Oral mucosal injury in oncology patients: perspectives on maturation of a field

In the past decade, there have been important strategic advances relative to pathobiological modeling as well as clinical management for oral mucositis caused by cancer therapies. Prior to the 1990s, research in this field was conducted by a relatively small number of basic and clinical investigators. Increasing interest among researchers and clinicians over the past twenty years has produced a synergistic outcome characterized by a number of key dynamics, including novel discovery models for pathobiology, increased experience in designing and conducting clinical trials, and creation of international collaborations among cancer care professionals who in turn have modeled clinical care paradigms based on state‐of‐the‐science evidence. This maturation of the science and its clinical translation has positioned investigators and oncology providers to further accelerate both the foundational research and the clinical modeling for patient management in the years ahead. The stage is now set to further capitalize upon optimizing the interactions across this interface, with the goal of strategically enhancing management of patients with cancer at risk for this toxicity while reducing the cost of cancer care.     

Atypical lymphoid leukemia in ataxia telangiectasia

We observed two sisters with ataxia telangiectasia, one of whom developed an atypical subacute lymphocytic leukemia characterized by atypical lymphocytes and absence of palpable lymphadenopathy or hepatosplenomegaly. The lack of organomegaly in this patient may have been due to the underlying ataxia telangiectasia, which was associated with lymphoid hypoplasia. Cytogenetic studies showed a marker chromosome 14 [t(14q11:14q34)] in both patients. The sister with leukemia had other complex chromosomal aberrations in addition to the marker chromosome 14 that were stable for more than 14 mo before the patient's death from complicating infection. The development of atypical T cell leukemia has not been previously described in ataxia telangiectasia. This case further illustrates the interesting interrelationships amoung immunosuppressed states, development of lymphoid malignancy, and an emerging pattern of a propensity to chromosome 14 abnormalities in various lymphoid malignancies.     

A multiparameter analysis of sickle erythrocytes in patients undergoing hydroxyurea therapy

During 24 weeks of hydroxyurea treatment, we monitored red blood cell (RBC) parameters in three patients with sickle cell disease, including F-cell and F-reticulocyte profiles, distributions of delay times for intracellular polymerization, sickle erythrocyte adherence to human umbilical vein endothelial cells in a laminar flow chamber, RBC phthalate density profiles, mean corpuscular hemoglobin concentration and cation content, reticulocyte mean corpuscular hemoglobin concentration, 1H-nuclear magnetic resonance transverse relaxation rates of packed RBCs, and plasma membrane lateral and rotational mobilities of band 3 and glycophorins. Hydroxyurea increases the fraction of cells with sufficiently long delay times to escape the microcirculation before polymerization begins. Furthermore, high pretreatment adherence to human umbilical vein endothelial cells of sickle RBCs decreased to normal after only 2 weeks of hydroxyurea treatment, preceding the increase in fetal hemoglobin levels. The lower adhesion of sickle RBCs to endothelium would facilitate escape from the microcirculation before polymerization begins. Hydroxyurea shifted several biochemical and biophysical parameters of sickle erythrocytes toward values observed with hemoglobin SC disease, suggesting that hydroxyurea moderates sickle cell disease toward the milder, but still clinically significant, hemoglobin SC disease. The 50% reduction in sickle crises documented in the Multicenter Study of Hydroxyurea in Sickle Cell Disease is consistent with this degree of erythrocyte improvement.     

Intra-renal and subcellular distribution of the human chloride channel, CLC-5, reveals a pathophysiological basis for Dent's disease

Dent's disease, which is a renal tubular disorder characterized by low molecular weight proteinuria, hypercalciuria and nephrolithiasis, is associated with inactivating mutations of the X-linked chloride channel, CLC-5. However, the manner in which a functional loss of CLC-5 leads to such diverse renal abnormalities remains to be defined. In order to elucidate this, we performed studies to determine the segmental expression of CLC-5 in the human kidney and to define its intracellular distribution. We raised and characterized antisera against human CLC-5, and identified by immunoblotting an 83 kDa band corresponding to CLC-5 in human kidney cortex and medulla. Immunohistochemistry revealed CLC-5 expression in the epithelial cells lining the proximal tubules and the thick ascending limbs of Henle's loop, and in intercalated cells of the collecting ducts. Studies of subcellular human kidney fractions established that CLC-5 distribution was associated best with that of Rab4, which is a marker of recycling early endosomes. In addition, confocal microscopy studies using the proximal tubular cell model of opossum kidney cells, which endogenously expressed CLC-5, revealed that CLC-5 co-localized with the albumin- containing endocytic vesicles that form part of the receptor-mediated endocytic pathway. Thus, CLC-5 is expressed at multiple sites in the human nephron and is likely to have a role in the receptor-mediated endocytic pathway. Furthermore, the functional loss of CLC-5 in the proximal tubules and the thick ascending limbs provides an explanation for the occurrences of low molecular weight proteinuria and hypercalciuria, respectively. These results help to elucidate further the patho-physiological basis of the renal tubular defects of Dent's disease.      

Unresectable non-oat cell carcinoma of the lung: definitive radiation therapy

Between 1976 and 1983, 267 patients with non-oat cell carcinoma of the lung were treated with radiation therapy alone. One hundred thirty-four patients had squamous cell carcinoma; 69, large cell carcinoma; and 64, adenocarcinoma. Stage III carcinoma was diagnosed in 87% of the patients. Total radiation dose was less than 45 Gy in 69 patients (low dose group), 45-55 Gy in 161 (middle dose group), and 55-65 Gy in 37 (high dose group); dosage was 180-200 cGy daily, 5 days per week. Minimum follow-up was 3 years (median, 6 years). Tumor control within the radiation fields was achieved in 12%, 43%, and 78% of the low, middle, and high dose groups, respectively. A complete response rate of 13%, 23%, and 35% and an overall response of 43%, 71%, and 86% were seen in the low, middle, and high dose groups, respectively. The 5-year recurrence-free survival rate for all patients was 7% and was dependent on radiation dose and tumor response. This study indicates that tumor control and complete response rates are improved with a radiation dose of 55-65 Gy and that complete responders have improved survival.     

An Unusual Complication of a Usual Guidewire during Central Venous Cannulation

How to cite this article: Palanisamy S, Arish BT, Segaran S, Ranjan RV. An Unusual Complication of a Usual Guidewire during Central Venous Cannulation. Indian J Crit Care Med 2022;26(6):761–762.