESIGN: Nonrandomized convenience sample, followed prospectively. METHODS: Twenty-three consecutive patients underwent 24 operations for primary hyperparathyroidism. All patients underwent preoperative technetium 99m-sestamibi planar scintigraphy, preoperative administration of 7.5 mg/kg methylene blue initiated within 60 minutes of surgical incision, and surgical neck exploration supervised by a single surgeon. RESULTS: All patients were cured of hypercalcemia. Sensitivity for sestamibi and for methylene blue staining was 76% and 79%, respectively. Specificity for sestamibi and for methylene blue was 98% and 93%, respectively. Agreement between sestamibi and methylene blue was 96%. CONCLUSIONS: Sestamibi scanning and methylene blue staining are useful, complementary localizing tools for patients undergoing surgery for primary hyperparathyroidism. When used together, these studies decrease operative time, justify unilateral exploration in patients with parathyroid adenoma, and increase the ease of identification of hyperplastic parathyroid glands.

Adult↗

Lifelong prevention of mesangial enlargement by whole pancreas transplantation in rats with diabetes mellitus.

BACKGROUND: Mesangial enlargement (ME) is one of the hallmark lesions of diabetic nephropathy and plays a major role in diabetic renal failure. Conventional treatment of type 1 diabetes mellitus with insulin injections, diet, and medications has often failed to prevent development and progression of ME, presumably because of difficulty in achieving tight metabolic control. Although many pancreas transplantations have been done in patients with type 1 diabetes mellitus, there is insufficient information about their influence on ME or other diabetic lesions that are responsible for its morbidity and mortality. HYPOTHESIS: Whole pancreas transplantation will prevent diabetic ME throughout the life of the rat with alloxan-induced diabetes mellitus. DESIGN: Mesangial enlargement was studied for 28 months by a highly reproducible quantitative morphologic method in 55 nondiabetic control rats, 57 control rats with alloxan-induced diabetes mellitus, 97 diabetic rats that received a pancreaticoduodenal isograft shortly after the induction of diabetes mellitus, and 126 diabetic rats that received a duct-ligated pancreas isograft shortly after the induction of diabetes mellitus. Mesangial enlargement was determined by measuring the area occupied by camera lucida tracings of the mesangium using an electronic planimeter connected to a computer. RESULTS: Monthly metabolic studies showed that whole pancreas transplantation maintained very tight metabolic control of diabetes mellitus. Alloxan-induced diabetes mellitus produced progressive accumulation of mesangial matrix and progressive enlargement of all elements of the mesangium during the study. The 2 types of whole pancreas transplants provided lifelong protection against abnormal ME (P = .006). CONCLUSIONS: These results, combined with our previous finding of lifelong prevention of abnormal glomerular capillary basement membrane thickening, demonstrate that whole pancreas transplantation performed early in the course of alloxan-induced diabetes mellitus is capable of preventing diabetic kidney lesions. Moreover, these results suggest that whole pancreas transplants might be useful preventive therapy in patients with diabetes mellitus who undergo kidney transplantation for renal failure, in whom recurrence of nephropathy often develops in the transplanted kidney.

Animals↗

Vocal fold granuloma: successful treatment with botulinum toxin.

Vocal fold granulomas are benign but frequently recurrent lesions that can cause frustration for both the patient and the treating physician. Etiologic factors include endotracheal intubation, vocal abuse, and gastroesophageal reflux. Conventional treatment for granulomas has included medical, voice, and surgical therapy, none with uniform success. In this study 8 patients with vocal fold granulomas were treated with intralaryngeal injection of botulinum toxin. The resultant temporary paresis of the vocal folds allowed for a window of time during which the vocal process could heal and the granulomas could resolve without being exposed to ongoing intermittent contact and friction with the opposing arytenoid. Although the underlying cause of a granuloma must also be addressed, we have found that botulinum toxin can be a useful adjunct to traditional therapy and can lead to avoidance of repetitive surgical procedures.

Adult↗

Budd-Chiari syndrome caused by Behçet's disease: treatment by side-to-side portacaval shunt.

BACKGROUND: Behçet's disease is a chronic multisystem vasculitis of unknown etiology that involves skin, mucous membranes, eyes, blood vessels, joints, central nervous system, digestive system, and occasionally other organs. Budd-Chiari syndrome from occlusion of the major hepatic veins is a rare and serious complication of Behçet's disease. Although the mortality rate of Behçet's disease is only 3% to 4%, development of Budd-Chiari syndrome in patients with Behçet's disease has been associated with a mortality rate of 61%. This report presents the largest reported experience of Behçet's disease-related Budd-Chiari syndrome confined to the hepatic veins, and results of treatment by side-to-side portacaval shunt (SSPCS). These results are compared with those we have obtained in Budd-Chiari syndrome confined to the hepatic veins without Behçet's disease, and with results of treatment of Budd-Chiari syndrome in Behçet's disease reported in the literature. STUDY DESIGN: SSPCS was performed in 5 patients with Behcet's disease who had developed acute Budd-Chiari syndrome, and 27 patients with Budd-Chiari syndrome from other causes. In all patients, Budd-Chiari syndrome was confined to the hepatic veins without involvement of the inferior vena cava (IVC). Patients were studied prospectively and were followed up at regular intervals for from 1.5 to 26 years (mean 10.6 years, 81% more than 5 years). Followup was 100%. Patients were mainly young adults; mean age was 24.6 years in the patients with Behçet's disease and 30.0 years in those without Behçet's disease. All patients had massive ascites, abdominal pain, hepatosplenomegaly, and abnormal liver function. Diagnosis was based on angiographic demonstration of occlusion of the major hepatic veins, and liver biopsy findings of intense hepatic congestion and necrosis. SSPCS was performed within 4 months of the onset of Budd-Chiari syndrome in all but 3 patients. Every year or two in followup, patients underwent liver biopsy and evaluation of SSPCS by Doppler duplex ultrasonography and angiography with pressure measurements. Outcomes criteria included mortality rate, SSPCS patency, maintenance of portal decompression, liver function, presence of ascites, presence of portal-systemic encephalopathy (PSE), need for diuretics, quality of life, and return to work. Our results were compared with those reported in the literature in 42 patients who had Budd-Chiari syndrome with Behçet's disease. RESULTS: SSPCS permanently reduced the mean portal vein-IVC pressure gradient (mm saline) from 205 to 7 in the 5 patients with Behçet's disease, and from 250 to 4 in the 27 without Behçet's disease. There was only one operative death, a patient without Behcet's disease. One patient with Behçet's disease died 2 years postoperatively from diffuse vasculitis, a complication of Behçet's disease, and the other 4 (80%) remain alive. All 26 operative survivors in the group without Behçet's disease (96%) are alive. Only one patient developed occlusion of the SSPCS, a man without Behçet's disease, and he required liver transplantation as a result of hepatic decompensation, PSE, and recurrent ascites. All other patients with or without Behçet's disease remained free of ascites, required no diuretics, were free of PSE, and had reversal of hepatic dysfunction. Serial liver biopsies showed normal architecture in 60% of patients with Behçet's disease and 46% of those without Behçet's disease. Return to fulltime work or housekeeping occurred in 80% of patients with Behçet's disease and 96% without Behçet's disease. Comparison of outcomes of our patients with 42 cases of Behçet's disease with Budd-Chiari syndrome reported in the literature, 79% of whom were treated medically, showed striking differences with an overall mortality rate of 61% in generally shortterm followup. (ABSTRACT TRUNCATED)

Adult↗

Quantitation of the change in GADD153 messenger RNA level as a molecular marker of tumor response in head and neck cancer.

Cells injured by exposure to cisplatin (cDDP) undergo a cellular injury response that shares characteristics with responses produced by many other injurious agents. We sought to determine whether the increase of the message of the "growth arrest and DNA damage-inducible" gene, GADD153, could be used to assess the extent of the cellular injury response in model systems and in patients with head and neck cancer after treatment with cDDP. The mRNA levels of GADD153, a gene highly transcriptionally activated by cDDP damage, were increased in a transient, concentration-dependent manner by cDDP when human UMSCC10b head and neck carcinoma cells were treated with cDDP both in vitro and when grown as tumor xenografts in nude mice. There was a good correlation between the change in level of GADD153 mRNA and UMSCC10b cell kill by cDDP in vitro (r = 0.98). The magnitude of the increase was proportionally reduced in UMSCC10b sublines that were 3- or 6-fold resistant to cDDP. GADD153 mRNA levels were measured in biopsies obtained before and 24 h after treatment with cDDP from 32 patients with stage III/IV head and neck cancer. There was a relationship between the increase in GADD153 mRNA levels and the response rate. Seven of the 32 patients had no response and no increase in GADD153 mRNA level. Among the eight patients who attained a partial response, the increase in GADD153 message ranged from 0.7-2.5-fold. In contrast, 17 of 32 patients had a complete response, and this was accompanied by a 2-9-fold induction of GADD153. The mean increase in the complete responders (3.8+/-2.2-fold) differed significantly from that for the partial responders (1.6+/-0.9) and nonresponders (0.8+/-0.5; P <0.05); the difference between the partial responders and nonresponders was also significant (P <0.05). An increase of GADD153 mRNA of 1.75-fold or higher predicted a complete response, with a sensitivity of 94% and a specificity of 87%. We conclude that the magnitude of the increase in GADD153 mRNA is a promising candidate for service as an intermediate marker of head and neck tumor response to cDDP. The fact that the change in GADD153 mRNA reflects the actual extent of injury sustained by the tumor makes it particularly attractive as a potential marker. One strength of this approach is that it can provide a measure of the effectiveness of therapy as early as 24-48 h after the first dose of treatment.

Animals↗

Observations on control of N2 and N3 neck disease in squamous cell carcinoma of the head and neck by intra-arterial chemoradiation.

Patients with head and neck squamous cell cancer with N2 and N3 neck disease have a poor prognosis and are at risk to fail regionally despite combined surgery and radiation. Twenty-two patients with N2 and N3 neck disease (and T3-4 primaries) were treated with intra-arterial, high-dose cisplatin (CDDP), 150 mg/m2 per week for 4 weeks, and concurrent radiation. All patients were followed for at least 2 years or until death from any cause. Twenty patients had a complete response at the primary site. Two of the 20 with a complete response later had a neck recurrence and died. Five patients with palpable nodes after treatment underwent fine-needle aspiration (FNA), one of which was positive and two suggestive of cancer. Six neck dissections were performed in this group, only two of which had positive nodes. This chemoradiation protocol may offer reasonable control of N2 and N3 neck disease in advanced head and neck squamous cell cancer. Neck dissection appeared to be necessary in only those patients with nodes 8 weeks after treatment in whom FNA was positive or suggestive of cancer. Because of the relatively small size of this series, additional accrual and monitoring of such patients is planned.

Adolescent↗

Phase I trial of retinoic acid and cis-platinum for advanced squamous cell cancer of the head and neck based on experimental evidence of drug synergism.

OBJECTIVE: Cis-platinum and 13-cis-retinoic acid have received much attention in the treatment of head and neck squamous cell cancer. Even though they have different mechanisms of action, little information is available on their interaction. This paper reviews experimental evidence for retinoic acid-cis-platinum synergy and presents toxicity data from patients with stage IV head and neck squamous cell cancer participating in a phase I trial combining 13-cis-retinoic acid and cis-platinum. METHODS: Patients were given 13-cis-retinoic acid orally daily for 7 days before and daily during high-dose (150 mg/m2 per week for 4 weeks) intraarterial cis-platinum treatment with concurrent radiation. Toxicity was scored with use of the cancer and leukemia group B scale. RESULTS: In the phase I clinical trial, 15 patients were treated to determine a maximum tolerated dosage for 13-cis-retinoic acid of 20 mg/day. Grade 4 hematologic toxicity was dose limiting in 3 of 8 patients treated with 40 mg/day and in 1 patient treated with 60 mg/day. There were no deaths caused by toxicity; 12 of the 15 patients received all four weekly doses and the remaining 3 received three doses. Of 10 patients with fully evaluable data, all achieved a complete response at the primary site and 9 had a complete response in the neck. One patient had persistent neck disease after chemoradiation, and this tumor was removed with neck dissection. CONCLUSIONS: 13-Cis-retinoic acid and cis-platinum are strongly synergistic against head and neck squamous cell cancer in vitro. Pretreatment with retinoic acid results in stronger synergy than concurrent drug exposure alone. Preliminary clinical experience with combined retinoic acid and cis-platinum in a design that parallels the in vitro study indicates that toxicity is acceptable with 13-cis-retinoic acid dosages of 20 mg/day in a high-dose-intensity intraarterial chemoradiation regimen.

Administration, Oral↗

Prevention of venous thrombosis in microvascular surgery by transmural release of heparin from a polyanhydride polymer.

BACKGROUND: The effects of transmurally released heparin on the patency of microvenous anastomoses were studied by using a bioerodible polymer delivery system in a rat microvascular thrombosis model. METHODS: A polyanhydride carrier with heparin was wrapped around the outside of a highly thrombogenic venous inversion graft in 14 animals, and patency rates were compared with those of 17 control animals. RESULTS: Anastomotic patency was significantly greater in the groups treated with transmurally released heparin, measured both at 24 hours (86% versus 16%; p < 0.02) and at 7 days (86% versus 36%; p < 0.05) after operation. No significant complications occurred. CONCLUSIONS: Controlled release of heparin by transmural delivery is an effective and safe form of local antithrombotic therapy and may have applications both in microvascular and large vessel surgery.

Anhydrides↗

Magnetic resonance imaging of intratemporal facial nerve lesions in the animal model.

The facial nerve is often injured in head trauma. Computed tomography (CT) is the diagnostic study most frequently used to evaluate temporal bone fractures, but it does not demonstrate all soft tissues well. Recently, magnetic resonance imaging (MRI) has been used to evaluate certain soft tissues, including cranial nerves. Experience with MRI evaluation of temporal bone trauma is limited and consists primarily of anecdotal reports. This study assesses the accuracy of MRI in evaluating experimentally induced acute intratemporal facial nerve lesions. The tympanic segments of the right facial nerve in nine rabbits were contused, and MRI scans were performed without and with gadolinium-diethyl-triamine-pentaacetic acid (Gd-DTPA) at varying intervals after surgery. MRI with Gd-DTPA accurately identified the lesion site in eight of nine subjects. Gd-DTPA-enhanced MRI appears to be useful in the evaluation of traumatic facial nerve injuries.

Animals↗

Free jejunal autograft combined with extensive esophagogastrectomy for unshuntable extrahepatic portal hypertension.

This is the first report of the use of a free jejunal autograft vascularized by the internal thoracic (internal mammary) artery and vein to restore continuity of the digestive tract after total gastrectomy and distal 65% esophagectomy for recurrent bleeding esophagogastric varices caused by unshuntable extrahepatic portal hypertension. The procedure was used in two young adults who, because of numerous previous abdominal operations, had a severely scarred and contracted intestinal mesentery that precluded conventional use of the small or large intestine with an intact blood supply to bridge the gap between the upper thoracic esophagus and the abdominal jejunum. Before referral, the two patients had 21 and eight bouts of variceal hemorrhage, respectively, that necessitated a cumulative total of 108 and 74 units of blood transfusion, necessitated 17 and 12 admissions to the hospital, and failed to respond to four and five operations and 14 and 18 sessions of endoscopic sclerotherapy. After extensive esophagogastrectomy combined with a free jejunal autograft, both patients have done well during follow-up of 9 and 3 years, respectively. Both have been in good to excellent health with stable weight, freedom from digestive tract bleeding, normal liver function, and no encephalopathy. These results confirm our recently reported conclusions regarding the uniform long-term effectiveness of extensive esophagogastrectomy in the treatment of unshuntable extrahepatic portal hypertension and suggest that thoracic and general surgeons familiar with microvascular techniques may find the free jejunal autograft to be useful in various circumstances in which it is necessary to replace all or a substantial part of the thoracic esophagus.

Adult↗

Prevention of microvascular thrombosis with controlled-release transmural heparin.

The use of controlled local-release heparin was studied as a means to prevent thrombosis in microvascular surgery, using a rat arterial inversion graft as a model. Polyvinyl alcohol embedded with heparin was placed around the outside of inversion graft anastomoses in 16 animals. Results were compared with control group animals in which polyvinyl alcohol alone was placed around the graft or systemic heparin was given. Vessel patency rates were significantly higher for animals receiving either systemic or transmural heparin than for animals in the control group. Controlled local delivery of heparin did not cause measurable systemic anticoagulation. However, the complication of local hematoma formation occurred as frequently as in the systemic heparin group. Controlled transmural release of heparin has an effective local antithrombotic effect and may hold promise for use in clinical practice.

Anastomosis, Surgical↗

Dopamine and norepinephrine in the alimentary tract changes after chemical sympathectomy and surgical vagotomy.

The aim of this study was to examine the distribution of dopamine and norepinephrine in the proximal alimentary tract of the rat and to assess the contributions of sympathetic and vagal fibers to the tissue concentrations of both catecholamines. Tissues were extracted in perchloric acid and the catecholamines were separated by high pressure liquid chromatography and detected electrochemically. In untreated rats (controls) both catecholamines were concentrated in the gastric muscle but norepinephrine levels were 6-8 times higher (corpus, dopamine 35 +/- 7 ng . g-1, norepinephrine 265 +/- 50 ng . g-1, mean +/- SE, n = 6). In the mucosa norepinephrine concentrations were 10-12 times higher (corpus, dopamine 12 +/- 3 ng . g-1, norepinephrine 140 +/- 26 ng . g-1). Chemical sympathectomy (6 hydroxydopamine, 100 mg . kg-1 ip 3 days) significantly reduced dopamine concentrations in muscle and norepinephrine in muscle, mucosa, pylorus and duodenum. In all tissues the effects on norepinephrine were greater. Surgical vagotomy significantly reduced dopamine concentrations in the gastric muscle, but not the mucosa. Norepinephrine concentrations in the stomach of vagotomized rats were significantly reduced only in the pylorus. Differences in the relative concentrations of dopamine and norepinephrine in gastric tissues of the normal rat and differences in the effects of sympathectomy and vagotomy suggest that dopamine and norepinephrine exist, to an extent, in separate populations of cells and that dopamine is not merely a precursor of norepinephrine. Gastric mucosal dopamine, which was mainly unaffected by either treatment, may exist in APUD cells.

Animals↗

Papillary thyroid carcinoma mistaken for malignant melanoma: pitfalls in diagnosis.

BACKGROUND: Immunohistochemical methods and aspiration cytology are used with increasing frequency in the diagnosis of head and neck histopathology. Magnetic resonance imaging is also gaining popularity as a diagnostic tool. METHODS: We report a case of papillary thyroid carcinoma which was initially misdiagnosed as malignant melanoma due to several confounding diagnostic test results. RESULTS: False-positive immunostaining of a cytologic preparation with a commercial preparation of HMB45 melanoma stain and characteristic MRI findings contributed to the erroneous diagnosis of malignant melanoma. CONCLUSIONS: Potential pitfalls in test interpretation are discussed, and recommendations for the judicious use of immunostaining, MRI, and other diagnostic studies are presented.

Adolescent↗

Sensorineural hearing loss and Kawasaki disease: a prospective study.

PURPOSE: Kawasaki disease (KD) is an acute, self-limited vasculitis of infants and children that is now the most common cause of acquired heart disease in the pediatric age group in the United States and Japan. Reports have documented the association of acute KD with sensorineural hearing loss. To assess the prevalence of hearing loss following acute KD in a geographically and ethnically diverse population, a prospective, multicenter study of hearing loss in patients with KD was conducted. MATERIALS AND METHODS: Patients with acute KD were enrolled in 7 clinical centers and underwent a primary audiologic evaluation within 30 days of the onset of fever. Patients were subsequently reevaluated after resolution of the acute phase of the disease. A questionnaire assessing risk factors for hearing loss was also administered. RESULTS: A total of 62 patients were evaluated during the 29-month study period. At the first audiologic evaluation, 19 patients (30.6%) had sensorineural hearing loss, 6 patients (9.7%) had conductive hearing loss, 17 patients (27.4%) had normal hearing, and 20 patients (32.3%) had inconclusive studies. Overall, 2 of 36 patients (5.5%) had sensorineural hearing loss documented on their second audiologic evaluation. No risk factors for hearing loss were identified by the questionnaire. CONCLUSIONS: Transient sensorineural hearing loss (20 to 35 dB) is a frequent complication of acute KD and may be related to salicylate toxicity in some patients. Persistent sensorineural hearing loss is uncommon. Parents and primary care providers should be made aware of the potential for persistent sensorineural hearing loss following resolution of KD, but routine audiologic screening of this patient population does not appear to be warranted.

Acoustic Impedance Tests↗