External laryngocele

Laryngocele is an extremely rare condition. A case of external laryngocele is being reported along with a brief review on its pathogenesis, clinical presentation and management.     

Immunocontraceptive activity guided fractionation and characterization of active constituents of neem (Azadirachta indica) seed extracts

A novel approach for immunocontraception by intervention of local cell mediated immunity in the reproductive system by using single intrauterine application of neem oil has been described earlier. The reversible block in fertility was reported to last for 107–180 days in female Wistar rats (Upadhyay et al., 1990. Antifertility effects of neem oil by single intrauterine administration: A novel method of contraception. Proceedings Of The Royal Society Of London B 242, 175–180) and 7–11 months in monkeys (Upadhyay et al., 1994. Long term contraceptive effects of intrauterine neem treatment (IUNT) in bonnet monkeys: An alternative to intrauterine contraceptive devices. Contraception 49, 161–167). The present study, describes the identification and characterization of the biologically active fraction from neem seeds (Azadirachta indica A. Juss. Family Meliaceae), responsible for the above activity in adult female Wistar rats. Initial studies with the mechanically extracted oil and solvent extracts of neem seeds have revealed that the antifertility activity was present in constituents of low to intermediate polarity. A hexane extract of neem seeds was reported to be biologically active (Garg et al., 1994. Comparison of extraction procedures on the immunocontraceptive activity of neem seed extracts. Journal of Ethnopharmacology 22, 87–92). Subsequently, hexane extract was sequentially fractionated through the last active fraction using various separation techniques and tested for antifertility activity at each step. Preparative HPLC was used for isolating individual components of the active fraction in quantities, sufficient for characterization. An analytical HPLC method was developed for standardization of the fraction. The active fraction was identified to be a mixture of six components, which comprises of saturated, mono and di-unsaturated free fatty acids and their methyl esters. Dose response study was performed with the last active fractions. The antifertility activity with the active fraction was reversible in nature and it was completely active until 5% concentration. There was no systemic toxic effect following the administration of the active fraction. This study, for the first time, proposes an active fraction from neem seeds, responsible for long term and reversible blocking of fertility after a single intrauterine administration with high efficacy.     

The pancreatic ductal epithelium serves as a potential pool of progenitor cells

Abstract:  With the increasing success of islet transplantation, β-cell replacement therapy has had renewed interest. To make such a therapy available to more than a few of the thousands of patients with diabetes, new sources of insulin-producing cells must become readily available. The most promising sources are stem cells, whether embryonic or adult stem cells. Clearly identifiable adult pancreatic stem cells have yet to be characterized. Although considerable evidence suggests their possibility, recent lineage-tracing experiments challenge their existence. Even in light of these lineage-tracing experiments, we suggest that evidence for neogenesis or new islet formation after birth remains strong. Our work has suggested that the pancreatic duct epithelium itself serves as a pool for progenitors for both islet and acinar tissues after birth and into adulthood and, thus, that the duct epithelium can be considered 'facultative stem cells'. We will develop our case for this hypothesis in this perspective.     

Significantly higher pathologic complete remission rate after neoadjuvant therapy with trastuzumab, paclitaxel, and epirubicin chemotherapy: results of a randomized trial in human epidermal growth factor receptor 2-positive operable breast cancer.

PURPOSE: The objective of this study was to determine whether the addition of trastuzumab to chemotherapy in the neoadjuvant setting could increase pathologic complete response (pCR) rate in patients with human epidermal growth factor receptor 2 (HER2) -positive disease. PATIENTS AND METHODS: Forty-two patients with HER2-positive disease with operable breast cancer were randomly assigned to either four cycles of paclitaxel followed by four cycles of fluorouracil, epirubicin, and cyclophosphamide or to the same chemotherapy with simultaneous weekly trastuzumab for 24 weeks. The primary objective was to demonstrate a 20% improvement in pCR (assumed 21% to 41%) with the addition of trastuzumab to chemotherapy. The planned sample size was 164 patients. RESULTS: Prognostic factors were similar in the two groups. After 34 patients had completed therapy, the trial's Data Monitoring Committee stopped the trial because of superiority of trastuzumab plus chemotherapy. pCR rates were 25% and 66.7% for chemotherapy (n = 16) and trastuzumab plus chemotherapy (n = 18), respectively (P = .02). The decision was based on the calculation that, if study continued to 164 patients, there was a 95% probability that trastuzumab plus chemotherapy would be superior. Of the 42 randomized patients, 26% in the chemotherapy arm achieved pCR compared with 65.2% in the trastuzumab plus chemotherapy arm (P = .016). The safety of this approach is not established, although no clinical congestive heart failure was observed. A more than 10% decrease in the cardiac ejection fraction was observed in five and seven patients in the chemotherapy and trastuzumab plus chemotherapy arms, respectively. CONCLUSION: Despite the small sample size, these data indicate that adding trastuzumab to chemotherapy, as used in this trial, significantly increased pCR without clinical congestive heart failure.     

Towards an effective social care model for arrest referral: Implications for criminal justice interventions for problem drug users

Aims: To assess an operational model for arrest-referral schemes that successfully facilitates the entry of highly entrenched and chaotic problem drug users into specialist drug-treatment services. Methods: (1) An examination of case records from a voluntary arrest-referral service (SMART CJS) based across the Thames Valley region of the UK during 2002-2003; (2) Probablistic database linkage of agency case records with the National Drug Treatment Monitoring System (NDTMS); (3) participant observation and semi-structured interviews with agency staff.

Findings: Over half of problem drug users (58%) maintained contact with the scheme following initial contact in police custody. Referrals were made to a wide range of social-care services in addition to specialist drug treatment to include prison-based services, housing support and primary care. This model was able to demonstrate very high levels of specialist drug treatment uptake (53%) following referral. There was a close relationship between the average length of time a problem drug user entered treatment following contact in police custody and the average length of an active case file. Such an approach was considered essential to maintain motivation with clients.

Discussion: This social care model has operational validity in ensuring treatment uptake of recidivist problem drug-using offenders. Continuity of care alongside referrals addressing wider community harms including social exclusion and public health should be encouraged.     

Development and evaluation of osmotically controlled oral drug delivery system of glipizide.

Extended release formulation of glipizide based on osmotic technology was developed and evaluated. The effect of different formulation variables, namely, level of solubility modifier in the core, membrane weight gain, and level of pore former in the membrane, were studied. Drug release was found to be affected by the level of solubility modifier in the core formulation. Glipizide release was inversely proportional to the membrane weight but directly related to the initial level of pore former (PVP) in the membrane. Burst strength of the exhausted shells increased with the weight gain of the membrane. On the other hand, burst strength decreased with an increase in the level of pore former in the membrane. Drug release from the developed formulations was independent of pH and agitational intensity, but dependent on the osmotic pressure of the release media. Results of SEM studies showed the formation of pores in the membrane from where the drug release occurred. The numbers of pores were directly proportional to the initial level of pore former in the membrane. The manufacturing procedure was found to be reproducible and formulations were stable after 3 months of accelerated stability studies.     

Acute hyperglycemia attenuates nerve conduction velocity and nerve blood flow in male Sprague–Dawley rats: reversal by adenosine

Hyperglycemia is implicated to play a major role in development of diabetic neuropathy. Since most of the diabetics are hyperglycemic much before they develop full-blown diabetes, we felt, it would be very important to know the effects of acute hyperglycemia on nerve function so that early pathophysiological events could be understood and appropriate therapeutic intervention can be made. Moreover, effect of acute hyperglycemia on motor nerve conduction velocity (MNCV) and nerve blood flow (NBF) is not known. Hence, we studied the effects of acute hyperglycemia on sciatic MNCV and sciatic NBF in healthy male Sprague-Dawley (SD) rats. Three different animal models of acute hyperglycemia (50% glucose (3 g kg(-1), i.v. (intra-venous) or i.p. (intra-peritoneally)) or 24 h post-streptozotocin (STZ) injected rats were used. Acute hyperglycemia but not mannitol or sucrose significantly attenuated MNCV and NBF. Adenosine (10 mg kg(-1), i.p.) prevented the acute hyperglycemia-induced attenuation of MNCV and NBF in all the three rat models of acute hyperglycemia. Adenosine effects were blocked by theophylline (50 mg kg(-1), i.p.) suggesting the role of adenosinergic receptor mediated mechanisms in acute hyperglycemia-induced neuropathy. Acute glucose administration in 8 weeks, STZ diabetic rats did not further affect MNCV or NBF. Adenosine (10 mg kg(-1), i.p.) did not produce any adverse effects on the blood pressure and heart rate. From the results, we conclude that acute hyperglycemia attenuates MNCV and NBF via an adenosinergic receptor-dependent mechanism.     

Fractures in large-segment allografts

Segment skeletal defects that result from resection of a malignant bone neoplasm commonly are reconstructed with large segment allografts. Excellent functional results after these reconstructions and significant complications have been reported. Although it is known that a common complication seen with the use of allografts is allograft fracture, the factors associated with allograft fracture are not entirely clear. In this study, the hypothesis was examined that allograft reconstructions, which use internal fixation devices that penetrate the cortex of the allograft, are associated with an increased risk of fracture. Findings from large segment allograft reconstructions in 74 patients with a minimum followup of 36 months were studied. These 74 patients include 35 patients whose outcomes were reported previously and now have additional followup and 39 patients whose outcomes are being reported for the first time. Thirty-one of the 74 (42%) allografts fractured, and the mean time to fracture was 26 months. When the fixation techniques resulted in cortical penetration of the allograft, fractures occurred in 27 of the 43 (63%) allografts, and when fixation of the graft to the host bone required no cortical penetration, only four of the 31 (13%) allografts fractured. Fractures occurred in 12 of 15 (80%) tibial allografts and in only two of 17 (12%) proximal femoral allografts; however, the anatomic site was not statistically independent of method of fixation because 14 of the 15 tibial grafts had cortical penetration and 15 of the 17 proximal femoral grafts had no cortical penetration. The authors' analysis indicates that internal fixation devices that require cortical penetration are associated with an increased risk of allograft fracture.