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.

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.

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.

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.

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.

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.

Perivascular delivery of heparin for the reduction of smooth muscle cell proliferation after endothelial injury.

Thin flexible sheets composed of poly(lactic acid) (PLA) laminated polyanhydride, poly(erucic acid dimer-sebacic anhydride) (P(EAD-SA)), loaded with heparin were evaluated in vitro and in vivo. PLA was used for coating the polyanhydride to improve the release profile and improve the strength of the films. Heparin was released constantly for 20 days from PLA-coated 2% loaded P(EAD-SA). The uncoated film of P(EAD-SA) released heparin for only 4 days. The localized delivery of heparin around the carotid artery was investigated by implanting polymer loaded with [3H]heparin around the carotid artery of rats and the heparin release and tissue distribution was monitored. The maximum heparin concentration in the artery exposed to the drug was on day 4 for the P(EAD-SA) uncoated device (fast releasing system) and day 11 for the coated devices. The control artery, the uncovered segments of the artery, and the surrounding tissue contained negligible amounts of radioactivity. These data confirm that heparin was delivered locally without systemic exposure. Two independent animal studies were conducted to evaluate the effectiveness of these heparin-releasing devices. In both studies the balloon catheter injury in a rat model was used. After inflicting an injury to the common carotid, a matrix oriented with its long axis along the artery was placed under the injured portion of the vessel. In both studies the treated rats showed a very thin layer of neointima where the control group showed a significant reduction of the artery internal diameter with SMC neointima ratio greater than 1.

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)

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.

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.

Effective advocacy for domestic violence victims. Role of the nurse-midwife.

A nurse-midwife may be one of the first professionals domestic-abuse victims talk to about the abuse. Like other health professionals who see abuse victims for health issues often unrelated to abuse, nurse-midwives have a special opportunity to identify, intervene, and support victims of domestic violence. Professionals working in health care will see abuse victims when they are living with their abusers and do not know that abuse is abnormal, when they attempt to leave their abusers, when they return to their abusers, and when they ultimately separate. Justice system professionals only see abuse victims when they have decided to try to leave. A thorough knowledge about relief available in the legal system for abuse victims will allow nurse-midwives to help battered women effectively. This article discusses the role nurse-midwives should play in assisting abuse victims who will be seeking help from the civil and criminal justice systems. Topics discussed include the importance of documenting injuries for use in future court cases, civil protection orders, criminal court prosecutions of the abuser, legal malpractice issues if health providers do not identify battered women, informing and referring domestic-violence victims, and the special needs of immigrant women. The article also discusses typical problems victims encounter in the legal system and ways victims can overcome these barriers.

A novel organ preservation protocol for advanced carcinoma of the larynx and pharynx.

OBJECTIVE: To pilot a targeted chemoradiation protocol for patients with advanced carcinoma of the larynx and pharynx that would circumvent upper aerodigestive tract dysfunction related to major oncologic surgery. DESIGN: Weekly intra-arterial infusions of supradose cisplatin (150 mg/m2 per week x 4) rapidly delivered to the tumor bulk, simultaneous intravenous sodium thiosulfate for systemic drug neutralization, and conventional external-beam irradiation (1.80-2.00 Gy per fraction x 35) were used. Between February 1991 and April 1994, 42 patients were treated who would otherwise have required a major resection of the tongue base, pharyngeal wall, or larynx. MAIN OUTCOME MEASURES: Tumor response, toxic effects, disease control above the clavicle, preservation of the larynx, maintenance of oral nutrition, and overall and disease-related 2-year survival. RESULTS: Three complications were related to the weekly transfemoral superselective intra-arterial procedures performed 160 times. Grade 3 to 4 chemotoxic effects were infrequent, occurring in 9 (5.5%) of 160 cycles, and only 1 patient required a radiotherapy break because of severe mucositis. A complete response in the primary site was obtained in 36 (86%) of 42 patients, 2 of whom had residual disease in the neck. Median follow-up was 13 months (range, 3-46 months). To date, there have been 5 recurrences: 2 regional and 3 distant. The 2-year overall and disease-related survival was 64% and 76%, respectively. The rate of disease control above the clavicle at 2 years was 86%. CONCLUSIONS: We believe this chemoradiation protocol represents an effective management scheme for patients with advanced head and neck cancer while minimizing dysfunction and possibly improving survival.

A look at the Violence Against Women Act and gender-related political asylum.

PIP: This article explores two developments in immigration law that have provided avenues for women seeking lawful immigration status to independently assert their rights. The Violence Against Women Act (VAWA) was signed into law on September 13, 1994 and contains the Battered Immigrant Women Provisions that allow battered women to obtain lawful permanent resident status through self-petitioning or suspension of deportation. VAWA applicants should obtain assistance from an immigration expert who can help them in acquiring work authorization and who could prove that the applicant's deportation would result in extreme hardship to themselves or to their children. Other requirements and important details of these provisions are substantially explained in the article. The second development involves the issuance by the Immigration and Naturalization Service (INS) on May 26, 1995, of a memorandum setting forth considerations for the evaluation of women's asylum claims. This memorandum is entitled "Considerations For Asylum Officers Adjudicating Asylum Claims From Women" and sets out guidelines that provides access to political asylum to women seeking protection from gender-specific persecution. A summary of the issues addressed by the INS gender guidelines are presented.^ieng

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.

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.

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.

A targeted supradose cisplatin chemoradiation protocol for advanced head and neck cancer.

BACKGROUND: Hypothesizing that cisplatin (DDP) drug resistance is dose dependent and the radiosensitizing effect of DDP is clinically beneficial, we conducted a chemoradiation protocol using extremely high doses of DDP delivered intra-arterially (IA) to locally advanced head and neck tumors. PATIENTS AND METHODS: Twenty-nine patients with untreated stage IV disease received 4 weekly infusions of 150 mg/m2, simultaneous systemic DDP neutralization with intravenous (IV) bolus sodium thiosulfate, and concomitant radiotherapy (180 to 200 cGy/day x 35 fractions). RESULTS: The complete response rate of the 24 evaluable patients as determined with repeat biopsies was 23/24 (96%). Of the 29 patients evaluable for toxicity, central nervous system complications related to the infusion technique occurred with 2/110 infusions, both of which were reversible. The rate of grade III to IV chemotoxicity was 13%. The median length of follow-up was 22 months. There have been 6 recurrences: 1 local; 3 regional; and 2 at distant sites. The projected overall and disease-free 3-year survival was 88% and 53%, respectively. CONCLUSION: We conclude that the combination of rapid selective delivery of supradose DDP/IV thiosulfate neutralization and concomitant radiotherapy can be safely and effectively applied to patients with advanced head and neck cancer. Preliminary survival analysis indicates that this approach may improve the prognosis for patients with an otherwise devastating disease.