The uses of computer-assisted surgical navigation in trans-nasal pituitary gland surgery.

OBJECTIVES: To examine the use of computer-assisted surgery in transnasal pituitary gland surgery. PATIENTS AND METHODS: Twenty cases of transnasal pituitary gland surgery using a computer-assisted navigation system, carried out between 2002 and 2004, were retrospectively studied. The subjects consisted of 7 men and 13 women aged between 27 and 77 years of ages. The pituitary tumours included 18 macroadenomas, a microadenoma and a craniopharyngioma. Ten of the cases presented with visual field and/or visual acuity disturbances. Seven of the cases presented with endocrine disorders. A computed tomography scanner destined for navigation purposes was carried out 24 hours before the operation. The computer-assisted system used was the Digipointeur (Collin ORL) based on a system of spatial localization in electromagnetic fields. RESULTS: Tumour removal was complete in 50% of cases and partial, as judged by MRI 3 months after the procedure, in 45% of the cases. In 40% of cases, the preoperative visual disturbances had completely disappeared at 3 months. A considerable clinical improvement was observed in all of the other cases. Peroperative complications were limited to two breaches of the meninges and one peroperative hemorrhage during the excision of a macroadenoma invading the cavernous sinus, necessitating the suspension of the operation. CONCLUSION: In our experience, the use of a computer-assisted system in transseptal pituitary surgery gives reliable millimetric surgical precision in the localization of vital internal anatomical structures, optimizes surgical resection and increases levels of safety.

[Follow-up of adult patients with myelomeningocele]. / Suivi à l'âge adulte des patients porteurs de myéloméningocèle.

The adult outcome of spina bifida patients is fraught with multiple problems reflecting the multisystemic nature of the disease. These problems result in both mortality, actually caused in most cases by the shunt, and morbidity, mostly affecting locomotion and sphincter control. These patients can thus lose ambulation and suffer from worsening incontinence and kidney function. The result in the vast majority of cases is a poor functional and socioprofessional outcome. The patients' demands regarding their occupational and affective lives, as well as procreation, must be heard. This requires a multidisciplinary approach, and pediatric and adult, as well as patient education and financial support for maintaining the patient's autonomy and medical acts allowing the viability of continued medical care.

[Surgical treatment of cortical and subcortical cavernomas. General principles and personal series of 20 cases treated between 2000 and 2006]. / Traitement chirurgical des cavernomes corticaux et sous-corticaux. Principes généraux et série personnelle de 20 cas opérés entre 2000 et 2006.

The surgical treatment of cortical or subcortical hemispheric cavernomas is founded on a series of questions: Is the cavernoma located in an eloquent or non-eloquent area? Is the cavernoma tangent to the cortex and visible immediately after the dura opening or deep seated in the hemisphere? Does the cavernoma lie in the depth of a sulcus and identifiable on the pretrans-sulcal approach MRI? Will perilesional tissue have to be removed to cure the epilepsy? What is the appropriate technology for each particular case: preoperative functional MRI, angiography, preoperative stereotactic guidance, peroperative ultrasonography, neuronavigation, peroperative neurophysiology and cortical stimulation, preoperative MRI? Based on a personal series of 20 cases operated on between 2000 and 2006, we describe our personal experience.

[The ventrolateral position]. / La position ventro-latérale.

AIM: To propose an alternative to the sitting position and the other horizontal positions while maintaining the advantages of the sitting position and assuring maximum safety for the patient particularly with respect to the risk of air embolism. POSITION: The patient is positioned as for the sitting position with the median axis of the posterior cranial fossa prolonging the spinal axis. The head is maintained by a Mayfield head holder and is inclined without force. The patient rests laterally on the apron, the thorax and the lower limbs resting on cushions. The upper limbs rest on the arm rests interdependent with the table facilitating surgical access and rolling movements. DATA: Since 1993, this position was used for 556 patients. For 81.3% of the patients lesions were located in the posterior cranial fossa and for 12.75% in the supratentorial region. Access to the cervical area was achieved for 4.7% of the patients. RESULTS: This position gave us access to the lesions without specific difficulties, irrespective of the patient's morphology. There were no air embolism events and no capnographic anomaly was reported. CONCLUSION: Since discontinuing use of the sitting position in our institution, we have found that the ventrolateral position can replace the sitting position advantageously. It allowed us to approach lesions located in a large area, from the cervical spine to the supratentorial area located behind external auditory meatus, and was compatible with anesthetic and surgical requirements.

[Endovascular treatment of a cervical vertebral artery pseudoaneurysm using covered stents. One case report]. / Traitement par endoprothèses couvertes d'un faux anévrysme de l'artère vertébrale cervicale. A propos d'un cas chez une adolescente.

Covered stents have been successfully used in the treatment of fusiform aneurysms and post dissection aneurysms in peripheral arteries as well as in post-traumatic arteriovenous fistulas. We report a case where a pseudoaneurysm of the cervical vertebral artery was excluded by placement of two covered stents, preserving patency of the parent artery, in a 15-year-old patient.

[Cerebellar, pulmonary and cutaneous localizations of juvenile xanthogranuloma]. / Localisations cérébelleuse, pulmonaires et cutanées d'un xanthogranulome juvénile.

BACKGROUND: Juvenile xanthogranuloma is one of the most common non-langerhan cell histiocytoses in children. Usually cutaneous, there are disseminated forms. However, neurological localizations remain exceptional. CASE REPORT: We report the case of a cerebellar localization, associated with cutaneous and pulmonary lesions in a 13-month old child. Surgical treatment of the cerebellar lesion was associated with vinblastin chemotherapy, that led to total regression of the cutaneous and pulmonary lesions, neurological stabilization, without recurrence on the control IRM, after a period of 7 years. DISCUSSION: This is the second reported case of histologically documented cerebellar juvenile xanthogranuloma. In the event of cutaneous juvenile xanthogranuloma, the neurological examination must be attentive and supplemented, in case of any suspicion, by medical imaging. We believe that surgical treatment of neurological juvenile xanthogranuloma is necessary, in the event of symptomatic lesions and accessible to surgery. No consensus has been reached on subsequent treatments (radiotherapy, chemotherapy) and must be discussed according to the clinical profile and data in the literature.

Treatment of fluconazole-refractory oropharyngeal candidiasis with itraconazole oral solution in HIV-positive patients.

This open-label, multicenter trial evaluated the efficacy and safety of a new oral solution formulation of itraconazole in HIV+/AIDS patients with fluconazole-refractory oropharyngeal candidiasis. Seventy-four HIV+/AIDS patients with mycologically confirmed oropharyngeal candidiasis who failed fluconazole therapy (200 mg/day) were treated with 100 mg of itraconazole oral solution administered twice daily (200 mg/day) for 14 days. Patients who demonstrated an incomplete response to treatment were treated for an additional 14 days (28 days total). Clinical responders were eligible for participation in a separate 6-month maintenance protocol. If they declined further treatment, responders were monitored for 6 weeks posttreatment. The primary efficacy parameter was clinical response (i.e., no lesions or symptoms) at end of treatment. Fungal cultures were performed at baseline and at the end of treatment. Among the 74 patients who had mycologically confirmed, fluconazole-unresponsive, oropharyngeal candidiasis at baseline, 41 (55%) achieved a clinical response by day 28. The median time to response was 7 days (range, 7 to 28 days). Candida albicans was the most common pathogen isolated, either alone (62%) or in combination with another Candida species (31%). All 22 patients who entered the optional, off-therapy, 6-week follow-up phase relapsed; mean time to relapse was 13 days. Itraconazole oral solution was well-tolerated; adverse events were predominantly gastrointestinal disturbances. This trial demonstrates that itraconazole oral solution is a useful therapy in the treatment of HIV-infected patients with fluconazole-refractory oropharyngeal candidiasis.

Ketoconazole 2% shampoo in the treatment of tinea versicolor: a multicenter, randomized, double-blind, placebo-controlled trial.

BACKGROUND: Tinea versicolor is a common superficial fungal infection caused by a lipophilic yeast. This chronically recurring opportunistic infection is especially prevalent in tropical and semitropical regions. The topical short-term application of ketoconazole 2% shampoo may provide effective and safe therapy for tinea versicolor. OBJECTIVE: The purpose of this study was to evaluate the efficacy and safety of a single application (1 day) versus three daily applications (3 days) of ketoconazole 2% shampoo versus placebo shampoo in the treatment of mycologically confirmed tinea versicolor. METHODS: Three hundred twelve patients were included in the primary analyses for this 31-day study. Global evaluation scores were measured on days 10 and 31 with a 5-point scale (1 = healed to 5 = worsening), and a cellophane tape test was done at baseline and days 3, 10, and 31. Efficacy was assessed by clinical response, defined as both a global evaluation score of 1 (healed) and a negative cellophane tape test on day 31. Signs and symptoms of tinea versicolor (scaling, itching, erythema, hypopigmentation, hyperpigmentation) also were evaluated at baseline, day 10, and day 31 with a 4-point scale (0 = absent to 3 = severe). RESULTS: Both regimens of ketoconazole shampoo were significantly (P < .001) more effective than placebo for rate of clinical response, global evaluation scores, and mycologic outcomes (cellophane tape test). The clinical response rates at day 31 were 73%, 69%, and 5% for the 3-day ketoconazole, 1-day ketoconazole, and placebo groups, respectively. The difference in the efficacy of the two ketoconazole treatment regimens was not statistically significant. There were no significant differences between any of the treatment groups in the number of patients who experienced adverse events. No serious adverse events occurred and no patient withdrew from the trial prematurely because of an adverse event. CONCLUSION: Ketoconazole 2% shampoo, used as a single application or daily for 3 days, is safe and highly effective in the treatment of tinea versicolor.

Enhanced bioavailability of itraconazole in hydroxypropyl-beta-cyclodextrin solution versus capsules in healthy volunteers.

The bioavailabilities and bioequivalences of single 200-mg doses of itraconazole solution and two capsule formulations were evaluated in a crossover study of 30 male volunteers. The two capsule formulations were bioequivalent. The bioavailabilities of the solutions itraconazole and hydroxyitraconazole were 30 to 33% and 35 to 37% greater, respectively, than those of either capsule. However, the maximum concentrations of the drug in plasma (Cmax), the times to Cmax, and the terminal half-lives were comparable for all three formulations. These data indicate that the bioavailabilities of itraconazole and hydroxyitraconazole are enhanced when administered as an oral solution instead of capsules.

Food interaction and steady-state pharmacokinetics of itraconazole oral solution in healthy volunteers.

STUDY OBJECTIVES: To evaluate the effect of food on the bioavailability of itraconazole (ITR) hydroxypropyl-beta-cyclodextrin (HP-beta-CD) solution under multiple-dose to steady-state conditions, and to determine the pharmacokinetics of ITR solution at steady state. DESIGN: Open-label, randomized, multiple-dose, crossover study SETTING: University-affiliated health center. PATIENTS: Thirty healthy men randomized to one of two treatment sequences (fasted-fed, fed-fasted). INTERVENTIONS: Subjects were either fasted or fed a standard breakfast before receiving ITR oral solution 200 mg once/day for 15 days. Crossover phases were separated by a 4-week washout period. MEASUREMENTS AND MAIN RESULTS: On day 1, blood samples were collected before the dose (time zero) and 0.5, 1, 2, 3, 4, 5, 6, 8, 12, and 24 hours after the dose. Trough samples were obtained before the dose on days 4, 7, 12, 13, and 14. On day 15, samples were obtained at the same times as day 1, and at 36, 48, 72, 96, 168, 240, and 360 hours. Samples were analyzed by high-performance liquid chromatography for ITR and its major metabolite hydroxyitraconazole (OH-ITR). Urine was collected on days 1 and 15 before and 0-8 and 8-24 hours after the dose; HP-beta-CD was measured by size-exclusion chromatography. Mean bioavailabilities of ITR and OH-ITR were 43% and 38% higher, respectively, when ITR solution was taken as a single dose under fasted conditions. With multiple dosing, steady state was achieved by day 14. At steady state, mean bioavailabilities were 29% and 17% higher, respectively, in the fasted state; terminal half-life was similar under fasted and fed conditions (mean 39.8 and 37.5 hrs for ITR, respectively; 27.3 and 26.2 hrs for OH-ITR, respectively). HP-beta-CD was eliminated almost exclusively in urine. CONCLUSION: The bioavailability of ITR and OH-ITR is enhanced when ITR oral solution is given in the fasted state; this was true for both single and multiple dosing to steady state.

[Unilateral endonasal approach to hypophyseal adenomas]. / Abord endonasal unilatéral des adénomes hypophysaires.

The endonasal approach for transsphenoidal hypophysectomy is a simple technique for exposing the floor of the sella turcica. In our institution we have operated 162 patients (64 microadenomas and 98 macroadenomas), over a ten-year period, by using that approach. The floor of the sella turcica is exposed through an incision performed posteriorly to the nostril at the junction of cartilaginous and bony septum. Postoperative rhinological complications are less frequently observed after unilateral endonasal approach than after sublabial one, and it is more comfortable for the patient. The morbidity of unilateral endonasal transsphenoidal approach is comparable to that of other series.

Effect of food and gastric acidity on absorption of orally administered ketoconazole.

Effects of food and gastric acidity on the bioavailability of ketoconazole tablets were investigated in 12 volunteers using a six-treatment, randomized, Latin-square crossover design. All volunteers received all treatments, as follows: (A) ketoconazole 200 mg administered after a fast; (B) ketoconazole 200 mg with a standardized high-fat meal; (C) ketoconazole 200 mg with a standardized high-carbohydrate meal; (D) ketoconazole 200 mg after pretreatment with glutamic acid hydrochloride 680 mg as capsules; (E) ketoconazole 200 mg in a simulated achlorhydric state induced with cimetidine and sodium bicarbonate; and (F) ketoconazole 200 mg administered with glutamic acid hydrochloride in a simulated achlorhydric state. Ketoconazole concentrations were measured by high-performance liquid chromatography in plasma samples drawn immediately before and at various times over 24 hours after drug administration. Bioavailability variables, including natural logarithm transformation for area under the concentration-time curve (AUC), were subjected to analysis of variance followed by Duncan's Multiple Range testing. Treatments B and C significantly prolonged the times required to achieve the peak plasma ketoconazole concentration, and treatment C also significantly reduced the peak plasma ketoconazole concentration (Cmax) compared with treatment A. There was a trend toward increased AUC values with treatment B and decreased AUC values with treatment C. Treatment D produced a higher Cmax compared with treatment A, and treatment E produced large, significant reductions in Cmax and AUC values compared with treatment A. Treatment F significantly increased AUC values and Cmax compared with treatment E.(ABSTRACT TRUNCATED AT 250 WORDS)

Trichlorfon-induced congenital cerebellar hypoplasia in neonatal pigs.

The neuroteratogenicity of trichlorfon was evaluated in 3 groups of pregnant sows (8/group). The treatments were: control (no trichlorfon), trichlorfon (60 mg/kg of body weight) in the feed only on day 55 of gestation, or trichlorfon (60 mg/kg of body weight) in the feed on day 55 and day 70 of gestation. One week after farrowing, all newborn pigs were removed from the sows and were euthanatized. Brain and cerebellum weights of the newborn pigs were recorded. Mean cerebellum weights and cerebellum/total brain weight ratios of the neonatal pigs were 3.780 and 0.106 (group 1, n = 26), 3.183 and 0.098 (group 2, n = 42), and 2.986 and 0.088 (group 3, n = 61). Although trichlorfon interfered with cerebellar development and the severity of the trichlorfon-induced cerebellar hypoplasia was dosage-related, ataxia did not develop in the neonatal pigs.

Characterization of a Pasteurella multocida (serotype B) bovine pneumonic pasteurellosis model and the effect of antimicrobials during peracute infection.

A method to produce bovine pneumonic pasteurellosis for experimental purposes was studied and the clinical response of experimentally infected calves to selected antimicrobials was characterized. Male Holstein calves stressed with multiple hot and cold water applications followed by intratracheal inoculation of broth cultures of Pasteurella multocida serotype B developed acute clinical illness consistent with pneumonia. Infected, untreated calves consistently developed classic pneumonic pasteurellosis, infected calves treated with either oxytetracycline or sulfadimethoxine recovered from acute clinical disease, and the uninfected controls remained healthy. This disease model offers potential for use in pharmacokinetic and target tissue drug concentration studies and for dosage titration of drugs intended for treatment of bacterial pneumonias.

Effects of poly I:C in porcine iron deficient neutropenia.

Withholding iron dextran treatment normally given to pigs at 1-3 days of age to prevent anemia resulted also in neutropenia. Polyinosinic acid:polycytidylic acid (poly I:C) at 0.5 mg/kg IV at 25 days of age resulted in induction of putative interferon 2 to 24 hours later, with significantly (P less than 0.05) lower concentrations in iron-deficient (Fe-) female pigs than in iron-supplemented (Fe+) female pigs. Poly I:C caused several transient toxic manifestations, including elevations in blood urea nitrogen, creatinine, aspartate aminotransferase, potassium (K), total bilirubin and phosphorus (P), marked leukopenia (both neutropenia and lymphopenia), and declines in serum albumin, calcium, cholesterol, glucose and globulin. Certain blood chemistries before poly I:C were significantly (P less than or equal to 0.05) different: albumin, globulin, cholesterol and K were higher in females than in males; albumin, globulin, glucose, P and K were higher in Fe- than in Fe+ pigs; and total carbon dioxide was higher in Fe+ than in Fe- pigs.

Disposition of ampicillin administered intravenously and intratracheally to young calves.

The profile of the blood concentration of ampicillin vs time was compared in 24 calves after ampicillin administration (10 mg/kg body weight) by the intratracheal (i.t.) and the intravenous (i.v.) routes in a crossover study. In a subsequent study, 12 of the calves were given ampicillin i.v. and 12 were given ampicillin i.t.; at 15 min and 2 h after drug administration, the calves were killed and lungs, kidneys, liver, urine and plasma were collected for ampicillin assay. The mean ampicillin concentration in blood after i.v. treatment was significantly (P less than 0.01) higher than after i.t. treatment. The mean ampicillin level in lungs after i.t. treatment was significantly higher than the level after i.v. treatment, but concentrations in kidneys, liver, urine and plasma after i.v. treatment were higher (but not significantly) than those after i.t. treatment.