Colorectal carcinoma in young adults: a retrospective study on Indian patients: 2000-2008.

AIM: To highlight an increased incidence of colorectal cancer (CRC) amongst young Indian adults. METHOD: A retrospective study of 305 cases of CRC admitted to SSKM Hospital, Kolkata, India during 2000-2008 was carried out. RESULTS: The ratio (0.64) of under-40 to above-40 CRC patients reported in this study is comparable to those from premier Oncology Centers in India (∼0.52) and is higher than those in the Indian National Cancer Registry (∼0.20) and international average (0.07). Distinctive tumour characteristics in younger patients including left-sided lesion (69.7%), presentation at an advanced (III/IV) stage (60%), poor histological differentiation (50%) and predominance of mucin-secreting adenocarcinoma (80%) are similar to those reported in the international literature. Some features are suggestive of hereditary non polyposis colorectal cancer syndrome, which may be a possible reason for the high proportion of young CRC patients. CONCLUSION: A high index of suspicion for CRC among young Indian adults is necessary.

Isolated myoepithelial duodenal hamartoma presenting with upper gastrointestinal bleed.

Myoepithelial duodenal hamartoma, a rare lesion, usually occurs as a part of diffuse gastrointestinal tract polyposis in Peutz-Jegher's and Gardner's syndromes. Solitary duodenal hamartoma in the absence of other manifestations of polyposis syndrome is rare. We report one such patient presenting with massive gastrointestinal bleeding.

Etiology and management of obscure gastrointestinal bleed--an appraisal from eastern India.

OBJECTIVES AND METHOD: Forty patients (mean age 45 years; 24 men) attending a tertiary care hospital in eastern India during the period 1996-2000 were investigated to evaluate the etiology and clinical spectrum of obscure gastrointestinal bleed. RESULTS: The patients presented to hospital after mean symptom duration of 2.5 years. They had received an average of 15 units of blood transfusion. Most patients presented with recurrent melena (85%); all had iron-deficiency anemia. A total of 230 investigations (89 gastroscopies, 54 colonoscopies, 25 double-contrast meal and follow-through studies, 14 small bowel enemas, 24 radionuclide scans, 16 mesenteric angiographies and 8 intraoperative endoscopies) yielded positive diagnosis in 87.5% of cases. The diseases encountered were small bowel and colonic angiodysplasias (32.5%), ileal Crohn's disease (20%), intestinal tuberculosis (10%), intestinal tumors (10%), nonspecific small bowel ulcers and strictures (7.5%), Meckel's diverticulum (5%) and hemobilia (2.5%). The etiology remained obscure in 5 (12.5%) cases. Overall success of surgery was 63%; in-hospital mortality was 7.5%. CONCLUSION: Though obscure gastrointestinal bleed is commonly caused by angiodysplasias, it can be an atypical presentation of Crohn's disease.

Ice cold carbonated water: a therapy for persistent hyperawareness of pharyngeal mucus and throat clearing.

Chronic throat clearing or a feeling of 'something' at the back of the oropharynx or nasopharynx is a common cause for referral to otorhinolaryngology services. While treatment of an underlying causative condition might be expected to improve these symptoms, in many cases a clear underlying cause is not found. Currently, there is no recognized treatment which is effective against these troublesome symptoms. This observational study investigated the effectiveness of a regime of sipping ice cold carbonated water to try to break the vicious cycle of throat clearing. Seventy-two patients with these symptoms who had previously been advised to use the regime were contacted with a postal questionnaire. Sixty-three per cent of patients documented an improvement in their symptom severity score. The most severely and most frequently affected patients had the greatest benefit. We conclude that the suggested regime can be effective in breaking the vicious cycle of persistent throat-clearing.

Recurrent pyogenic cholangitis.

A 26-year-old male presented with jaundice and recurrent cholangitis. Ultrasonography revealed dilated intra- and extrahepatic biliary tree packed with multiple calculi. Endoscopic retrograde cholangiopancreatography and computerised tomography scan confirmed the findings and a diagnosis of recurrent pyogenic cholangitis was made. Cholecystectomy, choledocholithotomy with removal of stones and Roux-en-Y choledochojejunostomy were performed.

A novel approach for the solid-phase synthesis of substituted cyclic guanidines, their respective bis analogues, and N-acylated guanidines from N-acylated amino acid amides.

An efficient method for the solid-phase synthesis of cyclic guanidines from N-acylated amino acid amides, bis cyclic guanidines from N-acylated dipeptides derived from orthogonally protected diamino acids, and N-acylated guanidines from disubstituted cyclic guanidines is described. The exhaustive reduction of N-acylated amino acid amides yields diamines that on treatment with cyanogen bromide lead to the formation of cyclic guanidines. Resin-bound orthogonally protected diamino acids (i.e., N(alpha)-Fmoc-N(x)-(Boc)-diamino acid, x = beta, gamma, delta, epsilon) were N-acylated following removal of the Fmoc group. Removal of the Boc functionality from the side chain then generated a primary amine. Subsequent coupling of Boc amino acids, followed by removal of the Boc group, generated dipeptides that were N-acylated. Exhaustive reduction of amide bonds of the N-acylated dipeptides generated tetraamines having four secondary amines, which upon cyclization with cyanogen bromide afforded the resin-bound trisubstituted bis cyclic guanidines. Treatment of the resin-bound disubstituted cyclic guanidines with carboxylic acids gave N-acylated guanidines. On the basis of their high yield and purity, bis cyclic guanidines derived from N(alpha)-Fmoc-N(epsilon)-Boc-lysine and N-acylated guanidines were chosen for preparation of mixture-based combinatorial libraries. Details of the preparation of these positional scanning libraries using the "libraries from libraries" concept are presented.

Solid-phase synthesis of substituted imidazoline-tethered 2,3-diketopiperazines, cyclic ureas, and cyclic thioureas.

Efficient methods for the solid-phase synthesis of imidazoline-tethered 2,3-diketopiperazines, cyclic ureas, and cyclic thioureas are described. Following the exhaustive reduction of resin-bound dipeptides derived from orthogonally protected diamino acids, the primary amine of the resulting tetraamines was selectively protected with Dde. The compounds were then selectively cyclized via their secondary amines with three different diimidazole derivatives ((COIm)(2), COIm(2), CSIm(2)). Upon Dde removal, the compounds were selectively N-acylated and dehydratively cyclized with POCl(3) to afford the imidazoline-tethered analogues in moderate yield and high purity. These procedures have been extended to prepare mixture-based combinatorial libraries. Details of the selection of building blocks for preparation of the positional scanning libraries based on the "libraries from libraries" approach are discussed.

Tethered libraries: solid-phase synthesis of substituted urea-linked bicyclic guanidines.

The general concept of tethered combinatorial libraries of compounds in which two pharmacophores are found is described. In particular, an improved method for the solid-phase synthesis of bicyclic guanidines from reduced N-acylated dipeptides, and its use in the synthesis of urea-linked bicyclic guanidines, is described. The exhaustive reduction of glutamine-containing resin-bound N-acylated dipeptides, using borane-THF, generated compounds containing three secondary amines and one primary amine. Following selective trityl protection of the primary amine, treatment of the three secondary amines with thiocarbonyldiimidazole (CSIm2) and mercuric acetate (Hg(OAc)2) generated the resin-bound bicyclic guanidines. Following trityl deprotection, an Fmoc-amino acid was coupled. Upon removal of the Fmoc protecting group, the resulting primary amine was treated with hexyl isocyanate to generate the urea-linked bicyclic guanidines. The desired products were cleaved from the resin using hydrogen fluoride. The selection of building blocks and characterization of controls for the synthesis of a combinatorial library is discussed.