Nimotuzumab, a promising therapeutic monoclonal for treatment of tumors of epithelial origin.

Nimotuzumab is a humanized therapeutic monoclonal antibody against epidermal growth factor receptor (EGFR). Clinical trials are ongoing globally to evaluate nimotuzumab in different indications. Nimotuzumab has been granted approval for use in squamous cell carcinoma of head and neck (SCCHN), glioma and nasopharyngeal cancer in different countries. This review focuses on the unique functional characteristics of nimotuzumab. Also, it discusses the safety and efficacy data obtained from the Phase IIb clinical trial conducted in India in SCCHN. Post marketing surveillance data from Cuba for the use of nimotuzumab in pediatric and adult glioma is also discussed. Overall, nimotuzumab has immense therapeutic potential in cancers of epithelial origin.

Proteomic analysis of urinary protein markers for accurate prediction of diabetic kidney disorder.

AIM OF THE STUDY: Microalbuminuria is currently the only diagnostic tool available for early diagnosis of diabetic nephropathy. The test is based on immunological detection of small quantities of albumin in the urinary samples of diabetes patients. There are several limitations of the use of microalbuminuria as an index of renal function. It is therefore desirable to identify additional protein markers that would augment prediction of diabetic nephropathy. The aim of this study is to identify urinary protein markers for specific and more accurate prediction of nephropathy in diabetes patients. DESIGN: 100 registered Type II diabetic patients were studied. Abundant proteins of microalbuminuria positive urinary samples of these patients were analyzed by proteomics approaches of 2-Dimentional Gel Electrophoresis (2DGE) and mass spectrometry. RESULTS: 2-DGE analysis of the urine sample revealed four main proteins along with albumin in these samples. These were zinc alpha-2 glycoprotein, alpha-1 acid glycoprotein, alpha-1 microglobulin and IgG as identified by Matrix Assisted Laser Desorption Ionization-Tune of Flight (MALDI-ToF) and by western blot. Twenty control samples and three cases with microalbuminuria negative to positive transition does suggest the early and co-appearance of the markers with albumin. We have also analyzed full length spectrum of these samples by MALDI-ToF. CONCLUSION: Our study shows the presence of additional proteins in urine samples of microalbuminuria positive diabetes patients. These proteins can be used as markers for specific and accurate clinical analysis of Diabetic nephropathy. We propose a mass spectrometry based high throughput diagnostic approach to detect these markers in the urine sample.

Recombinant antigen-based avidin-biotin microtiter enzyme-linked immunosorbent assay for serodiagnosis of invasive amebiasis.

An immunoscreening approach was used to isolate a strongly positive cDNA clone from an Entamoeba histolytica HK-9 cDNA expression library in the phage vector lambda ZAP-II. The 1.85-kb cDNA insert was found to be truncated and encoded the cysteine-rich, immunodominant domain of the antigenic 170-kDa subunit of the amebal galactose-N-acetylgalactosamine binding lectin. This domain was expressed as a glutathione S-transferase fusion protein in Escherichia coli. Inclusion bodies of the recombinant protein were solubilized with Sarkosyl, and the protein was enriched from the crude bacterial extract by thiol-affinity chromatography. The recombinant protein was used to develop a rapid, sensitive, and specific avidin-biotin microtiter enzyme-linked immunosorbent assay (ELISA) for invasive amebiasis. Sera from 38 individuals suffering from invasive amebiasis, 12 individuals with noninvasive amebiasis, 44 individuals with other infections, and 27 healthy subjects were screened by the recombinant antigen-based ELISA. The sensitivity and specificity of the assay were 90.4 and 94.3%, respectively, which correlated well with those of an ELISA developed with crude amebal antigen (r = 0.94; P < 0.0001), as well as with those of a commercially available serodiagnostic ELISA (r = 0.92; P < 0.0001). Thus, the bacterially expressed recombinant lectin can replace the crude amebal extract as an antigen in the serodiagnosis of invasive amebiasis by using avidin-biotin microtiter ELISA.

Colonoscopic polypectomy in children.

Between January 1984 and July 1990, a total of 129 colonoscopic snare polypectomies were performed during 77 sessions on 74 patients aged 2 to 12 years. Bleeding per rectum (mean duration, 10 months) was the chief presenting symptom and was present in all of these patients. In 89% of patients polypectomy was carried out without using general anesthesia. Ninety-six percent of patients had juvenile polyps. Two patients had familial polyposis coli and one patient had a solitary adenomatous polyp. The majority (98; 80%) of the polyps were located in the rectosigmoid region. Four patients developed complications, one needing emergency operation. There were no deaths in the series. It is concluded that colonoscopic snare polypectomy is a simple, effective, and safe procedure for treating colorectal polyps in children.

Double blind, controlled trial of 4-aminosalicylic acid and prednisolone enemas in distal ulcerative colitis.

Corticosteroid or 5-aminosalicylic acid enemas are the treatment of choice for distal ulcerative colitis but up to one third of patients may be unresponsive. As an alternative therapy might be advantageous, the efficacy of six weeks' treatment with 2 g 4-aminosalicylic acid (4-ASA) (n = 24) and 20 mg prednisolone enemas (n = 21) were compared in a double blind, randomised trial in patients with acute distal (less than 30 cm from the anus) ulcerative colitis. Baseline demography and clinical severity were similar in both groups. Five of 24 patients receiving 4-ASA and 4 of 21 receiving prednisolone did not complete the trial because of deteriorating symptoms, failure to improve, or side effects. At the time of leaving the trial, 24 hour stool frequency, the presence of blood in the stools, and histological and sigmoidoscopic appearances were similar in both groups. Symptomatic improvement occurred in 17 of 24 patients receiving 4-ASA compared with 11 of 21 receiving prednisolone (chi 2 = 1.62, NS). Complete symptomatic improvement occurred in 9 of 24 patients receiving 4-ASA compared with 5 of 21 receiving prednisolone (chi 2 = 0.98, NS). Histological improvement was seen in 9 of 24 patients on 4-ASA compared with 7 of 21 on prednisolone (chi 2 = 0.08, NS). One patient receiving 4-ASA was considered to have an idiosyncratic reaction to the drug but other side effects were not considered to be drug related. Thus, 4-ASA, previously used in the treatment of tuberculosis (para-aminosalicyclic acid), is as good as prednisolone in the treatment of distal ulcerative colitis and should be considered in patients unresponsive to steroids or in whom steroid treatment is undesirable.

Diagnostic efficiency of an ultrarapid endoscopy room test for Helicobacter pylori.

There are several reliable methods for detecting Helicobacter pylori but all have as a major disadvantage the time required to yield a definitive result. We have modified the standard urease test so that a positive result is available in one minute. We describe the use of this test in biopsy specimens from the gastric antrum from 220 consecutive patients referred for upper gastrointestinal endoscopy. The performance of the 'one minute test' was compared with a standard urease test, Gram stain, and microbiological culture. Using culture as the 'gold standard' 80 (36%) of the patients were H pylori positive. The one minute test produced no false positives and showed a sensitivity of 89% and specificity of 100%, while the predictive values of a positive and negative test were 100% and 94% respectively. The diagnostic efficiency of the test was 96% compared to 85% for both the Gram stain and direct urease test. All positive results using the one minute test were available within one minute. The test is easy to prepare and costs approximately pounds 0.04. This new modification of the urease test should be superior to the currently available urease tests because a reliable result will be available in almost 90% of infected individuals even before endoscopy is completed.

Antibodies to gut protozoa in commercial immunoglobulin preparations.

Using parasite agglutination, indirect immunofluorescence, enzyme-linked immunosorbent assay, and immunoblotting, Giardia lamblia specific antibody was detected in 5 commercially available immunoglobulin (IgG) preparations. IgG antibodies to Entamoeba histolytica were either present in very low titre or were absent. Immunoblotting showed that anti-G. lamblia antibodies were detected towards a range of Giardia proteins, 25-200 kDa. These findings raise the possibility that pooled human IgG preparations could be evaluated in the treatment of chronic giardiasis which is refractory to conventional therapy.

Review: new aminosalicylic acid derivatives for the treatment of inflammatory bowel disease.

Up to 20-30% of patients treated with sulphasalazine experience a variety of adverse effects, principally due to the carrier moiety sulphapyridine. In the last decade there has been a major drive to develop a new generation of 5-aminosalicylic acid (5-ASA) and 5-ASA-related drugs which not only have a high efficacy but are also devoid of the unwanted side-effects of sulphapyridine. Various forms of 5-ASA have been evaluated in ulcerative colitis and appear to be effective orally in preventing relapse and topically in the treatment of active distal colitis. More recently, topical 4-ASA has been found to be useful for the treatment of distal colitis with the advantage of better stability and lower cost compared with 5-ASA. In the foreseeable future it seems likely that these new aminosalicylic acid derivatives will become the drugs of choice in the treatment of inflammatory bowel disease and largely replace sulphasalazine.