Facilitated uptake of zinc into human erythrocytes. Relevance to the treatment of sickle-cell anaemia

The ability of a number of heterocyclic metal chelators to deliver zinc into red cells, to release the liganded zinc to haemoglobin and thereby cause a left shift in the oxygen dissociation curve of intact red cells has been investigated. Incubation of neutrally charged zinc-pyrone and zinc-pyridin-2-one complexes with red cells led to the rapid accumulation of zinc within cells, whereas unliganded zinc in the form of zinc acetate, zinc chloride or zinc sulphate accumulated only slowly. The rate at which zinc was delivered to red cells by pyrone and pyridin-2-one ligands increased with increasing lipid solubility of the ligands. The uptake of zinc into both normal adult and sickle red cells was associated with a dose-dependent increase in the oxygen affinity of haemoglobin. The degree of left shift in the oxygen dissociation curve following the incubation of red cells with zinc-pyrone and -pyridin-2-one complexes suggests that these complexes may find application as agents to increase the oxygen affinity of haemoglobin in sickle cell disease and thereby decrease the probability of intravascular sickling at low tissue oxygen tensions. Ethylmaltol appears to be a particularly useful agent due to its known low toxicity.     

Enhanced progesterone and testosterone secretion and depressed estradiol secretion in vitro from small white follicle cells of incubating turkey hens

This study was conducted to determine if lower steroid secretion by the small white follicles in incubating turkey hens contributes to lower circulating steroid concentrations during this time. Turkey hens were grouped as either laying or incubating. Serum samples and the ovarian small white follicles (SWF; 2-7 mm diameter) were collected from each hen. The SWF were pooled for each group and their cells were dispersed by trypsin digestion. Serum-luteinizing hormone (LH), progesterone (P), testosterone (T), and estradiol (E) concentrations were lower and serum prolactin concentration was higher during incubation than during egg laying. SWF cells from incubating hens secreted more P and T and less E in response to ovine luteinizing hormone (oLH) than did similar cell suspensions from laying hens. The incubating hens' SWF cells' capacity to secrete E but not their capacity to secrete P or T in vitro is consistent with the observed circulating levels. It is hypothesized that lower levels of circulating LH and/or higher levels of prolactin found in incubating hens may have a depressing effect on aromatase activity and/or an up-regulating effect on LH-induced P and T secretion by the SWF cells.     

Granulocytic sarcoma: An atypical presentation in the oral cavity

Acute myelogenous leukemia (AMU is a hematologic disorder that is characterized by an abnormal proliferation of immature myeloid cells. Granulocytic sarcomas are clusters of leukemic myeloid cells that may develop as a result of AML. Oral manifestations of AML are common and often involve enlargements of the gingiva and/or mucosal tissue from direct leukemia cell infiltration. We describe the case history of a 50-year-old man who had an ulcera-tive lesion of the oral mucosa that was determined to be a granulocytic sarcoma of AML-M0 subtype. The combination of both the subtype and clinical presentation of the leukemia makes this presentation unusual, and to the best of our knowledge, of a type that has not been previously reported in the literature.     

Evaluation of possible traumatic thoracic aortic injury using aortography and CT

To identify and compare the methods of evaluation for suspected traumatic aortic rupture, 1,031 trauma charts from 1983-1989 were reviewed. Fifty-nine patients were evaluated for possible aortic injury. Patients who died before completion of the CT or aortogram were excluded. Widening of the mediastinum on chest x ray was the most frequent indication for follow-up studies. Twenty-five had a CT of the aortic arch alone. No study showed disruption. There were no false negative studies. Thirty patients had only aortography. Twenty-four were read as normal (one false negative). Six were read as positive (one false positive). In four, both studies were performed (CT/aortography--TP/TP, TN/TN, TP/FN, FP/FP). (FP = False Positive, TP = True Positive, FN = False Negative, TN = True Negative.) Six received surgical repair of the aortic injury (one death). In this experience, CT was used successfully as a screening tool for aortic disruption. It was highly sensitive in recognizing aortic injuries when present (100% vs. 75% for aortography) and in most cases did not require aortographic verification. False positive rates were comparable (CT = 3.8%, aortography = 7.7%). Specificity was also comparable (CT = 96%, aortography = 92%). Overall, four aortograms were inaccurate while only one CT was inaccurate. We recommend the use of CT for the evaluation of widened mediastinum in the stable patient.     

Poverty, health services, and health status in rural America

Access to health services for everyone has been a major policy goal in the United States: inequitable access is assumed to lead to inequitable health status, particularly for low-income groups. A sophisticated model of the relation between poverty, health care needs, service use, and health outcomes is used to analyze cross-sectional data on 7,823 adults from 36 rural communities. Improved access and use are helpful, but evidence clearly indicates that combined health and social initiatives will be necessary to reduce inequalities in health status.     

Coronary stents.

In this article we review the early history of the coronary artery stent in clinical cardiology, cite a clinical case and assess the potential role of stents in revascularization in the future.     

Detection of undiagnosed coeliac disease with atypical features using antireticulin and antigliadin antibodies.

Eighteen patients with a variety of non-gastrointestinal symptoms were incidentally found to have circulating antireticulin antibody and on subsequent testing were also positive for antigliadin antibody. They prospectively underwent jejunal biopsy to determine whether or not they had coeliac disease. Their age range was 21-79 years (mean 42 years). Enteropathy was present in 13 (72 per cent) and was always associated with circulating IgA antigliadin antibody. Enteropathy was not present in the five cases who had only IgG antibody. Clinical improvement occurred in eight of 11 patients who complied with a gluten-free diet and was paralleled by an improvement in the mucosal histology in seven of eight who were re-biopsied. The most remarkable cases were two patients who presented with severe debility and no apparent haematological or biochemical abnormalities, and who subsequently made a dramatic recovery on a gluten-free diet. It is concluded that antireticulin antibody detected by routine autoantibody screening and confirmed to have IgA antigliadin antibody specificity is a useful indicator of an otherwise undiagnosed enteropathy. This serves to emphasize that the condition can sometimes be associated with atypical features and significant morbidity.     

A novel cubic phase of medium chain lipid origin for the delivery of poorly water soluble drugs.

The existence of a novel cubic liquid crystalline phase is described within the pseudo-ternary system comprising lauric acid, monolaurin, and simulated endogenous intestinal fluid (SEIF). This phase behaviour has been characterized using cross-polarizing light microscopy (CPLM), and the structure of the cubic phase identified by small angle X-ray scattering (SAXS). The presence of the cubic phase was found to be temperature sensitive within the 20-37 degrees C range making it putative material for in situ gelation purposes. The cubic phase was shown to have a high capacity to solubilise a model poorly water-soluble drug, cinnarizine, and initial in vitro release data highlight the potential of this phase to provide sustained release. Absorption of cinnarizine from the cubic phase was studied in an unconscious rat model via duodenal administration and blood sampling via the carotid artery. The rate of absorption was significantly reduced when compared to a simple suspension formulation, a likely combination of retarded erosion of the cubic phase together with hindered drug release from the cubic matrix. The results of this study suggest that this cubic phase may potentially be of benefit in the delivery of poorly water-soluble compounds due to its high loading capacity and potential for sustained release. The ability to manipulate this system using temperature may warrant further interest in delivery applications via other routes of administration.     

Human CD4+CD25+ Regulatory T Cells Suppress Anti-Porcine Xenogeneic Responses

Due to the shortage of human organs, xenotransplantation is being explored as an alternative to allotransplantation, but immune rejection remains a major hurdle to its implementation. We tested the ability of human CD4+CD25+ T cells (Treg cells) to suppress CD4+ T cell-mediated anti-porcine xenoresponses usingin vitroassays. Human Treg cells were hyporesponsive to porcine cell stimulation and suppressed the proliferative response of CD4+CD25- T cells in a dose-dependent manner, and comparison of the allo- and xenoresponses indicated that more Treg cells might be required to suppress the xenogeneic response than the allogeneic response. Stimulation of CD4+CD25- T cells with porcine cells resulted in secretion of IFN-gamma, TNF-alpha, IL-10, IL-6 and IL-2, and Treg cells suppressed the secretion of these cytokines, as well as the CD4+CD25- T-cell cytolytic response against porcine cells. These results suggest a potential role for Treg cells in promoting xenograft survival.