Is there any benefit in surgery for potentially malignant disorders of the oral cavity?

Oral epithelial dysplasia grading is currently recognised as the most useful prognostic indicator for predicting conversion of potentially malignant disorders of the oral cavity to squamous cell carcinoma. It is also used as a basis for deciding management options. However, the diagnosis of oral epithelial dysplasia is subjective and thus unreliable. Surgery is currently recommended for removal of high‐risk lesions; however, the evidence for its success is lacking, and in some cases, there have been reports of increased recurrence of malignancy following surgical excision. Molecular and genetic markers have been identified and show promising results in identifying which potential malignant disorders are at risk of malignant transformation. The current evidence available for prognosis of potential malignant disorders and its treatment is based on observational and retrospective data. No randomised control trials have been conducted to date to assess the efficacy of surgery in oral epithelial dysplasia. Until good quality evidence is available from well‐designed randomised control trials, experts still recommend the surgical removal of potential malignant disorders which are regarded as high risk.     

Distribution of Chlamydia trachomatis ompA genovars and the new variant of C. trachomatis in the Göteborg area, Sweden

The aims of this study were to assess the proportion of the new variant of Chlamydia trachomatis (nvCT) and the distribution of ompA genovars among C. trachomatis-positive patients in the Göteborg area, Sweden. Consecutive urine samples positive for C. trachomatis using BD ProbeTec ET (177 patients, 88 men and 89 women) were collected. An nvCT-specific real-time polymerase chain reaction (PCR) assay was used to investigate the nvCT prevalence. To identify the genovars, a 990-bp ompA DNA segment from 105 specimens was sequenced. Seventeen percent (30/177) of all specimens contained nvCT. Nine different genovars were identified. About 50% were of genovar E, followed by F 16%, G 11%, K 8%, and D 5%, representing about 90% of the specimens in Göteborg. The occurrence of nvCT and the dominance of genovar E in Göteborg is similar to those in other areas of Sweden. To cover about 90% of the C. trachomatis infections in Sweden, the serovars D, E, F, G, and K should be included in future vaccines based on the major outer membrane protein.     

Pharmacokinetic analysis and antiepileptic activity of two new isomers of N-valproyl glycinamide

Valproyl glycinamide (TV 1901-VPGD) is a new antiepileptic drug, which is currently undergoing clinical trials. The present study explored the pharmacokinetics and pharmacodynamics (anticonvulsant activity and neurotoxicity) of two new isomers of valproyl glycinamide: valnoctyl glycinamide (VCGD) and diisopropylacetyl (DIGD). Both VCGD and DIGD showed anticonvulsant activity and a safety margin in mice similar to those of VPGD. Following iv administration (556 mg) to six dogs, VCGD had a clearance (Cl) value of 3·8±1·1 L h⁻¹ (mean±SD), a volume of distribution (V_ss) of 15±2 L, and a half-life (t_1/2) of 1·9±0·3 h. DIGD had Cl, V_ss, and t_1/2 values of 10±0·8 L h⁻¹, 19±3 L, and 1·6±0·2 h, respectively. Neither VCGD nor DIGD operated as chemical drug delivery systems (CDDSs) of glycine, valnoctic acid, or diisopropyl acetic acid and both showed antiepileptic profiles different from that of valproic acid (VPA). Both glycinamides were biotransformed to their glycine analogues with similar fractions metabolized ( f_m): 59±5% (VCGD) and 62±15% (DIGD). The two glycine metabolites, valnoctyl glycine (VCGA) and diisopropylacetyl glycine (DIGA), were also administered to the same dogs in order to calculate the above f_m values. Both VCGA and DIGA had higher Cl and lower V_ss values than VCGD and DIGD and therefore their mean t_1/2 values were 0·43±0·02 and 0·30±0·07 h, respectively. VCGA and DIGA were excreted mainly intact in the urine, with fractions excreted unchanged ( f_e) of 60±9 and 55±7%, respectively. The improved pharmacokinetic profile of VCGD and DIGD relative to their glycine analogues may explain the similarity of their anticonvulsant activity to that of valproyl glycinamide. The current study demonstrates the benefit of the structure–pharmacokinetic–pharmacodynamic relationship (SPPR) approach in developing and selecting a potent antiepileptic compound in intact animals based not only on its intrinsic pharmacodynamic activity but also on its improved pharmacokinetic profile. © 1997 John Wiley & Sons, Ltd.     

Home intravenous antibiotic treatment for febrile episodes in immune-compromised pediatric patients

The purpose of this work was to assess the feasibility of home intravenous antibiotic treatment (HIAT) for febrile episodes in immune-compromised (neutropenic, splenectomized), low-risk pediatric patients. Thirty hematology-oncology patients who presented to our emergency room from January 1993 to January 1995 and who suffered from a febrile episode and were considered at low risk for septic complications were immediately discharged on HIAT. Patients were followed for at least 3 weeks after recovery. Patients and parents were retrospectively questioned about adverse effects and about their degree of satisfaction with home treatment. Patients who required hospitalization during this period were considered unresponsive to HIAT and were analyzed for causes and adverse effects. Thirteen out of 60 (22%) febrile episodes, or eight out of 42 (19%) episodes of fever and neutropenia eventually led to hospitalization. Pseudomonas species infections were associated with the highest rate of unresponsiveness (88%). A central venous catheter infection developed in two cases following HIAT (two cases out of 640 days of therapy). No other complications were identified. No infection-related morbidity was observed. Patients and parents were highly satisfied with HIAT and wanted to use it again, if necessary. Immediate discharge on HIAT for low-risk pediatric immune-compromised patients suffering from a febrile episode is feasible, safe, and well accepted by patients and families. Patients who are found to have Pseudomonas infections should probably be hospitalized. Our results are preliminary and must be confirmed by a prospective, randomized trial before definite recommendations can be made. Med. Pediatr. Oncol. 30:95–100, 1998. © 1998 Wiley-Liss, Inc.     

A novel reconstructive technique after endoscopic expanded endonasal approaches: vascular pedicle nasoseptal flap

BACKGROUND: In patients with large dural defects of the anterior and ventral skull base after endonasal skull base surgery, there is a significant risk of a postoperative cerebrospinal fluid leak after reconstruction. Reconstruction with vascularized tissue is desirable to facilitate rapid healing, especially in irradiated patients. METHODS: We developed a neurovascular pedicled flap of the nasal septum mucoperiosteum and mucoperichondrium based on the nasoseptal artery, a branch of the posterior septal artery (Hadad-Bassagasteguy flap [HBF]). A retrospective review of patients undergoing endonasal skull base surgery at the University of Rosario, Argentina, and the University of Pittsburgh Medical Center was performed to identify patients who were reconstructed with a vascularized septal mucosal flap. RESULTS: Forty-three patients undergoing endonasal cranial base surgery were repaired with the septal mucosal flap. Two patients with postoperative cerebrospinal fluid leaks (5%) were successfully treated with focal fat grafts. We encountered no infectious or wound complications in this series of patients. One patient experienced a posterior nose bleed from the posterior nasal artery. This was controlled with electrocautery and the flap blood supply was preserved. CONCLUSION: The HBF is a versatile and reliable reconstructive technique for defects of the anterior, middle, clival, and parasellar skull base. Its use has resulted in a sharp decrease in the incidence of postoperative cerebrospinal fluid leaks after endonasal skull base surgery and is recommended for the reconstruction of large dural defects and when postoperative radiation therapy is anticipated.     

High-frequency oscillatory ventilators in burn patients: experience of Riley Hospital for Children

The objective of the study is to review a single institution's experience with high-frequency oscillatory ventilation (HFOV) and compare patient characteristics, outcomes, and complications with other reported studies of HFOV use in burn patients with acute respiratory distress syndrome and respiratory failure. This study is a retrospective chart review of the burn patients treated with HFOV in Pediatric Burn Unit at Riley Hospital for Children from October 1996 to April 2007. Patient data were collected, including demographics, percentage of TBSA burn, percentage of full-thickness burn, mechanisms of burn, settings on conventional mechanical ventilation and HFOV, and blood gas data before initiation of HFOV and at 1, 3, 6, 12, 24, 72 (3 days), 120 (5 days), 168 (7 days), 240 (10 days), and 336 hours (14 days). Length of stay, mortality, and complications were also included. HFOV was used 24 times in 21 patients between October 1996 and April 2007 with a mean age of 10 ± 11 years. At initiation of HFOV, the PaO2/FiO2 and oxygenation index values were 109 ± 26 and 36 ± 12, respectively. At stop, the PaO2/FiO2 improved to 166 ± 24 with an average increase from before HFOV of 57 ± 39 (P < .002). At 5 days of HFOV, oxygenation index improved to 14.1 ± 1.7 (P < .02) but did not significantly improve at discontinuation of HFOV at 28.8 ± 6.2 (P = .11). The mortality rate during admission to the burn unit was 29%. Barotrauma occurred in 38% of patients during HFOV. Severe hypercapnea was present briefly in 49% of patients, and this was refractory to standard treatment in 19%. In our experience, HFOV in severe burn patients has significant, early, and sustained improvement in oxygenation. Earlier institution of HFOV seems to significantly lower rates of barotraumas.