Homeopathic Medicines in Second Wave of COVID-19: Prognostic Factor Research.

BACKGROUND: The clinical profile and course of COVID-19 evolved perilously in a second wave, leading to the use of various treatment modalities that included homeopathy. This prognostic factor research (PFR) study aimed to identify clinically useful homeopathic medicines in this second wave. METHODS: This was a retrospective, multi-centred observational study performed from March 2021 to May 2021 on confirmed COVID-19 cases who were either in home isolation or at COVID Care Centres in Delhi, India. The data were collected from integrated COVID Care Centres where homeopathic medicines were prescribed along with conventional treatment. Only those cases that met a set of selection criteria were considered for analysis. The likelihood ratio (LR) was calculated for the frequently occurring symptoms of the prescribed medicines. An LR of 1.3 or greater was considered meaningful. RESULTS: Out of 769 confirmed COVID-19 cases reported, 514 cases were selected for analysis, including 467 in home isolation. The most common complaints were cough, fever, myalgia, sore throat, loss of taste and/or smell, and anxiety. Most cases improved and there was no adverse reaction. Certain new symptoms, e.g., headache, dryness of mouth and conjunctivitis, were also seen. Thirty-nine medicines were prescribed, the most frequent being Bryonia alba followed by Arsenicum album, Pulsatilla nigricans, Belladonna, Gelsemium sempervirens, Hepar sulphuris, Phosphorus, Rhus toxicodendron and Mercurius solubilis. By calculating LR, the prescribing indications of these nine medicines were ascertained. CONCLUSION: Add-on use of homeopathic medicines has shown encouraging results in the second wave of COVID-19 in integrated care facilities. Further COVID-related research is required to be undertaken on the most commonly prescribed medicines.

Analysis of Non-Pivotal Bioequivalence Studies Submitted in Abbreviated New Drug Submissions for Delayed-Release Drug Products.

The US FDA's rule on "Requirements for Submission of Bioequivalence Data" requiring submission of all bioequivalence (BE) studies conducted on the same formulation of the drug product submitted for approval was published in Federal Register in January 2009. With the publication of this rule, we evaluated the impact of data from non-pivotal BE studies in assessing BE and identified the reasons for failed in vivo BE studies for generic oral delayed-release (DR) drug products only. We searched the Agency databases from January 2009 toDecember 2016 to identify Abbreviated New Drug Applications (ANDAs) submitted for DR drug products containing non-pivotal BE studies. Out of 202 ANDAs, 43 ANDAs contained 102 non-pivotal BE studies. Forty-nine non-pivotal BE studies were conducted on the to-be-marketed (TBM) formulation and 53 were conducted on formulations different from the TBM formulation. These experimental formulations primarily differed in the ratio of components of the enteric coating layer and/or amount (i.e., %w/w) of enteric coating layer. Of the 49 non-pivotal BE studies conducted on the TBM formulation, 41 failed to meet the BE acceptance criteria. The majority of failed non-pivotal BE studies on the TBM DR generic products had insufficient power, which was expected as these studies are exploratory in nature and not designed to have adequate power to pass the BE statistical criteria. In addition, among the failed non-pivotal BE studies on the TBM DR generic products, the most commonly failing pharmacokinetic parameter was Cmax. The data from these non-pivotal BE studies indicate that inadequate BE study design can lead to failure of the BE on the same formulation. Also, the non-pivotal BE studies on formulations different from the TBM formulation help us link the formulation design to the product performance in vivo. This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page.

Antioxidant and hepatoprotective potential of Lawsonia inermis L. leaves against 2-acetylaminofluorene induced hepatic damage in male Wistar rats.

BACKGROUND: Lawsonia inermis (Lythraceae) is an ethnomedicinal plant, traditionally known for curing several ailments such as skin diseases, bacterial infections, jaundice, renal lithiases and inflammation etc. The present work deals with assessment of in vitro antioxidant and in vivo hepatoprotective potential of butanolic fraction (But-LI) of Lawsonia inermis L. leaves. METHODS: Antioxidant activity was evaluated using deoxyribose degradation, lipid peroxidation inhibition and ferric reducing antioxidant power (FRAP) assay. In vivo protective potential of But-LI was assessed at 3 doses [100, 200 & 400 mg/kg body weight (bw)] against 2-acetylaminofluorene (2-AAF) induced hepatic damage in male Wistar rats. RESULTS: But-LI effectively scavenged hydroxyl radicals in deoxyribose degradation assay (IC50 149.12 µg/ml). Fraction also inhibited lipid peroxidation and demonstrated appreciable reducing potential in FRAP assay. Treatment of animals with 2-AAF resulted in increased hepatic parameters such as SGOT (2.22 fold), SGPT (1.72 fold), ALP (5.68 fold) and lipid peroxidation (2.94 fold). Different concentration of But-LI demonstrated pronounced protective effects via decreasing levels of SGOT, SGPT, ALP and lipid peroxidation altered by 2-AAF treatment. But-LI administration also restored the normal liver architecture as evident from histopathological studies. CONCLUSIONS: The present experimental findings revealed that phytoconstituents of Lawsonia inermis L. possess potential to effectively protect rats from the 2-AAF induced hepatic damage in vivo possibly by inhibition of reactive oxygen species and lipid peroxidation.

Inhibitory Activities of Butanol Fraction from Butea monosperma (Lam.) Taub. Bark Against Free Radicals, Genotoxins and Cancer Cells.

The present study was undertaken to investigate antioxidant, antigenotoxic, and antiproliferative activity of butanol fraction (Bmbu) from bark of medicinal plant Butea monosperma. Antioxidant potency of Bmbu was examined by various in vitro assays. It was also investigated for antigenotoxic activity using Escherichia coli. PQ37 employing SOS chromotest. Further, cytotoxic and apoptosis inducing activity of Bmbu was evaluated in MCF-7 breast cancer cells. Bmbu showed potent free radical scavenging ability in ABTS assay (IC50 56.70 µg/ml) and anti-lipid peroxidation ability (IC50 40.39 µg/ml). 4NQO and H2 O2 induced genotoxicity was suppressed by Bmbu in SOS chromotest by 74.26% and 82.02% respectively. It also inhibited the growth of MCF-7 cells with GI50 value of 158.71 µg/ml. Induction of apoptosis in MCF-7 cells by Bmbu treatment was deciphered using confocal microscopy, flow cytometry, and neutral comet assay. Bmbu treatment increased cell population in sub-G1 phase (69.6%) indicating apoptotic cells. Further, Bmbu treatment resulted in increased reactive oxygen species generation and decreased mitochondrial membrane potential indicating involvement of mitochondrial dependent pathway of apoptosis. HPLC profiling showed the presence of polyphenols such as ellagic acid, catechin, quercetin, and gallic acid as its major constituents. Consequently, it is suggested that the phytoconstituents from this plant may be further exploited for development of novel drug formulation with possible therapeutic implication.

Antiproliferative and Apoptosis Inducing Effects of Non-Polar Fractions from Lawsonia inermis L. in Cervical (HeLa) Cancer Cells.

Two non-polar fractions viz. hexane (Hex-LI) and chloroform fraction (CHCl3-LI) of Lawsonia inermis were studied for their antiproliferative potential in various cancer cell lines viz. HeLa, MCF-7, A549 and C6 glioma cells. Both the fractions showed more than 60 % of growth inhibition in all the tested cell lines at highest tested concentration. In clonogenic assay, different concentrations of Hex-LI and CHCl3-LI decreased the number and size of colonies as compared to control in HeLa cells. The apoptotic effects as nuclear condensation, fragmentation were visualized with Hoechst-33342 staining of HeLa cells using confocal microscope. Both fractions induced apoptotic cell death in human cervical carcinoma (HeLa) cells as evident from flow cytometric analysis carried out using Annexin V-FITC and propidium iodide dyes. CHCl3-LI treated cells significantly induced apoptosis (25.43 %) in comparison to control. Results from Neutral Comet assay demonstrated that both fractions induced double stranded breaks (DSB's) in HeLa cells. Our data indicated that Hex-LI and CHCl3-LI treated cells showed significant increase of 32.2 and 18.56 % reactive oxygen species (ROS) levels in DCFH-DA assay respectively. Further, experimental studies to decipher exact pathway via which these fractions induce cell death are in progress.

Persistence and biodegradation of quinalphos using soil microbes.

The present study reports the degradation of the persistent and toxic organophosphate, quinalphos, by employing microorganisms that were already members of the natural soil community for degradation. Bacillus and Pseudomonas spp., both of which are capable of degrading quinalphos from aqueous streams, were isolated from different contaminated soils. Batch experiments were performed to determine the natural and induced biodegradation of quinalphos in the aqueous medium. The rate of degradation was analyzed through determination of residual concentration using UV-Vis spectrophotometer and high-performance liquid chromatography. A single peak of a metabolite was observed on the 160th day, and identified as dihydroxy quinalphos oxon by mass spectrometry. The presence of quinalphos and its metabolite in water over an extended period prompted the authors to investigate its induced biodegradation using indigenous microbes extracted from soil. For biodegradation studies, the isolated microbes were inoculated into minimal media with quinalphos for 17 days. The results revealed that > 80% of quinalphos was degraded in 17 days in the presence of isolated microbes, and no metabolite was observed during the biodegradation process.

In Vitro Modulation of Genotoxicity and Oxidative Stress by Polyphenol-Rich Fraction of Chinese Ladder Brake (Pteris vittata L.).

Pteris vittata L. is a terrestrial genus growing in moist, shady forests and on hillsides. The plant has considerable ethnomedicinal importance. Investigations have been carried out on chemical profiling and antioxidant compounds from some genera of pteridophytes but studies on the biological properties of P. vittata are lacking. Therefore, the present study investigates antioxidant, antigenotoxic, and antiproliferative potential of the aqueous fraction of P. vittata (PWE). A battery of assays were carried out to assess the antioxidant potential of the PWE. SOS chromotest and DNA nicking assay were used to evaluate the antigenotoxicity of the fraction. The cytotoxic effect of PWE was analyzed using MTT and Neutral Single Cell Gel Electrophoresis comet assay. EC50 of 90.188 µg/ml, 80.13 µg/ml, 142.836 µg/ml, and 12.274 µg/ml was obtained in DPPH, superoxide anion scavenging, reducing power and lipid peroxidation assays, respectively. PWE was potent in inhibiting Fenton's reagent-induced nicking of pBR322 plasmid. The fraction significantly inhibited hydrogen peroxide (H2O2) and 4-nitroquinoline-N-oxide (4NQO) induced mutagenicity and a reduction in induction factor was found with increased PWE concentration. GI50 of 147.16 µg/ml was obtained in MTT assay in human MCF-7 breast cancer cell line. PWE induced apoptosis as confirmed from confocal microscopy studies. The protective effects can be attributed to the presence of the phytochemicals in PWE. These results will be helpful in the development of functional food characteristics, as well as unravel the benefits of pteridophytes as promoters of health.

Estimation of radon concentration in groundwater in the mining zone of Haryana, India, for lungs and stomach annual effective dose.

The groundwater is being used for drinking and irrigation purposes in vast swathes of the Aravalli Mountain range. Since the radioisotope presence in groundwater is affected by the local mining processes, the radiation monitoring in groundwater of mining regions is of paramount importance. In the present work, we have estimated the 222Rn presence in the mining region of Aravalli in the southern part of Haryana. We measured the Radon concentration in 51 water samples from the intended area using the RAD7 alpha detector. The measured radon concentration in some of the water samples collected from the vicinity of the mining zone is higher than that of the United Nations Scientific Committee on the Effects of Atomic Radiation recommended value. Furthermore, we have estimated the annual effective doses for the lungs and stomach contributed by ingestion and inhalation. Though the calculated dose values in collected samples are not in the critical range, further monitoring of background radiation in the Aravalli region is required.

Male breast cancer: a 30 year retrospective analysis from a tertiary cancer care centre.

Background: Male breast cancer (MBC) is one of the rare malignancies that account for less than 1% of all malignancies in males. However, the clinicopathological characteristics of MBC are not entirely similar to female breast cancer; but still, it is treated in line with the female breast cancer protocols. Aims: To retrospectively analyse trends in MBC as to its distribution, presentation, treatment, and outcome. Material and method: A total of 106 patients with MBC from 1991 to 2020 were analysed retrospectively. Frequency distribution analysis of the demographic and clinicopathological data and treatment variables was done. Results: Median age of presentation was 57 years; ranging from 30 to 86 years. Either of the sides was almost equally affected with an R: L ratio of 1.2:1. The average duration of complaint was 26.2 months (range 1-240 months). History of gynaecomastia was noted in 18 patients, significant benign prostate hypertrophy in 13, and hypertension needing medical treatment in 14 patients. The majority of the patients were smokers (72/106) and alcoholics (43/106). Five patients reported positive family history. 21 patients had metastatic disease at presentation and received palliative treatment. Stage II was seen in 36.8%, stage III in 43.4%, and stage IV in 19.8% of patients. Node positives were 63.2%. Pathology was invariably (90.5%) infiltrative ductal carcinoma. Radiation was administered in 85.8% of the patients, chemotherapy in 72.6% of patients, and hormonal treatment was given in 47.2% of patients. The median overall survival (OS) was 78 months. OS at 5 and 10 years was 78% and 58% respectively. Conclusion: Despite the possibility of MBC being apparent at an early stage, patients present with locally advanced disease. Radical surgery with adjuvant/neoadjuvant chemotherapy and adjuvant radiotherapy remains the gold standard. Cancer education campaigns must be run to catch the early disease and to radically treat the disease.

Pretreament neutrophil-lymphocyte ratio (NLR): A felicitous prognostic marker in carcinoma lung.

BACKGROUND: Mechanics of inflammation and oncogenesis are intertwined with each other. Thus, the role of inflammatory markers like neutrophil-lymphocyte ratio (NLR) as a foreteller of lung carcinoma is retrospectively appraised in this study. MATERIAL AND METHODS: Retrospective assessment of hospital records of carcinoma lung patients was done between January 2018 and January 2020 and pretreatment NLR was calculated. Median NLR was taken as cut off and thereafter correlation was studied between pretreatment NLR and overall survival, using Kaplan-Meier survival analysis. Cox regression analysis was applied to identify factors affecting survival. RESULTS: Study population included 135 eligible patients with median age of 60 years and male to female ratio of 8.6:1. 47.41% patients were of stage III and 52.59% patients belonged to stage IV. The duration of follow-up ranged between 0.5 and 22 months. Median NLR was 3.1 (range, 0.90-11.25) and median overall survival in patients with NLR <3.1 and ≥3.1 was 6 months versus 3 months, respectively (P-value = 0.001). NLR value in nonsmall cell and small cell lung cancer was analyzed separately and showed significant variation in median survival in nonsmall cell lung cancer patients only (P-value = 0.001). CONCLUSIONS: Study results summarized that pretreatment NLR can be taken as a cheap and easily available predictor of prognosis in carcinoma lung cases and more so in nonsmall cell lung carcinoma cases. Large prospective trials are warranted to further potentiate this fact.

Choices and Challenges With Treatment of Myasthenia Gravis in Pregnancy: A Systematic Review.

Myasthenia gravis (MG) is an autoimmune disease affecting young women in their second and third decades, coinciding with their reproductive years. We aim to explore the choices and challenges in the treatment of MG in pregnancy. Cochrane, PubMed, Google Scholar, and Embase were the four databases systematically searched for studies with patients reporting pregnancy outcomes for women with MG during pregnancy using the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) technique. Quality assessment was done using the Joanna Briggs Institute critical tool (JBI, Adelaide, Australia) for methodological quality. From 2000 to 2023, 40 studies from database search results were considered. There is a substantial risk of complications with MG, especially if it appears during pregnancy. In particular, widespread weakness is a cause of severe, life-threatening disorders, but several treatment options are available.

Exploring the Complex Connection Between Diabetes and Cardiovascular Disease: Analyzing Approaches to Mitigate Cardiovascular Risk in Patients With Diabetes.

Cardiovascular disease (CVD) is the primary cause of morbidity and mortality in individuals diagnosed with diabetes mellitus. This narrative review offers a comprehensive examination of the complex correlation between diabetes and cardiovascular complications. The objective of this review is to analyze the most recent evidence on preventive measures and treatment options for mitigating cardiovascular risk in patients with diabetes, by synthesizing existing literature. Insulin resistance plays a crucial role in connecting diabetes and CVD, leading to the development of dyslipidemia and atherogenesis. As a result, the risk of cardiovascular events in individuals with diabetes is significantly elevated. Moreover, the presence of hyperglycemia-induced oxidative stress and inflammation serves to intensify endothelial dysfunction and vascular damage, thereby exacerbating the risk of cardiovascular complications. The interaction between diabetes and CVD frequently speeds up the development of atherosclerotic plaque, making the plaque more prone to rupture. This can lead to severe cardiovascular events such as myocardial infarction and stroke. It is crucial to comprehend the intricate relationship between diabetes and CVD in order to formulate effective strategies aimed at enhancing patient outcomes and mitigating the burden associated with these interconnected chronic conditions. Healthcare practitioners can enhance the quality of life and reduce mortality rates associated with CVD in diabetic patients by thoroughly examining evidence-based preventive measures and treatment options. This approach allows them to make informed decisions when managing cardiovascular risk. In summary, this narrative review provides a valuable resource for healthcare professionals and researchers, presenting a comprehensive analysis of the complex relationship between diabetes and CVD. By providing a comprehensive analysis of the latest evidence and elucidating the underlying mechanisms, this review seeks to establish a foundation for the development of innovative strategies in diabetes management. These strategies have the potential to significantly improve cardiovascular outcomes and enhance overall patient care.

The surgical treatment of breast cancer in the elderly: a single institution comparative review of 5235 patients with 1028 patients ≥70 years.

As the wave of the baby boomers shifts the age demographic of patients, the current surgical management of breast cancer in elderly women (≥70 years of age) becomes relevant because deviation from standard treatment often occurs in this group. The purpose of this study was to determine the operative mortality when treated with standard surgical procedures and to investigate trends in the surgical management of breast cancer in the elderly. A total of 5,235 patients undergoing either mastectomy or breast conservation surgery (BCS) for invasive and ductal carcinoma in situ (DCIS) were identified in a retrospective review of a prospectively accrued data base between the years of 1994 and 2007 at the Moffitt Cancer Center. Of the 5,235 patients, 1,028 (20%) patients were ≥70 years of age. The 30-day and 90-day mortality in the elderly group (age ≥70 years) was 0.2% (95% CI 0.02-0.7%) and 0.7% (95% CI 0.3-1.4%), respectively. The 30-day and 90-day mortality among patients <70 years was 0 and 0.05% (2 of 4,207 patients) (95% CI 0.005-0.2), respectively. BCS rates for invasive carcinomas were the highest for patients between 40 and 70 years of age, whereas the mastectomy rates were higher among patients <40 years of age (53%). Elderly women were as likely as women <40 years to have BCS for invasive carcinoma (OR 1.1, 95% CI 0.8-1.5), but more likely to have BCS for DCIS (OR 1.9, 95% CI 1.1-3.3). Surgical mortality in elderly women treated for breast cancer was extremely low and was related to the extent of surgery performed. Breast cancer treatment differed by age groups.

Sentinel lymph node biopsy in patients with previous ipsilateral complete axillary lymph node dissection.

BACKGROUND: Prior ipsilateral completion axillary lymph node dissection (CALND) may be considered a contraindication to performing a sentinel lymph node (SLN) mapping in a patient with recurrent breast carcinoma. However, reoperative SLN biopsy following axillary dissection would determine if alternative lymphatic drainage pathways exist. If nodes were found to contain metastatic disease, staging and locoregional control of the disease could be affected. MATERIALS AND METHODS: An institutional breast cancer database and electronic health record (IRB No. 102554) prospectively accrued 6225 patients between 1994 and 2007. Under separate IRB approval (IRB No. 102552), this database was queried for patients with a prior history of CALND who received a SLN biopsy. Patients' demographic, clinical, and treatment variables were recorded. RESULTS: Of the 6225 patients, 45 (0.7%) were identified as having previously undergone breast-conservation surgery, CALND, and ipsilateral reoperative SLN mapping and biopsy. Of the 45 patients, 13 (29%) had a successful ipsilateral reoperative SLN mapping and biopsy. Nonaxillary drainage was identified in 5 patients with reoperative SLN biopsy. CONCLUSION: Reoperative SLN mapping and biopsy is feasible in the setting of local recurrence after previous CALND. This procedure performed for breast cancer recurrence provides important staging information while identifying extra-axillary drainage that could affect both staging and local control.

Effects of prior augmentation and reduction mammoplasty to sentinel node lymphatic mapping in breast cancer.

Previous plastic surgery procedures such as breast augmentation or reduction mammoplasty can potentially alter the lymphatic drainage of the breast. The purpose of this study is to determine the success rates of sentinel node lymphatic mapping in patients with previous plastic surgical procedures of the breast. A total of 83 patients with a history of plastic surgery of the breast that underwent subsequent sentinel node mapping between 1996 and 2008 were retrospectively analyzed. Eight-three patients that underwent a total of 108 sentinel node biopsies. Hundred cases (93%) previously underwent breast augmentation and eight cases (7%) previously underwent reduction mammoplasty. The mean time between the previous plastic surgical procedures and the sentinel node biopsy was 10.3 years (range: 2 months-32 years). Indications for the mapping procedure were invasive cancer (n = 64), ductal carcinoma in situ (n = 17), and prophylactic mastectomy (n = 27). The identification rate of the sentinel node was 95.3% (103/108). The success rate based on type of procedure was 96% (96/100) for augmentation and 87.5% (7/8) for reduction mammoplasty. With a mean follow-up of 3.4 years, there has been only one local axillary recurrence that occurred at the time of an ipsilateral breast recurrence following lumpectomy. Lymphatic mapping can be successfully performed in patients who have previously undergone plastic surgery operations.

Are mastectomies on the rise? A 13-year trend analysis of the selection of mastectomy versus breast conservation therapy in 5865 patients.

BACKGROUND: The equivalency of survival between mastectomy and breast conservation therapy (BCT) has long been established, resulting in two decades of predominant BCT. Recently, surgeons have recognized a trend toward increasing mastectomy. Institutional trends of mastectomy and BCT were reviewed, confirming this perception in the surgical treatment of breast cancer. This report evaluates the factors that influence patient decisions to choose surgical therapies. METHODS: Patients who underwent mastectomy or BCT for invasive and in situ breast cancer were identified upon retrospective review of a prospectively accrued breast cancer database between 1994 and 2007. Univariate and multivariate logistic regression analysis were used to estimate the odds ratio (OR) of the association between mastectomy and patients' clinicopathologic characteristics. RESULTS: Of the 5,865 patients, 3,736 underwent BCT and 2,129 underwent mastectomy. The overall surgical volume decreased during the study period. Mastectomy rates during the periods of 1994-1998, 1999-2003, and 2004-2007 were 33%, 33%, and 44%, respectively (P < 0.01). Immediate reconstruction rates decreased during the same time periods from 16%, 5%, and 7%, respectively (P < 0.01). On logistic regression analysis, gender, age < 40 years, increase tumor size, and lymphovascular invasion were significant independent predictors of mastectomy. The mastectomy rate increased during the period 1999-2003 (OR 1.2) and during 2004-2007(OR 1.8). CONCLUSIONS: The perception of an increasing choice toward mastectomy has been confirmed at this institution. Possible reasons are younger population with higher lifetime risk, higher stage disease, and more biologically aggressive or diffuse tumors. Patient preference, fear of genetic or recurrence risk, and "intangible" factors seem to shift decisions toward mastectomy.

Non-familial paediatric colorectal cancers--an 18 years' experience.

BACKGROUND: Primary gastrointestinal malignancies constitute only 1% of all paediatric neoplasms. AIM: The aim of this study was to describe our 18 years' experience with non-familial paediatric colorectal malignancies, outlining pertinent features of diagnosis, treatment and outcome. METHODS: 9 patients of non-familial paediatric colorectal malignancies were admitted in PGIMS, Rohtak, Haryana between 1990 and 2008. After the initial surgical management, the advanced cases underwent chemotherapy and radiation therapy where required and were followed up. RESULTS: There were six male and three female patients (age range: 7 to 16 years). Three tumours arose in the rectum, three in the sigmoid colon, one each in the splenic flexure and appendix, and there was one case of diffuse colonic polyposis. All cases presented with obstruction and rectal bleeding. Two cases of sigmoid carcinoma were unresectable and expired 4 months post-surgery. The rest responded to radical resection. Three patients required palliative radiation therapy. Due to the advanced stage, chemotherapy was given to all the carcinoma patients. One patient had local recurrence after 5 months and another developed distant metastasis. The rest are on follow-up and clinically and radiologically disease free. CONCLUSION: Paediatric colorectal malignancy is a rare entity, usually diagnosed in the later stages, culminating in advanced disease. A majority of cases undergo radical resection due to the advanced stage of presentation. Advanced stages may also require chemotherapy and radiation therapy.

Feasibility of sentinel lymph node biopsy through an inframammary incision for a nipple-sparing mastectomy.

BACKGROUND: Nipple-sparing mastectomy (NSM) via an inframammary (IM) incision has been described for selected patients with breast cancer. However, the application of sentinel lymph node (SLN) mapping via an IM incision for NSM has yet to be reported. The objective of this study is to determine the technical feasibility of performing SLN through an IM incision without making an axillary counterincision. METHODS: We retrospectively reviewed our single-institutional experience with SLN biopsy and NSM through IM incisions between January 2006 and March 2008. Clinicopathologic factors were analyzed regarding indications, technical details, postoperative morbidity, and follow-up. RESULTS: Fifty-two patients underwent 87 NSM through an IM incision (17 unilateral, 35 bilateral) with immediate reconstruction and SLN biopsy. Indications for surgery included invasive breast cancer (n = 21), ductal carcinoma in situ (DCIS) (n = 18), and prophylactic (n = 48). Mean tumor size of invasive carcinoma was 2.1 cm. The mean mastectomy specimen weight was 437 g. Subareolar injection consisted of blue dye (n = 43), technetium sulfur colloid (n = 2), or combination injection (n = 42). SLN biopsy through an IM incision was successfully performed in 84 of 87 cases (96.6%). A mean of 2.8 SLN were removed with a positive sentinel node encountered in 8 of 21 patients (38%) with invasive cancer. No complications were observed regarding the SLN portion of the operation. With a median follow-up of 6.5 months (range, 0.4-23 months), there have been no axillary local recurrences. CONCLUSION: SLN biopsy can be performed through an IM incision during a NSM, avoiding a secondary axillary incision.

Pharmacokinetics and brain uptake of diazepam after intravenous and intranasal administration in rats and rabbits.

The purpose of this study was to investigate the plasma pharmacokinetics and brain uptake of a lipophilic benzodiazepine anticonvulsant, diazepam in New Zealand white rabbits and Sprague-Dawley rats to evaluate the possible absorption pathways after intravenous and intranasal administration. The intranasal formulation was prepared by dissolving DZ and 1% sodium glycocholate into microemulsion system composed of 15% ethyl laurate, 25% Labrasol, 37.5% Transcutol P, 12.5% ethanol, and 10% water. Diazepam was administered intravenously (1 mg/kg) or intranasally (2 mg/kg) to rats and rabbits. Drug concentrations in the plasma and six different regions of the brain tissues, i.e., olfactory bulb, olfactory tract, anterior, middle, and posterior segments of cerebrum and cerebellum were analyzed by LC/MS method after solid phase extraction. After i.n. administration, DZ was rapidly absorbed into the systemic circulation, and readily and homogeneously distributed into the different regions of brain tissues with a t(max) of 5 and 10 min in rats and rabbits, respectively. The bioavailability of DZ in rat plasma (68.4%) and brain (67.7%) were 32-47% higher than those observed in rabbit plasma (51.6%) and brain (45.9%). The AUC(brain)/AUC(plasma) ratios in rabbits after i.n. administration (3.77+/-0.17) were slightly lower than from i.v. administration (4.23+/-0.08). However, in rats the AUC(brain)/AUC(plasma) ratios after i.v. (3.03+/-0.07) and i.n. (3.00+/-0.32) administration were nearly identical. The plasma pharmacokinetic and distribution studies in the two animal models clearly showed that lipophilic DZ molecules reached the brain predominantly from the blood by crossing the blood-brain barrier after i.n. administration with no significant direct nose-to-brain transport via olfactory epithelium.