Impact of collaboration between psychologists and dermatologists: UK hospital system example.

There is a strong known link between the mind and the skin, with studies indicating that some individuals who live with skin disorders can exhibit high levels of psychological distress. Historically, the psychological impact of skin conditions has often been disregarded by health professionals, friends, and family members. However, more recently, clinicians are becoming aware of the benefits of combining medical and psychological treatment for these patients. Within the United Kingdom, this is becoming more popular within dermatology due to a recent study that measured clinical utility and cost savings. Understanding the theory behind psychocutaneous medicine enables dermatologists to work alongside psychologists to provide holistic treatment by meeting the medical and psychological needs of our patients.

Single-blind, placebo controlled randomised clinical study of chitosan for body weight reduction.

BACKGROUND: Chitosan is a dietary fibre which acts by reducing fat absorption and thus used as a means for controlling weight. Weight loss clinical trial outcomes, however, have contradictory results regarding its efficacy. The primary objective of the present study was to evaluate the efficacy and safety of a chitosan from fungal origin in treatment of excess weight in the absence of dietary restrictions. METHODS: A phase IV, randomised, multicentre, single-blind, placebo-controlled, clinical study was conducted by administering chitosan capsules (500 mg, five/day) and indistinguishable placebo capsules as daily supplements to 96 overweight and obese subjects for 90 days. The study participants were divided in 2:1 ratio to receive either chitosan (n = 64) or placebo (n = 32). Efficacy was assessed by measuring body weight, body composition parameters, anthropometric measurements, HbA1C level and lipid profile at day 45 and day 90. Also, short form-36 quality of life (QoL) questionnaire was assessed to evaluate improvement in life-style and dietary habits were recorded for calorie intake. Safety was assessed by evaluating safety parameters and monitoring adverse events. RESULTS: The mean changes in body weight were -1.78 ± 1.37 kg and -3.10 ± 1.95 kg at day 45 and day 90 respectively in chitosan group which were significantly different (p < 0.0001) as compared to placebo. BMI was decreased by10.91 fold compared to placebo after 90 day administration. In concert with this, there was also reduction in body composition and anthropometric parameters together with improvement in QoL score. Chitosan was also able to reduce HbA1C levels (below 6 %) in subjects who had initial higher values. The mean caloric intake shows that there was no change in dietary habits of subjects in both groups. Lipid levels were unaffected and all adverse events were mild in nature and unrelated to study treatment. CONCLUSION: Chitosan from fungal origin was able to reduce the mean body weight up to 3 kg during the 90 day study period. Together with this, there was also improvement in body composition, anthropometric parameters and HbA1C, reflecting overall benefits for the overweight individuals. Additionally, there was also improvement in QoL score. It was safe and well tolerated by all subjects. TRIAL REGISTRATION: CTRI/2014/08/004901.

Development and application of a validated HPLC method for the analysis of dissolution samples of levothyroxine sodium drug products.

A rapid, selective, and sensitive gradient HPLC method was developed for the analysis of dissolution samples of levothyroxine sodium tablets. Current USP methodology for levothyroxine (L-T(4)) was not adequate to resolve co-elutants from a variety of levothyroxine drug product formulations. The USP method for analyzing dissolution samples of the drug product has shown significant intra- and inter-day variability. The sources of method variability include chromatographic interferences introduced by the dissolution media and the formulation excipients. In the present work, chromatographic separation of levothyroxine was achieved on an Agilent 1100 Series HPLC with a Waters Nova-pak column (250 mm × 3.9 mm) using a 0.01 M phosphate buffer (pH 3.0)-methanol (55:45, v/v) in a gradient elution mobile phase at a flow rate of 1.0 mL/min and detection UV wavelength of 225 nm. The injection volume was 800 µL and the column temperature was maintained at 28°C. The method was validated according to USP Category I requirements. The validation characteristics included accuracy, precision, specificity, linearity, and analytical range. The standard curve was found to have a linear relationship (r(2)>0.99) over the analytical range of 0.08-0.8 µg/mL. Accuracy ranged from 90 to 110% for low quality control (QC) standards and 95 to 105% for medium and high QC standards. Precision was <2% at all QC levels. The method was found to be accurate, precise, selective, and linear for L-T(4) over the analytical range. The HPLC method was successfully applied to the analysis of dissolution samples of marketed levothyroxine sodium tablets.

Process analytical technology (PAT) for biopharmaceutical products: Part I. concepts and applications.

Process analytical technology (PAT) has been gaining momentum in the biotech community due to the potential for continuous real-time quality assurance resulting in improved operational control and compliance. In this two part series, we address PAT as it applies to processes that produce biotech therapeutic products. In the first part, we address evolution of the underlying concepts and applications in biopharmaceutical manufacturing. We also present a literature review of applications in the areas of upstream and downstream processing to illustrate how implementation of PAT can help realize advanced approaches to ensuring product quality in real time. In the second part, we will explore similar applications in the areas of drug product manufacturing, rapid microbiology, and chemometrics as well as evolution of PAT in biotech processing.

Process analytical technology (PAT) for biopharmaceutical products: Part II. Concepts and applications.

Implementing real-time product quality control meets one or both of the key goals outlined in FDA's PAT guidance: "variability is managed by the process" and "product quality attributes can be accurately and reliably predicted over the design space established for materials used, process parameters, manufacturing, environmental, and other conditions." The first part of the paper presented an overview of PAT concepts and applications in the areas of upstream and downstream processing. In this second part, we present principles and case studies to illustrate implementation of PAT for drug product manufacturing, rapid microbiology, and chemometrics. We further present our thoughts on how PAT will be applied to biotech processes going forward. The role of PAT as an enabling component of the Quality by Design framework is highlighted. Integration of PAT with the principles stated in the ICH Q8, Q9, and Q10 guidance documents is also discussed.

Renal cell carcinoma in children and young adults: analysis of clinicopathological, immunohistochemical and molecular characteristics with an emphasis on the spectrum of Xp11.2 translocation-associated and unusual clear cell subtypes.

AIMS: Recent studies suggest that paediatric renal cell carcinoma (RCC) may represent a distinct group of tumours; however, its biological behaviour and classification remain poorly understood. The aim was to analyse 13 RCCs from patients < or =23 years of age to determine their clinicopathological, immunohistochemical and molecular characteristics. METHODS AND RESULTS: The histological spectrum included: Xp11.2 translocation-associated (6/13 patients, 46%), clear cell (5/13 patients, 38%), papillary (1/13 patients) and unclassified (1/13 patients) types. The Xp11.2 translocation-associated RCCs had a wide morphological spectrum, with high nuclear grade cells with abundant cytoplasm ranging from clear to granular and architecture ranging from solid to papillary. These tumours lacked cytokeratin expression and were confirmed by nuclear reactivity for TFE3 protein. Most of these translocation-associated tumours presented at high stage and had an unfavourable outcome. Three clear cell RCCs had unusual features that have not been previously characterized, including solid and cystic architecture, cells with abundant eosinophilic cytoplasm yet low nuclear grade and focal cytoplasmic inclusions, resembling oncocytoma. Deletion of subtelomeric 3p25 was observed in two of these RCCs. CONCLUSIONS: Xp11.2 translocation-associated RCC represents a predominant and aggressive subtype in the paediatric age group. Increased awareness of this subtype is important due to its heterogeneous morphology.

Stability indicating validated HPLC method for quantification of levothyroxine with eight degradation peaks in the presence of excipients.

A simple, sensitive, accurate, and robust stability indicating analytical method is presented for identification, separation, and quantitation of l-thyroxine and eight degradation impurities with an internal standard. The method was used in the presence of commonly used formulation excipients such as butylated hydroxyanisole, povidone, crospovidone, croscarmellose sodium, mannitol, sucrose, acacia, lactose monohydrate, confectionary sugar, microcrystalline cellulose, sodium laurel sulfate, magnesium stearate, talc, and silicon dioxide. The two active thyroid hormones: 3,3',5,5'-tetra-iodo-l-thyronine (l-thyroxine-T4) and 3,3',5-tri-iodo-l-thyronine (T3) and degradation products including di-iodothyronine (T2), thyronine (T0), tyrosine (Tyr), di-iodotyrosine (DIT), mono-iodotyrosine (MIT), 3,3',5,5'-tetra-iodothyroacetic acid (T4AA) and 3,3',5-tri-iodothyroacetic acid (T3AA) were assayed by the current method. The separation of l-thyroxine and eight metabolites along with theophylline (internal standard) was achieved using a C18 column (25 degrees C) with a mobile phase of trifluoroacetic acid (0.1%, v/v, pH 3)-acetonitrile in gradient elution at 0.8 ml/min at 223 nm. The sample diluent was 0.01 M methanolic NaOH. Method was validated according to FDA, USP, and ICH guidelines for inter-day accuracy, precision, and robustness after checking performance with system suitability. Tyr (4.97 min), theophylline (9.09 min), MIT (9.55 min), DIT (11.37 min), T0 (11.63 min), T2 (14.47 min), T3 (16.29 min), T4 (17.60 min), T3AA (22.71 min), and T4AA (24.83 min) separated in a single chromatographic run. Linear relationship (r2>0.99) was observed between the peak area ratio and the concentrations for all of the compounds within the range of 2-20 microg/ml. The total time for analysis, equilibration and recovery was 40 min. The method was shown to separate well from commonly employed formulation excipients. Accuracy ranged from 95 to 105% for T4 and 90 to 110% for all other compounds. Precision was <2% for all the compounds. The method was found to be robust with minor changes in injection volume, flow rate, column temperature, and gradient ratio. Validation results indicated that the method shows satisfactory linearity, precision, accuracy, and ruggedness and also stress degradation studies indicated that the method can be used as stability indicating method for l-thyroxine in the presence of excipients.

Molecular weight determination for colloidal iron by Taguchi optimized validated gel permeation chromatography.

Method development of gel permeation chromatography (GPC) is a time-consuming task, since finding appropriate operating conditions has traditionally been a trial-and-error process. A novel approach in the field of GPC using experimental design called Taguchi is presented. This experimental design was used to compare the net effects of various conditions which were both qualitative and quantitative in nature. Quantitative factors included mobile phase pH, flow rate, temperature of column and detector, and injection volume. The qualitative factors were treated as noise which included enclosure of GPC system and position of waste container with respect to refractive index detector. The method was efficient as opposed to a one-factor-at-a-time approach. Taguchi optimized conditions included pH of 7.2, flow rate of 0.4 mL/min, temperature of 35 degrees C for column and detector, as well as injection volume of 10 microL. The optimized factors yielded acceptable results in terms of weight average molecular weight (m.w.), standard deviation and signal-to-noise ratio. Standard curves were constructed using dextran m.w. standards (12,000-270,000 Da) over the analytical range. The method was validated according to ICH guidelines. Log-linear function was used for m.w. standard curve and weight average m.w. was calculated utilizing trapezoidal approach. A correlation coefficient of >0.99 was obtained for both intra-day and inter-day standard calibration curves. Inter-day accuracy ranged from 91 to 108% and precision was <2.0%.

Quality by design: characterization of self-nano-emulsified drug delivery systems (SNEDDs) using ultrasonic resonator technology.

In the present work, a novel application of ultrasonic measurements is detailed to characterize nano-emulsion formulations as a part of the overall Quality by Design (QbD) goal. Ultrasonic resonator technology (URT) was utilized to measure sound velocity and absorption of self-nanoemulsified drug delivery systems (SNEDDs) consisting of various ratios of oil:surfactant:co-surfactant. A QbD concept was used to create different SNEDDs formulations utilizing sweet orange oil (oil), Emulphor-620 (surfactant), and Capmul (co-surfactant) by dissolving Cyclosporine A in oil. The mixture was emulsified in water and ultrasonic measurements were carried out in an ultrasonic resonator system isothermally for a period of about 15-20min. Compressibility of the individual components in the droplets, hydration of the droplets and the influence of the composition on droplet stability were studied by systematic ultrasonic measurements at a single resonator frequency. The adiabetic compressibilities for the oil, aqueous and interfacial components were 68, 44.6, and 53 [10(-11)Pa(-1)], respectively as calculated using Urick's equation. Also the ultrasonic absorption correlated droplet size of nano-emulsions linearly with R(2) of 0.84 indicating this can be used as an additional technique to measure the droplet size of nano-emulsions. Correlation of ultrasonic data with formulation components indicated that the ultrasonic velocity correlated negatively with increasing oil amount in the formulation as well as surfactant-to-cosurfactant ratios where as droplet diameter correlated positively with these formulation factors. It can be envisioned from the results that the compressibility of the media increases with the addition of the oily component and thus reducing the sound velocity. Thus URT enabled direct and convenient analysis of the physical properties as well as influence of formulation factors of nano-emulsions which is an important indication of stability of these nano-emulsions.

The role of sialomucin CD164 (MGC-24v or endolyn) in prostate cancer metastasis.

BACKGROUND: The chemokine stromal derived factor-1 (SDF-1 or CXCL12) and its receptor CXCR4 have been demonstrated to be crucial for the homing of stem cells and prostate cancers to the marrow. While screening prostate cancers for CXCL12-responsive adhesion molecules, we identified CD164 (MGC-24) as a potential regulator of homing. CD164 is known to function as a receptor that regulates stem cell localization to the bone marrow. RESULTS: Using prostate cancer cell lines, it was demonstrated that CXCL12 induced both the expression of CD164 mRNA and protein. Functional studies demonstrated that blocking CD164 on prostate cancer cell lines reduced the ability of these cells to adhere to human bone marrow endothelial cells, and invade into extracellular matrices. Human tissue microarrays stained for CD164 demonstrated a positive correlation with prostate-specific antigen levels, while its expression was negatively correlated with the expression of androgen receptor. CONCLUSION: Our findings suggest that CD164 may participate in the localization of prostate cancer cells to the marrow and is further evidence that tumor metastasis and hematopoietic stem cell trafficking may involve similar processes.

Comparison of monoclonal antibody (P504S) and polyclonal antibody to alpha methylacyl-CoA racemase (AMACR) in the work-up of prostate cancer.

AIM: Studies using a monoclonal (P504S) and a polyclonal antibody (p-AMACR) to alpha-methylacyl-CoA racemase (AMACR) have shown variable expression in prostate cancer (PCa). The goal is to compare the sensitivity of both antibodies in PCa and evaluate their utility in the work-up of atypical prostate needle biopsies (NBXs). METHODS AND RESULTS: A tissue microarray (TMA) with 248 samples of benign prostate, high-grade prostatic intraepithelial neoplasia (HGPIN) and PCa samples, 20 NBXs with minute PCa and 32 NBXs with 'atypical' foci were stained with P504S and p-AMACR. Ninety percent of PCa (76/76 TMA, 16/20 NBXs) showed predominantly strong p-AMACR expression while 87% (65/69 TMA, 16/20 NBXs) showed variable P504S expression (sensitivity 90% versus 87%, P = 0.10). In HGPIN, P504S and p-AMACR were positive in 77% and 91% of samples, respectively. In the 'atypical' NBXs group, 53% were classified as PCa, 12% benign and 35% atypical, suspicious for PCa, after review of the basal marker. Of atypical, suspicious for PCa, P504S/p-AMACR helped convert the diagnosis to PCa in 5/11 (45%) cases, where, despite negative basal cell markers, morphology was less than optimal. CONCLUSIONS: Differences between P504S and p-AMACR appear marginal and clinically insignificant. AMACR is negative in a subset of unequivocal minute PCa with both antibodies. However, when utilized in proper context, AMACR may offer significant advantage in converting an 'atypical' diagnosis to PCa where morphology and basal markers are less than optimal in resolving the diagnosis.

A validated HPLC assay for simultaneous analysis of salmon calcitonin and duck ovomucoid.

A highly sensitive and selective analytical HPLC method is reported for the simultaneous measurement of salmon calcitonin (sCT) and its enzyme inhibitor, duck ovomucoid (dOVM). The method used a reversed phase C-18 column (4.6 x 250 mm, 5 microm) at room temperature. The elution was achieved using a gradient technique (20-35% B for 10 min, 35-37% B from 10th to 20th min and 37-20% B from 20th to 25th min). The mobile phase used was 0.05% v/v trifluoroacetic acid (TFA) in water and 0.05% v/v TFA in acetonitrile with a flow rate of 1 ml/min. Detection was carried out by UV spectrophotometry at 210 nm. sCT and dOVM were eluted at 7.8 and 15.4 min respectively, free from any interfering endogenous peaks during a run time of 25 min. Linear relationships were observed between the detector response and the concentrations of the analytes (10-100 microg/ml for CT (r2 = 0.996) and 10-100 microg/ml for the dOVM (r2 = 0.999)). The assay was found to be highly selective and sensitive due to the absence of any interfering peaks. The lower C.V. and % error values of the assay indicates that the assay could accurately and precisely quantitate both sCT and dOVM in the examined concentration range. This method can be usedfor the simultaneous quantitative analysis of sCT and dOVM.

Asian Indian women: knowledge, attitudes and behaviors toward breast cancer early detection.

Education programs have been developed to promote adherence to recommended breast cancer screening guidelines. Few studies have assessed the degree to which ethnic subgroups are perceiving and acting on the proffered information. Such assessment is vital to the creation of efficient public health interventions. This paper describes the reported breast cancer knowledge, attitudes, and screening behaviors of 194 American Asian Indian women. While monthly breast self exam adherence was low, only 40.7%, 61.3% of women 40 and older, and 70% of women 50 and older, reported having had a mammogram within the past 12 months. These rates for annual mammography screening are high relative to many other ethnic groups. While the results are encouraging, the respondents may not be representative of all Asian Indian women. The majority of these women reported that their breast cancer knowledge is inadequate. They were willing to be called upon to share with others any knowledge they gained. There is a clear opportunity for public health nurses to provide Asian Indian women with a more comprehensive understanding of breast health and disease. Those women can then share their health knowledge with other women within their ethnic group.

Development of visual cortical axons: layer-specific effects of extrinsic influences and activity blockade.

During normal cortical development, individual pyramidal neurons form intracortical axonal arbors that are specific for particular cortical layers. Pyramidal neurons within layer 6 are able to develop layer-specific projections in cultured slices of ferret visual cortex, indicating that extrinsic influences, including patterned visual activity, are not required (Dantzker and Callaway [1998] J Neurosci 18:4145-4154). However, when spontaneous activity is blocked in cultures with tetrodotoxin, layer 6 pyramidal neurons fail to preferentially target their axons to layer 4. To determine whether mechanisms that regulate the development of layer 6 pyramidal neuron arbors can be generalized to pyramidal neurons in other layers, we examined the development of layer 5 and layer 2/3 pyramidal neurons in cultured slices of ferret visual cortex prepared on postnatal day 14 or 15. Layer 5 pyramidal neurons developed layer-specific axonal arbors during 5-7 days in vitro. However, unlike layer 6 pyramidal neurons, layer 5 pyramidal neurons formed layer-specific axonal arbors in the presence of tetrodotoxin. In contrast to layer 5 and layer 6 pyramidal neurons, layer 2/3 pyramidal neurons did not form appropriate layer-specific projections during 5-7 days in vitro. Taken together, these data suggest that the development of layer-specific axons is regulated by different mechanisms for neurons in different layers and cannot be categorically classified as either activity-dependent or independent. Instead, the type of pyramidal neuron, the layers targeted, and the type of activity must be considered.

Histologic and histochemical characterization of seminal vesicle intraluminal secretions.

CONTEXT: We have observed intraluminal crystalloid morphology in seminal vesicles that is superficially similar to that seen in prostate neoplasia, but found little information on such morphology in the literature. DESIGN: Two hundred fifty-three prostate specimens (163 needle biopsies, 75 radical prostatectomies with prostate carcinoma, 11 prostates from autopsy, and 4 cystoprostatectomies without prostate carcinoma) were examined for seminal vesicle secretions, which were categorized as (a) dense platelike inspissated, (b) fluidlike, (c) crystalloid morphology, and (d) absent. Histochemical stains (periodic acid-Schiff with and without diastase, Alcian blue at pH 2.5, and mucicarmine) were performed to characterize the nature of secretions. RESULTS: Proteinaceous secretions were identified in 82% of seminal vesicles examined. Of these, 61% had predominantly dense, platelike, inspissated secretions, 15% had predominantly fluidlike secretions, and 24% had predominantly crystalloid morphology. Although in some cases the crystalloid morphology resembled that of prostatic intraluminal crystalloids, the seminal vesicle crystalloids differed in that they were invariably multiple, had curved edges, and had varied forms (elliptical, cylindrical, rodlike, and rectangular). Seventy-one percent of seminal vesicle crystalloids were associated with dense, platelike, inspissated secretions and appeared to be created by fracturing within platelike secretions. There was no relationship between seminal vesicle crystalloid morphology and associated malignancy in the prostate gland, as it was seen in 24% of cases with prostate carcinoma and 25% of cases without prostate carcinoma (P = 1.0000). Fluidlike secretions were positive for Alcian blue (pH 2.5) and mucicarmine, whereas dense platelike secretions and crystalloid morphology were negative for Alcian blue (pH 2.5) and mucicarmine. CONCLUSIONS: Seminal vesicle secretions are fairly common and, when fluidlike, are composed of acid mucopolysaccharides. Inspissation of secretions appears to be associated with loss of acidity, presumably resulting in dense platelike secretions and crystallization. Awareness of both the crystalloid morphology in seminal vesicle tissue and the distinguishing features from prostatic crystalloids may be important while interpreting prostate needle biopsies in which seminal vesicle epithelium may be confused for prostate carcinoma because of a small acinar morphology with accompanying cytologic atypia and crystalloid morphology.

Photostimulable storage phosphor image acquisition: evaluation of three commercially available state-of-the-art systems.

Photostimulable storage phosphor (PSP) image acquisition systems have been available for several years. The technology has had the opportunity to mature; however, there has not been an independent comparison of recently marketed commercial systems. For this study, three computed radiography (CR) systems using PSP technology (Kodak CR System 400 with autoloader [Eastman Kodak, Rochester, NY], Fuji FCR AC-3CS [Fuji Medical Systems, Stamford, CT], and Agfa ADC Compact [Bayer Corp, Ridgefield Park, NJ]) were connected to an IBM RadWorks diagnostic radiology workstation (IBM Corp, White Plains, NY) and evaluated for conformance to their performance specifications using guidance provided in the most recent draft acceptance testing protocol from Task Group No. 10, American Association of Physicists in Medicine. In addition, the physical requirements (e.g., space and power) and connectivity to another manufacturer's diagnostic workstation were examined. X-ray technologist comfort with each PSP imaging system and an assessment by our supporting biomedical equipment maintenance activity of their ability to service each PSP imaging system were also considered.

The impact of a picture archiving and communication system on nuclear medicine examination interpretation.

Radiographic correlation is essential for many of the examinations performed in nuclear medicine. The purpose of this study was to evaluate the impact of a picture archiving and communications system (PACS) on the function and efficiency of a nuclear medicine department at a tertiary care institution. We evaluated 250 consecutive noncardiac nuclear medicine imaging examinations and asked the interpreting physician the following questions: (1) Was PACS used in the interpretation of the study? (2) Did the use of PACS expedite examination completion or aid in study interpretation? And (3) Did the use of PACS permit a definitive diagnosis to be made? PACS was accessed for correlative radiographic images in 155 of the 250 (62%) nuclear medicine examinations. Images available on PACS for review aided in study interpretation in 74% (115 of 155) of cases. The use of PACS was thought to expedite examination completion in 55% (86 of 155) of cases. The system was accessed but not operational in only 1% of cases (2 of 155). PACS provides reliable, rapid access to multimodality correlative radiographic images that aid in the interpretation of nuclear medicine examinations. Such systems also increase the efficiency of a nuclear medicine service by allowing timely and conclusive interpretations to be made.

Fracture of the hyoid bone.

A patient complaining of dysphagia was diagnosed as suffering from a fracture of the hyoid bone. The fracture was fixed using the modern technique of tension band wiring. There was subsequent relief of the symptoms. A review of the literature and our perspective is included.