Neonatal hyperlipidemia with pancreatitis: Novel gene mutation of lipoprotein lipase.

Lipoprotein lipase (LPL) deficiency is an autosomal recessive metabolic disorder with varying presentation in infancy and childhood, whereas clinical manifestations are rare in neonatal period. The estimated prevalence is one in a million births. A 23-day-old baby was admitted with complaints of fever, vomiting, and lethargy. Blood sample drawn appeared lipemic. Lipemia retinalis was noted on funduscopic examination. Biochemical analysis revealed abnormal lipid profile with severe hypertriglyceridemia (10,300 mg/dL) and elevated serum lipase level (517 IU/L) indicative of LPL deficiency with acute pancreatitis. LPL deficiency was suspected and was confirmed by molecular genetic testing, which revealed a novel mutation in LPL gene. Dietary management and gemfibrozil were started following which serum triglyceride level decreased and serum lipase level normalized. The patient is following up regularly for growth and development monitoring.

E-Cadherin truncation and sialyl Lewis-X overexpression in oral squamous cell carcinoma and oral precancerous conditions.

The present study aimed to determine significance of E-cadherin, a cell adhesion molecule, and sialyl Lewis-X (sLeX), a cell surface antigen, in oral carcinogenesis. Expressions of E-cadherin and sLeX were detected using western blot analysis from oral malignant (n=25), and oral precancerous tissues (OPC, n=20) and their adjacent normal tissues. An altered expression of E-cadherin (E-cad) and sLeX was observed in malignant and precancerous tissues. E-cad western blot revealed presence of two bands, a 120 kDa (native, E-cad120) and a 97 kDa (known as truncated E-cad97). The accumulation of truncated E-cad97 and sLeX in malignant and OPC tissues compared to their adjacent normal tissues was observed. Receiver's Operating Characteristics (ROC) curve analysis showed good discriminatory efficacy of E-cad97, E-cad97:120 ratio and sLeX between the malignant and adjacent. normal tissues. Further, a positive correlation of E-cad97 and sLeX overexpression with advanced stage of the disease and lymphnode metastasis was observed. The data suggest that E-cadherin truncation and sLeX overexpression are early events which may facilitate the tumor cells to metastasize. Also, overexpression E-cad97 and sLeX in OPC tissues may be useful to predict metastatic potentials of tumors at an early stage of oral carcinogenesis. Key words: Oral cancer, oral precancerous conditions, E-cadherin, sialyl Lewis-X, metastasis.

Ultra low dose interleukin-2 therapy promotes a type 1 cytokine profile in vivo in patients with AIDS and AIDS-associated malignancies.

This study was undertaken to determine if prolonged daily subcutaneous administration of ultra low dose IL-2 could influence the constitutive endogenous production of a type 1 (IFN-gamma) cytokine in patients with AIDS or AIDS-associated malignancies. Using a quantitative reverse transcription PCR assay, we demonstrate that daily administration of one type 1 cytokine, IL-2, for 3 mo increases significantly the constitutive endogenous gene expression of another type 1 cytokine, IFN-gamma, in vivo. The predominant source of IFN-gamma appears to be IL-2-expanded natural killer cells and CD8(+) T cells. Moreover, PBMC obtained from these patients during IL-2 therapy showed normalization of a profound deficit in IFN-gamma protein production after stimulation with extracts from infectious agents in vitro. Our data suggest that prolonged exogenous administration of a type 1 cytokine in a nontoxic fashion to patients with AIDS and AIDS-associated malignancies can enhance significantly the endogenous type 1 cytokine profile in vivo. Consequently, ultra low dose IL-2 therapy has the potential to improve the immunodeficient hosts' immune response to infectious pathogens that require IFN-gamma for clearance.

Photoassociation in cold atoms via ladder excitation.

We explore 2-color photoassociative ionization in cold Rb vapor and present experimental evidence that the molecular ions are produced from the stepwise excitation of a ladder of molecular states. We also explore a new process, dubbed photoassociative-dissociative ionization, by which atomic ions are created by excitation through a ladder of molecular states, finally autoionizing to a dissociative potential curve of Rb2+. We submit that these experiments could be the starting point for the same sort of high resolution spectroscopy that has already been done for lower electronic states of cold Rb2 at large internuclear separation.

Role of pretherapeutic biomarkers in predicting postoperative radiotherapy response in patients with advanced squamous cell carcinoma.

PURPOSE: To assess the role of biomarker levels in predicting radiotherapy (RT) response in patients with squamous cell carcinoma of buccal mucosa treated with postoperative RT. MATERIALS AND METHODS: Thirty-one patients with squamous cell carcinoma of buccal mucosa who received postoperative RT were enrolled for the study. Glutathione S-transferase (GST), glutathione reductase (GR), superoxide dismutase (SOD) and catalase activity were analysed from primary tumour and adjacent normal mucosa of the same patients before RT. p53 and p21ras were localized immunohistochemically. RESULTS: Enzyme activation was predicted by comparing the levels of these enzymes in tumour and adjacent normal mucosa. Deactivation of GST, activation of GR, SOD and catalase were associated with poor response to RT. p53 immunoreactivity was associated with failure to respond to RT. CONCLUSIONS: These markers may be useful in predicting treatment outcome in patients receiving postoperative RT, although this conclusion requires confirmation in a larger group of patients.

Amperometric determination of hydralazine hydrochloride in a flowing stream at the glassy carbon electrode.

A flow-injection method for the determination of hydralazine hydrochloride based on electrochemical oxidation at the glassy carbon electrode is presented. The amperometric method is highly specific and may be used to determine hydralazine hydrochloride in the presence of other drugs commonly found in its pharmaceutical dosage forms or administered concurrently in therapeutic situations. By using an electrode potential of +650 mV versus an Ag/AgCl reference electrode, a calibration curve was found to be linear in the 1-50-micrograms/mL concentration range, with minimum detectability at 10 ng (signal-to-noise ratio, 2). When the method was applied to the analysis of hydralazine hydrochloride in selected pharmaceutical dosage forms, it showed good accuracy and precision. Although automation was not used in this study, the method could readily be incorporated in automated systems because it employs the technique of continuous analysis in a flowing stream.

Automated continuous-flow determinations of serum proteins by pulse polarography.

A new flow-through cell is described for application of the dropping mercury electrode to the determination of serum proteins in an automated continuous-flow system. By using differential pulse polarography with short controlled drop times, it is possible to run a rapid automated system at sampling rates of up to 120 per hour with approximately +/- 1% precision and less than 3% carry-over. With the Brdicka reagent, hexa-amminecobalt(III) chloride, various serum proteins can be determined in the range 5-50 mug/ml. The method therefore offers a rapid and sensitive automated procedure for determination of serum proteins.

Serum glutathione-S-transferase and glutathione reductase activity in head and neck cancer patients.

Glutathione, an antioxidant plays an important role in phase-II detoxification of carcinogens. The levels of reduced glutathione are maintained by glutathione-depleting as well as replenishing enzymes such as glutathione-s-transferase (GST) and glutathione reductase (GR), respectively. Pre and post treatment changes in GST and GR activities in head and neck cancer patients were analysed. Serum GST and GR were analysed from untreated head and neck cancer patients (PT) (n=146), controls with habit of tobacco (VHT) (n=25) as well as without (no) habit of tobacco (NHT) (n=25) and patients with oral precancerous conditions (OPC) (n=50). The cancer patients were followed-up after initiation of anticancer therapy. Follow-up blood samples were collected. Serum GST and GR activities were estimated by highly sensitive and specific spectrophotometric methods. Untreated cancer patients showed elevated mean serum GST and GR activities as compared to NHT. Patients with OPC had declined mean GST activity as compared to WHT and untreated cancer patients. Paired t-test revealed that complete responders (CR) showed significantly elevated GST levels and declined GR activities (p < 0.001) as compared to those in PT. No correlation was found between stage of the disease and GST, GR activity. Paired t-test showed significant decreased in GR activity in nonresponders (NR) treated with radiotherapy (p=0.01). The study suggested that analysis of glutathione and glutathione-depleting enzymes can be helpful for treatment monitoring of head and neck cancer patients.

The calcium channel antagonist, verapamil, potentiates the inhibitory action of morphine on intestinal and biliary motility.

The effects of morphine and verapamil have been assessed on the gastrointestinal propulsion of charcoal meal and egg yolk-induced gall bladder emptying in mice. Each drug significantly inhibited these functions. In combination, an additive effect was seen on the inhibition of gastrointestinal transit, whilst verapamil potentiated the morphine-induced inhibition of gall bladder emptying. It is concluded that calcium ion channel antagonists may potentiate the activity of opiate drugs.

Gamete intrafallopian transfer: A preliminary experience.

BACKGROUND: After in vitro fertilizationand embryo transfer for tubal infertility, gamete intrafallopian transfer has been introduced for patients with non-tubal infertility. However, the gametes need to be transferred in 2 to 5 minutes and the distance between the operating theatre and tissue culture laboratory delayed its introduction at our hospital. METHODS AND PATIENTS: To overcome this problem we designed a box in which gametes could be stored. Using gametes taken from this box and employing the standard technique, we achieved 5 pregnancies in 39 infertile women. RESULTS: From 41 treatment cycles, 39 women underwent oocyte retrieval. Five pregnancies were achieved of which 4 delivered live births at full term and 1 ended in abortion. Our first gamete intrafallopian transfer baby was born on 6 January 1988. CONCLUSION: The gamete intrafallopian transfer technique can be successfullyadapted for India.

Alterations in plasma lipid profile patterns in head and neck cancer and oral precancerous conditions.

BACKGROUND: The changes in lipid profile have long been associated with cancer because lipids play a key role in maintenance of cell integrity. AIMS: The present study evaluated alterations in plasma lipid profile in untreated head and neck cancer patients as well as patients with oral precancerous conditions (OPC) and its association with habit of tobacco consumption. MATERIAL AND METHODS: This hospital-based case control study included 184 head and neck cancer patients, 153 patients with OPC and 52 controls. Plasma lipids including: (i) Total cholesterol, (ii) LDL cholesterol (LDLC), (iii) HDL cholesterol (HDLC) (iv) VLDL cholesterol (VLDLC) and (v) triglycerides were analysed by spectrophotometric kits. STATISTICAL ANALYSIS USED: Student's t-test was performed to compare mean values of the parameters. RESULTS: A significant decrease in plasma total cholesterol and HDLC was observed in cancer patients (P=0.008 and P=0.000 respectively) as well as in patients with OPC (P=0.014 and P=0.000, respectively) as compared to the controls. The plasma VLDL and triglycerides levels were significantly lower in cancer patients as compared to the patients with OPC (P=0.04) and controls (P=0.059). The tobacco habituates showed lower plasma lipid levels than the non-habituates. Our data strengthen the evidence of an inverse relationship between plasma lipid levels and head and neck malignancies as well as OPC. CONCLUSION: The lower levels of plasma cholesterol and other lipid constituents in patients might be due to their increased utilization by neoplastic cells for new membrane biogenesis. The findings strongly warrant an in-depth study of alterations in plasma lipid profile in head neck cancer patients.

Early experience with titanium elastic nails in a trauma unit.

The Titanium Elastic Nail (TEN) offers a number of potential advantages over traditional ways of treating long bone fractures particularly in the paediatric population. These advantages include earlier mobilisation and shorter hospital stay and less risk of loss of fracture position. These advantages are most apparent and significant when treating femoral fractures in children where the length of hospital stay is reduced from several weeks to a typical period of 5 to 8 days. We have reviewed our early experience of using these implants over the past 2 years. Patients were assessed clinically and radiologically. 13 patients were treated using the TEN during this period. There were 2 femoral fractures, 4 humeral fractures, 1 tibial and 6 forearm fractures treated using the Titanium Elastic Nail. All fractures united during the study period. However 1 humeral fracture required a secondary bone grafting and plating for delayed union and 1 fracture lost position during follow-up. Insertion point pain was a problem in 4 patients but this resolved after nail removal in all. There was 1 superficial wound infection which resolved with antibiotics and 1 superficial wound infection of an open fracture wound which resolved following nail removal and antibiotics. There were no cases of deep infection. There were no limb length discrepancy or rotational or angular malalignment problems. Biomechanical principles and technical aspects of this type of fixation are discussed.

Efatutazone, an oral PPAR-γ agonist, in combination with paclitaxel in anaplastic thyroid cancer: results of a multicenter phase 1 trial.

PURPOSE: A phase 1 study was initiated to determine the safety, potential effectiveness, and maximal tolerated dose and recommended phase 2 dose of efatutazone and paclitaxel in anaplastic thyroid cancer. EXPERIMENTAL DESIGN: Patients received efatutazone (0.15, 0.3, or 0.5 mg) orally twice daily and then paclitaxel every 3 weeks. Patient tolerance and outcomes were assessed, as were serum efatutazone pharmacokinetics. RESULTS: Ten of 15 patients were women. Median age was 59 years. Seven patients received 0.15 mg of efatutazone, 6 patients received 0.3 mg, and 2 patients received 0.5 mg. One patient receiving 0.3 mg of efatutazone had a partial response from day 69 to day 175; 7 patients attained stable disease. Median times to progression were 48 and 68 days in patients receiving 0.15 mg of efatutazone and 0.3 mg of efatutazone, respectively; corresponding median survival was 98 vs 138 days. The median peak efatutazone blood level was 8.6 ng/mL for 0.15-mg dosing vs 22.0 ng/mL for 0.3-mg twice daily dosing. Ten patients had grade 3 or greater adverse events (Common Terminology Criteria for Adverse Events), with 2 of these (anemia and edema) related to efatutazone. Thirteen events of edema were reported in 8 patients, with 2 of grade 3 or greater. Eight patients had ≥1 serious adverse event, with 1 of these (anemia) attributed to efatutazone and 1 (anaphylactic reaction) related to paclitaxel. The maximal tolerated dose was not achieved. Angiopoietin-like 4 was induced by efatutazone in tissue biopsy samples of 2 patients. CONCLUSIONS: Efatutazone and paclitaxel in combination were safe and tolerated and had biologic activity.

Well-differentiated neuroendocrine tumors: a review covering basic principles to loco-regional and targeted therapies.

Neuroendocrine tumors (NETs) are a complex group of malignancies with variable prognosis and response to treatment. For pancreatic neuroendocrine and carcinoid tumors, traditional cytotoxic chemotherapies have demonstrated minimal activity. Current approaches for treatment of metastatic disease use a combination of loco-regional and targeted biological therapies. Clinical trials remain critical for evaluation of new and promising therapeutic options for patients with NETs.