Off with the blues: Therapeutic plasma exchange in a case of copper sulphate poisoning.

CuSO4 (Copper sulphate) poisoning though rare, is associated with high mortality. It involves multiple organ systems and if not dealt with promptly can lead to death. Supportive care and chelation therapy along with TPE (therapeutic plasma exchange), whole blood exchange or red cell exchange can be employed in management. We report such a case where swift clinical improvement was seen after TPE.

The spectrum of ABO haemolytic disease of the fetus and newborn in neonates born to group O mothers.

BACKGROUND AND OBJECTIVES: ABO haemolytic disease of the fetus and newborn (HDFN) is a lesser recognized entity; however, the severity may vary in neonates. This prospective observational study was performed to determine the severity and risk of ABO-HDFN in neonates born to O group mothers. MATERIALS AND METHODS: A total of 260 neonates born to non-alloimmunized blood group O mothers were recruited. Blood group O neonates were excluded from the study. Neonatal direct antiglobulin test (DAT) was performed using the column agglutination technique. They were monitored for clinical and laboratory parameters and followed up at 6-8 weeks. The maternal anti-A and anti-B titres (IgM and IgG) were also done. RESULTS: A total of 176 neonates with blood group A (77/260; 29.6%) and B (99/260; 38.1%) were finally included in the study, and 15 (8.5%) of them were DAT positive. Overall, 26.7% (47/176) neonates received phototherapy, 172 (97.7%) survived and none required readmission. The median (inter-quartile range [IQR]) maternal IgG anti-B titre (32 [32-64]) was significantly higher (p < 0.001) than the IgG anti-A titre (16 [8-64]). The maximum total serum bilirubin in neonates had a significant positive association with neonatal birth weight (p = 0.045), positive DAT (p = 0.006) and requirement of phototherapy (p < 0.001). The relative risk (95% CI) of a DAT-positive neonate requiring phototherapy was 4.55 (3.12-6.33). CONCLUSION: The frequency of ABO incompatibility in neonates born to group O mothers was 67.69% (176/260). The maternal IgG titre of ≥64 could be a good predictor for identifying the neonates at risk of developing hyperbilirubinaemia requiring phototherapy.

Effect of Yoga Lifestyle in Patients with Heart Failure: A Randomized Control Trial.

Background: In spite of significant advances in the management of heart failure (HF), morbidity and mortality remain high. Therefore, there is a need for additional strategies. We did a randomized clinical trial to study effect of yoga in patients with HF in terms of quality of life (QOL), left ventricle ejection fraction (LVEF), C-reactive protein (CRP), and NTproBNP. Materials and Methods: 60 patients with stable HF New York Heart Association Class II with LVEF 30%-40% were randomized into control group (CG) and yoga group (YG). CG received the guideline-based therapy and YG in addition practiced the yoga, one hour daily for 3 months. All patients were assessed for QOL, CRP, NTProBNP, and LVEF at baseline and after 3 months. Results: A significant difference was observed in all four parameters in the YG as compared to the CG (P < 0.01) after 12 weeks. QOL as assessed by Minnesota living with heart failure questionnaire score improved significantly in YG as compared to CG (10 V/s 14, P < 0.001). There was a significant improvement within YG in terms of LVEF (33.4-36.8, P = 0.001), and the percentage change in LVEF was significant between the groups (10% V/s 5%, P = 0.001). NTproBNP also significantly reduced by 69.8% from 755 to 220 Pmol/l in YG as compared to 39.3% in CG (679-406 Pmol/l). CRP decreased by 49.3% (5.36-2.73 mg/L) in YG and 35.8% (5.39-3.45 mg/L) in CG. Conclusion: The result of this pilot study suggests that addition of yoga to guideline-based therapy for HF patients significantly improves QOL, LVEF, and NTProBNP and reduces CRP level. Larger studies are needed to confirm these findings.

Rapidly Progressive Frontotemporal Dementia With Amyotrophic Lateral Sclerosis in an Elderly Female.

A 69-year-old female with a family history significant for early onset dementia and a past medical history significant for coronary artery disease, primary hypertension, type two diabetes mellitus, and Crohn's disease presents to our facility with rapidly progressive cognitive decline, delusions, hallucinations, and ambulatory dysfunction over the past two months. Neurological examination was remarkable for bilateral horizontal nystagmus, tongue fasciculations, bilateral upper extremity incoordination, and bilateral lower extremity spasticity, atrophy, and weakness. Laboratory and microbiological testing were remarkable for low serum thiamine levels. Computed tomography (CT) of the head without contrast showed significant brain atrophy in the frontal and temporal regions as compared to a CT without contrast of the head 5 years prior. Magnetic resonance imaging (MRI) of the head with and without contrast showed significant atrophy in the frontal and temporal regions as well as the cerebellum. Follow-up electromyography was consistent with lower motor neuron disease. The patient was given adequate thiamine supplementation for her thiamine deficiency and discharged on donepezil with instructions to follow up with the amyotrophic lateral sclerosis clinic for further monitoring and initiation of riluzole.

Assessment of yogic relaxation techniques for its anxiolytic effects in patients requiring endodontic treatment: A prospective, randomized controlled study.

BACKGROUND: The aim of the study is to assess the anxiolytic effects of yogic relaxation technique (YRT) in patients requiring root canal treatment (RCT). MATERIALS AND METHODS: In this prospective, randomized, placebo-controlled study, 30 patients undergoing RCT with baseline visual analog scale for anxiety (VAS-A) of score >4 were divided into Group 1: YRTs; Group 2: alprazolam (0.25 mg/0.5 mg), and Group 3: placebo. After 30 min of completion of YRT, endodontic treatment was performed. Reduction in anxiety was analyzed using state anxiety score (domain) of the state-trait anxiety inventory scale. RESULTS: There was no significant difference in anxiety score 1 h before RCT between groups (P = 0.401). Ten minutes before (P < 0.0001) and after RCT (P < 0.0001), there was significant difference between groups (yogic relaxation vs. alprazolam [P < 0.0001]; yogic relaxation vs. placebo [P < 0.0001]). Ten minutes before RCT, yoga relaxation showed significant difference in anxiety score for pain versus alprazolam and placebo (P < 0.0001 for both). Ten minutes after RCT, the change from baseline in mean anxiety score for pain was significantly different with yogic relaxation (versus alprazolam [P = 0.043]; versus placebo [P = 0.002]). As per the global assessment of efficacy, the response was excellent in 9 (90%), 2 (20%), and 1 (10%) patients in yoga relaxation group, alprazolam group, and placebo group, respectively. Difference in response between three groups was significant (P < 0.0001). There was no significant difference in the global assessment of tolerability between three groups (P = 0.535). No adverse events were reported. CONCLUSION: Before RCT, YRT is an effective alternative to anxiolytic agents, alprazolam.

Stimuli Responsive In Situ Gelling Systems Loaded with PLGA Nanoparticles of Moxifloxacin Hydrochloride for Effective Treatment of Periodontitis.

The objectives of the present research work were systematic development of novel in situ gel formulation containing nanoparticles for localised delivery of moxifloxacin against bacterial periodontitis. PLGA nanoparticles were prepared and optimised in a systematic manner. Factor screening was performed with the help of half-factorial design to identify the influential factors, while response surface optimisation of the nanoparticles was conducted using central composite design. The optimum nanoparticle formulation was chosen on the basis of lower particle size, higher drug entrapment and controlled drug release characteristics up to 1 week time period, while the optimum in situ gel was selected on the basis of faster gelling and higher viscosity and gel strength properties for improved retention in the periodontium. In vivo histopathological studies and in vivo gamma scintigraphy studies revealed the extended release, superior efficacy and enhanced retention of nanoparticle-loaded in situ gelling system. Results obtained from in vivo histopathological studies after 1 week treatment with in situ gel formulation containing nanoparticles of moxifloxacin were found to be better than with 3 weeks treatment of marketed gel formulation. Overall, the studies ratify successful development of an effective site-specific drug delivery system with enhanced biopharmaceutical attributes for the periodontitis treatment.

Effect of alternative positions of neonates prior to delayed cord clamping on placental transfusion: a randomized control trial.

Objective: To determine the effect of alternative positions (relative to placenta) of normal term neonates, prior to the recommended delayed cord clamping, on placental transfusion and short-term neonatal outcome.Methods: Normal term neonates born vaginally were randomly assigned to be placed either on mother's abdomen (Group AL, n = 97) or 20 cm below the introitus (Group BL, n = 102) for 90 seconds after delivery. Subsequently the cord was clamped. Outcome measures were anthropometry, hematological profile including ferritin at birth and at 3-4 months; and adverse effects, polycythemia, and jaundice.Results: Both groups had comparable outcome measures at birth. At 3-4 months, mean hemoglobin (AL: 12.0 ± 0.9 g/dl, BL: 12.3 ± 1.1 g/dl; p = .02, 95% CI: 0.03-0.58) and hematocrit (AL: 36.1 ± 2.7%, BL: 37 ± 3.2%; p = .01, 95% CI: 0.1-1.75) were significantly higher in BL group. Anthropometry, serum ferritin, incidence of anemia and iron deficiency at 3-4 months were similar in both groups. There was no significant difference in polycythemia, jaundice requiring phototherapy or respiratory distress between the two groups.Conclusions: Placing the baby below the placenta resulted in a statistically significant increase in hemoglobin and hematocrit at 3-4 months without any adverse outcomes. However, this meager quantum of increase did not translate into reduction of risk of anemia or improvement in iron stores.

Altered Red Cell Indices in Repeat Blood Donors: Experience of a North Indian Blood Bank.

Subclinical Iron deficiency appearing in blood donors after blood donation is a recognized problem. Donors at an increased risk of iron deficiency need to be identified. Blood donors meeting national selection criteria were included in the study. Complete blood counts were done using Sysmex XP-100 three part hematology analyzer. Differences in RBC indices among donor groups defined by previous donations were then analyzed statistically. Six hundred and seventy three males and ninety six females were studied. In males, Kruskal-Wallis test showed significant differences between groups defined by number of donations for MCH and MCV (P value < 0.001), but not for MCHC (P value = 0.09) and RDW (P value = 0.6). Post-hoc tests showed statistically significant difference between donors having six or more donations compared to donors having no previous donations for both MCH as well as MCV. No significant difference was found between donor subgroups in females for any of the indices; however, no female donated blood more than three times in the study. There is increased risk for iron deficiency in donors having six or more previous donations, and evidence for starting an iron screening and supplementation programme for these donors.

Profertility effects of Shilajit on cadmium-induced infertility in male mice.

Shilajit is claimed as a Vajikarak (aphrodisiac) and used for the treatment of male infertility by traditional healers of the Indian subcontinent. Therefore, the present investigation was designed to assess the effectiveness of Shilajit for treatment of male infertility resulting from exposure to perilous chemicals. Effect of daily oral administration (p.o.) of Shilajit (50 mg, 100 mg and 200 mg/Kg BW) was investigated for a single spermatogenic cycle (35 days) in cadmium-induced (2 mg/Kg BW, p.o. for 35 days) infertile adult (12-14 week) swiss male mice. Shilajit treatment increased weights of reproductive organs, testicular daily sperm production, activities of testicular Δ5 3ß-HSD and 17 ß-HSD enzymes and serum level of testosterone. Histopathological evaluation of testis revealed that Shilajit restored spermatogenesis as reflected by a gradual augmentation in germ cell layers with increased doses of Shilajit compared to cadmium-treated mice. Further, Shilajit treatment reverted back the adverse effects of cadmium on motility and concentration of spermatozoa. Secretory activities of the epididymis and seminal vesicle and libido, fertility and the number of litters per female were also improved by Shilajit in cadmium-treated mice. Results thus suggest the potent androgenic nature of Shilajit and its role in fertility improvement against cadmium-induced infertility.

Red cell alloimmunization in RhD positive pregnant women and neonatal outcome.

The frequency of red blood cell (RBC) alloimmunization in RhD positive pregnant women is not known in our population. We planned to determine its frequency and correlation with neonatal outcome. We included 1000 RhD positive pregnant women: 500 had 'normal pregnancy' (Group I) and another 500 had 'high risk pregnancy' (Group II). ABO and extended Rh phenotyping were done by tube technique, antibody screening and identification by gel technique. For alloimmunized women, the paternal and neonatal ABO and extended Rh typing were done. Neonatal direct antiglobulin test (DAT) was also done and their clinical outcome observed. The frequency of RBC alloimmunization was 0.7% (7/1000) and all these women were from group II (p = 0.015). The alloantibodies were anti-E (85.7%), anti-c (71.4%), anti-Cw (14.3%) and anti-S (14.3%). Also, 6 women had history of transfusion (p < 0.01). Of the 7 neonates born to alloimmunized mothers, 4 (57.14%) had a positive DAT. The mean duration of phototherapy was higher in the DAT positive neonates (p < 0.01) and 2 (50%) required exchange transfusion. Thus, the frequency of alloimmunization was 0.7% in RhD positive pregnant women. High risk pregnancies and antenatal patients having a history of blood transfusion should be considered for regular antibody screening.

Insight to drug delivery aspects for colorectal cancer.

Colorectal cancer (CRC) is the third most common cancer diagnosed worldwide in human beings. Surgery, chemotherapy, radiotherapy and targeted therapies are the conventional four approaches which are currently used for the treatment of CRC. The site specific delivery of chemotherapeutics to their site of action would increase effectiveness with reducing side effects. Targeted oral drug delivery systems based on polysaccharides are being investigated to target and deliver chemotherapeutic and chemopreventive agents directly to colon and rectum. Site-specific drug delivery to colon increases its concentration at the target site, and thus requires a lower dose and hence abridged side effects. Some novel therapies are also briefly discussed in article such as receptor (epidermal growth factor receptor, folate receptor, wheat germ agglutinin, VEGF receptor, hyaluronic acid receptor) based targeting therapy; colon targeted proapoptotic anticancer drug delivery system, gene therapy. Even though good treatment options are available for CRC, the ultimate therapeutic approach is to avert the incidence of CRC. It was also found that CRCs could be prevented by diet and nutrition such as calcium, vitamin D, curcumin, quercetin and fish oil supplements. Immunotherapy and vaccination are used nowadays which are showing better results against CRC.

An evaluation and comparison of the efficacy of nanocrystalline calcium sulfate bone grafts (NanoGen) and medical-grade calcium sulfate bone grafts (DentoGen) in human extraction sockets.

BACKGROUND: Grafting a fresh extraction socket is essential for successful regeneration of bone and maximizing volume preservation. Various synthetic grafts have been used to simulate bone formation. The purpose of the present study was to evaluate clinical, histomorphometric, and radiographic healing at 1-month, 3-month, and 4-month time points after tooth extraction with placement of calcium sulfate hemihydrate putty bone grafts NanoGen and DentoGen to determine their efficacy in ridge preservation following tooth extraction. METHOD: Sixty subjects who were in need of extraction were recruited. The subjects were randomly assigned their group based on computer software for both the test groups (NanoGen and DentoGen). DentoGen is a medical-grade calcium sulfate hemihydrate with particle of 30 µm, and NanoGen is a nanocrystalline version of DentoGen with particle size 400 µm to 800 µm. Data were recorded at 1, 3, and 4 months after extraction socket grafting. Bone biopsies were taken at 4 months for histomorphometric analysis. RESULTS: The mean percentage of bone formed by NanoGen was 51.19 ± 9.53% and by DentoGen 50.67 ± 16.16% after 4 months. No statistically significant difference was noted in the mean bone formation by NanoGen and DentoGen at various time intervals; no bone graft remnants of DentoGen were found at 4 months. The mean percentage of bone graft remnants left after 4 months for NanoGen was 6.83 ± 16% in the maxilla and 7.38 ± 21% in the mandible. The mean percentage of soft tissue formed was significantly higher with DentoGen in mandibular socket sites. On radiographic evaluation the mean percentage of socket fill with DenoGen was found to be 23.1 ± 11.65%, 50 ± 9.6%, and 76.7 ± 11% and with NanoGen was 29.2 ± 12.8%, 52.8 ± 15.6%, and 76.47 ± 12.43% at 1 month, 3 months, and 4 months postoperative intervals, respectively. CONCLUSION: Both the materials investigated in the study showed excellent bone forming capacity, but the nanocrystalline version (NanoGen) of calcium sulfate was found to have clinical and biologic advantages over DentoGen.

Selective estrogen receptor modulators regulate stromal proliferation in human benign prostatic hyperplasia by multiple beneficial mechanisms--action of two new agents.

The existing drugs for benign prostatic hyperplasia (BPH) are partially effective with undesirable side-effects; hence new agents acting by different mechanism(s) are required as supplements. Modulation of estrogen receptor signaling using selective estrogen receptor modulators (SERMs) offers an alternative approach for BPH management. Using human BPH-derived stromal cells and tissue explants in culture we evaluated two SERMs, DL-2-[4-(2-piperidinoethoxy)phenyl]-3-phenyl-2 H-1-benzopyran (BP) and Ormeloxifene (Orm) in comparison to Tamoxifen (Tam) and 4-hydroxytamoxifen (OHT). BP, OHT and Tam were more effective than Orm in reducing stromal cell proliferation of human BPH. BP was either equipotent or more effective than OHT and Tam in increasing estrogen receptor(ER)-ß, TGFß1, Fas and FasL, and in decreasing ER-α, AR, EGF-R and IGF-I expressions in BPH stromal cells. BP, Tam and Orm (1.0 mg/Kg) reduced rat prostate weights by almost same extent as Finasteride (Fin, 5.0 mg/Kg); however combination treatment (SERM+Fin) was more effective. BP was exceptionally efficient in reducing IGF-1 and cleaving PARP while combination treatments more effectively increased bax:bcl-2 ratio. Fin reduced acinar diameter and prostatic DHT level but increased testosterone, estradiol (E(2)) and E(2)/T+DHT ratio. SERMs, especially BP, reduced epithelial cell height drastically without significantly altering steroid hormone levels and E(2)/T+DHT ratio. Combination treatment reduced both acinar diameter and epithelial cell height with modest increase in E(2), T and E(2)/T+DHT. The study reveals the potential of SERMs per se for BPH management, and more effectively in combination with a 5α-reductase inhibitor. BP appears promising for further evaluation as a drug candidate for BPH and prostate cancer.

Synergistic chemoprotective mechanisms of dietary phytoestrogens in a select combination against prostate cancer.

Combination of dietary phytoestrogens with diverse molecular mechanisms may enhance their anticancer efficacy at physiological concentrations, as evidenced in epidemiological studies. A select combination of three dietary phytoestrogens containing 8.33 µM each of genistein (G), quercetin (Q) and biochanin A (B) was found to be more potent in inhibiting the growth of androgen-responsive prostate cancer cells (LNCaP) as well as DU-145 and PC-3 prostate cancer cells in vitro than either 25 µM of G, B or Q or 12.5+12.5 µM of G+Q, Q+B or G+B. Subsequent mechanistic studies in PC-3 cells indicated that the action of phytoestrogens was mediated both through estrogen receptor (ER)-dependent and ER-independent pathways as potent estrogen antagonist ICI-182780 (ICI, 5 µM) could not completely mask the synergistic anticancer effects, which were sustained appreciably in presence of ICI. G+Q+B combination was significantly more effective than individual compounds or their double combinations in increasing ER-ß, bax (mRNA expression); phospho-JNK, bax (protein levels); and in decreasing bcl-2, cyclin E, c-myc (mRNA expression); phospho-AKT, phospho-ERK, bcl-2, proliferating cell nuclear antigen (protein levels) in PC-3 cells. Phytoestrogens also synergistically stimulated caspase-3 activity. Our findings suggest that selectively combining anticancer phytoestrogens could significantly increase the efficacy of individual components resulting in improved efficacy at physiologically achievable concentrations. The combination mechanism of multiple anticancer phytochemicals may be indicative of the potential of some vegetarian diet components to elicit chemopreventive effects against prostate cancer at their physiologically achievable concentrations, in vivo.

Hypocalcemia in the newborn.

Hypocalcemia is a frequently observed clinical and laboratory abnormality in neonates. Ionic calcium is crucial for many biochemical processes including blood coagulation, neuromuscular excitability, cell membrane integrity, and many of the cellular enzymatic activities. Healthy term infants undergo a physiological nadir in serum calcium levels by 24-48 h of age. This nadir may drop to hypocalcemic levels in high-risk neonates including infants of diabetic mothers, preterm infants and infants with perinatal asphyxia. The early onset hypocalcemia which presents within 72 h requires treatment with calcium supplementation for at least 72 h. In contrast, late onset hypocalcemia usually presents after 7 days and requires longer term therapy.

Hypocalcemia in the newborn.

Healthy term babies undergo a physiological nadir in serum calcium levels by 24-48 hours of age. The nadir may be related to the delayed response of parathyroid and calcitonin hormones in a newborn. This nadir may drop to hypocalcemic levels in high-risk neonates including infants of diabetic mothers, preterm infants and infants with perinatal asphyxia. The early onset hypocalcemia which presents within 72 hours, requires treatment with calcium supplementation for at least 72 hours. In contrast, late onset hypocalcemia usually presents after 7 days and requires long term therapy. Ionized calcium is crucial for many biochemical processes and total serum calcium is a poor substitute for the diagnosis of hypocalcemia.