The effect of COVID-19 on general anaesthesia rates for caesarean section. A cross-sectional analysis of six hospitals in the north-west of England.

At the onset of the global pandemic of COVID-19 (SARS-CoV-2), guidelines recommended using regional anaesthesia for caesarean section in preference to general anaesthesia. National figures from the UK suggest that 8.75% of over 170,000 caesarean sections are performed under general anaesthetic. We explored whether general anaesthesia rates for caesarean section changed during the peak of the pandemic across six maternity units in the north-west of England. We analysed anaesthetic information for 2480 caesarean sections across six maternity units from 1 April to 1 July 2020 (during the pandemic) and compared this information with data from 2555 caesarean sections performed at the same hospitals over a similar period in 2019. Primary outcome was change in general anaesthesia rate for caesarean section. Secondary outcomes included overall caesarean section rates, obstetric indications for caesarean section and regional to general anaesthesia conversion rates. A significant reduction (7.7 to 3.7%, p < 0.0001) in general anaesthetic rates, risk ratio (95%CI) 0.50 (0.39-0.93), was noted across hospitals during the pandemic. Regional to general anaesthesia conversion rates reduced (1.7 to 0.8%, p = 0.012), risk ratio (95%CI) 0.50 (0.29-0.86). Obstetric indications for caesarean sections did not change (p = 0.17) while the overall caesarean section rate increased (28.3 to 29.7%), risk ratio (95%CI) 1.02 (1.00-1.04), p = 0.052. Our analysis shows that general anaesthesia rates for caesarean section declined during the peak of the pandemic. Anaesthetic decision-making, recommendations from anaesthetic guidelines and presence of an on-site anaesthetic consultant in the delivery suite seem to be the key factors that influenced this decline.

Correction to: Cesarean delivery to prevent anal incontinence: a systematic review and meta-analysis.

The original article can be found online.

Repeat cytoreductive surgery with or without intraperitoneal chemotherapy for recurrent epithelial appendiceal neoplasms.

BACKGROUND: With recurrence rates after primary cytoreductive surgery (CRS) in excess of 50 per cent, repeat CRS is being performed increasingly, but survival outcomes have not been reported widely. This study examined the outcomes following repeat CRS for appendiceal cancer with peritoneal surface malignancy (PSM), and evaluated its feasibility and safety. METHODS: A retrospective cohort of patients who had surgery between 1996 and 2018 were analysed. Patients who underwent a single CRS procedure with or without heated intraperitoneal chemotherapy (HIPEC) were compared with those who had multiple procedures with or without HIPEC. Perioperative morbidity and survival outcomes were analysed. RESULTS: Some 462 patients were reviewed, 102 of whom had repeat procedures. For high-grade tumours, patients who had a single CRS procedure had significantly reduced overall survival (OS) compared with those who had repeat CRS (55·6 versus 90·7 months respectively; P = 0·016). For low-grade tumours, there was no difference in OS (P = 0·153). When patients who had a single procedure were compared with those who had multiple procedures, there was no significant difference in major morbidity (P = 0·441) or in-hospital mortality (P = 0·080). For multiple procedures, no differences were found in major morbidity (P = 0·262) or in-hospital mortality (P = 0·502) when the first procedure was compared with the second. For low-grade cancers, the peritoneal carcinomatosis index was a significant prognostic factor for OS (hazard ratio (HR) 1·11, 95 per cent c.i. 1·05 to 1·17; P < 0·001), whereas for high-grade cancers repeat CRS (HR 0·57, 0·33 to 0·95; P = 0·033), complete cytoreduction score (HR 1·55, 1·01 to 2·40; P = 0·046) and presence of signet ring cells (HR 2·77, 1·78 to 4·30; P < 0·001) were all significant indicators of long-term survival. CONCLUSION: In selected patients presenting with PSM from epithelial appendiceal neoplasms, repeat CRS performed in high-volume centres could provide survival benefits.

ANTECEDENTES: En países de bajos y medianos ingresos (low- and middle-income countries, LMIC) hay que desarrollar estrategias de futuro para incrementar la disponibilidad de equipos quirúrgicos, adquisición, capacitación, uso, mantenimiento y complicaciones relacionadas con las unidades electroquirúrgicas (electrosurgical unit, ESU) y los equipos de laparoscopia. MÉTODOS: Se realizó una encuesta entre los cirujanos que asistieron a la reunión anual del Colegio de Cirujanos de África Oriental, Central y Meridional (College Of Surgeons of East, Central and Southern Africa, COSECSA) en diciembre de 2017 y a la reunión anual de la Sociedad Quirúrgica de Kenia (Surgical Society of Kenya, SSK) en marzo de 2018. Se encuestaron también a los técnicos de equipos biomédicos (Biomedical Equipment Technicians, BMET) y se recopilaron los registros de mantenimiento en Kenia entre febrero y marzo de 2018. RESULTADOS: Participaron 80 sujetos, 59 cirujanos de 11 países africanos y 21 BMET de Kenia. Se recopilaron 36 registros de mantenimiento. Todos los cirujanos de COSECSA y SSK disponían de ESU, pero menos de la mitad (49%) disponían de equipos de laparoscopia. Como principales problemas se detectaron la reutilización de accesorios desechables en las ESU y las dificultades para disponer de CO2. Más de las tres cuartas partes (78%) de los cirujanos contaban con equipos de mantenimiento para las ESU, pero solo el 59% disponía de mantenimiento para los equipos de laparoscopia en su centro. CONCLUSIÓN: A pesar de la disponibilidad de equipos quirúrgicos, en estos LMIC se detectaron serias dificultades en su mantenimiento, hecho que limita la implementación de la cirugía abierta y laparoscópica.

Priorities and preferences for school-based mental health services in India: a multi-stakeholder study with adolescents, parents, school staff, and mental health providers.

BACKGROUND: Schools are important settings for increasing reach and uptake of adolescent mental health interventions. There is limited consensus on the focus and content of school-based mental health services (SBMHSs), particularly in low-resource settings. This study elicited the views of diverse stakeholders in two urban settings in India about their priorities and preferences for SBMHSs. METHODS: We completed semi-structured interviews and focus group discussions with adolescents (n  =  191), parents (n  =  9), teachers (n  =  78), school counsellors (n  =  15), clinical psychologists/psychiatrists (n  =  7) in two urban sites in India (Delhi and Goa). Qualitative data were obtained on prioritized outcomes, preferred content and delivery methods, and indicated barriers. RESULTS: All stakeholders indicated the need for and acceptability of SBMHSs. Adolescents prioritized resolution of life problems and exhibited a preference for practical guidance. Parents and teachers emphasized functional outcomes and preferred to be involved in interventions. In contrast, adolescents' favored limited involvement from parents and teachers, was related to widespread concerns about confidentiality. Face-to-face counselling was deemed to be the most acceptable delivery format; self-help was less frequently endorsed but was relatively more acceptable if blended with guidance or delivered using digital technology. Structured sensitization was recommended to promote adolescent's engagement. Providers endorsed a stepped care approach to address different levels of mental health need among adolescents. CONCLUSION: SBMHSs are desired by adolescents and adult stakeholders in this setting where few such services exist. Sensitization activities are required to support implementation. School counsellors have an important role in identifying and treating adolescents with different levels of mental health needs, and a suite of interventions is needed to target these needs effectively and efficiently.

Cesarean delivery to prevent anal incontinence: a systematic review and meta-analysis.

BACKGROUND: Cesarean delivery (CD), is increasingly recommended as a mode of delivery that prevents the anal incontinence (AI) that arises in some women after vaginal delivery (VD). The assessment of the efficacy of CD in this regard was the subject of this systematic review. METHODS: Searches were conducted in Medline, EMBASE and the Cochrane Library. Both randomized (RCTs) and non-randomized trials (NRTs) comparing the risk of sustained fecal and/or flatus incontinence after VD or CD were sought from 1966 to 1 January, 2019. Studies were eligible if they assessed AI more than 6 months after birth, and had statistical adjustment for at least one of the three major confounders for AI: age, maternal weight or parity. In addition, each study was required to contain more than 250 participants, more than 50 CDs and more than 25 cases of AI. Data after screening and selection were abstracted and entered into Revman for meta-analysis. Analyses were done for combined fecal and flatus incontinence (comAI), fecal incontinence (FI), gas incontinence (GI), CD before or during labor, time trend of incontinence after delivery, assessment of both statistical and clinical heterogeneity, parity and late incident AI. RESULTS: Out of the 2526 titles and abstracts found, 24 eligible studies were analyzed, 23 NRTs and one RCT. These included women with 29,597 VDs and women with 6821 CDs. Among the primary outcomes, VD was found not to be a significant predictor of postpartum comAI compared to CD in 6 studies, incorporating 18,951 deliveries (OR = 0.74; 0.54-1.02). VD was also not a significant predictor of FI in 14 studies, incorporating 29,367 deliveries, (OR = 0.89; 0.76-1.05). VD was not a significant predictor of GI in six studies, incorporating 6724 deliveries (OR = 0.96; 0.79-1.18). The strength of the grading of recommendations, assessment, development and evaluations (GRADE) evidence for each of these was low for comAI and moderate for FI and GI (upgrade for lack of expected effect). Time trend FI showed incontinence at 3 months often resolved at 1 year. Other secondary analyses assessing parity, delayed incidence of FI, clinical and statistical heterogeneity, spontaneous VD only, late risk of incidence of AI, and CD in or prior to labor all had similar results as in the primary outcomes. CONCLUSIONS: There are three components of pelvic floor dysfunction that are thought to be caused by VD and hopefully prevented by CD: AI, urinary incontinence and pelvic floor prolapse. Of these, AI was not found to be reliably prevented by CD in this review.

Outcomes of early carotid stenting and angioplasty in large-vessel anterior circulation strokes treated with mechanical thrombectomy and intravenous thrombolytics.

Introduction Proximal cervical internal carotid artery stenosis greater than 50% merits revascularization to mitigate the risk of stroke recurrence among large-vessel anterior circulation strokes undergoing mechanical thrombectomy. Carotid artery stenting necessitates the use of antiplatelets, and there is a theoretical increased risk of hemorrhagic transformation given that such patients may already have received intravenous thrombolytics and have a significant infarct burden. We investigate the outcomes of large-vessel anterior circulation stroke patients treated with intravenous thrombolytics receiving same-day carotid stenting or selective angioplasty compared to no carotid intervention. Materials and methods The study cohort was obtained from the National (Nationwide) Inpatient Sample database between 2006 and 2014, using International Statistical Classification of Diseases, ninth revision discharge diagnosis and procedure codes. A total of 11,825 patients with large-vessel anterior circulation stroke treated with intravenous thrombolytic and mechanical thrombectomy on the same day were identified. The study population was subdivided into three subgroups: no carotid intervention, same-day carotid angioplasty without carotid stenting, and same-day carotid stenting. Outcomes were assessed with respect to mortality, significant disability at discharge, hemorrhagic transformation, and requirement of percutaneous endoscopic gastronomy tube placement, prolonged mechanical ventilation, or craniotomy. Results This study found no statistically significant difference in patient outcomes in those treated with concurrent carotid stenting compared to no carotid intervention in terms of morbidity or mortality. Conclusions If indicated, it is reasonable to consider concurrent carotid stenting and/or angioplasty for large-vessel anterior circulation stroke patients treated with mechanical thrombectomy who also receive intravenous thrombolytics.

Newborn Screening Guidelines for Congenital Hypothyroidism in India: Recommendations of the Indian Society for Pediatric and Adolescent Endocrinology (ISPAE) - Part II: Imaging, Treatment and Follow-up.

The Indian Society for Pediatric and Adolescent Endocrinology has formulated Clinical Practice Guidelines for newborn screening, diagnosis and management of congenital hypothyroidism (CH). This manuscript, part II addresses management and follow-up. RECOMMENDATIONS: Screening should be done for every newborn using cord blood, or postnatal blood ideally at 48 to 72 h of age. Neonates with screen TSH > 20 mIU/L serum units (or >34 mIU/L for samples taken between 24 and 48 h of age) should be recalled for confirmation. For screen TSH > 40 mIU/L, immediate confirmatory venous T4/FT4 and TSH, and for mildly elevated screen TSH, a second screening TSH at 7 to 10 d of age, should be taken. Preterm and low birth weight infants should undergo screening at 48-72 h age. Sick babies should be screened at least by 7 d of age. Venous confirmatory TSH >20 mIU/L before age 2 wk and >10 mIU/L after age 2 wk, with low T4 (<10 µg/dL) or FT4 (<1.17 ng/dL) indicate primary CH and treatment initiation. Imaging is recommended by radionuclide scintigraphy and ultrasonography after CH is biochemically confirmed but treatment should not be delayed till scans are performed. Levothyroxine is commenced at 10-15 µg/kg in the neonatal period. Serum T4/FT4 is measured at 2 wk and TSH and T4/FT4 at 1 mo, then 2 monthly till 6 mo, 3 monthly from 6 mo-3 y and every 3-6 mo thereafter. Babies with the possibility of transient CH should be re-evaluated at age 3 y, to assess the need for lifelong therapy.

Cost-effectiveness of community screening for glaucoma in rural India: a decision analytical model.

OBJECTIVES: Studies in several countries have demonstrated the cost-effectiveness of population-based screening for glaucoma when targeted at high-risk groups such as older adults and with familial history of disease. This study conducts a cost-effective analysis of a hypothetical community screening and subsequent treatment programme in comparison to opportunistic case finding for glaucoma in rural India. STUDY DESIGN: A hypothetical screening programme for both primary open-angle glaucoma and angle-closure disease was built for a population aged between 40 and 69 years in rural areas of India. METHODS: A decision analytical model was built to model events, costs and treatment pathways with and without a hypothetical screening programme for glaucoma for a rural-based population aged between 40 and 69 years in India. The treatment pathway included both primary open-angle glaucoma and angle-closure disease. The data on costs of screening and treatment were provided by an administrator of a tertiary eye hospital in Eastern India. The probabilities for the screening and treatment pathway were derived from published literature and a glaucoma specialist. The glaucoma prevalence rates were adapted from the Chennai Glaucoma Study findings. RESULTS: An incremental cost-effectiveness ratio value of ₹7292.30 per quality-adjusted life-year was calculated for a community-screening programme for glaucoma in rural India. The community screening for glaucoma would treat an additional 2872 cases and prevent 2190 person-years of blindness over a 10-year period. CONCLUSIONS: Community screening for glaucoma in rural India appears to be cost-effective when judged by a ratio of willingness-to-pay thresholds as per WHO-CHOICE guidelines. For community screening to be cost-effective, adequate resources, such as trained medical personnel and equipment would need to be made available.

Newborn Screening Guidelines for Congenital Hypothyroidism in India: Recommendations of the Indian Society for Pediatric and Adolescent Endocrinology (ISPAE) - Part I: Screening and Confirmation of Diagnosis.

The Indian Society for Pediatric and Adolescent Endocrinology has formulated locally relevant Clinical Practice Guidelines for newborn screening, diagnosis and management of primary congenital hypothyroidism (CH). RECOMMENDATIONS: Screening should be done for every newborn using cord blood, or postnatal blood, ideally at 48 to 72 h of age. On this screen sample, neonates with TSH > 20 mIU/L serum units (or >34 mIU/L for samples taken between 24 to 48 h of age) should be recalled for confirmation. For screen TSH > 40 mIU/L, immediate confirmatory venous T4/FT4 and TSH, and for milder elevation of screen TSH, a second screening TSH at 7 to 10 d of age, should be taken. Preterm and low birth weight infants should undergo screening at 48-72 h postnatal age. Sick babies should be screened at least by 7 d of age. Venous confirmatory TSH >20 mIU/L before age 2 wk and >10 mIU/L after age 2 wk, with low T4 (<10 µg/dL) or FT4 (<1.17 ng/dL) indicate primary CH and treatment initiation. Imaging is recommended by radionuclide scintigraphy and ultrasonography after CH is biochemically confirmed but treatment should not be delayed till scans are performed. Levothyroxine is commenced at 10 to 15 µg/kg in the neonatal period. Serum T4/FT4 is measured at 2 wk and TSH and T4/FT4 at 1 mo, then 2 monthly till 6 mo, 3 monthly from 6 mo-3 y and every 3-6 mo thereafter. Babies with the possibility of transient congenital hypothyroidism should be re-evaluated at age 3 y, to assess the need for lifelong therapy.

Percutaneous lung ablation of pulmonary recurrence may improve survival in selected patients undergoing cytoreductive surgery for colorectal cancer with peritoneal carcinomatosis.

PURPOSE: To analyze the outcomes of patients developing pulmonary metastases (PM) following cytoreductive surgery (CRS) and perioperative intra-peritoneal chemotherapy (IPC) for colorectal cancer (CRC) with peritoneal carcinomatosis. PATIENTS AND METHODS: A retrospective analysis of patients undergoing CRS/IPC for CRC from 1996 to 2016 was performed. Lung-specific disease-free and patient overall survival was analyzed. Patients undergoing percutaneous lung ablative therapy (PLAT) for PM were compared to patients receiving systemic chemotherapy alone. RESULTS: 273 patients underwent CRS/IPC for CRC. Of these, 61 (22%) developed PM. Median time to development of PM was 8 months (range 0-52 months) and 41 patients (67%) had metachronous lesions. Twenty-one PM patients underwent PLAT, either by radio-frequency or micro-wave ablation, for an average of 3 lesions (range 1-12) and 13 (62%) had bilobar disease. The most common post-interventional complication was the development of pneumothorax (71%). Overall survival following development of PM was 18 months and higher in patients undergoing PLAT compared to those treated with systemic chemotherapy (26 vs. 14 months, p = 0.03). In eight cases (38%) local tumor recurrence developed post-PLAT. A peritoneal carcinomatosis index >10 (HR 3.48, 95% CI 1.69-7.19), presence of liver metastases (HR 2.49, 95% CI 1.24-5.03) and PLAT (HR 0.43, 95% CI 0.20-0.93) were identified as significant predictors of overall survival following diagnosis of PM. CONCLUSION: PM develop in approximately a fourth of patients undergoing CRS/IPC for CRC. Of these, about 1/3 may be eligible for PLAT. PLAT is a valuable treatment option providing good local control and potentially prolongation of overall survival.

Economic burden of diagnosed pertussis among individuals with asthma or chronic obstructive pulmonary disease in the USA: an analysis of administrative claims.

Individuals with chronic respiratory conditions may be at increased risk for pertussis. We conducted a retrospective administrative claims analysis to examine the incidence and economic burden of diagnosed pertussis among adolescents and adults in the USA with chronic obstructive pulmonary disease (COPD) or asthma. Patients aged ⩾11 years with diagnosed pertussis and pre-existing COPD (n = 343) or asthma (n = 1041) were matched 1:1 to patients with diagnosed pertussis but without COPD or asthma. Differences in all-cause costs ('excess' costs) during the 45-day and 3-month and 6-month periods before and after the pertussis index date were calculated; adjusted excess costs were estimated via multivariate regressions. The incidence of diagnosed pertussis was higher among patients with COPD or asthma than among matched patients. Compared with matched patients, patients with pertussis and pre-existing COPD or asthma accrued greater all-cause adjusted costs across study periods ($3694 and $1193 more, respectively, in the 45-day period; $4173 and $1301 more in the 3-month period; and $6154 and $1639 more in the 6-month period; all P < 0·0001). Patients with pre-existing COPD or asthma experience an increased economic burden after diagnosed pertussis and may especially benefit from targeted tetanus, diphtheria, and acellular pertussis vaccination strategies.

Preparation and formulation of transferosomes containing an antifungal agent for transdermal delivery: Application of Plackett-Burman design to identify significant factors influencing vesicle size.

Transferosomes containing an anti-fungal agent were prepared by Rotary Flask Evaporation -Sonication method. Eight batches were prepared in triplicate and vesicle size of each batch was determined. Plackett-Burman Design was employed to identify significant formulation and process parameters affecting vesicle size. The amount of lipid and surfactant, volume of ethanol and hydration medium as well as hydration time significantly affect the vesicle size.

Enhancement of dissolution of Telmisartan through use of solid dispersion technique - surface solid dispersion.

The present study was aimed to increase the solubility of the poorly water soluble drug Telmisartan by using Surface solid dispersion (SSD) made of polymers like Poloxamer 407, PEG 6000 by Solvent evaporation method. The drug was solubilized by surfactants and/or polymers then adsorbed onto the surface of extremely fine carriers to increase its surface area and to form the SSD which give the more Surface area for absorption of the drug. A 2(2) full factorial design was used to investigate for each carrier the joint influence of formulation variables: Amount of carrier and adsorbent. Saturation solubility studies shows the improvement in solubility of drug batch SSD 8 give more solubility improvement than the other batch, in-vitro dissolution of pure drug, physical mixtures and SSDs were carried out in that SSDs were found to be effective in increasing the dissolution rate of Telmisartan in form of SSD when compared to pure drug. Also FT-IR spectroscopy, differential scanning calorimetry and X-ray diffractometry studies were carried out in order to characterize the drug and Surface solid dispersion. Furthermore, both DSC and X-ray diffraction showed a decrease in the melting enthalpy and reduced drug crystallinity consequently in SSDs. However, infrared spectroscopy revealed no drug interactions with the carriers.

Development and characterization of microemulsion containing antihypertensive agent using factorial design.

Microemulsion which act as a carrier for drug having poor water solubility, were formulated by the use of excipients having safety of administration and solubility of drug component. The phase study was carried out using isopropyl myristate, cremophor-el, propylene glycol and water with different ratios of components. Microemulsion region was chosen on basis of area covered. The % oil and % surfactant were selected as the independent factors and particle size and viscosity were selected as the dependent factors for the 2(2) Full Factorial Design. The optimized formulation showed the overcoming of the dissolution barrier helping in the formulation and administration.

Parentage verification in field progeny testing program of Mehsana buffalo.

The present study was undertaken to construct a multiplex microsatellite panel for parentage testing in Mehsana buffalo (Bubalus bubalis). The study was based on a total of 212 Mehsana buffalos (100 dams, 100 daughters, and 12 sires). Genomic DNA was extracted from blood and semen samples. A panel of 10 microsatellite markers (CSSM61, ILSTS29, ILSTS17, ILSTS28, CSSM57, CSSM22, ILSTS61, CSSM8, ETH152, and ILSTS11) was amplified in a single multiplex reaction and analyzed by capillary electrophoresis on an automated DNA sequencer. The expected heterozygosity ranged from 0.642 to 0.833 (mean 0.762). The total exclusion probability using 10 microsatellite loci with 1 known parent was 0.993. Seven out of 10 microsatellite loci revealed relatively high polymorphic information content (>0.7). Eighty-one daughters out of 100 daughters qualified by compatibility according to Mendelism. The results suggest that multiplex microsatellite panel is a fast, robust, reliable, and economic tool to verify the parentage as well as to assign the putative sire to daughters under progeny testing with very high accuracy and hence can be used in routine parentage testing.

Should waist circumference be replaced by index of central obesity (ICO) in definition of metabolic syndrome?

Waist circumference has been widely used as the parameter of central obesity in defining metabolic syndrome. Global consensus definition of metabolic syndrome has suggested various race- and gender-specific cutoffs of waist circumference for quantifying central obesity. We have earlier proposed that using index of central obesity (ICO), the need for race- and gender-specific cutoffs may be obviated. We propose that waist circumference be supplanted with index of central obesity in all definitions of metabolic syndrome. Using index of central obesity a common cutoff of 0.5 applicable across races and genders might be obtained. Moreover, it will enhance the sensitivity of definition by diagnosing subjects who are shorter than general population. Among 258 male and 242 female diabetic patients, subjects with metabolic syndrome (defined as per gender-specific waist circumference cutoffs), were found to have a common lower range of index of central obesity suggesting that a common cutoff of waist circumference may be obtained. In another study from National Health and Nutrition Examination Survey database, replacing index of central obesity with waist circumference was found to enhance the specificity and sensitivity of definition of metabolic syndrome.

Exploration of Novel Co-processed Multifunctional Diluent for the Development of Tablet Dosage Form.

The aim of this investigation was to develop a novel multifunctional co-processed diluent consisting of microcrystalline cellulose (Avicel PH 102), crospovidone (Polyplasdone XL) and polyethylene glycol 4000. Colloidal silicon dioxide and talc were also incorporated as minor components in the diluent to improve tableting properties. Melt granulation was adopted for preparation of co-processed diluent. Percentage of Avicel PH 102, Polyplasdone XL and polyethylene glycol 4000 were selected as independent variables and disintegration time was chosen as a dependent variable in simplex lattice design. The co-processed diluent was characterised for angle of repose, bulk density, tapped density, Carr's index, percentage of fines and dilution potential study. Acetaminophen and metformin were used as poorly compressible model drugs for preparation of tablets. The blend of granules of drug and extra-granular co-processed diluent exhibited better flow as compared to the blend of drug granules and physical mixture of diluents blend. The diluent exhibited satisfactory tableting properties. The tablets exhibited fairly rapid drug release. In conclusion, melt granulation is proposed as a method of preparing co-processed diluent. The concept can be used to bypass patents on excipient manufacturing.

Distribution and function of polycystin-2 in mouse retinal ganglion cells.

The polycystin family of transient receptor potential (TRP) channels form Ca(2+) regulated cation channels with distinct subcellullar localizations and functions. As part of heteromultimeric channels and multi-protein complexes, polycystins control intracellular Ca(2+) signals and more generally the translation of extracellular signals and stimuli to intracellular responses. Polycystin-2 channels have been cloned from retina, but their distribution and function in retinal ganglion cells (RGCs) have not yet been established. In the present study, we determined cellular and subcellular localization as well as functional properties of polycystin-2 channels in RGCs. Polycystin-2 expression and distribution in RGCs was assessed by immunohistochemistry on vertical cryostat section of mouse retina as well as primary cultured mouse RGCs, using fluorescence microscopy. Biophysical and pharmacological properties of polycystin-2 channels isolated from primary cultured RGCs were determined using planar lipid bilayer electrophysiology. We detected polycystin-2 immunoreactivity both in the ganglion cell layer as well as in primary cultured RGCs. Subcellular analysis revealed strong cytosolic localization pattern of polycystin-2. Polycystin-2 channel current was Ca(2+) activated, had a maximum slope conductance of 114 pS, and could be blocked in a dose-dependent manner by increasing concentrations of Mg(2+). The cytosolic localization of polycystin-2 in RGCs is in accordance with its function as intracellular Ca(2+) release channel. We conclude that polycystin-2 forms functional channels in RGCs, of which biophysical and pharmacological properties are similar to polycystin-2 channels reported for other tissues and organisms. Our data suggest a potential role for polycystin-2 in RGC Ca(2+) signaling.