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Biomedical subjects

A Jain

Publications and source records attributed to A Jain.

At least 19 recordsLinked to original sources
PubMed2006

Nephrogenic systemic fibrosis among liver transplant recipients: a single institution experience and topic update.

Nephrogenic systemic fibrosis (NSF) is a recently characterized systemic fibrosing disorder developing in the setting of renal insufficiency. NSF's rapidly progressive nature resulting in disability within weeks of onset makes early diagnosis important. Two reports of NSF after liver transplantation are known of. We present three cases of NSF developing within a few months after liver transplantation and review the current literature. Loss of regulatory control of the circulating fibrocyte, its aberrant recruitment, in a milieu of renal failure and a recent vascular procedure appear important in its development. Known current therapies lack consistent efficacy. Only an improvement in renal function has the greatest likelihood of NSF's resolution. Delayed recognition may pose a significant barrier to functional recovery in the ubiquitously deconditioned liver transplant patient. Early recognition and implementation of aggressive physical therapy appear to have the greatest impact on halting its progression.

Aged↗
PubMed2006

Epidermal growth factor receptor dimerization status determines skin toxicity to HER-kinase targeted therapies.

Skin toxicity, a common drug-related adverse event observed in cancer patients treated with epidermal growth factor receptor (EGFR)-directed therapies is rarely seen with therapies targeting HER2. This study reports the significance of the EGFR and HER2 dimerization status in skin with regard to these dermatologic side effects. We demonstrate the differential effect of HER-directed therapies on the ligand driven activation status of EGFR, HER2 and MAPK in normal human epidermal keratinocytes. EGFR-directed therapies, such as gefitinib and cetuximab, inhibited ligand-induced activation of EGFR and MAPK in human keratinocytes. Pertuzumab, an antibody interfering with functional HER2 heterodimerization, failed to block ligand-induced HER signaling in primary keratinocytes. Using a novel proximity-based dimerization assay (eTagtrade mark) we show that EGFR homodimers are the predominant HER dimer pair in normal primary kertinocytes and in normal skin tissue from 16 patients with solid malignancies. The presence of [p]EGFR and [p]MAPK, but the absence of [p]HER2, demonstrates productive signaling via EGFR but not HER2 in human skin. These data illustrate the importance of the EGFR dimerization partner in human skin and suggests that inhibition of EGFR homodimer signaling rather than EGFR/HER2 heterodimer signaling maybe the key molecular event determining dermatologic toxicity discrepancies observed between EGFR-targeted versus HER2-targeted therapies.

Antibodies, Monoclonal↗
PubMed2006

Levels of lipid peroxides and antioxidants in smokers and nonsmokers.

BACKGROUND AND OBJECTIVE: The aim of the study was to evaluate the relationship between cigarette smoking and periodontal damage in terms of the levels of free radicals and antioxidants. MATERIAL AND METHODS: Thirty-five healthy subjects in the age group 25-56 yr and with chronic moderate inflammatory periodontal disease (attachment loss of 3-4 mm) were selected. All subjects were matched with respect to the clinical parameters plaque index, gingival index and attachment loss. Of the 35 subjects, 25 were smokers (smoking a minimum of 15 cigarettes/day) and 10 were nonsmokers. Smokers were subdivided into three subgroups: group I (10 subjects smoking 15-20 cigarettes/day); group II (10 subjects smoking 21-30 cigarettes/day) and group III (five subjects smoking > 50 cigarettes/day). Gingival tissue (obtained during Modified Widman surgery) and blood samples were collected from each of the subjects and analyzed for the following parameters: lipid peroxide, superoxide dismutase, catalase, glutathione and total thiol. RESULTS: The level of lipid peroxide was lowest in nonsmokers (2.242 +/- 0.775 in tissue and 1.352 +/- 0.414 in blood) and highest in smokers smoking > 50 cigarettes/day (6.81 +/- 1.971 in tissue and 4.96 +/- 0.890 in blood), both in tissue and in blood. The increase was statistically significant in all groups, except in tissue of group I smokers. Catalase showed a similar trend, where the levels increased from 0.245 +/- 0.043 in controls to 0.610 +/- 0.076 in group III smokers for tissue, and from 0.231 +/- 0.040 in controls to 0.568 +/- 0.104 in group III smokers for blood. The increase was statistically significant for all groups. Total thiol levels were also higher in smokers than in controls (0.222 +/- 0.050 in controls vs. 0.480 +/- 0.072 in group III smokers in tissue; 0.297 +/- 0.078 in controls vs. 0.617 +/- 0.042 in group III smokers in blood). Except for group I in both tissue and blood, the increase was statistically significant. The superoxide dismutase (SOD) level was higher in nonsmokers (2.406 +/- 0.477 in tissue and 2.611 +/- 0.508 in blood) than in group III smokers (1.072 +/- 0.367 in tissue and 0.938 +/- 0.367 in blood), both in tissue and in blood, but this was significant only in the case of blood and for group III smokers in tissue. The glutathione level in tissue was consistently lower in smokers than in controls, showing a decrease from 121.208 +/- 37.367 in controls to 46.426 +/- 14.750 in group III smokers, but the decrease was not significant in group I smokers. In the case of blood, the glutathione level dropped from 262.074 +/- 68.751 in controls to 154.242 +/- 51.721 in group III smokers, but was statistically significant only for group III smokers. CONCLUSION: The study results show that smoking increases the level of free radicals in periodontal tissues, which in turn may be responsible for the destruction seen in periodontal diseases.

Adult↗
PubMed2006

Survival of liver transplant patients coinfected with HIV and HCV is adversely impacted by recurrent hepatitis C.

Although liver transplantation (LTx) in HIV-positive patients receiving highly active antiretroviral therapy (HAART) has been successful, some have reported poorer outcomes in patients coinfected with hepatitis C virus (HCV). Here we discuss the impact of recurrent HCV on 27 HIV-positive patients who underwent LTx. HIV infection was well controlled post-transplantation. Survival in HIV-positive/HCV-positive patients was shorter compared to a cohort of HIV-negative/HCV-positive patients matched in age, model for end-stage liver disease (MELD) score, and time of transplant, with cumulative 1-, 3- and 5-year patient survival of 66.7%, 55.6% and 33.3% versus 75.7%, 71.6% and 71.6%, respectively, although not significantly (p = 0.07), and there was a higher likelihood of developing cirrhosis or dying from an HCV-related complication in coinfected subjects (RR = 2.6, 95% CI, 1.06-6.35; p = 0.03). Risk factors for poor survival included African-American race (p = 0.02), MELD score > 20 (p = 0.05), HAART intolerance postLTx (p = 0.01), and postLTx HCV RNA > 30000000 IU/mL (p = 0.00). Recurrent HCV in 18 patients was associated with eight deaths, including three from fibrosing cholestatic hepatitis. Among surviving coinfected recipients, five are alive at least 3 years after LTx, and of 15 patients treated with interferon-alpha/ribavirin, six (40%) are HCV RNA negative, including four with sustained virological response. Hepatitis C is a major cause of graft loss and patient mortality in coinfected patients undergoing LTx.

Adult↗
PubMed2006

Acute pseudo-obstruction of the colon (Ogilvie's syndrome) following instrumental vaginal delivery.

Acute pseudo-obstruction of the colon (Ogilvie's syndrome) is an adynamic ileus without mechanical obstruction of the bowel. Predisposing factors include: abdominal and pelvic surgery, or trauma, or severe pre-existing systemic illness. In obstetrics, many cases have been reported after caesarean delivery, but none following a vaginal delivery. Conservative and pharmacological therapies are effective in many patients, but surgical intervention may be required. Early diagnosis and appropriate treatment is imperative to avoid caecal rupture, faecal peritonitis and the associated high maternal mortality. High index of clinical suspicion and proper assessment of the gastrointestinal system in the post-surgical patient are vital to the management of this uncommon but potentially serious condition met with in obstetrics practice.

Adult↗
PubMed2006

Occurrence of overlooked zoonotic tuberculosis: detection of Mycobacterium bovis in human cerebrospinal fluid.

The paucibacillary nature of the cerebrospinal fluid (CSF) has been a major obstacle in the diagnosis of human tuberculous meningitis (TBM). This study shows that with molecular techniques direct precise determination to the species level of mycobacterial pathogens can be made. The present report describes the utility of a nested PCR (N-PCR) assay (A. Mishra, A. Singhal, D. S. Chauhan, V. M. Katoch, K. Srivastava, S. S. Thakral, S. S. Bharadwaj, V. Sreenivas, and H. K. Prasad, J. Clin. Microbiol. 43:5670-5678, 2005) in detecting M. tuberculosis and M. bovis in human CSF. In 2.8% (6/212) of the samples, M. tuberculosis was detected, and in 17% (36/212), M. bovis was detected. Mixed infection was observed in 22 samples. Comparative analysis of clinical diagnosis, smear microscopy, and N-PCR in 69 patients (TBM, 25; non-TBM, 44) showed that the sensitivity of N-PCR (61.5%) was greater than that of smear microscopy (38.4%). Determination to the species level is important from the viewpoint of determining the prevalence of these mycobacteria in a community and would influence strategies currently adopted for the prevention of tuberculosis.

Animals↗
PubMed2006

Postthyroplasty implant extrusion.

The case of a 57-year-old gentleman with a left-sided vocal cord palsy following a surgical procedure done elsewhere is being reported. His main problem was dysphonia, and speech therapy did not improve his voice much. A thyroplasty type 1 was done to improve his voice. A Silastic implant was inserted for medialization of vocal cords with a good postoperative result. The patient was followed up in the clinic and presented again 7 months after surgery with extrusion of the Silastic implant. Quite remarkably, his voice did not deteriorate even after the extrusion of the Silastic implant. This could be due to formation of fibrous tissue holding the cords in the medial position. The patient retained an excellent voice, and no further procedure was necessary.

Biocompatible Materials↗
PubMed2006

Administration of an alginate based gastric reflux suppressant on the bioavailability of omeprazole.

BACKGROUND & OBJECTIVE: Omeprazole treats gastro-oesophageal reflux disease (GORD) by inhibition of acid secretion whereas alginate based reflux suppressants work by forming a low density raft of near neutral pH which floats on the stomach contents and physically impedes gastro-oesophageal reflux. There is limited pharmacokinetic information regarding possible drug interaction between these two types of products, although these may be frequently co-prescribed to improve symptom control in GORD patients. This study was designed to determine whether the administration of a 10 per cent w/v liquid alginate suspension affected the pharmacokinetic profile of omeprazole. METHODS: This was a randomized, two-treatment, two-sequence, two-period crossover study in 26 volunteers. Each treatment was dosed for 3 consecutive days with a washout period of 7 days between dosing periods. Blood samples for pharmacokinetic analysis were taken over the 24 h period following the final dose of omeprazole. RESULTS: Geometric means and ratios were as follows: C(max) was 555 for omeprazole/alginate and 558 for omeprazole alone (ratio 99.55%, 90% confidence interval 82.75-119.75%; AUC(0-t) was 2050 for omeprazole/alginate and 2094 for omeprazole alone (ratio 97.90%, 90% confidence interval 87.83-109.12%); AUC(0-a) was 2247 for omeprazole/alginate and 2231 for omeprazole alone (ratio 100.74%, 90% confidence interval 90.05-112.70%). Mean values for T(max), K(el) and T(1/2) were also similar for the two treatment regimens. INTERPRETATION & CONCLUSION: As the 90 per cent confidence intervals for the geometric mean ratios for C(max), AUC(0-t), and AUC(0-alpha) are all contained within the bioequivalence interval of 80-125 per cent, it can be concluded that the administration of this liquid alginate suspension does not affect the pharmacokinetic profile of omeprazole.

Adolescent↗
PubMed2005

A rare case of disseminated cutaneous zoster in an immunocompetent patient.

BACKGROUND: Disseminated cutaneous herpes zoster in healthy persons is uncommon, though it has been described in immunocompromised patients. CASE PRESENTATION: We describe a case of disseminated cutaneous herpes zoster in an elderly man with no apparent immunosuppressive condition. The patient was treated successfully with intravenous Acyclovir. CONCLUSION: We suggest that disseminated zoster can occur in an immunocompetent host and should be promptly recognized and treated to prevent serious complications.

Acyclovir↗
PubMed2005

Design and development of multivesicular liposomal depot delivery system for controlled systemic delivery of acyclovir sodium.

The aim of the present study was to design a depot delivery system of acyclovir sodium using multivesicular liposomes (MVLs) to overcome the limitations of conventional therapies and to investigate its in vivo effectiveness for sustained delivery. MVLs of acyclovir were prepared by the reverse phase evaporation method. The loading efficiency of the MVLs (45%-82%) was found to be 3 to 6 times higher than conventional multilamellar vesicles (MLVs). The in vitro release of acyclovir from MVL formulations was found to be in a sustained manner and only 70% of drug was released in 96 hours, whereas conventional MLVs released 80% of drug in 16 hours. Following intradermal administration to Wistar rats, the MVL formulations showed effective plasma concentration for 48 hours compared with MLVs and free drug solution (12-16 hours). C(max) values of MVL formulations were significantly less (8.6-11.4 microg/mL) than MLV and free drug solution (12.5 microg/mL). The AUC(0-48) of the MVL formulations was 1.5- and 3-fold higher compared with conventional liposomes and free drug solution, respectively. Overall, formulations containing phosphatidyl glycerol as negatively charged lipid showed better results. The MVL delivery system as an intradermal depot offers the advantage of a very high loading and controlled release of acyclovir for an extended period of time. The increase in AUC and decrease in C(max) reflects that the MVL formulations could reduce the toxic complications and limitations of conventional iv and oral therapies.

Acyclovir↗
PubMed2005

Tacrolimus for primary liver transplantation: 12 to 15 years actual follow-up with safety profile.

BACKGROUND: Tacrolimus has been increasingly used for liver transplantation during the last decade. The drug has immunological advantages in short- to medium-term follow-up. However, data on longitudinal follow-up are lacking. AIM: The aim of the present report was to examine the impact of tacrolimus in primary adult and pediatric liver transplantation (LTx) patients. MATERIAL AND METHOD: One thousand consecutive primary LTx patients were performed under tacrolimus between August 1989 and December 1992 were followed up until August 2004. Mean follow-up was 13.4 +/- 0.92 (range, 11.7-15) years. There were 600 males and 400 females with a mean age of 42.6 +/- 20.2 years. There were 166 children (age 18 years or younger) and 834 adults, of whom 204 were older than 60 years (seniors). RESULTS: Four hundred ninety-seven (49.7%) patients died in the follow-up period. The overall 15-year actuarial patient survival rate was 51.4%. The survival rate for children was significantly better (81.3%) compared with adults (47.5%) and seniors (36.4%) (P = .0001). One hundred fifty-one patients received a second LTx, 22 patients received a third LTx, and 4 patients received a fourth LTx. Over all 15 years the actuarial graft survival rate was 46.1%. At last follow-up, 69.1% of patients were off steroids. The majority of late deaths were due to age-related complications, recurrence of disease, and De novo cancers. CONCLUSION: The data on longitudinal follow-up have shown actuarial survival for children to be significantly better than in adults and seniors. Graft loss from immunological causes are rare even with long-term follow-up.

Adult↗
PubMed2005

Does valganciclovir hydrochloride (valcyte) provide effective prophylaxis against cytomegalovirus infection in liver transplant recipients?

INTRODUCTION: Cytomegalovirus (CMV) infection after solid organ transplantation is one of the most common viral infections, causing significant morbidity and mortality if not treated promptly. Ganciclovir has proven to be effective for the prophylaxis and treatment of CMV. However, oral absorption of ganciclovir is poor. Recently, oral administration of valganciclovir hydrochloride (Valcyte) has been observed to display 10-fold better absorption than oral ganciclovir. Valganciclovir has increasingly been used as prophylaxis against CMV after solid organ transplantation. The purpose of this study was to examine the efficacy of valganciclovir prophylaxis therapy after primary liver transplantation. PATIENTS AND METHODS: Between July 2001 and May 2003, 203 consecutive liver transplant recipients, including 129 men and 74 women of overall mean age 53 +/- 11 years, received valganciclovir (900 mg/d or 450 mg every other day depending on renal function) for 3 to 6 months after primary liver transplantation. All patients were followed up for a minimum of 6 months. Mean follow-up was 19 +/- 5.8 months. CMV DNA in peripheral blood was tested using polymerase chain reaction (PCR) amplification. Symptomatic CMV was stratified according to the CMV immunoglobulin (Ig)G status of the donor and recipient at the time of liver transplantation. Donors and recipients were classified preoperatively into groups according to the presence or absence of CMV as follows: group 1 (n = 73; donor CMV+, recipient CMV+); group 2 (n = 41; donor CMV-, recipient CMV+); group 3 (n = 54; donor CMV+, recipient CMV-; high-risk group); and group 4 (n = 35; donor CMV-, recipient CMV-). RESULTS: Twenty-nine patients (14.3%) developed symptomatic CMV disease at 169 +/- 117 days after liver transplantation: group 1, 16.4% versus group 2, 7.3% versus group 3, 25.9% versus group 4, 0%. Of these patients, 5 also had invasive CMV on liver biopsy, which was performed owing to abnormal liver functions. All 29 patients were treated with intravenous ganciclovir. One patient died owing to disseminated CMV, whereas the remaining 28 patients responded to treatment. Interestingly, 8 patients, including 1 who had invasive CMV hepatitis, developed symptomatic CMV within 90 days of liver transplantation even while on prophylactic valganciclovir. CONCLUSION: Valganciclovir failed to provide adequate prophylaxis following liver transplantation in our patients. The overall rate of CMV in seropositive donors and/or recipients was 17%, and in the high-risk group was 26%. Further prospective studies with measurement of ganciclovir concentrations are needed to elucidate the reasons for this unexpected failure.

Adult↗