Urticaria After Lidocaine Use for Pecto-Intercostal Nerve Block.

Urticaria within one hour of lidocaine injection is a sign of type I (immediate) hypersensitivity to lidocaine, yet most patients suspected of having a lidocaine allergy do not exhibit urticaria. Aside from being a sign of a rare lidocaine allergy, urticaria can also be a symptom of COVID-19. COVID-19 patients who experience urticaria after receiving lidocaine require careful evaluation to determine the cause. Here, we present a case of a patient exhibiting urticaria one hour after a lidocaine injection for the Pecto-intercostal nerve block to treat COVID-19-induced costochondritis.

The Future of Obsessive-Compulsive Spectrum Disorders: A Research Perspective.

Obsessive-compulsive disorder (OCD) sits at the epicenter of a spectrum of related conditions (often referred to as obsessive-compulsive related disorders (OCRD) or obsessive-compulsive spectrum disorders (OCSD)) that can be as disabling as they are varied in presentation. Research in the field now encompasses diverse disciplines ranging from inflammatory mechanisms to computational psychiatry, to neurocognitive endophenotypes to functional imaging to pharmacogenomics to brain stimulation approaches. As these disorders become more clearly elucidated, there is a need to continually re-evaluate the implications of research findings and to incorporate these findings into new treatment approaches that benefit both patients and clinicians. Even the Diagnostic and Statistical Manual of Mental Disorders 5th Edition (DSM-5) is intended to be flexible and to incorporate validated and reliable biomarkers and neuroscience findings as they become available. This concluding chapter highlights just a few areas of study that promise to influence our understanding of the pathophysiology and clinical practice of OCRD. These include patient-centered outcomes research, the study of developmental brain trajectories in spectrum conditions, robot models of OCRDs, goal-directed versus habit-based behaviors, pharmacogenomics, problematic use of the Internet, and digital interventions. For example, digital medicine may become increasingly useful by identifying patients early on in the course of their illness; providing biomarkers to subtype patients; predicting treatment response; serving as a more proximal outcome measure of treatment response; or providing easily accessible and less costly forms of care. In order to address unmet clinical needs in OCRD, it is helpful to take an interdisciplinary perspective, and the work described in this collection of articles is likely to be invaluable in shaping the future of the field.

Celiac plexus neurolysis for abdominal cancers: going beyond pancreatic cancer pain.

INTRODUCTION: Celiac plexus neurolysis (CPN) has been verified for mitigating pancreatic cancer pain. However, information regarding CPN's use beyond this remains limited. OBJECTIVES: Identify which cancers benefit from CPN, which symptoms improve, and when symptoms improve. METHODS: Retrospective analysis was conducted on 173 patients who received CPN for pain caused by various malignancies. Mean symptom changes on the MD Anderson Symptom Inventory (MDASI) from baseline to 2 weeks, 1 month, and 2 months after CPN were analyzed overall and then by cancer type: pancreatic (all stages and stages III-IV), hepatobiliary, and nonpancreatic, nonhepatobiliary gastrointestinal (NPNH-gastrointestinal). RESULTS: Eighty-two pancreatic, 43 NPNH-gastrointestinal, 14 hepatobiliary, and 34 patients with other cancers met inclusion criteria. Statistically significant changes included decrease in the pain score at 1 month by 1.01 points for all cancers, 1.65 points for all pancreatic cancers, and 1.88 points for late-stage pancreatic cancers. At 2 months, pain decreased by 1.50 points for all cancers, 1.68 points for all pancreatic cancers, 2.37 points for late-stage pancreatic cancers, and 1.50 points in NPNH-gastrointestinal cancers. At 2 months, quality of life improved by 1.07 points for all cancers and 1.53 points for all pancreatic cancers. Sleep improved at 2 months for all cancers by 0.73 points and 1.60 points in late-stage pancreatic cancers. At 2 months, pancreatic cancer patients improved in general activity by 0.93 points, walking by 1.00 points, and working by 1.12 points. CONCLUSION: Celiac plexus neurolysis can decrease cancer symptom burden beyond pain including quality of life and sleep for pancreatic and nonpancreatic cancers, as well as general activity for pancreatic cancers.

Facile synthesis of pristine graphene-palladium nanocomposites with extraordinary catalytic activities using swollen liquid crystals.

Amazing conductivity, perfect honeycomb sp(2) arrangement and the high theoretical surface area make pristine graphene as one of the best materials suited for application as catalyst supports. Unfortunately, the low reactivity of the material makes the formation of nanocomposite with inorganic materials difficult. Here we report an easy approach to synthesize nanocomposites of pristine graphene with palladium (Pd-G) using swollen liquid crystals (SLCs) as a soft template. The SLC template gives the control to deposit very small Pd particles of uniform size on G as well as RGO. The synthesized nanocomposite (Pd-G) exhibited exceptionally better catalytic activity compared with Pd-RGO nanocomposite in the hydrogenation of nitrophenols and microwave assisted C-C coupling reactions. The catalytic activity of Pd-G nanocomposite during nitrophenol reduction reaction was sixteen times higher than Pd nanoparticles and more than double than Pd-RGO nanocomposite. The exceptionally high activity of pristine graphene supported catalysts in the organic reactions is explained on the basis of its better pi interacting property compared to partially reduced RGO. The Pd-G nanocomposite showed exceptional stability under the reaction conditions as it could be recycled upto a minimum of 15 cycles for the C-C coupling reactions without any loss in activity.

Angiotensin type 2-receptor (AT2R) activation induces hypotension in apolipoprotein E-deficient mice by activating peroxisome proliferator-activated receptor-γ.

Angiotensin II (Ang II) modulates blood pressure and atherosclerosis development through its vascular type-1 (AT1R) and type-2 (AT2R) receptors, which have opposing effects. AT2R activation produces hypotension, and is anti-atherogenic. Targeted overexpression of AT2Rs in vascular smooth muscle cells (VSMCs) indicates that these effects are due to increased nitric oxide (NO) generation. However, the role of endogenous VSMC AT2Rs in these events is unknown. Effect of 7-day low-dose Ang II-infusion (12 µg/kg/hr) on blood pressure was tested in 9-week-old apoE((-/-)) mice fed a low or high cholesterol diet (LCD or HCD, respectively). Cardiac output was measured by echocardiography. Immunohistochemistry was performed to localize and quantify AT2Rs and p-Ser(1177)-endothelial nitric oxide synthase (eNOS) levels in the aortic arch. PD123319 and GW-9662 were used to selectively block the AT2R and peroxisome proliferator-activated receptor-γ (PPAR-γ), respectively. Ang II infusion decreased blood pressure by 12 mmHg (P < 0.001) in LCD/apoE((-/-)) mice without altering cardiac output; a response blocked by PD123319. Although, AT2R stimulation neither activated eNOS (p-Ser(1177)-eNOS) nor changed plasma NO metabolites, it caused an ~6-fold increase in VSMC PPAR-γ levels (P < 0.001) and the AT2R-mediated hypotension was abolished by GW-9662. AT2R-mediated hypotension was also inhibited by HCD, which selectively decreased VSMC AT2R expression by ~6-fold (P < 0.01). These findings suggest a novel pathway for the Ang II/AT2R-mediated hypotensive response that involves PPAR-γ, and is down regulated by a HCD.

Angiotensin-I-converting enzyme in cancer patients.

Serum levels of angiotensin-I-converting enzyme (ACE) were assayed before, during, and after radiation therapy in 209 patients receiving treatment for neoplastic disease. Daily fluctuations in the measured ACE levels were minimized by comparing all patient values to that of a simultaneously run sample from a standard source of serum obtained by pooling sera from young, healthy volunteers. Most of the patients tested presented with a normal to low ACE level, with the mean value for all patients being 70% of the standard value. More patients with primary lung cancer displayed values that were low (107 of 120) than did patients with disease outside the lung (44 of 78), this difference being statistically significant at p less than 0.001. In addition, more patients with lung cancer had values less than 70% of the standard than did patients with disease outside the lungs. These initial results suggest that monitoring of serum ACE levels may be useful in the management of patients with malignant disease in the lung.

Phase I trial of continuous infusion carboplatin and etoposide in children with refractory acute leukemia: a Pediatric Oncology Group study.

PURPOSE: The purpose of this phase I study was to determine the toxicities and response to continuous infusion carboplatin in combination with a fixed dose of etoposide (VP-16) in children with refractory acute leukemia. PATIENTS AND METHODS: From January 1989 to February 1992, 20 patients received 28 courses of treatment. Each course of treatment consisted of a 1-hour intravenous (IV) infusion of VP-16 100 mg/m2/d for 5 days, followed by a 23-hour IV infusion of carboplatin each day. The initial, total 5-day dose of carboplatin (1,000 mg/m2) was escalated by 250- to 375-mg increments to a final, total dose of 1,875 mg/m2 over 5 days. RESULTS: Significant marrow suppression was observed in all patients, with prolonged marrow aplasia at the 1,875-mg/m2 dose level. Grade III diarrhea occurred in three patients; 10 patients experienced life-threatening infection and three had severe thrombocytopenic bleeding. Major marrow responses (two complete remissions and two partial remissions) occurred in four patients (20%). CONCLUSION: In view of the apparent antileukemic efficacy and minimal extramedullary toxicity, carboplatin deserves further study in a phase II trial.

The failure of microglia in normal brain to exhibit mononuclear phagocyte markers.

The origin of brain macrophages or "reactive microglia" has been the subject of considerable controversy. The fundamental question is whether or not there is a morphologically and functionally distinct population of cells, called microglia, which are resident in normal brain and differentiate into macrophages in response to inflammatory stimuli. The present study was performed to determine if any cells in the normal brain have the common markers of mononuclear phagocytes; phagocytosis, IgGFc receptors or macrophage specific antigens. In studies of the newborn and the adult murine brain and adult human brain no cells were detected which had any of those markers, although the highly sensitive marker methods were capable of detecting mononuclear phagocytes in all other tissues where they are known to occur. The results suggest that microglia, if they exist as a distinct cell type, are unrelated to mononuclear phagocytes. Furthermore, they suggest, but do not prove, that all inflammatory macrophages are derived from hematogenous precursors.

Combination of radiation therapy and intracranial bleomycin in the 9L rat brain tumor model.

The rat 9L brain tumor model was used to investigate the therapeutic potential of a combined modality approach using intracranial Bleomycin and radiation therapy. Bolus Bleomycin was delivered intracranially into the tumor volume via cannula guides; for continuous infusions, osmotic mini-pumps were implanted subcutaneously between the scapulae with flexible tubing to deliver the drug directly into the tumor and brain. Two to six bolus injections of Bleomycin (1 unit/kg each) over 5-11 days produced modest (usually statistically significant, p less than 0.05) increases in the median survival time compared to controls. Continuous infusion of Bleomycin by osmotic pump (10 units/kg over 7 days or 15 units/kg over 14 days) was also effective at significantly increasing median survival times compared to that of controls. Radiation therapy schedules of 10 daily fractions in 12 days (2 weeks) or 10 twice-daily fractions in 5 days produced dose-dependent increases in median survival time. Multiple bolus injections of Bleomycin when combined with fractionated radiation therapy significantly increased the median survival time due to fractionated radiation therapy alone for low doses (40 or 50 Gy). However, at higher radiation doses, the addition of Bleomycin either had no effect on median survival time or actually shortened it. Continuous infusion of Bleomycin by osmotic pump was effective when added to low dose radiation therapy in several experiments, twice for a total radiation dose of 50 Gy and once for radiation therapy of 60 Gy. However, it was also observed (once for 60 Gy and twice for 70 Gy) that the addition of continuous infusion Bleomycin either had no effect or served to decrease the improvement of median survival time obtained by radiation therapy alone. Thus, we conclude that increases in normal tissue toxicity can prevent full attainment of improved therapeutic advantage from the addition of Bleomycin to fractionated radiation therapy in the rat 9L model. These results should be considered when attempts are made to combine radiation therapy and intracranial Bleomycin for the treatment of patients with primary malignant brain tumors.

A phase I/II study of the use of Fluosol as an adjuvant to radiation therapy in the treatment of primary high-grade brain tumors.

The main objective of this study was to evaluate the safety and efficacy of a perfluorochemical emulsion, Fluosol, with short-term high inspired oxygen tension as an adjuvant to radiation therapy in the treatment of high-grade tumors of the brain. Radiation was delivered to the whole brain at 1.8 Gy per daily treatment for 5 weeks to a total dose of 45 Gy. The radiation portals were then reduced in size to encompass the known volume of tumor, as determined by the presurgical contrast-enhancing ring on computed tomography (CT), plus a 3-cm margin. An additional 10 treatments of 2 Gy each were given to the smaller volume, to bring the total tumor dose to 65 Gy in 7 weeks. This report describes the experience of the first 18 patients treated at the University of Kansas Medical Center on this study, whose median follow-up time from the date of surgery is 77 weeks (62-115 w). Immediately following Fluosol administration on a Monday, patients breathed 100% oxygen for at least 45 minutes prior to and throughout their radiation treatment. On each subsequent day of the weeks in which they received Fluosol, patients breathed 100% oxygen. Hematology and blood chemistries were also drawn prior to Fluosol treatment each Friday during treatment and at the 2-week, 3-month, and 6-month follow-up visits. The median age of the patients was 45 years (16-72); 13 patients were male and 15 carried the diagnosis of glioblastoma multiforme (3 had anaplastic astrocytoma). Two thirds of the patients had an initial allergic reaction to the Fluosol consisting of back pain, shortness of breath, and flushing, but all responded to 50-100 mg of Benadryl. During radiation therapy, all patients developed scalp erythema and complete alopecia by the end of 3 weeks, but no patient required a treatment rest. The serum levels of SGOT, SGPT, and alkaline phosphatase were examined before and throughout the Fluosol treatment and, by week 5, 11/18 of the patients had increased values of all three enzymes above the upper range of normal. These increases persisted through the end of treatment, but most values returned to essentially normal by the 3-month follow-up visit. We conclude that Fluosol, given in the manner described above, appears to be associated with minimal significant side effects and no changes could be detected in the white matter of any of the patients at the time of their magnetic resonance imaging study at 6 months follow-up.(ABSTRACT TRUNCATED AT 400 WORDS)

Pattern of immunoglobulin (Ig) and T-cell receptor (TCR) gene rearrangements in childhood acute lymphoblastic leukemia in India.

In 120 cases of acute lymphoblastic leukemia (median age 8 years), IgH chain gene was rearranged in 99% B-Cell Precursor (BCP) ALLs and 13% T-ALLs. One or the other TCR locus was rearranged not only in all T-ALLs, but also in 87% of BCP-ALLs. TCR-beta rearrangement in BCP-ALL was associated with a higher mean age at presentation (8.7 vs. 6.2 years, P=0.008), lower mean platelet counts (61.2x10(9)/l vs. 103.7x10(9)/l, P=0.003) and a poorer DFS (% cummulative survival 0 vs. 88.9+/-10.5, P=0.004). TCR-gamma rearrangement in T-ALL was associated with a higher mean WBC count (186.3x10(9)/l vs. 63. 4x10(9)/l, P=0.002). Also, the pattern of rearrangement of these genes appeared to be different from the West; viz. TCR-beta rearrangement in a higher proportion of BCP-ALLs (58%, 95% confidence intervals 45-69%), invariable deletion of Cgamma1 and only monoallelic rearrangement for TCR-delta locus. This repertoire of gene rearrangement may have a bearing on the poor treatment outcome reported previously from our geographic region.

Incidence, clinical characteristics and early treatment outcome in Indian patients of childhood acute lymphoblastic leukemia with ALL-1 gene rearrangement.

In a series of 185 patients (median age 7 years) of acute lymphoblastic leukaemia (ALL) from India, the overall incidence of ALL-1 gene rearrangement using the Southern blot technique was 11.4% (21/185). The incidence amongst the infants (age < or = 1 year, 70%) was significantly higher when compared to patients > 1 - < or = 10 years (7.4%, P = 0.00001) as well as > 10 years old (9.3%, P = 0.0001). ALL-1 gene rearrangement was associated with significantly higher WBC count (P = 0.01) and CD10 negativity (P = 0.00000001). Complete remission (CR) and relapse rates in 98 patients evaluable for response to therapy on a uniform therapy protocol was independent of ALL-1 gene status.

Phase I trial of indicine-N-oxide in children with leukemia and solid tumors: a Pediatric Oncology Group study.

A phase I trial of indicine-N-oxide was carried out in 12 children with solid tumors and in 16 with leukemia. Doses of 5, 6, and 7.5 g/m2 were given parenterally as a 15-min infusion every 3 weeks. The maximum tolerated dose in patients with solid tumors was 7.5 g/m2 and the dose-limiting toxicity was myelosuppression. In leukemia, the maximum tolerated dose was 6.0 g/m2 and hepatotoxicity was dose-limiting. Half of the children with leukemia showed elevations in transaminase levels and one child died of massive hepatic necrosis. This hepatotoxicity limits the use of indicine-N-oxide in children with leukemia. Antineoplastic activity was limited to a transient reduction in the numbers of circulating leukemic cells.

Primary cutaneous aspergillosis in a leukemic child.

Primary cutaneous aspergillosis is rare. In this report we describe a primary skin infection by Aspergillus flavus in a child with leukemia. The lesions were characterized by erythematous macules and papules associated with pain and itching, followed by a rapid progression to ulcers and central black eschars with a raised erythematous border. A favorable response to topical nystatin therapy was observed. The multiple cutaneous lesions seen in our patient were most likely due to primary inoculation near the site of intravenous infusion with subsequent local lymphatic spread.

Development of normal tissue damage in the rat subsequent to thoracic irradiation and prior treatment with cancer chemotherapeutic agents.

The effect of combined modalities (radiotherapy-chemotherapy) on the development of long-term normal tissue damage was investigated in rats. Animals received single I.P. injections of Hank's balanced saline solution, adriamycin (ADR, 1.0 mg/kg), bleomycin (BLM, 10 units/kg), or dihydroxyanthraquinone (DHAQ, 3.0 mg/kg); and/or irradiation of the chest with 25 MV x-rays (12 Gy) at 0, 43, 93, or 199 days after drug treatment. Only animals treated with DHAQ displayed appreciable toxicity, with more animals dying at less than 200 days when radiation was added at 0 or 43 days. Although animals treated with BLM or radiation exhibited evidence of lung damage (histologically by 199 days and radiographically by 300 days), their survival was not compromised. The simultaneous administration of x-ray and BLM produced enhanced effects as compared to either agent alone. These results demonstrate an enhancement of normal tissue damage by combined treatment with radiation and chemotherapeutic agents, not only for acute toxicity but also for long-term effects. This damage was ultimately expressed as alteration of lung structure (histologically and radiographically) in the case of BLM, and as animal lethality in the case of DHAQ. In addition, there was a reduction in the degree of enhancement observed as a function of the separation in time between treatment with chemotherapeutic agents and subsequent irradiation. These factors should be considered when combined modality therapy is used for treatment of cancer in the thoracic region.

Bone marrow transplantation.

Bone marrow transplantations have a definite role in treatment of leukemias and lymphomas. In acute myeloid leukemia and CML an allogeneic transplant using an HLA identical donor certainly provides a far superior survival than chemotherapy. Patients with Ph' chromosome need to be transplanted in first remission if a suitable donor is available. In recurrent lymphomas the best results are achieved if the patient is transplanted in complete remission. Transplantation done using minor mismatched family donors or unrelated donors are still considered experimental and more data is needed before final recommendations can be made. Availability of supportive services is an absolute must prior to establishing transplant program. Selection of patients for transplantation should be done after carefully reviewing the indications and discussing with the family the emotional, financial and physical burden of the procedure. For selected indications in leukemias and lymphomas, BMT may be the only viable treatment option and therefore must be considered.

Oncogenes: present status.

Oncogenes are genes associated with causation of cancer. They were originally associated with the ability of retroviruses to cause tumors in animals. These viral oncogenes (V-onc) have their cellular counterparts (C-onc) called Proto oncogenes. Function of Proto oncogenes is to maintain cellular growth and development. Activation of these proto-oncogenes can occur due to mutation which leads to uncontrolled cell growth. The Proto oncogenes can be grouped into different categories based on their protein products, i.e. protein kinases, growth factors, growth factor receptors, and DNA binding proteins. There are also genes that normally suppress malignant transformation and these are called anti oncogenes. Loss of their suppressor activity leads to unimpeded growth. Oncogene abnormalities are seen in pediatric leukemias, lymphomas, and various solid tumors. Anti oncogenes are associated with retinoblastoma (Rb gene), Wilms' tumor, rhabdomyosarcoma and neuroblastoma, etc. Identification of these abnormalities have diagnostic, prognostic and therapeutic implications. The utility of oncogenes in classification of human cancer and monitoring cancer therapy is quite clear, but the future of these for therapeutic interventions remains uncertain. Role of c-abl oncogene in chronic myeloid leukemia (CML), bcl-2, in lymphomas, N-myc in neuroblastomas and retinoblastoma (Rb) gene in retinoblastomas is well understood and used in designing proper therapeutic approaches. Since oncogenes also control normal cellular function, their use for therapy may be limited by the amount of damage to normal cells. Their maximum therapeutic benefit may be realized only when used in combination with other modalities.

Malignancies in Down syndrome.

Down Syndrome (DS) is associated with an increased incidence of malignancies, especially leukaemias. We came across 8 DS children presenting with malignancies and having trisomy 21 as the sole cytogenetic abnormality. Of these 8 DS cases, 4 presented with acute lymphocytic leukaemia, 2 with acute myeloid leukaemia and one case each with Hodgkin's disease and Wilms' tumour. There are contradictory reports regarding the distribution of myeloid versus lymphoid malignancies in DS children and their response to therapy. The exact mechanism by which patients with DS are predisposed to develop malignancies is unclear. However, presence of the extra chromosome no. 21 is presumed to disrupt the genetic balance which increases generalized susceptibility to genetic and environmental trauma. Furthermore, an increased methotrexate toxicity observed in these patients should also be taken into consideration in designing treatment for DS children with malignancies.