Evaluation of Pain Preoperatively and Postoperatively in Patients with Chronic Pancreatitis Undergoing Longitudinal Pancreaticojejunostomy.

Chronic pancreatitis is a fairly common condition with pain being the major symptom, and longitudinal pancreaticojejunostomy (LPJ) is performed for symptomatic relief. The aim of the study is to assess relief of pain post-LPJ for chronic pancreatitis and to evaluate the factors influencing relief of symptoms. A prospective observational non-interventional study enrolling 28 patients. This study involved a questionnaire studying various risk factors and pain related to chronic pancreatitis, pancreaticojejunostomy, and postoperative assessment of pain relief at 1 and 6 months from surgery. Pain was assessed using Visual analogue scale (VAS). In chronic pancreatitis, there is a significant relief in symptoms of pain post-LPJ; the degree of relief was less in the alcoholics vs non-alcoholics (p = 0.09) and smokers. There was also reduction in analgesic requirement and frequency of acute attacks of pain. Fifty-seven percent of patients had a complete remission of their pain after LPJ for CP. In chronic pancreatitis, there is a significant relief in symptoms of pain post-LPJ, although the degree of relief is less in the alcoholics and smokers.

Isolated peritoneal donor-related plasmacytoma 3 years after liver transplantation: a case report.

Organ transplantation carries a risk of disease transmission from donor to recipient, primarily infection or malignancy. Although donors are thoroughly screened, donor-related malignancies are reported to occur in 0.01% of solid organ transplants. Plasma cell neoplasm, to the best of our knowledge, has not been reported as a donor-transmitted malignancy in liver transplantation. We describe a liver transplant from a donor with unrecognized plasmacytoma requiring retransplantation. Three years after the first transplant a single peritoneal mass was detected on surveillance imaging and radically excised; HLA phenotyping confirmed the mass to be an isolated extra-medullary plasmacytoma of chimeric donor and recipient origin.

Successful isolated intestinal transplantation in sensitized recipients with the use of virtual crossmatching.

We evaluated virtual crossmatching (VXM) for organ allocation and immunologic risk reduction in sensitized isolated intestinal transplantation recipients. All isolated intestine transplants performed at our institution from 2008 to 2011 were included in this study. Allograft allocation in sensitized recipients was based on the results of a VXM, in which the donor-specific antibody (DSA) was prospectively evaluated with the use of single-antigen assays. A total of 42 isolated intestine transplants (13 pediatric and 29 adult) were performed during this time period, with a median follow-up of 20 months (6-40 months). A sensitized (PRA ≥ 20%) group (n = 15) was compared to a control (PRA < 20%) group (n = 27) to evaluate the efficacy of VXM. With the use of VXM, 80% (12/15) of the sensitized patients were transplanted with a negative or weakly positive flow-cytometry crossmatch and 86.7% (13/15) with zero or only low-titer (≤ 1:16) DSA. Outcomes were comparable between sensitized and control recipients, including 1-year freedom from rejection (53.3% and 66.7% respectively, p = 0.367), 1-year patient survival (73.3% and 88.9% respectively, p = 0.197) and 1-year graft survival (66.7% and 85.2% respectively, p = 0.167). In conclusion, a VXM strategy to optimize organ allocation enables sensitized patients to successfully undergo isolated intestinal transplantation with acceptable short-term outcomes.

Leiomyosarcoma of inferior vena cava.

Malignancy arising from the blood vessels is a very rare finding in daily clinical practice. In addition, the finding can often be misdiagnosed and ill-treated. These tumors usually go unnoticed unless it has metastasized to distant tissues. Among these rare tumors, leiomyosarcoma is the most common. It mostly arises in the inferior vena cava (IVC). Clinical signs and symptoms are very vague. Usually it is often misdiagnosed as an abscess cavity in the liver or primary hepatic malignancy (when present at level II) or as a thrombus in the IVC. Radiological investigations are the key to proper diagnosis. Depending upon the exact location, further treatment options vary. Generally, it is believed that level II and level III tumors are amenable to surgery followed by chemo or radiotherapy. We present a rare case of leiomyosarcoma of IVC at level II being diagnosed with proper radiological investigations and its management with further stress on offering chemo-radiotherapy after its surgical removal as compared to only surgery performed earlier. This case report will throw some light on the proper management of such rare tumors in terms of their exact diagnosis and treatment in order to prolong patient survival.

Liver transplantation in the management of hepatic epithelioid hemangioendothelioma: a single-center experience and review of the literature.

Hepatic epitheliod hemangioendothelioma (HEHE) is a rare tumor of vascular origin with unpredictable malignant potential. We describe our experience with four biopsy-proven HEHE cases that were considered for orthotopic liver transplant (OLT). Three patients had preserved hepatic function and despite extensive disease burden did not develop disease progression while awaiting OLT. We were able to utilize the review process allowed by United Network of Organ Sharing to obtain additional priority for OLT for these patients. This led to expedited organ allocation and excellent post-OLT outcomes.

Circumcaval ureter.

We report a case of circumcaval ureter diagnosed preoperatively by 'fish-hook' appearance on intravenous pyelogram. At surgery, patient was treated by 'Anderson Hones' pyeloplasty leaving the retrocaval segment in-situ.

Use of a fluorescence spectroscopic readout to characterize the interactions of Cdc42Hs with its target/effector, mPAK-3.

The family of p21-activated kinases (PAKs) has been shown to contain a domain that can independently bind to the Ras-like proteins Cdc42Hs and Rac. We have expressed a 72 amino acid recombinant form of this p21-binding domain (PBD) from mPAK-3 in Escherichia Coli for use in structure-function studies. The protein can be purified on a nickel affinity resin due to a hexa-His tag that is incorporated onto the amino terminus of the domain. PBD binds to Cdc42Hs in a guanine nucleotide-dependent manner as demonstrated by a novel fluorescence assay that takes advantage of the spectroscopic properties of N-methylanthraniloyl (Mant)-guanine nucleotides. Ionic strength has little effect on the affinity of PBD for Cdc42Hs, but alkaline pH values tend to weaken the interaction. We have shown that the inhibition of the GTPase activity of Cdc42Hs, as well as a previously undescribed inhibition of guanine nucleotide dissociation, is mediated by the PBD portion of the mPAK-3 molecule. These findings suggest that PBD binding alters the geometry of the guanine nucleotide binding site on Cdc42Hs, perhaps as an outcome of the target/effector molecule binding in close proximity to the nucleotide domain. We therefore tested if mutations in the effector region of Cdc42Hs (32-40), which in Ras are very close to the guanine nucleotide binding site, had any effect on PBD binding. Changing tyrosine 32 to lysine (Y32K) resulted in a small (5-fold) inhibition of PBD binding, but the very conservative mutation D38E yielded at least a 50-fold decrease in affinity. Finally, the catalytic domain of the GTPase activating protein, Cdc42-GAP, was shown to inhibit PBD binding in a competitive manner, indicating that this target molecule and the negative regulator (GAP) bind to overlapping sites on the Cdc42Hs molecule.

Antipyrine and doxycycline pharmacokinetics in patients with thyroid disorders.

Pathological conditions are known to affect pharmacokinetics of many drugs. Antipyrine half-life is used as a marker of liver microsomal enzyme function. Antipyrine pharmacokinetics, therefore, was investigated in 23 thyrotoxic and 11 euthyroid goitre patients. Of these, 11 thyrotoxic and 9 euthyroid goitre patients also participated in doxycycline bioavailability studies. In thyrotoxic patients, antipyrine half-life and AUCo infinity and doxycycline Cpmax and AUCo infinity were found to be reduced as compared to those of healthy euthyroid normal subjects. Following treatment of thyrotoxicosis, the antipyrine half-life and AUCo infinity returned to normal. Doxycycline AUCo infinity returned to near normal range but Cpmax did not.

Suitability of laboratory animals for screening anti-hyperlipidemic agents.

The present study was undertaken to evaluate and compare the lipid profiles of various laboratory animals to that of human beings. The human subjects and animals included in the study were from three age groups based on key physiological states. A record of the usual dietary constituents and their daily consumption was maintained. The results indicated that the lipid profile of pigs and dogs bears similarity to that of human beings. Results also revealed that lipid profile was labile in the second group of these animals indicating that this age is suitable to bring about the required changes to produce a hyperlipidemic animal.

Centbutindole vs trifluoperazine: a double-blind controlled clinical study in acute schizophrenia.

Twenty-nine acute schizophrenic patients were treated under double-blind conditions for six weeks with either centbutindole in a dose range of 3 mg/day to 4.5 mg/day or trifluoperazine in the dose range of 15 mg/day to 22.5 mg/day. Both drugs produced a significant improvement in initial psychopathology. No significant differences were demonstrated between the two treatment conditions.

Influence of menstrual cycle on antipyrine pharmacokinetics in healthy Indian female volunteers.

The effect of the menstrual cycle on antipyrine pharmacokinetics was studied in 11 normal, healthy Indian female volunteers. Antipyrine half-life, apparent volume of distribution, clearance and AUC were calculated by standard methods. Results indicated that in females, antipyrine half-life was significantly longer on day 5 as compared with that on days 15 and 21 of the menstrual cycle. It appears that hormonal changes during the menstrual cycle affect the pharmacokinetics of drugs in normal healthy females.

Effect of iron deficiency anaemia and its treatment on the absorption and elimination of phenformin.

1. The extent of phenformin absorption and its rate of urinary excretion have been assessed in adult patients with iron deficiency anaemia, a condition which compromises gastrointestinal function. 2. Phenformin (100 mg) was administered orally to patients before treatment, three days after the start of a course of iron treatment (oral 300 mg b.d. or total intravenous iron) and at the end of 28 days, when haemoglobin was over 10 gm%. 3. No significant difference was found between mean total amounts of phenformin and 4-hydroxyphenformin excreted in urine, before treatment or after 3 or 28 days replacement therapy. It is concluded that phenformin absorption is not affected by iron deficiency. 4. In addition, iron deficiency had no significant effect on phenformin elimination half-life.

Plasma rifampicin levels during oral contraception.

PIP: Researchers conducted a study on the effect of oral contraceptives (OCs) on rifampicin plasma levels in 6 healthy women between 19-38 years old. These women's weight ranged between 40-60 kg an their height between 150-160 cms. All hemoglobin levels were 10 g. They had not used OCs for 3 months before the research began. As a control, the volunteers 1st did not receive an OC and had a menstrual cycle. Blood samples were collected between days 15-28 of the menstrual cycle. They took a daily low dose OC containing 1 mg norethisterone acetate and 30 mcg ethinyl estradiol in the next cycle. Before and after the 2nd OC cycle, they took 450 mg of rifampicin while the stomach was void and laboratory personnel estimated plasma levels of rifampicin by microbiological assay at 0, 1, 2, 4, 6 and 8 hours. When the women were taking no OC, peak plasma levels of rifampicin ranged between 8.2-36 mcg/ml, while they varied between 11.25-29 mcg/dl during the 2nd OC cycle. Further, the time of peak concentration of rifampicin when the women did not use an OC occurred between 2-4 hours in 5 women and at 6 hours for the other woman. During OC administration, all the women's peak concentration was 2 or 4 hours. The area under curve (AUC) of rifampicin while no OC was used extended from 29.85-176 + or - 22.1 mcg/ml/hour and 61.9-157.7 + or - 14.9 mcg/ml/hour while the women took the OC. No significant difference existed between before and during OC use plasma levels of rifampicin and AUC. Even though studies show that rifampicin treatment reduces plasma levels of OCs, these results demonstrate that a low dose OC does not change rifampicin levels.^ieng

Effect of ascariasis and its treatment on drug absorption.

Ascariasis has been reported to impair the absorption of nutrients, vitamin A, and D-xylose, which is corrected on treatment. The effect of ascariasis and its treatment on the absorption of sulphadimidine and isoniazid has been investigated. There was no difference between drug absorption before and after the treatment or in comparison with a normal population.

Effect of pectin and kaolin on bioavailability of co-trimoxazole suspension.

Bioavailability of co-trimoxazole suspension was determined with and without concurrent administration of pectin and kaolin in 8 volunteers. Twenty ml suspension of co-trimoxazole containing 160 mg trimethoprim (TMP) and 800 mg sulphamethoxazole (SMX) and co-trimoxazole suspension along with 20 ml of pectin-kaolin suspension were administered in a random order with 7 days interval. Plasma estimation of trimethoprim and sulphonamide was carried out at serial intervals. Area under curve (AUC) and Cmax of TMP were significantly higher when co-trimoxazole suspension alone was used. No statistically significant changes were observed in case of sulphamethoxazole. Clinical study is necessary to verify whether concurrent administration of co-trimoxazole and pectin-kaolin leads to loss of antibacterial efficacy.