Clinical and economic implications of the use of nanoparticle paclitaxel (Nanoxel) in India.

Paclitaxel (Taxol), one of the most commonly used chemotherapeutic agents, is poorly soluble in water and requires cremophor, which often causes infusion reactions, as a solvent. Nanoxel, a nanoparticle formulation of the taxane, has been approved by the Indian regulatory authority. In the present article, we aim to describe the experience with the use of Nanoxel in India and its clinical and economic implications. We present three retrospective series in a common practice environment and an economic model. The first series shows no reactions in 596 Nanoxel infusions; the second series shows comparable adverse events other than infusion reactions between 83 patients who received Nanoxel and 32 treated with conventional paclitaxel. The third reveals comparable clinical outcomes for 51 patients treated with Nanoxel or conventional paclitaxel for gastroesophageal tumors. Finally, we describe an economic model which estimates savings of 21 580 Indian rupees per cycle with Nanoxel vis-à-vis conventional paclitaxel in the treatment of solid tumors in India. In conclusion, in an era in which the greatest challenge we face as medical oncologists is how to conciliate hard-won and incremental--but small--improvements in survival with exponentially rising drugs costs, it is refreshing to see a potential new formulation of a commonly used drug that may actually generate cost-savings while improving clinical outcomes and patient well-being. Further studies are clearly warranted to determine the optimal dose and schedule for Nanoxel as well as its comparative effectiveness to cremophor-based paclitaxel.

Relationship between the deep peroneal nerve and dorsalis pedis artery in the foot: a cadaveric study.

The aim of our work was to study the relationship between deep peroneal nerve (DPN) and dorsalis pedis artery (DPA) so that the frequency of these variations can be kept in mind by the angiographers and surgeons to ensure safe surgical approach during flap surgery. Ninety-two legs in 46 cadavers were dissected to study the relationship between DPN and DPA on the dorsum of the foot. The relationship of neurovascular bundle of the dorsum of the foot was classified into four types. Type I: division of the DPN distal to the midpoint between the two malleoli (observed in 26 limbs). In Type II, the division of the DPN was midway between the two malleoli (seen in 20 limbs). Both Type I and II are further divided into two subtypes (a and b) depending upon the crossing pattern of terminal branches of the DPN over DPA. In Type III, multiple branches of DPN were noted in two limbs. In Type IV, the looping pattern of DPN around the DPA was considered and was seen in eight limbs. Awareness of possible variations in the relationship of the DPA to DPN on the dorsum of the foot is important for vascular and reconstructive surgeons. Because it might help in decreasing confusion when considering treatment options like microvascular anastomosis in reconstruction of the leg.

Accessory brachialis muscle: a case report.

Variations of arm flexors are not uncommon with the exception of brachialis muscle. The role of brachialis is critical as it is the primary flexor of the elbow joint. Variations of brachialis are rare in literature. We present a case of an accessory-brachialis muscle (AcBr), found during routine cadaveric dissection. The AcBr originated from the lateral aspect of the brachialis muscle and lateral intermuscular septum. During its course towards the elbow, it crossed over the radial nerve and the distal tendon splits into two. The medial slip ran over the ulnar artery and merged with the deep fascia covering the pronator teres muscle, whereas lateral slip was inserted to the fascia covering the supinator. In the ipsilateral arm, an additional lateral cutaneous nerve of forearm (LCNF) was found coursing over the brachialis muscle medial to the LCNF. Clinical consideration of the present variations has been discussed. The present variation should be considered in the etiology of radial-tunnel syndrome (RTS).

Weakness of extensor hallucis longus after removal of non-vascularised fibula as an autograft.

The upper three-quarters of the fibula is commonly used as a non-vascularised autograft. Subsequent to this isolated weakness of extensor hallucis longus may occur. We have studied 26 patients in whom the upper and middle thirds of the fibula had been harvested as a graft through Henry's posterolateral approach. Isolated weakness of extensor hallucis longus was found after operation in ten patients but not in the remainder. EMG and nerve-conduction studies confirmed injury of the nerve to extensor hallucis longus in those with weakness. We dissected 40 cadaver limbs and found that those in which the nerve to extensor hallucis longus ran close to the fibular periosteum were at risk. The injury is mostly incomplete and recovery occurs within four to six months.

Frequency analysis of EEG in rats during the preconvulsive period of O2 poisoning.

The EEG of rats exposed to hyperbaric oxygenation (HBO) displays electrical discharges prior to the onset of generalized clinical convulsions (GCC). The characteristics of preconvulsive electrocorticogram (ECoG) in awake, unrestrained rats exposed to 3, 4, and 5 ATA O2 were determined. The ECoG was continuously monitored and analyzed by a hybrid analog-digital system until GCC developed. The time integral of rectified voltage of the individual delta (0.5-4 c/s), theta (4-8 c/s), alpha (8-13 c/s) beta 1 (13-20 c/s), and beta 2 (20-30 c/s) bands were plotted vs. time. An elevation in delta and a temporary reduction in alpha activity before the onset of the first electrical discharge (FED) was observed. There was a continuous reduction in beta 1 and beta 2 frequency bands during the entire pre-electrical discharge period. The activity of theta, and alpha frequency bands was significantly elevated only about 1 min before the onset of the FED, and of beta 1 and beta 2 during appearance of the FED. The possible relationship between the occurrence of preconvulsive EEG changes and pathological effects of hyperbaric oxygenation is discussed.

Infants of diabetic mothers--an analysis of 50 cases.

In a prospective study of 50 infants of diabetic mothers, 40% were large, 44% appropriate and 16% small for gestational age, 36% were preterm, 24% of the mothers were managed by dietary modification, 62% received insulin, 10% were treated with oral hypoglycemic agents while 4% did not receive any treatment as they were diagnosed postpartum, 58% mothers, underwent cesarean section (38% elective and 20% emergency procedures), 34% had normal vaginal deliveries, 6% were delivered by forceps and 2% by vacuum. Sixty-four per cent were infants of gestational diabetic (IGDM) and 36% of preconceptional diabetic mothers (IPDM). The morbidity and mortality was lesser in IGDM compared to IPDM. Hypoglycemia was documented in 50%, polycythemia in 20%, birth asphyxia in 18%, respiratory distress syndrome and hypocalcemia in 14% each, transient tachypnea of the newborn in 12%, hyperbilirubinemia in 8%, congenital anomalies in 4% and cardiomyopathy, birth trauma and meconium aspiration in 2% each. Pretherapy serum insulin levels were estimated in 10 babies, and 6 babies were subjected to 2D-echocardiography. The overall mortality was 20%. Infants born to mothers on oral hypoglycemic agents had a poor outcome.

Formulation and evaluation of gastroretentive microballoons containing baclofen for a floating oral controlled drug delivery system.

The objective of the present study was to fabricate and evaluate a multiparticulate oral gastroretentive dosage form of baclofen characterized by a central large cavity (hollow core) promoting unmitigated floatation with practical applications to alleviate the signs and symptoms of spasticity and muscular rigidity. Solvent diffusion and evaporation procedure were applied to prepare floating microspheres with a central large cavity using various combinations of ethylcellulose (release retardant) and HPMC K4M (release modifier) dissolved in a mixture of dichloromethane and methanol (2:1). The obtained microspheres (700-1000 µm) exhibit excellent floating ability (86 ± 2.00%) and release characteristics with entrapment efficiency of 95.2 ± 0.32%. Microspheres fabricated with ethylcellulose to HPMC K4M in the ratio 8.5:1.5 released 98.67% of the entrapped drug in 12 h. Muscle relaxation caused by baclofen microspheres impairs the rotarod performance for more than 12 h. Abdominal X-ray images showed that the gastroretention period of the floating barium sulfate- labeled microspheres was no less than 10 h. The buoyant baclofen microspheres provide a promising gastroretentive drug delivery system to deliver baclofen in spastic patients with a sustained release rate.

Estimation of factors from natural and anthropogenic radioactivity present in the surface soil and comparison with DCF values.

A study was conducted to evaluate the absorbed rate coefficient of (238)U, (232)Th, (40)K and (137)Cs present in soil. A total of 31 soil samples and the corresponding terrestrial dose rates at 1 m from different locations were taken around the Anushaktinagar region, where the litho-logy is dominated by red soil. A linear regression model was developed for the estimation of these factors. The estimated coefficients (nGy h(-1) Bq(-1) kg(-1)) were 0.454, 0.586, 0.035 and 0.392, respectively. The factors calculated were in good agreement with the literature values.

Analysis of hydrological trend for radioactivity content in bore-hole water samples using wavelet based denoising.

A wavelet transform based denoising methodology has been applied to detect the presence of any discernable trend in (137)Cs and (90)Sr activity levels in bore-hole water samples collected four times a year over a period of eight years, from 2002 to 2009, in the vicinity of typical nuclear facilities inside the restricted access zones. The conventional non-parametric methods viz., Mann-Kendall and Spearman rho, along with linear regression when applied for detecting the linear trend in the time series data do not yield results conclusive for trend detection with a confidence of 95% for most of the samples. The stationary wavelet based hard thresholding data pruning method with Haar as the analyzing wavelet was applied to remove the noise present in the same data. Results indicate that confidence interval of the established trend has significantly improved after pre-processing to more than 98% compared to the conventional non-parametric methods when applied to direct measurements.

Effect of various polymers concentrations on physicochemical properties of floating microspheres.

Floating microspheres have emerged as a potential candidate for gastroretentive drug delivery system. For developing a desired intragastric floatation system employing these microspheres, it is necessary to select an appropriate balance between buoyancy and drug releasing rate. These properties mainly depend on the polymers used in the formulation of the microspheres. Hence it is necessory to study the effect of these polymer concentrations on the various physicochemical properties of the microspheres. Floating microspheres were prepared by emulsion solvent evaporation technique utilising different polymers such as ethyl cellulose, Eudragit(®) RS and Eudragit(®) RL by dissolving them in a mixture of dichloromethane and methanol. Release modifiers studied were hydroxypropyl methylcellulose K4M, hydroxypropyl methylcellulose E50 LV and Eudragit(®) EPO. Prepared microspheres were analysed for particle size, surface morphology, entrapment efficiency, buoyancy, differential scanning calorimetry and in-vitro drug release. Ethyl cellulose and Eudragit(®) EPO resulted microspheres with high percentage yield, excellent spherical shape but had very less buoyancies with a high cumulative drug release. Ethyl cellulose microspheres prepared using hydroxypropyl methylcellulose K4M showed more sustained drug release and high buoyancies than that of the microspheres formulated with the hydroxypropyl methylcellulose E50 LV. Amongst these hydroxypropyl methylcellulose E50 LV showed good balance between buoyancy and the drug release.

Effect of vitamin E administration on histopathological changes in rat testes following torsion and detorsion.

INTRODUCTION: Testicular torsion is a medical emergency, especially in male neonates and adolescents. It is a common clinical outcome and a significant urological issue. From the literature, it is evident that the use of antioxidants in the prevention of testicular reperfusion injury following detorsion is conflicting. This study was conducted to investigate the role of vitamin E in testicular reperfusion injury following detorsion. METHODS: Male Wistar albino rats were divided into Groups I, II, III and IV. Only Group IV rats were pre-treated with vitamin E 100 mg/kg body weight for 30 days. Ischaemia was induced manually by rotating the rat testis to 720 degrees clockwise and counter rotating for reperfusion. The testes were fixed in Bouin's fluid and processed for histopathological examination. RESULTS: A significant decrease in the standard tubular diameter and epithelial height was observed in Group III rats compared to those in Groups I and II. However, the seminiferous tubules in Group IV rats showed recovery in the standard tubular diameter and epithelial height when compared with the untreated control groups. CONCLUSION: The results showed that vitamin E, when administered before torsion of the spermatic cord in rats, provided significant protection against acute testicular torsion and detorsion injury.

Lymph node central necrosis on computed tomography as predictor of extracapsular spread in metastatic head and neck squamous cell carcinoma: pilot study.

OBJECTIVE: This study aimed (1) to investigate the relationship between the presence of lymph node central necrosis, viewed on pre-operative computed tomography imaging, and the occurrence of histopathologically determined metastatic lymph node extracapsular spread and (2) to determine whether a larger scale study would be valuable. MATERIALS AND METHODS: Pre-operative computed tomography scans, surgical records and post-operative histopathological analysis results were reviewed for 19 consecutive neck dissections performed in 17 patients with head and neck squamous cell carcinoma. RESULTS: A total of 20/26 (77 per cent) lymph nodes with central necrosis had extracapsular spread on histopathological analysis. Twenty of 21 (95 per cent) lymph nodes with extracapsular spread had central necrosis on pre-operative computed tomography. Thirty-four of 40 (85 per cent) lymph nodes without extracapsular spread had no evidence of central necrosis on computed tomography. Only three of 12 (25 per cent) patients with lymph node central necrosis identified on pre-operative computed tomography were found to have actual necrosis on final histopathological analysis. CONCLUSIONS: Lymph node central necrosis viewed on pre-operative computed tomography scans is a useful indicator of metastatic lymph node extracapsular spread, with a sensitivity of 95 per cent, a specificity of 85 per cent, a positive predictive value of 69 per cent and a negative predictive value of 98 per cent. Lymph node diameter is not a sensitive indicator of extracapsular spread.

Anatomy of plantaris muscle: a study in adult Indians.

AIM: The plantaris muscle (PM) and its tendon is subject to considerable variation in both the points of origin and of insertion. The present study was carried out to fi nd the different types of origin, insertion and possible variations of the PM in the population of southern costal region of India. MATERIALS AND METHODS: 52 embalmed (Formalin fixed) cadaver lower limbs of 26 males (age ranged 48-79 years, mean age 68 years) were dissected, to study the origin and insertion of PM. Various dimensions (length and width) of plantaris muscle belly and its tendon were also measured. RESULTS: Three types of origin and equal number of insertion were noticed in the present study. The PM took origin from type I: Lateral Supracondylar ridge, Capsule of Knee joint and Lateral head of gastrocnemius in 73.07% cases; type II: Capsule of Knee joint and Lateral head of gastronemius in 5.76% cases; type III: Lateral Supracondylar ridge , Capsule of Knee joint , Lateral head of gastrocnemius and fibular collateral ligament in 13.46% cases. The plantaris tendon was inserted into type I: to the flexor retinaculum of foot in 28.84% cases; type II: independently to the os calcaneum in 36.53% cases; type III: to the tendocalcaneus at various levels in 26.92% cases. In four lower limbs (7.69%) the plantaris muscle was completely absent. Additionally the length and width of the plantaris muscle and its tendon were measured to know any side difference. There were no statistically significant differences between the measurements of left and right side (p>0.05). CONCLUSION: Present study will help the surgeons while attempting various surgical procedures in and around the posterior aspect of knee involving plantaris.