Larynx preservation with combined chemotherapy and radiation therapy in advanced but resectable head and neck cancer

Forty patients with advanced, resectable squamous cell carcinoma of the larynx, oropharynx, or hypopharynx whose surgery would have required total laryngectomy (TL), were treated with one to three cycles of cisplatin-based chemotherapy before local therapy with the goal of larynx preservation. Clinical complete responses (CRs) or partial responses (PRs) to chemotherapy were seen in 26 of 40 patients (65%). Three patients with primary-site disease unresponsive to chemotherapy underwent resection of the primary lesion and neck dissection followed by radiation therapy (RT). Thirty-seven patients were referred after chemotherapy for RT +/- neck dissection. Thirty-one of 40 patient (78%) were rendered disease-free (no evidence of disease [NED]). With a median follow-up of 49 months (range, 31 to 76), the overall actuarial survival rate for the group was 58% at 2 years and 33% at 5 years. The failure-free survival rate was 42% and 33% at 2 and 5 years, respectively. Seven patients refused recommended TL throughout their course. This may have adversely affected survival results. A greater proportion of patients who achieved a CR or PR to chemotherapy remained disease-free compared with those who achieved less than a PR (P less than .001). Sixteen patients relapsed, 10 with locoregional disease. Six patients underwent TL, either for initial induction failure or at relapse, for an actual larynx-preservation rate of 34 of 40 patients (85%). If the seven patients who refused TL are included, the anticipated preservation rate is 27 of 40 patients (68%). Larynx preservation with combined chemotherapy and radiation is feasible and effective in patients with advanced, resectable squamous cell carcinoma of the head and neck (SCHN). This treatment approach requires a motivated patient, careful patient monitoring, and close interdisciplinary cooperation among oncologists.     

Health Insurance Status and Eligibility Among Patients who Seek Healthcare at a Free Clinic in the Affordable Care Act Era

Free clinics provide care to over 1.8 million people in the United States every year and are a valuable safety net for uninsured and underinsured patients. The Affordable Care Act has resulted in millions of newly insured Americans, yet there is continued demand for healthcare at free clinics. In this study, we assessed health insurance status and eligibility among 489 patients who visited a free clinic in 2016. Eighty-seven percent of patients seen were uninsured, 53.1% of whom were eligible for health insurance (Medicaid or subsidized insurance premiums). The majority of these patients completed health insurance applications at their visit with the help of a navigator. A majority of patients who were not eligible for health insurance lacked citizenship status. This study highlights that a significant number of patients who visit free clinics are eligible for health insurance, and that free clinics are important sites for health insurance navigation programs.     

Chediak-Higashi gene in humans. I. Impairment of natural - killer function

Natural-killer (NK)-cell function was profoundly depressed in donors homozygous for the Chediak-Steinbrinck-Higashi syndrome (C-HS) gene when compared with age- and sex-matched normals. This apparent defect was not simply a result of a delayed response because little cytolysis was evident in kinetics experiments even after 24 h of incubation. NK cells from C-HS donors failed to lyse adherent (MDA, CEM, and Alab) or nonadherent (K562 and Molt-4) tumor cell lines or nontransformed human fetal fibroblasts. Therefore, the apparent C-HS defect was not a result of a shift in target selectivities. In addition, the depressed reactivity did not appear to be a result of suppressor cells or factors because: (a) enriched NK populations (nonadherent lymphocytes bearing receptors for the Fc portion of IgG) from C-HS donors were low in NK-cell function, (b) C-HS mononuclear cells did not inhibit the cytotoxicity of normal cells in coculture experiments, and (c) cells from the C-HS donors remained poorly reactive even after culture for up to 7 d. The nature of the defective NK activity in C-HS patients is not clear but may lie within the lytic mechanism rather than at the level of the recognition structure or population size because the frequency of target-binding cells was normal. In vitro NK activity could be partially restored by interferon treatment. Combined with the results presented in the following paper (4), these observations suggest that the C-HS gene causes a selective immunodeficiency disorder, mainly involving NK cells. This finding, in conjunction with the high incidence of spontaneous possibly malignant, lymphoproliferative disorders in these patients, may have important implications regarding the theory of immune surveillance mediated by NK cells.     

Macrophage microbicidal activity. Correlation between phagocytosis-associated oxidative metabolism and the killing of candida by macrophages

The mechanisms by which macrophages kill ingested microorganisms were explored using Candida albicans and Candida parapsilosis. The results indicate that efficient macrophage candidacidal activity depends upon the generation of oxygen metabolites by the phagocytic cell: (a) peritoneal macrophages from mice infected with bacillus Calmette-Guerin (BCG) or injected intraperitoneally with lipopolysaccharide (LPS) released more superoxide anion (0(2)(-)) during phagocytosis of candida and killed candida better than did resident macrophages; (b) cells of the macrophage-like line J774.1, which released negligible amounts of O(2)(-), could ingest the candida normally but not kill them; (c) killing of candida by resident, LPS- elicited, and BCG-activated macrophages was inhibited by agents that scavenge O(2)(-), hydrogen peroxide (H(2)0(2)), hydroxyl radical (x OH), and singlet oxygen; and (d) all three macrophage types killed C. parapsilosis more effectively than C. albicans, and (7. parapsilosis stimulated a more prompt and vigorous burst of macrophage oxygen consumption and 0(2)(-) release than did C. albicans. Macrophages ingested C. parapsilosis slightly more quickly than C. albicans, but phagocytosis of both strains was equivalent by 60 min of incubation. Although C. albicans contained higher concentrations of the oxygen-metabolite scavengers superoxide dismutase and catalase, neither fungal species scavenged 0(2)(-) or H(2)0(2) effectively; and C. albicans was killed more easily than C. parapsilosis by a xanthine oxidase system that generates primarily H(2)O(2) at pH 7, or 0(2)(-) and x OH at pH 10. Thus, the decreased killing of C. albicans appears to result primarily from the capability of this species to elicit less vigorous stimulation of macrophage oxidative metabolism. This capability may have general relevance to the pathogenicity of microorganisms.     

Blood preservation. XXXIV. DHA maintains 2,3-DPG and its adverse effect on ATP is reversed with extra phosphate

We have found that the addition of 10 mM inorganic phosphate to DHA in CPD-adenine maintains ATP levels at normal or higher than normal values for six weeks of storage. 2,3-DPG values are slightly lowered by the extra phosphate, but are still maintained at approximately half normal for four weeks by the DHA. The addition of a higher phosphate concentration, 20 mM, to DHA produced lower levels of ATP and 2,3-DPG than those observed with 10 mM phosphate, although both levels were better than in the CPD-adenine control. pH values in this experiment were lowest in the three preservatives containing DHA, probably indicating increased lactate production due to metabolism of this triose sugar, in addition to dextrose present in CPD.     

Characteristics of human large granular lymphocytes and relationship to natural killer and K cells

Recent evidence, has demonstrated an association between a subpopulation of peripheral blood mononuclear cells, morphologically identified as large granular lymphocytes (LGL), and natural killer (NK) activity. We have now evaluated more directly the role of LGL in both NK activity and antibody- dependent cellular cytotoxicity (ADCC), by using highly enriched populations of LGL, obtained by centrifugation of peripheral blood mononuclear cells on Percoll discontinuous density gradients. Both spontaneous and interferon- augmented NK and ADCC activities were exclusively associated with the LGL- enriched, low density fractions. The majority of LGL formed conjugates with NK-susceptible and antibody-coated target cells. Approximately 20 percent of small conventional lymphocytes also formed conjugates with the target cells for NK, but this was not associated with cytotoxic activity. Virtually all LGL were found to have receptors for the Fc portion of IgG (FcγR). The frequency of LGL among blood leukocytes was 2-6 percent. LGL could be enriched to an average purity of 95 percent by combining discontinuous density gradient centrifugation with subsequent adsorptions of the low density fractions on monolayers of immobilized immune complexes. About 50 percent of LGL were found to be FcγR-bearing T cells (T(G)), forming low affinity rosettes with sheep erythrocytes at 4 degrees C. Only 10-20 percent of LGL formed high affinity rosettes with sheep erythrocytes at 29 degrees C. LGL could be enriched to a purity of more than 90 percent by depleting high affinity rosette-forming cells from low density Percoll fractions. LGL were only a subpopulation of T(G) cells, because some lymphocytes with conventional morphology also adhered to the immobilized immune complex monolayers and formed high affinity rosettes with sheep erythrocytes. Separation of these cells from LGL by discontinuous density gradient centrifugation indicated that they are not cytotoxic, suggesting a morphological and functional subdivision of T(G) cells. The verification in this study that virtually all human NK and K cells have a characteristic morphology adds a useful parameter to the monitoring of human lymphocytes, and the ability to purify these cells by simple physical procedures should be invaluable in their further characterization.     

Methicillin-resistant Staphylococcus aureus colonisation: epidemiological and molecular characteristics in an acute-care tertiary hospital in Singapore

Current knowledge of methicillin-resistant Staphylococcus aureus (MRSA) colonisation in relation to epidemiological characteristics is incomplete. We conducted a cross-sectional study at an acute-care tertiary infectious diseases hospital of MRSA isolates identified through routine surveillance from January 2009 to December 2011. We randomly selected 205 MRSA isolates (119 inpatients) from 798 isolates (427 inpatients) for molecular profiling using multilocus sequence typing. Multilevel multinomial logistic regression was used to estimate odds ratio (OR) assessing the predilection of MRSA strains for anatomic sites, and associations of strains with human immunodeficiency virus (HIV) infection. The most frequent sequence types (STs) were 239, 22 and 45. The proportion of ST22 increased over the sampling period, replacing ST239 as the dominant lineage. However, ST239 remained the most prevalent among HIV-seropositive individuals who were six times more likely to be colonised with this strain than non-HIV patients (adjusted OR (aOR) 6.44, 95% confidence interval (CI) 1.94–21.36). ST45 was >24 times more likely to be associated with perianal colonisation than in the nares, axillae and groin sites (aOR 24.20, 95% CI 1.45–403.26). This study underlines the clonal replacement of MRSA in Singapore as previously reported but revealed, in addition, key strain differences between HIV-infected and non-infected individuals hospitalised in the same environment.Key words: Epidemiology, hospital microbiology, hospital-acquired (nosocomial) infections, methicillin-resistant S. aureus (MRSA), molecular epidemiology     

Spectrin-alpha I/61: a new structural variant of alpha-spectrin in a double-heterozygous form of hereditary pyropoikilocytosis

Recent biochemical studies have led to the identification of abnormal spectrins in the erythrocytes of patients with hereditary pyropoikilocytosis (HPP) and hereditary elliptocytosis (HE). In this report we describe the biochemical characterization of the erythrocytes from a proband with severe HPP who is doubly heterozygous for two mutant spectrins (Sp): Sp alpha I/74 and a new, previously undetected, mutant of alpha-spectrin designated Sp alpha I/61. The proband's erythrocytes are unstable when exposed to 45 degrees C, and her membrane skeletons exhibit instability to shear stress. The content of spectrin in the proband's erythrocyte membranes is decreased to 75% of control values. The amount of spectrin dimers in crude 4 degrees C spectrin extracts is increased (58%) as compared with control values (6% +/- 4%). Limited tryptic digestion reveals a marked decrease in the normal 80,000-dalton alpha I domain, an increase in the 74,000-dalton fragment that is characteristic of Sp alpha I/74, and an increase in a series of new fragments of 61,000, 55,000, 21,000, and 16,000 daltons. Both parents are asymptomatic, but they have increased amounts of spectrin dimers (17% to 25%). Limited tryptic digestion of the father's spectrin demonstrates the presence of a previously identified abnormal spectrin (Sp alpha I/74) that is characterized by a decrease in content of the 80,000-dalton peptide and an increase in concentration of the 74,000-dalton peptide. The mother's spectrin digests show a decrease in the amount of 80,000-dalton peptide and the formation of new peptides of 61,000, 55,000, 21,000, and 16,000 daltons. The data indicate that this severe form of HPP is due to the inheritance of two distinct abnormal spectrins, Sp alpha I/74 and a new spectrin mutant, Sp alpha I/61.