Infrequent loss of heterozygosity of the major tumour suppressor genes in Indian oral cancers

The loss of heterozygosity (LOH) in tumour suppressor gene loci such as p53, retinoblastoma (rb) and adenomatous polyposis coli (apc) were analyzed in oral cancer tissues with matched controls by employing polymerase chain reaction based/restriction fragment length polymorphism (PCR-RFLP), variable number of tandem repeats (PCR-VNTR) analysis and microsatellite assay. The PCR-RFLP analysis showed an infrequent LOH in rb (17%), p53 (11%) and apc (10%) loci in these cases. The microsatellite assay also revealed only a low frequency of LOH in the microsatellite markers such as TP53 (25%), D5S505 (10%) and D3S1067 (0%) in the same samples. In contrast to the present study, similar studies from Western countries have reported a high frequency of LOH in p53, rb and apc genes in oral cancer tissues. The present preliminary study indicates that the gene aberration by LOH may be an insignificant mechanism in Indian oral cancers with respect to the tumour suppressor genes examined.     

MediGuide—impact on catheter ablation techniques and workflow

Since the introduction of percutaneous intervention in modern medical science, specifically cardiovascular medicine fluoroscopy has remained the gold standard for navigation inside the cardiac structures. As the complexity of the procedures continue to increase with advances in interventional electrophysiology, the procedural times and fluoroscopy times have proportionately increased and the risks of radiation exposure both to the patients as well as the operator continue to rise. 3D electroanatomic mapping systems have to some extent complemented fluoroscopic imaging in improving catheter navigation and forming a solid platform for exploring the electroanatomic details of the target substrate. The 3D mapping systems are still limited as they continue to be static representations of a dynamic heart without being completely integrated with fluoroscopy. The field needed a technological solution that could add a dynamic positioning system that can be successfully incorporated into fluoroscopic imaging as well as electroanatomic imaging modalities. MediGuide is one such innovative technology that exploits the geo-positioning system principles. It employs a transmitter mounted on the X-ray panel that emits an electromagnetic field within which sensor-equipped diagnostic and ablation catheters are tracked within prerecorded fluoroscopic images. MediGuide is also integrated with NavX mapping system and helps in developing better 3D images by field scaling—a process that reduces field distortions that occur from impedance mapping alone. In this review, we discuss about the principle of MediGuide technology, the catheter ablation techniques, and the workflow in the EP lab for different procedures.     

High prevalence of low vitamin D and musculoskeletal complaints in women with breast cancer

Reduced vitamin D levels may play a significant role in the development of fractures and musculoskeletal pains reported in patients on aromatase inhibitors (AIs) for breast cancer. In this study, we evaluated the vitamin D status in postmenopausal women with non-metastatic breast cancer who were about to start AI therapy. This study was conducted on community dwelling postmenopausal subjects, aged 35-80 years, with early non-metastatic breast cancer (up to stage IIIA), who were about to start therapy using third generation AIs. Symptoms of joint and muscle pains were obtained using a modified Leuven menopausal questionnaire. 25-hydroxyvitamin D [25(OH)D] was evaluated by radioimmunoassay while bone mineral density (BMD) of the lumbar spine and the proximal femur by dual energy x-ray absorptiometry (DXA). Of the 145 participants (mean age = 60.96 ± 0.88 years), 63 of 145 (43.5%) had baseline levels of 25(OH)D of < 20 ng/mL (deficient), 50 of 145 (34.5%) had levels between 20 and 29 ng/mL (insufficient), and only 32 of 145 (22%) had ≥ 30 ng/mL (sufficient); thus, 113 of 145 (78%) had low 25(OH)D levels (i.e., < 30 ng/mL). Arthralgias and myalgias were found in 61.3% and 43% of patients, respectively; and of those, 83.3% and 88.1% had 25(OH)D of < 30 ng/mL, respectively. Prevalence of vitamin D deficiency is high in breast cancer women and this may increase the risk of bone loss and fractures in those who are going to start AIs. Moreover, musculoskeletal pains are common in breast cancer women, even before the initiation of AIs and in association with low vitamin D in the majority. Future studies may be needed to establish the contribution of low vitamin D, if any, on the prevalence of musculoskeletal pains in women on AIs.     

PITYRIASIS VERSICOLOR: A CLINICOMYCOLOGICAL AND EPIDEMIOLOGICAL STUDY FROM A TERTIARY CARE HOSPITAL

Background:

Pityriasis versicolor is a mild, chronic, usually asymptomatic superficial fungal infection of the stratum corneum, caused by Malassezia yeasts. The purpose of the present study is to assess the clinical profile of a group of patients with pityriasis versicolor and to find out the epidemiological characteristics in this part of India as well as any association, if any, with other diseases.

Materials and Methods:

For this purpose, 110 consecutive patients of pityriasis versicolor were evaluated clinically and diagnosis was confirmed mycologically at a tertiary care hospital in Kolkata. All data were recorded in a predesigned, pretested semi-structured schedule. The total duration of study period was 12 months.

Results:

Majority of the patients were young adults. Most of the patients were asymptomatic. There is prominent seasonal variation of the patients with a peak in August and September months. Most of the lesions were hypopigmented scaly macules and were KOH positive. Most commonly involved sites were chest, face and back. Seborrheic dermatitis sometimes coexisted with pityriasis versicolor and a number of patients also had diabetes mellitus and immunosuppressive conditions.

Conclusions:

Overall, the clinicomycological and epidemiological profile of pityriasis versicolor infection as observed in a tertiary care setting in eastern India does not differ significantly from those observed by previous workers elsewhere.     

Cardiac catheterization in patients with end‐stage liver disease: Safety and outcomes

Introduction : Patients with end‐stage liver disease (ESLD) awaiting transplant are at increased risk of bleeding. Nevertheless, these patients routinely undergo cardiac catheterization for various indications. Safety and outcomes of cardiac catheterization in these patients are not well reported. Methods : In a case–control study 43 patients with ESLD who underwent angiography for liver transplant work‐up were compared to 43 age and gender‐matched controls with no liver dysfunction. In‐hospital outcomes and procedural variables were compared. Results : Patients with ESLD had a lower baseline hemoglobin (12.1 ± 2.1 vs. 13.7 ± 1.8, P < 0.0005), lower platelet counts (86.8 ± 66 vs. 247 ± 80, P < 0.0001) and higher international normalized ratio (INR) (1.4 ± 0.2 vs. 1.1 ± 0.2, P < 0.0001) than controls. Among ESLD group, five (11.6%) patients received platelet transfusions, one received blood transfusion, and three patients (7%) with INR > 1.6 received fresh frozen plasma (FFP) compared with none in the control group. Smaller size (four French) vascular sheaths were used more frequently in the group with ESLD (16% vs. 4%, P = 0.04). There were no significant vascular or bleeding complications in either group. Conclusions : Elective cardiac catheterization can be safely performed in patients with ESLD with outcomes (vascular and bleeding complications, length of hospital stay and in‐hospital mortality) similar to patients without liver disease despite significant thrombocytopenia and elevated INR in patients with ESLD. Practices such as platelet transfusion for platelets <60,000 μL, prophylactic FFP transfusion for INR ≥≥ 1.6, less frequent use of antiplatelet therapy and more frequent use of smaller vascular sheaths may have contributed to the safety of cardiac catheterization in ESLD patients. © 2010 Wiley‐Liss, Inc.     

Impact of Local Resources on Hospitalization Patterns of Medicare Beneficiaries and Propensity to Travel Outside Local Markets

Purpose: To examine how local health care resources impact travel patterns of patients age 65 and older across the rural urban continuum.
Methods: Information on inpatient hospital discharges was drawn from complete 2004 hospital discharge files from the Healthcare Cost and Utilization Project (HCUP) State Inpatient Databases (SID) for New York, California, and Florida, and the 2003 hospital discharge file for Pennsylvania. The study population was Medicare patients with admissions for ambulatory care sensitive conditions. Analysis was at the patient-level, and area contextual variables were developed at the Primary Care Service Area (PCSA) level. Local resources considered included inpatient supply, provider supply, supply of international medical graduates, and critical access hospitals (CAHs) in the patient's PCSA.
Findings: Findings generally confirmed enhanced retention of the elderly in local markets with greater availability of community resources, although we observed considerable heterogeneity across states. Community resource variables such as median household income or inpatient hospital capacity were stronger and more consistent predictors along the urban rural continuum than any of the provider or CAH variables. Only in California and New York did we see significant effects for provider supply or CAH, but they were robust across the 2 states and models of travel propensity, always reducing the travel propensity.
Conclusions: Findings support policies aimed at augmenting supplies of critical access hospitals in rural communities, and increasing primary care physicians and hospital resources in both rural and urban communities.     

Anti-nidatory effect of a single, early post-ovulatory administration of mifepristone (RU 486) in the rhesus monkey

The hypothesis that post-coital administration of mifepristone(RU 486) as a single dose in the early luteal phase can be aneffective anti-nidatory strategy was tested using the rhesusmonkey as the experimental model. Incidence of pregnancy, vaginalbleeding patterns, profiles of menstrual cyclicity and of serumlevels of progesterone and oestrogen were examined followingadministration of RU 486 as a single dose of 10 mg/kg and 2mg/kg body weight on the second day after ovulation. In controlmonkeys (group 1; n = 5) receiving the vehicle alone (benzylbenzoate: olive oil, 1: 4, v/v) there was a 60% pregnancy rate.Following s.c. administration of RU 486 at both doses, no pregnancywas recorded in a total of 33 treatment cycles in 12 monkeys.Five monkeys received RU 486 at 10 mg/kg s.c. (group 2) in threeconsecutive cycles. All animals had complete inhibition of implantation;in addition, the treatment cycle length was prolonged (P <0.001) due to an extension of the luteal phase. The subsequentfollicular phase was unaffected. Mild, premature vaginal bleedingduring the luteal phase was recorded in five treatment cycles,3–5 days after drug application. Though the serum profilesof progesterone and oestrogen in these monkeys showed markedindividual variations, there was a characteristic progesteronerebound about 18–20 days after drug administration. Monkeysin group 3 were given RU 486 at 2 mg/kg, s.c. either for threeconsecutive cycles (group 3a; n = 4) or for two consecutivecycles (group 3b; n = 3). Premature luteal phase vaginal bleedingoccurred only in four treatment cycles, within 2–6 dayspost-treatment. An increase in both the duration (P < 0.001)and degree (P < 0.001) of menstrual flow as compared withthe pre-treatment cycles was recorded in six treatment cyclesof three monkeys in group 3. These animals did not have prematureluteal phase vaginal bleeding. Collectively, 100% protectionagainst pregnancy with no change in the cycle length was obtainedin all seven monkeys in 18 treatment cycles. Analysis of pooleddata revealed that the subsequent follicular phase, as wellas the ovarian steroid hormone profiles of treatment cycleswere unaffected. Thus, a single application of RU 486 in theearly secretory phase appears to be a potential anti-implantationstrategy for intercepting pregnancy in the primate.     

Stability of antibody drug conjugate formulations evaluated using solid-state hydrogen-deuterium exchange mass spectrometry

Antibody drug conjugates (ADCs) have been at the forefront in cancer therapy due to their target specificity. All the FDA approved ADCs are developed in lyophilized form to minimize instability associated with the linker that connects the cytotoxic drug and the antibody during shipping and storage. We present here solid-state hydrogen-deuterium exchange with mass spectrometric analysis (ssHDX-MS) as a tool to analyze protein structure and matrix interactions for formulations of an ADC with and without commonly used excipients. We compared results of the ssHDX-MS with accelerated stability results using size-exclusion chromatography and determined that the former technique was able to successfully identify the destabilizing effects of mannitol and polysorbate 80. In comparison, Fourier-transform infrared spectroscopy results were inconclusive. The agreement between ssHDX-MS and stressed stability studies supports the potential of ssHDX-MS as a method of predicting relative stability of different formulations.