Inflammation in the Uvula Mucosa of Patients With Obstructive Sleep Apnea

This study was conducted to determine whether inflammation is present in the uvula mucosa of patients with obstructive sleep apnea (OSA). Uvulas were obtained by uvulopalatopharyngoplasty in 21 patients with moderate OSA (mean apnea/hypopnea index and standard error of the mean: 32±4) and by autopsy in 5 individuals not known to have OSA. Using point counting in five randomly selected high-power microscopic fields (×100), the authors found that the number of leukocytes in the lamina propria of the uvula mucosa was significantly higher in patients with OSA than in the controls (179±12 cells vs. 71±4 cells, respectively;P<.05). This was due to a significant increase in the number of plasma cells in patients with OSA as compared with controls (89±15 cells vs. 21±5 cells, respectively; P<.05). The thickness of the lamina propria (an index of interstitial edema) was also significantly increased in patients with OSA compared with controls (0.99±0.12 mm vs. 0.27±0.02 mm, respectively; P<0.05). The authors conclude that inflammation, characterized by plasma cell infiltration and interstitial edema, is present in the uvula mucosa of patients with moderate OSA. They also suggest that soft palate inflammation contributes to upper airway occlusion observed during sleep in these patients.     

Dummies and the sudden infant death syndrome.

The association between dummy use and sudden infant death syndrome (SIDS) was investigated in 485 deaths due to SIDS in the postneonatal age group and compared with 1800 control infants. Parental interviews were completed in 87% of subjects. The prevalence of dummy use in New Zealand is low and varies within New Zealand. Dummy use in the two week period before death was less in cases of SIDS than in the last two weeks for controls (odds ratio (OR) 0.76, 95% confidence interval (CI) 0.57 to 1.02). Use of a dummy in the last sleep for cases of SIDS or in the nominated sleep for controls was significantly less in cases than controls (OR 0.44, 95% CI 0.26 to 0.73). The OR changed very little after controlling for a wide range of potential confounders. It is concluded that dummy use may protect against SIDS, but this observation needs to be repeated before dummies can be recommended for this purpose. If dummy sucking is protective then it is one of several factors that may explain the higher mortality from SIDS in New Zealand than in other countries, and may also explain in part the regional variation within New Zealand.     

Facial nerve near the external auditory meatus in man: Computer reconstruction study—Preliminary report

The anatomy of the facial nerve relative to its intratemporal and extratemporal courses varies over time with developmental changes. Otologic and parotid surgery in infants and children demands detailed knowledge of the precise anatomy of the facial nerve with respect to the tympanic ring and external auditory canal, The authors analyzed this area using our three-dimensional (3-D) computer-aided reconstruction and measurement method studying the spatial relations of the facial nerve to the tympanic ring and stylomastoid foramen. Temporal bones from five normal individuals aged 36 gestational weeks, 3 months, 8 months, 4 years, and 17 years were retrieved from the temporal bone collection stored at the Elizabeth McCullough Knowles Otopathology Laboratory in Pittsburgh. Three-dimensional reconstruction of the facial nerve comparing the developmental anatomy across the various age groups provides the surgeon with the technical information necessary to address problems in this area.     

Complications of endoscopic sinus surgery: Analysis of 2108 patients—incidence and prevention

The incidence of complications of endoscopic sinus surgery (ESS) in a combined experience with 2108 total patients is compared to complications in 11 other series of patients (2583 total) who underwent ESS and 6 series of patients (2110 total) who underwent traditional endonasal sinus surgery. The incidence of major perioperative complications was 0.85%, with cerebrospinal fluid (CSF) leak being the most common. The most common minor complications of ESS were those related to orbital penetration and middle turbinate adhesions; minor complications occurred in 6.9% of the 2108 patients. There were no statistically significant differences in the overall incidences of major complications between this series and the other two groups. Recommendations are made for the prevention of complications during ESS.     

Adenosine-mediated killing of cultured epithelial cancer cells

Because micromolar concentrations of adenosine (Ado) have been documented recently in the interstitial fluid of carcinomas growing in animals, we examined the effects of low concentrations of Ado on the growth of cultured human carcinoma cells. Ado alone had little effect upon cell growth. In the presence of one of a number of Ado deaminase (ADA) inhibitors, Ado led to significant growth inhibition of all cell lines tested. Similar effects were found when ATP, ADP, or AMP was substituted for Ado. Surprisingly, the ADA inhibitor coformycin (CF) had a much greater potentiating effect than did 2'-deoxycoformycin (DCF), although DCF is a more potent ADA inhibitor. The growth inhibition of the Ado/CF combination was not abrogated by pyrimidines or caffeine, a nonspecific Ado receptor blocker. Toxicity was prevented by the addition of the Ado transport inhibitor dipyridamole or the Ado kinase inhibitor 5'-amino 5'-deoxyadenosine. S-Adenosylhomocysteine hydrolase is not involved because neither homocysteine thiolactone nor an S-adenosylhomocysteine hydrolase inhibitor (adenosine dialdehyde) potentiated toxicity of the Ado/CF combination. Unexpectedly, substitution of 2'-deoxyadenosine (the toxic moiety in congenital ADA deficiency) for Ado, did not lead to equivalent toxicity. The Ado/CF combination inhibited DNA synthesis and brought about morphological changes consistent with apoptosis. Together, these findings indicate that the Ado-mediated killing proceeds via an intracellular route that requires the action of Ado kinase. The enhanced cofactor activity of CF may be attributable to its being a more potent inhibitor of AMP deaminase than is DCF.     

Oestradiol skin delivery from ultradeformable liposomes: refinement of surfactant concentration

The aims of this study were to refine ultradeformable liposomes for oestradiol skin delivery and to evaluate Span 80 and Tween 80 as edge activators compared with sodium cholate. Vesicles containing phosphatidylcholine (PC) mixed with edge activators and oestradiol were prepared. Entrapment efficiency and vesicle size were determined. Interactions between activators and vesicles were investigated using differential scanning calorimetry. Transepidermal permeation of oestradiol from vesicles was studied compared to saturated aqueous control in vitro. The maximum flux (J(max)) and its time (T(max)) were calculated from the flux curves and skin deposition was assessed. The compositions of refined formulations were predicted, liposomes prepared, and tested against control. Entrapment efficiency depended on PC concentration with some contribution from sodium cholate and Tween 80. Vesicle sizes ranged from 124 to 135 nm. Edge activators interacted with lipid bilayers and disrupted packing. The refined edge activator concentrations in PC vesicles were 14.0, 13.3 and 15.5% w/w for sodium cholate, Span 80 and Tween 80, respectively; they increased J(max) by 18, 16 and 15-fold and skin deposition by 8, 7 and 8-fold compared with control. Ultradeformable vesicles thus improved skin delivery of oestradiol compared to control and Span 80 and Tween 80 were equivalent to sodium cholate as edge-activators.     

Risk factors for surgical wound infections in patients undergoing head and neck oncologic surgery

Risk factors for surgical wound infection are difficult to establish in head and neck surgery. Flap reconstruction, which correlates with tumour size and surgical procedure, appears to be the main risk factor. Attempts should be made by the surgical staff to improve surgical procedures in terms of duration of surgery and choice of the procedure. The intraoperative choice between primary closure and flap reconstruction should be studied further. More subtle risk factors may appear in studies of large groups of patients and/or if a distinction is drawn between early and late SWI.     

Otogenic intracranial infections in adults

OBJECTIVE: To assess the type and bacteriology of otologic diseases associated with bacterial meningitis in adults. METHOD: Retrospective review of 79 patients over an 18-year period. RESULTS: Acute otitis media was diagnosed in 32 patients, chronic otitis in 29 (16 with cholesteatoma), and cerebrospinal fluid leak in 18. Streptococcus pneumoniae was a common cause of meningitis-complicating acute otitis media (69%) or cerebrospinal fluid leak (50%), whereas other bacteria or negative cultures were found in the cerebrospinal fluid of patients with chronic otitis. Surgery was performed promptly in 26 patients; four patients died. CONCLUSIONS: Early diagnosis of otogenic bacterial meningitis is essential to allow appropriate antimicrobial treatment. Antimicrobials active on gram negative bacilli and anaerobes should be used in patients with chronic otitis. An emergency surgical procedure is required in patients whose neurologic or infectious status fails to improve under antimicrobial treatment.     

Phase I study of docetaxel and topotecan in patients with solid tumors

Purpose: Both docetaxel (DOC), a promoter and stabilizer of microtubule assembly, and topotecan (TOPO), a topoisomerase I inhibitor, have shown antitumor activity in a variety of solid tumor malignancies. This phase I trial was conducted to determine the overall and dose-limiting toxicities (DLT), the maximum tolerated dose (MTD) and the pharmacokinetics of the combination of DOC and TOPO in patients with advanced solid tumor malignancies. Methods: DOC was administered first at 60 mg/m² without G-CSF and at 60, 70, and 80 mg/m² with G-CSF by 1-h infusion on day 1 of the odd-numbered cycles (1, 3, 5, etc.) and on day 4 of the even-numbered cycles (2, 4, 6, etc.). TOPO 0.75 mg/m² was administered as a 30-min infusion on days 1, 2, 3 and 4 of each cycle. G-CSF 300 μg was administered subcutaneously (s.c.) on days 5–14. Cycles were repeated every 21 days. All patients were premedicated with dexamethasone 8 mg orally every 12 h for a total of six doses starting on the day before DOC infusion. Results: A total of 22 patients were treated. Six patients were treated in cohort I with DOC and TOPO doses of 60 and 0.75 mg/m², respectively, without G-CSF, and two patients developed DLT (febrile neutropenia). Four patients were treated in cohort II with DOC and TOPO doses of 60 and 0.75 mg/m², respectively, with G-CSF, and no DLT was observed. Four patients were treated in cohort III with DOC and TOPO doses of 80 and 0.75 mg/m², respectively, with G-CSF, and three developed DLT (febrile neutropenia). DOC was then de-escalated to 70 mg/m² and delivered with TOPO 0.75 mg/m² and G-CSF (cohort IV). Eight patients were treated at this dose level, and one DLT (febrile neutropenia) was observed. Two patients developed a severe hypersensitivity reaction shortly after the DOC infusion was started, one in cycle 1 and one in cycle 2. Both patients were removed from the study. Two patients developed severe dyspnea in the presence of progressive pulmonary metastases. Other nonhematological toxicities were mild. One patient with extensively pretreated ovarian carcinoma had a partial response, and eight patients with various solid tumor malignancies had stable disease with a median time to progression of 12 weeks (range 9–18 weeks). Administration of TOPO on days 1–4 and DOC on day 4 resulted in increased neutropenia. Conclusions: DOC 80 mg/m² given first as a 1-h infusion on day 1 with TOPO 0.75 mg/m² given as a 0.5-h infusion on days 1, 2, 3 and 4 with G-CSF was considered the MTD. The recommended phase II dose for DOC given on day 1 is 70 mg/m² with TOPO 0.75 mg/m² given on days 1, 2, 3 and 4 every 21 days with G-CSF 300 μg s.c. on days 5–14. The alternative schedule with DOC given on day 4 and TOPO on days 1–4 is not recommended. Received: 18 February 2000 / Accepted: 19 July 2000