Surgery for Syringomyelia: An Analysis Based on 163 Surgical Cases

Summary ? Object. The authors analyzed the cases of 163 patients with syringomyelia to assess the appropriate surgical procedure. Methods. Depending on the aetiological factors and treatment considerations the series was classified into three groups. Group I were cases where there was no definite demonstrable aetiological factor; Group II cases had basilar invagination and/or Chiari malformation; and Group III consisted of cases where the syrinx was secondary to an obvious aetiology, such as a mass lesion either in the posterior cranial fossa or in the spine or a severe kyphotic spinal deformity. Post-traumatic syringomyelia and syrinx in association with spina bifida were not studied. Conclusions. We concluded that for Group I cases syringosubarachnoid shunting is the ideal form of treatment. In Group II cases foramen magnum bony decompression is satisfactory and physiological. Good results were obtained even in cases where either a foramen magnum decompression alone or in combination with a syringo-subarachnoid shunt was done. Only syringosubarachnoid shunt (without a foramen magnum decompression) in Group II cases was found to produce poor outcome. Group III cases should be treated for the primary aetiological problem. Only syrinx drainage procedure without treatment of aetiology in these cases produced poor results. It was observed that clinical outcome rather than radiological improvement is the reliable indicator of the surgical result.     

Value of ultrasonography in laryngeal and laryngopharyngeal cancers

High-resolution sonography has improved in the past few years and has become a very valuable tool in the diagnosis of diseases of the head and neck. Ultrasonography (US) is commonly the first imaging modality after clinical examination. It is inexpensive, noninvasive and is easily tolerated by patients. It provides valuable diagnostic information with a high degree of diagnostic accuracy. This article provides the most up-to-date information about the indications, findings and limitations of high-resolution sonography in the evaluation of laryngeal and laryngopharyngeal cancers.     

Influence of glucose kinetics on plasma lactate concentration and energy expenditure in severely burned patients

BACKGROUND: In critically ill patients, elevation in the plasma lactate concentration has traditionally been interpreted as indicating a deficiency in oxygen availability and is often an impetus to increase oxygen delivery clinically. However, another possible basis for increased lactate concentrations may be simply a mass effect from increased pyruvate availability (i.e., accelerated glycolysis). METHODS: In six hypermetabolic burned patients, the rates of glucose production and oxidation were quantified using a tracer infusion of 6,6 d2 glucose combined with indirect calorimetry. Measurements were obtained after a 9-hour fast and after a 3-hour infusion of unlabeled glucose at 30 micromol/kg/min. No patient was overtly septic, hypoxic, or hypovolemic. RESULTS: The infusion of glucose significantly increased the arterial glucose concentration and rate of glucose oxidation, with a corresponding increase in the arterial plasma concentration of lactate and pyruvate. Resting energy expenditure and oxygen consumption were not affected by the infusion of glucose. CONCLUSIONS: These findings show that elevations in plasma lactate in severely injured patients may, in part, be related to increases in glucose flux and not entirely a reflection of any deficit in oxygen availability. Such findings highlight a potential pitfall for interpreting plasma lactate concentrations as an index of tissue oxygen availability in hypermetabolic patients.     

Comparative preclinical and clinical pharmacokinetics of a cremophor-free, nanoparticle albumin-bound paclitaxel (ABI-007) and paclitaxel formulated in Cremophor (Taxol).

PURPOSE: To compare the preclinical and clinical pharmacokinetic properties of paclitaxel formulated as a Cremophor-free, albumin-bound nanoparticle (ABI-007) and formulated in Cremophor-ethanol (Taxol). EXPERIMENTAL DESIGN: ABI-007 and Taxol were given i.v. to Harlan Sprague-Dawley male rats to determine pharmacokinetic and drug disposition. Paclitaxel pharmacokinetic properties also were assessed in 27 patients with advanced solid tumors who were randomly assigned to treatment with ABI-007 (260 mg/m(2), 30 minutes; n = 14) or Taxol (175 mg/m(2), 3 hours; n = 13), with cycles repeated every 3 weeks. RESULTS: The volume of distribution at steady state and clearance for paclitaxel formulated as Cremophor-free nanoparticle ABI-007 were significantly greater than those for paclitaxel formulated with Cremophor (Taxol) in rats. Fecal excretion was the main elimination pathway with both formulations. Consistent with the preclinical data, paclitaxel clearance and volume of distribution were significantly higher for ABI-007 than for Taxol in humans [21.13 versus 14.76 L/h/m(2) (P = 0.048) and 663.8 versus 433.4 L/m(2) (P = 0.040), respectively]. CONCLUSIONS: Paclitaxel formulated as ABI-007 differs from paclitaxel formulated as Taxol, with a higher plasma clearance and a larger volume of distribution. This finding is consistent with the absence of paclitaxel-sequestering Cremophor micelles after administration of ABI-007. This unique property of ABI-007 could be important for its therapeutic effectiveness.     

Bexarotene and erlotinib for aerodigestive tract cancer.

PURPOSE: The epidermal growth factor receptor (EGFR) and cyclin D1 are overexpressed in lung carcinogenesis. The rexinoid, bexarotene, represses cyclin D1 and EGFR expression in vitro. It was hypothesized that combining bexarotene with the EGFR inhibitor, erlotinib, would augment clinical activity. PATIENTS AND METHODS: In vitro studies and a phase I clinical trial were performed. Twenty-four patients with advanced aerodigestive tract cancers were enrolled; 79% had non-small-cell lung cancer (NSCLC). The primary objective was to determine the maximum-tolerated dose. Clinical activity was a secondary objective. RESULTS: Combining erlotinib with bexarotene enhanced growth suppression in vitro compared with each single-agent treatment. This cooperatively repressed cyclin D1 expression. Clinically, the most frequent toxicities were mild hypertriglyceridemia and skin rash. Two serious treatment-related adverse events occurred (creatine phosphokinase elevation attributed to antilipid therapy and a case of generalized pain). Five objective responses (four partial and one minor) were observed in NSCLC patients. Responses were observed in males and smokers. EGFR sequence analyses did not reveal activating mutations in tumors from assessable responding patients. Median time to progression was 2.0 months; overall survival time was 14.1 months; and 1-year survival rate was 73.8%. CONCLUSION: The recommended phase II doses are erlotinib 150 mg/d and bexarotene 400 mg/m2/d orally. These agents can be administered in combination at the recommended single-agent doses without added toxicity. Overall survival and clinical features of responding patients differ from prior reports of single-agent erlotinib treatment. These findings are encouraging and warrant further investigation of this regimen.     

Rigid and flexible docking studies on PPAR-γ agonists: key interactions for a better antihyperglycemic activity and in silico pharmacodynamic activity versus experimental in vivo activity

We report both automated rigid and flexible ligand docking simulations performed on fifty peroxisome proliferator-activated receptor (PPAR-γ) agonists, namely, glitazones. The binding conformations and binding affinities of these agonists were obtained by the use of the Autodock 4.1 with Lamarckian genetic algorithm (LGA). All the 50 flexible docks are considered as well-docked as all of them were bound to the ligand binding domain of PPAR-γ. The predicted binding affinity values (pKa) were found to have some degree of correlation with their experimental in vivo activity values. The head group hydrogen bond interactions via H323 and H449 histidine residues were found to play a significant role. The results obtained will be valuable in designing newer selective PPAR-γ agonists.     

Spontaneous evolution of an unusual cortical malformation in SOX2 anophthalmia syndrome

Brain malformations such as agenesis and dysgenesis of corpus callosum, pituitary hypoplasia, hypothalamic hamartoma, mesial temporal periventricular heterotopia, and abnormally oriented and misshapen hippocampi have been described with SOX2 gene mutations. A neocortical malformation is presented here in association with SOX2 deletion that over time underwent spontaneous evolution and decrease in size.