A survey on clinical presentation and nutritional status of infants with suspected cow' milk allergy

Background  

Cow's milk is the most common food allergen in infants and the diagnosis of cow's milk allergy is difficult, even with the use of several diagnostic tests. Therefore, elimination diets and challenge tests are essential for the diagnosis and treatment of this disorder. The aim of this study is to report the clinical presentation and nutritional status of children evaluated by pediatric gastroenterologists for the assessment of symptoms suggestive of cow's milk allergy.     

Significance of DNA Replication Licensing Proteins (MCM2, MCM5 and CDC6), p16 and p63 as Markers of Premalignant Lesions of the Uterine Cervix: Its Usefulness to Predict Malignant Potential

Cervical cancer continues to be a leading cancer among women in many parts of the world. Nation-wide screening with the Pap smear has not been implemented in India due to the lack of adequately trained cytologists. Identification of biomarkers to predict malignant potential of the identified low risk lesions is essential to avoid excessive retesting and follow up. The current study analyzed the expression patterns of DNA replication licensing proteins, proliferation inhibitor protein p16INK4A and tumor suppresser protein p63 in cervical tissues and smears to assess the ability of these proteins to predict progression. Methods: Cervical smears and corresponding tissues were immunostained using mouse monoclonal antibodies against MCM2, MCM5, CDC6, p16 and p63. Smears were treated with a non-ionic surfactant sodium deoxycholate prior to immuno-cytochemistry. The standard ABC method of immunohistochemistry was performed using DAB as the chromogen. The immunostained samples were scored on a 0-3+ scale and staining patterns of smears were compared with those of tissue sections. Sensitivity and specificity for each of these markers were calculated taking histopathology as the gold standard. Result: All the markers were positive in malignant and dysplastic cells. MCM protein expression was found to be up-regulated in LSIL, HSIL and in malignancies to a greater extent than p16 as well as p63. CDC6 protein was preferentially expressed in high grade lesions and in invasive squamous cell carcinomas. A progressive increase in the expression of DNA replication licensing proteins in accordance with the grades of cervical intraepithelial lesion suggests these markers as significant to predict malignant potential of low grade lesions in cervical smears. Conclusion: MCMs and CDC6 can be applied as biomarkers to predict malignant potential of low grade lesions identified in screening programmes and retesting     

Novel sst(4)-selective somatostatin (SRIF) agonists. 2. Analogues with beta-methyl-3-(2-naphthyl)alanine substitutions at position 8

We present a family of human sst(4)-selective, high-affinity (IC(50) = 2-4 nM) cyclic somatostatin (SRIF) octapeptides. These peptides result from the substitution of dTrp(8) in H-c[Cys(3)-Phe(6)-Phe(7)-DTrp(8)-Lys(9)-Thr(10)-Phe(11)-Cys(14)]-OH (SRIF numbering) (ODT-8) by one of the four conformationally biased stereoisomers of beta-methyl-3-(2-naphthyl)alanine (beta-Me2Nal). Whereas H-c[Cys-Phe-Phe-DNal-Lys-Thr-Phe-Cys]-OH (ODN-8, 2) has high affinity and marginal selectivity for human sst(3) (Reubi et al., Proc. Natl. Acad. Sci. U.S.A. 2000, 97, 13973-13978), H-c[Cys-Phe-Tyr-D-threo-beta-Me2Nal-Lys-Thr-Phe-Cys]-OH (5) has high affinity for all sst's except for sst(1); H-c[Cys-Phe-Tyr-L-threo-beta-Me2Nal-Lys-Thr-Phe-Cys]-OH (6) has high affinity for sst(4) (IC(50) = 2.1 nM), with more than 50-fold selectivity toward the other receptors. Analogues 7 and 8, containing d- and l-erythro-beta-Me2Nal instead of the corresponding threo derivatives at position 8, are essentially inactive at all receptors. Substitution of Tyr(7) in 5 and 6 by Aph(7) resulted in 9 and 10 with similar affinity patterns overall yet lowered affinity. The substitution of DCys(3) for Cys(3) in 5 and 6 yielded H-c[DCys-Phe-Tyr-D-threo-beta-Me2Nal-Lys-Thr-Phe-Cys]-OH (11) and H-c[DCys-Phe-Tyr-L-threo-beta-Me2Nal-Lys-Thr-Phe-Cys]-OH (12), with biological profiles almost identical to those of their parents 5 and 6 (i.e., high affinity for sst(2-5) for 11 and high affinity and selectivity for sst(4) for 12). Analogue 12, with high sst(4) affinity combined with the highest sst(4) selectivity among all tested compounds, is an agonist in the cAMP accumulation assay (EC(50) = 1.29 nM). Cold monoiodination of 12 yielded 14, with loss of sst(4) selectivity and loss of high affinity (IC(50) = 21 nM). Introduction of Tyr(2) in 9 and 10 and substitution of Cys(3) by dCys(3), to yield 15 and 16 (IC(50) = 9.8 and 61 nM, respectively, for sst(4) and limited selectivity), failed to generate a high-affinity (125)iodinatable sst(4)-selective ligand. Substitution of Phe by Tyr at position 11 in H-c[DCys-Phe-Phe-L-threo-beta-Me2Nal-Lys-Thr-Phe-Cys]-OH yielded 18 (IC(50) = 11.8 nM at sst(4)), with limited sst(4) selectivity (30-fold or greater at the other receptors) yet only slightly improved affinity over that of 14. Cold monoiodination of 18 yielded 20 (IC(50) = 30 nM at sst(4) and high selectivity). Whereas we were able, in this study, to identify a new family of sst(4)-selective, high-affinity compounds, our additional goal, to identify highly potent and sst(4)-selective ligands amenable to (125)iodination, could not be achieved satisfactorily. On the other hand, some of the diastereomers identified in this study, such as 5, 11, 17, and 19, are very potent ligands at all receptors but sst(1).     

Efficacy of fixed low-dose isotretinoin (20 mg, alternate days) with topical clindamycin gel in moderately severe acne vulgaris

Background  In view of the potentially serious side-effects of standard isotretinoin (0.5–1.0 mg/kg per day) therapy for acne, we studied the safety and efficacy of low-fixed dose isotretinoin plus topical 1%clindamycin gel in the treatment of moderate grade of acne.
Methods  In this prospective, non-comparative study, 320 adult patients, with moderately severe acne were enrolled and treated with fixed-dose isotretinoin at 20 mg every alternate day (approximately 0.15 mg/kg/day to 0.28 mg/kg/day) for 6 months along with topical clindamycin gel. All female patients were assessed for polycystic ovarian disease. Patients were followed up for 6 months.
Results  A total of 305 patients completed the study. Overall, patients received a mean of 38.4 mg/kg cumulative dose of isotretinoin, and very good results were observed in 208 (68.20%), while good response was seen in 59 (19.34%) of patients. Failure of the treatment occurred in 38 (12.46%), while relapses occurred in 50 (16.39%) of patients. Relapses were commoner in females, and 37 of 43 (86.04%) patients had polycystic ovarian disease. Though mild chelitis (91%) and xerosis (43%) were common, laboratory abnormalities in the form of elevated hepatic enzymes (5%) and elevated serum lipids (6%) were rare.
Conclusion  Six months of treatment with fixed-dose, alternate-day isotretinoin (20 mg) plus topical 1%clindamycin gel was found to be effective in the treatment of moderate acne in adult patients, with a low incidence of side-effects.

Conflicts of interest

None declared     

Gallstone Obstructive Ileus 3 Years Post-cholecystectomy to a Patient with an Old Ileoileal Anastomosis

The present case is one of gallstone obstructive ileus due to gallstones 3 yr after laparoscopic cholecystectomy. It is interesting because of the sex of the patient, the fact that ileus occurred 3 yr after cholecystectomy and that the localization of the obstruction was an old side-to-side ileoileal anastomosis due to a diverticulectomy following intussusception of Meckels'' diverticulum at the age of 3.     

Bombesin receptor antagonists may be preferable to agonists for tumor targeting.

Two bombesin analogs, Demobesin 4 and Demobesin 1, were characterized in vitro as gastrin-releasing peptide (GRP) receptor agonist and antagonist, respectively, and were compared as (99m)Tc-labeled ligands for their in vitro and in vivo tumor-targeting properties. METHODS: N(4)-[Pro(1),Tyr(4),Nle(14)]Bombesin (Demobesin 4) and N(4)-[d-Phe(6),Leu-NHEt(13),des-Met(14)]bombesin(6-14) (Demobesin 1) were characterized in vitro for their binding properties with GRP receptor autoradiography using GRP receptor-transfected HEK293 cells, PC3 cells, and human prostate cancer specimens. Their ability to modulate calcium mobilization in PC3 and transfected HEK293 cells was analyzed as well as their ability to trigger internalization of the GRP receptor in transfected HEK293 cells, as determined qualitatively by immunofluorescence microscopy and quantitatively by enzyme-linked immunosorbent assay (ELISA). Further, their internalization properties as (99m)Tc-labeled radioligands were tested in vitro in both cell lines. Finally, their biodistribution was analyzed in PC3 tumor-bearing mice. RESULTS: A comparable binding affinity with the 50% inhibitory concentration (IC(50)) in the nanomolar range was measured for Demobesin 4 and Demobesin 1 in all tested tissues. Demobesin 4 behaved as an agonist by strongly stimulating calcium mobilization and by triggering GRP receptor internalization. Demobesin 1 was ineffective in stimulating calcium mobilization and in triggering GRP receptor internalization. However, in these assays, it behaved as a competitive antagonist as it reversed completely the agonist-induced effects in both systems. (99m)Tc-Labeled Demobesin 1 was only weakly taken up by PC3 cells or GRP receptor-transfected HEK293 cells (10% and 5%, respectively, of total added radioactivity) compared with (99m)Tc-labeled Demobesin 4 (45% of total added radioactivity in both cell lines). Remarkably, the biodistribution study revealed a much more pronounced uptake at 1, 4, and 24 h after injection of (99m)Tc-labeled Demobesin 1 in vivo into PC3 tumors than (99m)Tc-labeled Demobesin 4. In vivo competition experiments demonstrated a specific uptake in PC3 tumors and in physiologic GRP receptor-expressing tissues. The tumor-to-kidney ratios were 0.7 for Demobesin 4 and 5.2 for Demobesin 1 at 4 h. CONCLUSION: This comparative in vitro/in vivo study with Demobesin 1 and Demobesin 4 indicates that GRP receptor antagonists may be superior targeting agents to GRP receptor agonists, suggesting a change of paradigm in the field of bombesin radiopharmaceuticals.     

Male pattern androgenetic alopecia in an Indian context: a perspective study

BACKGROUND: Androgenetic alopecia (AGA) has received scant attention, despite it being a common entity that may result in significant psychosocial morbidity. There are some patients who do not fit into any of the proposed types. Moreover, there have been no published studies of pattern and prevalence of AGA in males in an Indian context. Hence, the present study was an attempt to classify AGA in males with the aim of producing a simple, effective and easily reproducible classification. METHODS: In total, 150 male patients were clinically diagnosed as AGA. After obtaining informed consent from all patients, a detailed history/examination was carried out, including a hair pull test, a trichogram investigation and a biopsy. Classification of AGA was subsequently attempted across Norwood guidelines. RESULTS: A gradual shift in the type of AGA from the earlier types (II and III) to more severe types (VI) with increasing age was significant. Twenty-seven patients did not fit into specific patterns according to Hamilton and Norwood classifications. In addition, type 'a' variant was recorded in 20% of patients, clearly indicating limitations of the existing classifications. CONCLUSIONS: It was possible to classify 80% of the AGA, with II (28%) and III (15%) being the most common types of AGA. Twenty-seven patients (18%) could not be classified as a significant finding. There was considerable overlap in types IV, V and VI in the Norwood classification with the 'a' variants further confusing the picture.     

Somatostatin receptor 1 selective analogues: 2. N(alpha)-Methylated scan

Des-AA(1,2,5)-[d-Trp(8)/d-Nal(8),IAmp(9)]SRIF (AA = amino acid, Nal = 3-(2-naphthyl)-alanine, IAmp = 4-(N-isopropyl)-aminomethylphenylalanine, SRIF = somatostatin), with or without a tyrosine or monoiodotyrosine, were scanned with the introduction of a backbone N-methyl group and tested for binding affinity at the five human somatostatin receptors (sst(1)(-)(5)). N(alpha)-Methylation resulted in loss of sst affinity (2- to >5-fold) when introduced at residues Lys(4) (6), Phe(6) (7), Phe(7) (8), Thr(10) (11), and Phe(11) (12) of the parent compound Des-AA(1,2,5)-[d-Nal(8),IAmp(9)]SRIF (4). N(alpha)-Methylation was tolerated at residues Cys(3) (5), d-Nal(8) (9), Thr(12) (13), and Cys(14) (15) with retention of binding sst affinity and selectivity and resulted in an increase in sst binding affinity at positions IAmp(9) (10) and Ser(13) (14). In these series, the d-Trp(8) substitution versus d-Nal(8) is clearly superior. C-Terminally lysine-extended analogues (21-25) retained sst(1) selectivity and binding affinity when compared to their d-Nal(8)- (4) or d-Trp(8)- (3) containing parent. Des-AA(1,2,5)-[d-Trp(8), (N(alpha)Me)IAmp(9)]SRIF (17), Des-AA(1,2,5)-[d-Trp(8),IAmp(9),(N(alpha)Me)Ser(13)]SRIF (19), Des-AA(1,2,5)-[d-Trp(8),IAmp(9),(N(alpha)Me)Cys(14)]SRIF (20), Des-AA(1,2,5)-[d-Trp(8),(N(alpha)Me)IAmp(9),Tyr(11)]SRIF (34), and Des-AA(1,2,5)-[d-Agl(8)(N(beta)Me,2-naphthoyl),IAmp(9),Tyr(11)]SRIF (42) (Agl = aminoglycine) are sst(1) agonists in their ability to inhibit forskolin-induced cAMP production.