<Emphasis Type="Italic">In Vitro</Emphasis> and <Emphasis Type="Italic">In Vivo</Emphasis> Comparison of Gemcitabine and the Gemcitabine Analog 1-(2′-deoxy-2′-fluoroarabinofuranosyl) Cytosine (FAC) in Human Orthotopic and Genetically Modified Mouse Pancreatic Cancer Models

Purpose

Although gemcitabine is a mainstay of pancreatic cancer therapy, it is only moderately effective, and it would be desirable to measure drug uptake in patients. 1-(2′-deoxy-2′-fluoroarabinofuranosyl) cytosine (FAC), is an analog of gemcitabine, and when labeled with F-18, it may be a potential surrogate PET tracer for the drug.

Procedures

[¹⁸F]FAC was synthesized to a radiochemical purity of >96 %. The human tumor lines AsPC1, BxPC3, Capan-1, Panc1, and MiaPaca2 were grown orthotopically in nude mice. KPC mice that conditionally express oncogenic K-ras and p53 mutations in pancreatic tissue were also used. The intra-tumoral distributions of [¹⁴C]gemcitabine and [¹⁸F]FAC were mapped with autoradiography. The inter-tumor correlation between [¹⁴C]gemcitabine and [¹⁸F]FAC was established in the orthotopic tumors. Expression of the equilibrative and concentrative nucleoside transporters (ENT, CNT) in vitro was detected by western blotting. Drug uptake was characterized in vitro using [³H]gemcitabine and the effect of transporter inhibition on gemcitabine and FAC uptake was investigated. The relative affinity of cells for gemcitabine and FAC was tested in competition assays.The cell lines differed in sensitivity to transport inhibitors and in competition studies. There was a good in vivo correlation between the total uptake of [¹⁸F]FAC and [¹⁴C]gemcitabine, measured across all orthotopic tumors. Using the KPC and BxPC3 models, we found that [¹⁴C]gemcitabine and [¹⁸F]FAC were largely co-localized.

Conclusions

In the lines examined here, [¹⁸F]FAC uptake correlates well with gemcitabine in vivo, supporting the notion that [¹⁸F]FAC can serve as a PET radiotracer surrogate to determine the uptake and distribution of gemcitabine within pancreatic tumors.

     

Anesthetic Management of Clinically Silent Familial Pheochromocytoma with MEN 2A: A Report of Four Cases

Familial pheochromocytomas are commonly associated with multiple endocrine neoplasia type 2 (MEN 2) syndrome. Majority of the patients present with normal clinical and biochemical parameters in the preoperative period, the incidence of hypertension being only 50 %. Even though patients may be clinically asymptomatic, surveillance and proper preoperative evaluation is important, as surgery for associated tumors may precipitate a hypertensive crisis and result in severe complications. A family of 19 members, of which 12 were positive for MEN 2A syndrome, presented to our hospital. Seven of the 12 patients had pheochromocytoma and medullary thyroid carcinoma (MTC), while the other 5 had only raised plasma calcitonin levels. Two of the 7 patients presented with bilateral pheochromocytoma and underwent an open adrenalectomy. The other 5 patients had a left-sided adrenal tumor and underwent left laparoscopic adrenalectomy under combined general and epidural anesthesia. We present our experience with four of these five cases. We here state that how paucity of literature on perioperative preparation of clinically and biochemically silent pheochromocytomas led to serious intraoperative complications in one of four cases.     

Influence of Different Growth Regulators on In Vitro Multiplication of Mixed Diploid Banana (<Emphasis Type="Italic">Musa</Emphasis> AB)

The commercial scale banana multiplication through micropropagation is concentrated mainly on the Cavendish group of bananas. Other varieties, though possess a wide array of desirable characters, have been conveniently neglected owing to their inherent problems such as difficult aseptic establishment, low multiplication rate, culture browning, difficult hardening, etc. The mixed diploid bananas including the Ney Poovan are among the choicest of bananas relished in many parts of the world. To promote its cultivation, systematic studies were undertaken and the lines possessing superior attributes have been identified. In order to multiply the clones in large number, a viable multiplication protocol is a must. The present study dealt with optimizing the plant growth regulator requirements of the growing cultures for obtaining superior multiplication and in vitro rooting. Out of the different cytokinins as benzyl aminopurine, 2-isopentenyl adenine, meta topolin (mT), and thidiazuron (TDZ) tested, only TDZ was found to promote shoot multiplication in both types of propagules i.e. single and double bud explants, although shorter plantlets were noticed in the treatment. In vitro root induction parameters were found to be superior when indole butyric acid was used as auxin source. This report could help in improving the multiplication rate of this least attempted group of bananas. As per the present knowledge it is the first report on the use of TDZ and mT in mixed diploid banana.     

Age,subjective stress,and depression after ischemic stroke

The incidence of stroke among younger adults in the United States is increasing. Few studies have investigated the prevalence of depressive symptoms after stroke among different age groups or the extent to which subjective stress at the time of stroke interacts with age to contribute to post-stroke depression. The present study examined whether there exists an age gradient in survivors’ level of depressive symptoms and explored the extent to which financial, family, and health-related stress may also impact on depression. Bivariate analyses (N = 322) indicated significant differences in depression and stress by age group, as well as differences in age and stress by 3-month depression status. Linear regression analyses indicated that survivors between the ages of 25–54 and 55–64 years old had, on average, significantly higher depressive symptom scores. Those with financial, family, and health-related stress at the time of stroke, irrespective of age, also had significantly higher scores.     

Sudden‐Onset Bilateral Blindness in a Young Girl Receiving Parenteral Nutrition: Case Report and Review of Literature

Background:Parenteral nutrition (PN) via a central venous catheter is routinely used for surgical patients without a functioning gastrointestinal tract. Complications of PN can be metabolic and thrombotic. Blindness is a rare and unexpected complication. Case: A young female patient with postcorrosive pyloric stenosis was started on PN through an indwelling central venous catheter. On the sixth day of PN, the patient reported sudden painless bilateral complete loss of vision. Examination revealed bilateral normal‐sized pupils with normal pupillary reaction. There was complete bilateral absence of visual acuity with no perception of light. Fundus examination was normal. Magnetic resonance imaging revealed an acute infarct in the left occipital lobe, left corpus callosum, and posteromedial aspect of the left thalamus. No cardiac source of the thrombus could be identified. After supportive treatment, the vision started improving after 3 days; recovery was 95% after 10 days. A feeding jejunostomy was performed urgently under local anesthesia, and 1 month of enteral nutrition was administered. One month after the event, the patient's vision returned to normal. Definitive surgery in the form of antrectomy with Billroth II reconstruction was performed 8 weeks later. Conclusion: Blindness secondary to central venous catheterization is very rare; possible mechanisms are venous thrombosis with paradoxical emboli, air emboli, or accidental arterial puncture. Clinicians must exercise caution while using PN. A high index of suspicion is required to diagnose and treat unexpected complications.     

Clinico-Epidemiological Profile,Pandemic Influenza A H1N1/2009 and Seasonal Influenza,August 2009-March 2013, Himachal Pradesh,India

Background:

Novel influenza A (H1N1) virus emerged in April, 2009, spread rapidly to become pandemic by June, 2009. Objective: To study the clinco-epidemiological profile of pH1N1and seasonal influenza (SI) from 2009 to 2013.

Materials and Methods

Retrospective, hospital-based study was done by reviewing medical records for collecting demographic and clinical profile of the study samples.

Result:

Out of 969 samples, positivity and case fatality for pH1N1 and SI was 9.39 and 20.87% vs 11.76 and 7.89%, respectively. Among pH1N1and SI, sex distribution, mean age, and age group involved were 54.95% females, 37.10 years, and 20-29 years (23.08%) vs 43.86% females, 40.32 years, and 20-29 years (22.81%), respectively. Mortality shift was observed from younger to older and healthier, 75% to comorbid, 100% from 2009-2010 to 2012-13 for pH1N1.

Conclusion:

We observed seasonal variation, cocirculation, similar clinical features, decreased virulence, and community spread with respect to pH1N1 and SI from 2009-2013.     

Managing Patients with Cutaneous B-Cell and T-Cell Lymphomas Other Than Mycosis Fungoides

Cutaneous lymphomas (CL) are a heterogeneous group of neoplasms characterized with clinical and histopathological variation, as well as overlap with benign dermatoses. Diagnosis and treatment of CLs is challenging and often requires a multidisciplinary approach. However, prognostic knowledge of these conditions and awareness of treatment options can help optimize appropriate use of available regimens, thereby improving care for patients. Here, we review the most recent literature and outline treatment themes for managing patients with cutaneous B-cell and T-cell lymphomas other than mycosis fungoides.     

Food Protein-Induced Enterocolitis Syndrome (FPIES): Review of Recent Guidelines

Purpose of Review

To increase understanding of food protein-induced enterocolitis syndrome (FPIES), a non-immunoglobulin E (IgE)-mediated reaction to food, by reviewing a growing body of literature, including recently published international consensus guidelines.

Recent Findings

FPIES primarily affects infants and young children and is characterized by the delayed onset of gastrointestinal symptoms, predominantly repetitive vomiting, in response to a trigger food. Symptoms are often severe and can lead to shock. Diagnosis can be challenging due to a wide differential diagnoses and lack of disease biomarkers. FPIES is a clinical diagnosis, with allergy testing playing a very limited role, if any. Medically supervised oral food challenges are used to monitor resolution of disease, which generally occurs in early childhood.

Summary

FPIES is an important condition presenting to clinicians in a variety of settings. Recent international consensus guidelines and a growing body of literature can better equip practitioners to care for these often-challenging patients.