e-TEP repair for midline primary and incisional hernia: technical considerations and initial experience.

INTRODUCTION: The Enhanced-View Totally Extra Peritoneal Rives-Stoppa (e-TEP-RS) Technique for the repair of large, complex, ventral abdominal hernias has gained popularity especially in overcoming the disadvantages with Intra Peritoneal Onlay Mesh (IPOM) repairs and to enable siting of a large prosthetic mesh in an anatomical plane distinct from the abdominal cavity and its contents. Evolving variations of the original technique have allowed the definitive repair of such defects in a reproducible manner. We present our initial experience of this approach and detailed steps of our native technical modifications in overcoming the challenges in performing this complex and potentially challenging procedure. MATERIALS AND METHODS: This is a retrospective review of the clinical data of midline, large, complex, ventral abdominal hernia patients who underwent e-TEP-RS with and without Transversus Abdominis Release (TAR). Patients, with or without Diastasis of Rectus Abdominis Muscle (DRAM) were included. Key outcomes measured were post-operative pain, operative morbidity, readmission, Quality of Life (QoL), hernia recurrence. RESULTS: A total of 58 midline, ventral abdominal hernia patients who underwent e-TEP-RS with and without Transversus Abdominis Release (TAR), between March 2018 and December 2019 were studied. Mean defect area was 41.0 ± 28 cm2 and the mean mesh surface area was 473.5 ± 165 cm2. e-TEP-RS was done in 35 cases, e-TEP RS TAR in 15 cases and e-TEP-RS with e-TEP inguinal in 08 cases. There was no intraoperative morbidity. Mean duration of surgery was 156.2 ± 40 min and mean blood loss was 40.5 ± 26 cc. The CCS QoL scores improved from 34.6 (± 2) pre-operatively to 27.2 (± 4) at the end of 6 months. One patient had a supra-umbilical recurrence following bilateral TAR over the superior edge of the mesh. Follow-up ranged from 6 to 22 months, with a mean of 14 months. Major complications (n = 12; 20.7%) were seroma formation and prolonged ileus. CONCLUSION: The e-TEP-RS technique for large, complex, midline, ventral abdominal hernias can be used with excellent results and acceptable morbidity. This technique is technically challenging and should be mastered in relatively smaller ventral hernias to achieve good results before attempting it in larger, complex ones.

Imaging diagnosis of aortic stenosis.

Aortic valve stenosis (AS) is the commonest primary valve disorder with increasing prevalence with age. Trans-thoracic echocardiogram is the main imaging technique used to diagnose AS, but discrepancy in diagnosis has been described in almost one third of cases. Other imaging methods, particularly electrocardiogram (ECG)-gated computed tomography, have now emerged to further clarify the diagnosis of AS by both demonstrating the degree of calcification in the valve as well as aortic valve area. Cardiac magnetic resonance imaging allows accurate quantification of ventricular function and evaluation of the myocardium. This paper provides a comprehensive review of the diagnosis of AS for the radiologist.

Effect of γ-radiation on post-harvest storage life and quality of onion bulb under ambient condition.

Different doses of gamma Irradiation (0 Gy, 10 Gy, 60 Gy, 100 Gy and 200 Gy) were evaluated as potential treatment to extend the storage period and maintain the quality attributes of onion bulbs (cv. Punjab Noraya) at ambient temperature for a period of 144 days. It was observed that storage parameters such as physiological loss in weight, sprouting percentage, rotting percentage and quality traits like total soluble solids, firmness, color parameters, ascorbic acid and pyruvic acid varied significantly (p < 0.05) during storage period with respect to doses of irradiation. No rotting and sprouting were observed upto 24 days and 84 days, respectively in both gamma irradiated and un-irradiated bulbs. At 5 months of storage, the physiological loss in weight varied from 28.5 to 63.6% in all treatments. Physiological weight loss and rotting percentage were higher in the untreated (control) as well as bulbs radiated @ 10 Gy and 200 Gy. Firmness was better retained in the bulbs irradiated with gamma rays @ 120 Gy bulbs upto 84 days of storage. However, no clear-cut pattern for colour changes (L, a, b values) was observed with respect to the irradiation doses. TSS in bulbs decreased upto 36 days of storage and thereafter increased upto 48th day of storage irrespective of the dose of gamma irradiation. Ascorbic acid content of bulbs decreases significantly in all the irradiation treatments during storage but pyruvic acid initially increased, then decreased and again increased at the end of the storage period in un-irradiated and irradiated treatments. It is concluded that onion bulbs irradiated with gamma rays @ 120 Gy resulted in minimum loss in weight, rotting and sprouting while maintained best quality for 3 months of storage at ambient storage conditions.

Complete Remission of Post-transplantation Recurrence of Focal Segmental Glomerulosclerosis With the Use of Adrenocorticotrophic Hormone Gel: Case Report.

BACKGROUND: Post-transplantation recurrence of primary focal and segmental glomerulosclerosis (FSGS) is estimated to occur in 30%-50% of cases and doubles the risk of allograft failure. Treatment of recurrent FSGS is challenging because specific pathogenic targets are unknown and available therapeutic options have limited efficacy. CASE REPORT: We report a case of recurrent FSGS with nephrotic-range proteinuria (urine protein creatinine ratio [UPCR], >50) and debilitating edema that was resistant to rituximab and plasmapheresis. The patient had a remarkable response to adrenocorticotropic hormone (ACTH) gel and achieved complete remission (UPCR, 0.5; serum albumin, 4.1 g/dL; serum creatinine, 1.0 mg/dL) which was maintained over 10 months on this treatment. CONCLUSIONS: We conclude that ACTH gel is a potential therapeutic option for post-transplantation recurrence of FSGS and warrants further evaluation.

Cardiac sarcoidosis: diagnosis and management.

Cardiac sarcoidosis is one of the most serious and unpredictable aspects of this disease state. Heart involvement frequently presents with arrhythmias or conduction disease, although myocardial infiltration resulting in congestive heart failure may also occur. The prognosis in cardiac sarcoidosis is highly variable, which relates to the heterogeneous nature of heart involvement and marked differences between racial groups. Electrocardiography and echocardiography often provide the first clue to the diagnosis, but advanced imaging studies using positron emission tomography and MRI, in combination with nuclear isotope perfusion scanning are now essential to the diagnosis and management of this condition. The identification of clinically occult cardiac sarcoidosis and the management of isolated and/or asymptomatic heart involvement remain both challenging and contentious. Corticosteroids remain the first treatment choice with the later substitution of immunosuppressive and steroid-sparing therapies. Heart transplantation is an unusual outcome, but when performed, the results are comparable or better than heart transplantation for other disease states. We review the epidemiology, developments in diagnostic techniques and the management of cardiac sarcoidosis.

Predictors of paravalvular aortic regurgitation following self-expanding Medtronic CoreValve implantation: the role of annulus size, degree of calcification, and balloon size during pre-implantation valvuloplasty and implant depth.

OBJECTIVES: We sought to investigate the role of balloon size during pre-implantation valvuloplasty in predicting AR and optimal Medtronic CoreValve (MCS) implantation depth. BACKGROUND: Paravalvular aortic regurgitation (AR) is common following MCS implantation. A number of anatomical and procedural variables have been proposed as determinants of AR including degree of valve calcification, valve undersizing and implantation depth. METHODS: We conducted a multicenter retrospective analysis of 282 patients who had undergone MCS implantation with prior cardiac CT annular sizing between 2007 and 2011. Native valve minimum (Dmin), maximum (Dmax) and arithmetic mean (Dmean) annulus diameters as well as agatston calcium score were recorded. Nominal and achieved balloon size was also recorded. AR was assessed using contrast angiography at the end of each procedure. Implant depth was measured as the mean distance from the nadir of the non- and left coronary sinuses to the distal valve frame angiographically. RESULTS: 29 mm and 26 mm MCS were implanted in 60% and 39% of patients respectively. The majority of patients (N=165) developed AR <2 following MCS implantation. AR ≥3 was observed in 16% of the study population. High agatston calcium score and Dmean were found to be independent predictors of AR ≥3 in multivariate analysis (P<0.0001). Nominal balloon diameter and the number of balloon inflations did not influence AR. However a small achieved balloon diameter-to-Dmean ratio (≤0.85) showed modest correlation with AR ≥3 (P=0.04). This observation was made irrespective of the degree of valve calcification. A small MCS size-to-Dmean ratio is also associated with AR ≥3 (P=0.001). A mean implantation depth of ≥8+2mm was also associated with AR ≥3. Implantation depth of ≥12 mm was associated with small MCS diameter-to-Dmean ratio and increased 30-day mortality. CONCLUSION: CT measured aortic annulus diameter and agatston calcium score remain important predictors of significant AR. Other procedural predictors include valve undersizing and low implantation depth. A small achieved balloon diameter-to-Dmean ratio might also predict AR ≥3. Our findings confirm that a small achieved balloon size during pre-implantation valvuloplasty predicts moderate-severe AR in addition to previously documented factors.

Acute pyelonephritis in diabetes mellitus: Single center experience.

Diabetes mellitus is a common cause of pyelonephritis. Both emphysematous pyelonephritis (EPN) and non-EPN (NEPN) are associated with poor outcome. This study was aimed at analyzing the clinical features, microbiological profile, prognostic factors, and treatment outcome of pyelonephritis in diabetic patients. A total of 105 diabetic patients with pyelonephritis were admitted from July 2010 to June 2012. Patients were treated with appropriate antibiotics and percutaneous drainage (PCD) as indicated. Nephrectomy was carried out in patients of EPN who were refractory to conservative measures. NEPN and EPN were seen in 79 (75.2%) and 26 (24.7%) patients, respectively. Escherichia coli was the most common organism. Pyelonephritis was associated with renal abscess and papillary necrosis in 13 (12.4%) and 4 (3.8%) patients with EPN and NEPN, respectively. Worsening of renal functions were seen in 92 and 93% of patients with EPN and NEPN, respectively. Class 1 EPN was seen in 2 (7.7%), Class II in 8 (30.7%), IIIa in 7 (27%), IIIb in 5 (19.3), and IV in 4 (15.4%) patients. Antibiotics alone were sufficient in 38.5% of EPN versus 62% in NEPN; additional PCD was required in 42.3% in EPN and 21.4% in NEPN. Nephrectomy was required in 5 (19.2%) EPN patients with Class IIIB or IV. A total of 13 patients (12.4%) expired, 4 (15.4%) in EPN, and 9 (11.4%) in NEPN group. Patients with EPN had a higher incidence of shock (6% vs. 0; P < 0.05) and poorly controlled blood sugar (26% vs. 50%; P < 0.05) compared with NEPN. Presence of shock and altered sensorium were associated with poor outcome in patients with EPN. Diabetics with pyelonephritis have severe disease. Patients of EPN have poorer treatment outcome compared with those with NEPN. However, there is no difference in the mortality, but a greater need of nephrectomy in EPN compared with NEPN patients. Presence of shock and altered sensorium at presentation were poor prognostic factors in EPN.

Low cost technology for screening early cancerous lesions of oral cavity in rural settings.

BACKGROUND: Low cost technologies are needed in resource poor rural settings for detection of pre-cancer and cancer lesions of the oral cavity. AIM: The study was undertaken to investigate the feasibility of a low cost technology (Magnivisualizer) for the early detection any lesions of the oral cavity among tobacco users in a resource poor rural field setting. SUBJECTS AND METHODS: A total of 1329 tobacco users were motivated to come forward for oral examination in the camp organized for this purpose. Their oral cavities were screened with a torch and Magnivisualizer by a Dentist. RESULTS: With torch light, 104/1329 (7.8%) lesions were identified, though only 62/104 (59.6%) positive lesions could be differentiated into various categories. However, through Magnivisualizer 156/1329 (11.7%) lesions were detected and 153/156 (98.1%) positive lesions were differentiated into different categories. CONCLUSION: Magnivisualizer offers an alternative instrument for detecting most of the early cancerous and high-grade precancerous lesions and it can be used in the rural field settings.

Outcomes of spousal versus related donor kidney transplants: A comparative study.

This study was designed to compare the outcomes of spousal donor (SD) with related donor (RD) kidney transplants performed at our center between January 2010 and October 2012. A total of 323 adult, ABO-compatible kidney transplants (SD 150 [46.4%], RD 173 [53.6%]) were included. Data on outcomes at 6 months post-transplant was collected retrospectively (2010-2011) and prospectively (January-October 2012). Majority of the donors (SD 88%, RD 72.2%) were females. In the SD group, donors were younger (SD 35.6 ± 8.2 years, RD 45.2 ± 11.5 years; P < 0.0001), whereas recipients were older (SD 42.2 ± 8.3 years, RD 30.0 ± 9.5 years; P < 0.0001). A significantly higher proportion of patients in the SD group were given induction therapy (43% vs 12%; P < 0.001). Biopsy proven acute rejections were more common in the RD group (16% vs 28.3%; P = 0.01). Majority (80.8%) of the acute rejections occurred in the first 2 weeks post-transplant in both groups. Isolated acute cellular rejections (ACRs) and isolated antibody mediated rejections constituted 50% and 25% of rejection episodes in both groups, whereas the remainder had histological evidence of both. The proportion of steroid responsive ACRs was similar in both groups (SD 83.3%, RD 65.4%; P = 0.2). The number of patients with abnormal graft function at the end of the study was higher in the RD group (2.3% vs. 12.3%; P = 0.001). Patient survival and infection rates were similar in the two groups. We conclude that short-term outcomes of SD transplants are not inferior to RD transplants. Lesser use of induction therapy in the RD group may explain the poorer outcomes as compared to the SD group.

Role of inflammatory gene polymorphisms in left ventricular dysfunction (LVD) susceptibility in coronary artery disease (CAD) patients.

RATIONALE: Inflammation exacerbates a number of deleterious effects on the heart, most notable being left ventricular dysfunction (LVD). A promoter polymorphism of the NFKB1 gene (encodes p50 subunit) results in lower protein levels of NFkB p50 subunits, which in its dimmer (p50) form has anti-inflammatory effects. The active NFkB transcription factor promotes the expression of over 150 target genes including IL6 and TNF-α. Therefore, the aim of the present study was to assess the association of NFKB1, IL6 and TNF-α gene polymorphisms with LVD in coronary artery disease (CAD) patients. METHODS AND RESULTS: The present study included a total of 830 subjects (600 CAD patients and 230 controls) and was carried out in two (primary and replication) cohorts. CAD patients with reduced left ventricle ejection fraction (LVEF ≤45%) were categorized having LVD. The NFKB1 -94 ATTG ins/del (rs28362491), IL6 -174 G/C (rs1800795) and TNF-α -308 G/A (rs1800629) polymorphisms were genotyped by PCR/ARMS-PCR methods. The results of the primary cohort were validated in a replicative cohort and pooled by meta-analysis using Fisher's and Mantel-Haenszel test. The analysis showed that NFKB1 ATTG/ATTG genotype was significantly associated with LVD (Fisher's method p-value=0.007, Mantel-Haenszel OR=2.34), LV end diastole (p-value=0.013), end systole (p-value=0.011) dimensions, LV mass (p-value=0.024), mean LVEF (p-value=0.001) and myocardial infarction (p-value=0.043). CONCLUSION: Our data suggests that NFKB1 -94 ATTG ins/del polymorphism plays significant role in conferring susceptibility of LVD and ATTG/ATTG genotype may modulate risk of heart failure by increasing ventricular remodeling and worsening LV function.

Association of matrix metalloproteinases (MMP2, MMP7 and MMP9) genetic variants with left ventricular dysfunction in coronary artery disease patients.

BACKGROUND: Left ventricular dysfunction (LVD) is a condition resulting from clustered structural or functional cardiac disorder that reduces the ability of the ventricle to fill with or eject blood. The impaired ventricular function can be attributed to unfavorable ventricular remodeling. Among the pathways that contribute to remodeling process, matrix metalloproteinases (MMPs) appear to be of particular interest. We explored the association of MMP2 (C-735T, rs2285053), MMP7 (A-181G, rs11568818) and MMP9 (R279Q, rs17576), (P574R, rs2250889), (R668Q, rs17577) genetic variants with LVD in coronary artery disease (CAD) patients. METHODS: The study included 310 consecutive patients with angiographically confirmed CAD and 230 healthy controls. Among patients with CAD, 95 with reduced left ventricle ejection fraction (LVEF ≤ 45) were categorized as LVD. Polymorphisms were determined by PCR-RFLP. RESULTS: The MMP9 R668Q genetic variant was significantly associated with LVD (LVEF ≤ 45) (p value=0.009; OR=3.82). To validate our results, we performed a replication study in additional 200 cases with similar clinical characteristics and results again confirmed consistent findings (p value=0.033; OR=3.59). Also the frequency of haplotype R,P,Q comprising R668Q variation in MMP 9 was significantly higher in reduced LVEF subjects (p value=0.008; OR=1.83). CONCLUSION: MMP9 R668Q plays important role in conferring susceptibility of LVD.

Impact of renin-angiotensin-aldosterone system gene polymorphisms on left ventricular dysfunction in coronary artery disease patients.

BACKGROUND: Left ventricular dysfunction (LVD), followed by fall in cardiac output is one of the major complications in some coronary artery disease (CAD) patients. The decreased cardiac output over time leads to activation of the renin-angiotensin-aldosterone system which results in vasoconstriction by influencing salt-water homeostasis. Therefore, the purpose of the present study was to explore the association of single nucleotide polymorphisms (SNPs) in angiotensin I converting enzyme; ACE (rs4340), angiotensin II type1 receptor; AT1 (rs5186) and aldosterone synthase; CYP11B2 (rs1799998) with LVD. METHODS AND RESULTS: The present study was carried out in two cohorts. The primary cohort included 308 consecutive patients with angiographically confirmed CAD and 234 healthy controls. Among CAD, 94 with compromised left ventricle ejection fraction (LVEF ⩽ 45) were categorized as LVD. The ACE I/D, AT1 A1166C and CYP11B2 T-344C polymorphisms were determined by PCR. Our results showed that ACE I/D was significantly associated with CAD but not with LVD. However, AT1 1166C variant was significantly associated with LVD (LVEF ⩽ 45) (p value=0.013; OR=3.69), but CYP11B2 (rs1799998) was not associated with either CAD or LVD. To validate our results, we performed a replication study in additional 200 cases with similar clinical characteristics and results again confirmed consistent findings (p value=0.020; OR=5.20). CONCLUSION: AT1 A1166C plays important role in conferring susceptibility of LVD.

The impact of VKORC1-1639 G>A polymorphism on the maintenance dose of oral anticoagulants for thromboembolic prophylaxis in North India: A pilot study.

BACKGROUND: The dose requirements for oral anticoagulants in thromboembolic events are influenced by promoter polymorphism in the VKORC1 gene. However, limited data are available on the influence of the polymorphism in various Indian populations. The present study aimed at determining the relationship between the VKORC1-1639 G>A genotypes and maintenance doses of oral anticoagulants for therapeutically stable INR values in patients taking Acitrom after valve replacement surgery. MATERIALS AND METHODS: Fifty patients from the northern Indian region were genotyped for VKORC1-1639 G>A by polymerase chain reaction and restriction fragment length polymorphism. Means of the weight-normalized daily Acitrom dose were calculated for every patient. RESULTS AND DISCUSSION: The VKORC1 1639G>A minor allele frequency in the study population (n = 50) was found to be 22%. The patients with a wild type genotype required the maximum drug dose as suggested for full functionality of the enzyme. Heterozygous patients were found to have an intermediate drug dose and the patients with a variant homozygous genotype had the minimum maintenance drug dose requirement. These findings are in concurrence with the effect of the promoter polymorphism on vitamin K epoxide reductase activity.1639G>A minor allele frequency in the study population (n = 50) was found to be 22%. The patients with a wild type genotype required the maximum drug dose as suggested for full functionality of the enzyme. Heterozygous patients were found to have an intermediate drug dose and the patients with a variant homozygous genotype had the minimum maintenance drug dose requirement. These findings are in concurrence with the effect of the promoter polymorphism on vitamin K epoxide reductase activity. CONCLUSION: The VKORC1-1639 G>A status can be indicative of establishing the therapeutic dose of oral anticoagulants in Indian patients.

Association of death receptor 4, Caspase 3 and 5 gene polymorphism with increased risk to bladder cancer in North Indians.

PURPOSE: Perturbed apoptosis due to missense alterations in candidate tumor suppressor gene Death receptor 4 (DR4) and in caspases (Casp) lead to deregulated cell proliferation and cancer predisposition. Some data indicate that normal variations within the sequence of apoptotic genes may lead to suboptimal apoptotic capacity and therefore increased cancer risk. To test our proposal we examined whether six single nucleotide polymorphisms (SNPs) of the DR4 and Casp3, 5 genes contrive the risk of bladder cancer (BC) in a North Indian population. MATERIALS AND METHODS: Genotyping was performed in 200 BC patients and 225 controls by Allele-specific PCR and by polymerase chain reaction-restriction fragment length polymorphism. RESULTS: In DR4 Arg141His, BC patients having AA genotype (p = 0.036; OR = 2.51. In Casp5Leu13Phe G > C, significant association was observed with GC (p = 0.025; OR = 1.78) and also in GC + CC (p = 0.026; OR = 1.68). C allele carriers in Casp5Ala90Thr T > C showed low risk of BC (p = 0.036; OR = 0.83). While in Casp3 G > A, AG (p = 0.003; OR = 2.11), GG (p = 0.050; OR = 2.18), G allele (p < 0.001; OR = 1.85) and its carrier AG + GG (p = 0.001; OR = 2.12) have shown significant BC risk. Significant association between DR4 Ala228Glu polymorphism and smoking was observed in BC risk. Haplotype analysis demonstrated that DR4 (Thr209Arg-Arg141His-Ala228Glu) C-G-C is associated with 1.8 folds (OR = 1.85; p = 0.033) risk. GG genotype of Casp3 G > A polymorphism showed increased risk of recurrence (p = 0.009; HR = 5.20). CONCLUSION: This study provided new support for the association of DR4 and Casp3, 5 in BC development, the tumorigenic effect of which was observed to be more enhanced in case of smoking exposure.

A rare case of persistent pupillary membrane associated with high myopia and amblyopia.

PURPOSE: To present the management of a rare case of persistent pupillary membrane (PPM) associated with high myopia and amblyopia. CASE: A 12-year-old boy presented with progressive diminution of vision in the right eye since childhood. Examination (OD) showed several fine strands of iris attached to the collarette and to the anterior lens capsule with a clump of iris pigment adherent over it. Some of these strands even wrinkled on pupillary contraction. The patient was also examined on slit-lamp.The patient was operated for lens extraction with PCIOL implantation. RESULTS: The patient regained useful vision after surgery. CONCLUSION: This is a rare case of persistent pupillary membrane associated with high axial myopia.

Prospective randomized clinical trial comparing lightweight mesh and heavyweight polypropylene mesh in endoscopic totally extraperitoneal groin hernia repair.

BACKGROUND: The purported advantage of lightweight large-pore meshes is improved biocompatibility that translates into lesser postoperative pain and earlier rehabilitation. However, there are concerns of increased hernia recurrence rate. We undertook a prospective randomized clinical trial to compare early and late outcome measures with the use of a lightweight (Ultrapro) mesh and heavyweight (Prolene) mesh in endoscopic totally extraperitoneal (TEP) groin hernia repair. METHODS: A prospective study was performed on 402 patients (191 in Ultrapro and 211 in Prolene group) with bilateral groin hernias who underwent endoscopic TEP groin hernia repair from March 2006 to June 2007. All operations were performed by five consultants following a standardized operative protocol. Chronic groin pain and hernia recurrence were evaluated as primary outcome measures. Secondary outcome measure were early postoperative pain, operative time, number of fixation devices required to fix the mesh, return to normal daily activities of work, seroma, and testicular pain. RESULTS: At 1-year follow-up, incidence in Ultrapro versus Prolene group for chronic groin pain was 1.6% vs. 4.7% (p = 0.178) and recurrence was 1.3% vs. 0.2% (p = 0.078). In Ultrapro versus Prolene group, mean visual analogue score for postoperative pain at day 7 was 1.07 vs. 1.31 (p = 0.00), mean return to normal activities was 1.82 vs. 2.09 days (p = 0.00), and mean number of fixation devices per patient required to fix the mesh was 4.22 vs. 4.08 (p = 0.043). CONCLUSION: Lightweight meshes appear to have advantages in terms of lesser pain and early return to normal activity. However, more patients had hernia recurrence with lightweight meshes, especially for larger hernias. We surmise that the lightweight meshes have greater tendency to get displaced from their intended position during desufflation at the conclusion of endoscopic TEP repair.

Involvement of histamine and histamine H2 receptors in nicotinamide-induced differentiation of human amniotic epithelial cells into insulin-producing cells.

OBJECTIVE AND DESIGN: Human amniotic epithelial cells (HAEC) resemble stem cells in their ability to differentiate into all three germ layers: endoderm, mesoderm, and ectoderm. Histamine receptors are expressed on HAEC. We examined the influence of histamine, and H(1) and H(2) antagonists on the generation of pancreatic islet beta-like cells from HAEC. MATERIALS AND METHODS: HAEC were isolated after term pregnancies (N = 12) and cultured for 14 days with nicotinamide (10 mM) in normoxia. Altogether, 72 cultures were established. Histamine (100 microM) effects were investigated with mepyramine (10 microM) or cimetidine (10 microM). After 7 and 14 days, the mean concentration of C-peptide (MCCP) in the culture medium was measured immunoenzymatically as a marker of pancreatic differentiation. RESULTS: MCCP was approximately threefold higher on day 14, compared to day 7. Histamine significantly increased MCCP, and more evident differences were observed after 7 days of culture than after 14 days. The mean percent increase +/-SEM in MCCP amounted to 142.19 +/- 21.7 and 79.03 +/- 12.35 compared to the controls on day 7 and 14, respectively. H(2) blockade significantly reduced histamine-related increase in MCCP, both on day 7 and 14 by 88.7 +/- 14.3 and 39.2 +/- 12.4%, respectively. H(1) receptor antagonist did not affect MCPP. CONCLUSION: Nicotinamide-induced pancreatic differentiation of HAEC into beta-like cells may be augmented, probably at its earlier stage, by histamine acting via H(2) receptors.