Screening for diabetic retinopathy: the utility of nonmydriatic retinal photography in Egyptian adults

BACKGROUND AND OBJECTIVE: Drug resistance has become a major cause of treatment failure in patients with acute leukemia. P-glycoprotein (Pgp), which is associated with the multidrug resistance (MDR) phenotype, has been reported to be an important predictor of treatment outcome. The aim of this study was to analyze the value of Pgp expression in bone marrow or peripheral blood as a predictor of the response to remission induction chemotherapy as well as the duration of remission in patients with de novo acute myeloid leukemia (AML). DESIGN AND METHODS: We examined the expression of Pgp in 82 patients with de novo AML using an immunocytochemical assay with the C219 monoclonal antibody. RESULTS: Twenty-seven of the 82 patients (33%) were C219-positive in from 1% to 100% of their cells. Thirteen cases (16%) showed a positive reaction in more than 50% of the leukemic cells. Only hyperleukocytosis was significantly associated with higher expression of Pgp. Although 8 of the 13 cases (62%) with more than 50% of cells having Pgp expression were CD34-positive, this association was not statistically significant. A univariate analysis of resistance to induction therapy showed a significantly higher resistance rate in patients with increased Pgp expression (P = 0.01) as well as in those patients with decreased reactivity to myeloperoxidase. The multivariate analysis revealed the independent prognostic value of Pgp expression. C219 reactivity did not have an influence on remission duration. INTERPRETATION AND CONCLUSIONS: Our data indicate that P-glycoprotein expression is a reliable marker of resistance to induction treatment in patients with de novo AML.     

Differential expression of CD14, CD36 and the LDL receptor on human monocyte-derived macrophages. A novel cell culture system to study macrophage differentiation and heterogeneity

Multiple heterogeneous groups of subjects (both sexes and a wide range of maximal oxygen uptake VO2max, body mass, body surface area (AD),% body fat, and AD/mass coefficient) exercised on a cycle ergometer at a relative (%VO2max, REL) or an absolute (60 W) exercise intensity in a cool (CO 21 degrees C, 50% relative humidity), warm humid (WH 35 degrees C, 80%) and a hot dry (HD 45 degrees C, 20%) environment. Rectal temperature (Tre) responses were analysed for the influence of the individual's characteristics, environment and exercise intensity. Exposures consisted of 30-min rest, followed by 60-min exercise. The Tre was negatively correlated with mass in all conditions. Body mass acted as a passive heat sink in all the conditions tested. While negatively correlated with VO2max and VO2max per kilogram body mass in most climates, Tre was positively correlated with VO2max and VO2max per kilogram body mass in the WH/REL condition. Thus, when evaporative heat loss was limited as in WH, the higher heat production of the fitter subjects in the REL trials determined Tre and not the greater efficiency for heat loss associated with high VO2max. Body fatness significantly affected Tre only in the CO condition, where, with low skin blood flows (measured as increases in forearm blood flow), the insulative effect of fat was pronounced. In the warmer environments, high skin blood flows offset the resistance offered by peripheral adipose tissue. Contrary to other studies, Tre was positively correlated with AD/mass coefficient for all conditions tested. For both exercise types used, being big (a high heat loss area and heat capacity) was apparently more beneficial from a heat strain standpoint than having a favourable AD/mass coefficient (high in small subjects). The total amount of variance in Tre responses which could be attributed to individual characteristics was dependent on the climate and the type of exercise. Though substantial for absolute exercise intensities (52%-58%) the variance explained in Tre differed markedly for relative intensities: 72% for the WH climate with its limited evaporative capacity, and only 10%-26% for the HD and CO climates. The results showed that individual characteristics play a significant role in determining the responses of body core temperature in all conditions tested, but their contribution was low for relative exercise intensities when evaporative heat loss was not restricted. This study demonstrated that effects of individual characteristics on human responses to heat stress cannot be interpreted without taking into consideration both the heat transfer properties of the environment and the metabolic heat production resulting from the exercise type and intensity chosen. Their impact varies substantially among conditions.     

Hereditary febrile seizures: phenotype and evidence for a chromosome 19p locus

Three flagellates of the family Trypanosomatidae were isolated from mango fruits (Mangifera indica) and from the stems of clover (Trifolium glomeratum) and Amaranth (Amaranthus retroflexus) in southeastern Spain and were adapted to in vitro culture in monophase media. The parasites showed an ultrastructural pattern similar to that of other species of the genus Phytomonas. Mango and clover isolates differed from amaranth isolates in ultrastructural terms. The isolates were characterized by isoenzymatic analysis and by kDNA analysis using five different restriction endonucleases. With eight of the nine enzymatic systems, mango and clover isolates were distinguished from those of amaranth. Nevertheless, with the enzymes malate dehydrogenase and superoxide dismutase, flagellates isolated from clover were differentiated from those isolated from mango. Electrophoretic and restriction-endonuclease analysis of kDNA minicircles showed similar restriction cleavage patterns for the isolates from mango and clover, whereas the patterns of the amaranth isolates differed. The results of the present study confirm that the strains isolated from mango and clover constitute a phylogenetically closely related group of plant trypanosomatids, which is more distantly related to the strain isolated from amaranth. The similarities in the results obtained for isolates from mango and clover foliage, on the one hand, and those obtained from tomato and cherimoya fruits (studied previously), on the other, as well as the geographic proximity of the different plants support the contention that only one strain is involved, albeit one strain that can parasitize different plants. Furthermore, some of the plants appear to act as reservoirs for the parasites. On the other hand, the metabolism studies using [1H]-nuclear magnetic resonance spectroscopy did not reveal that the catabolism of Phytomonas in general follows a pattern common to all the species or isolates. Phytomonas are incapable of completely degrading glucose, excreting a large part of their carbon skeleton into the medium as fermentative metabolites (acetate, ethanol, glycine, glycerol, and succinate).     

Complex intracranial aneurysms: combined operative and endovascular approaches

OBJECTIVE: Endovascular management of complex intracranial aneurysms is increasingly being considered as an alternative to standard surgical clipping. However, little attention has been paid to the complementary nature of surgery and endovascular therapy. METHODS: Between September 1992 and May 1997, 12 patients with complex intracranial aneurysms were treated with combined operative and endovascular methods. Seven patients demonstrated subarachnoid hemorrhage (two of Grade II, two of Grade III, and three of Grade IV). Five patients demonstrated unruptured aneurysms, i.e., three giant aneurysms (one vertebrobasilar junction aneurysm, one middle cerebral artery bifurcation aneurysm, and one internal carotid artery-ophthalmic artery aneurysm), one large internal carotid artery-ophthalmic artery aneurysm, and one middle cerebral artery serpentine aneurysm. Management strategies involved either surgery followed by endovascular therapy (S-E; n = 5) or endovascular therapy followed by surgery (E-S; n = 7). S-E paradigms included aneurysm exploration followed by endovascular treatment (S-E1; n = 3), partial aneurysm clipping followed by endovascular aneurysm packing (S-E2; n = 1), and extracranial-to-intracranial bypass followed by endovascular parent vessel occlusion (S-E3; n = 1). E-S paradigms included superselective angiography followed by surgical clipping (E-S1; n = 2), Guglielmi detachable coil partial dome packing followed by delayed surgical clipping (E-S2; n = 2), proximal temporary vessel balloon occlusion followed by aneurysm clipping (E-S3; n = 2), and proximal permanent vessel occlusion followed by surgical aneurysm decompression for mass effect treatment (E-S4; n = 1). RESULTS: Eleven aneurysms (92%) were completely eliminated. The remaining aneurysm was 90% obliterated and remained quiescent at the 34-month follow-up examination, despite presenting with subarachnoid hemorrhage. No patient experienced repeat bleeding (follow-up period, 23+/-28 mo). There were no deaths. One patient achieved a fair outcome (Glasgow Outcome Scale score of III); all other patients experienced excellent outcomes (Glasgow Outcome Scale score of I). In all cases, the aneurysm management paradigm chosen had a positive effect on definitive therapy. CONCLUSION: Several factors can contribute to the complexity of intracranial aneurysms. Management strategies that combine operative and endovascular techniques in a complementary way, for the best possible outcomes for these patients, can be designed accordingly.     

Thiopurine methyltransferase genotype predicts therapy-limiting severe toxicity from azathioprine

BACKGROUND: Substantial hematologic toxicity limits the use of azathioprine. OBJECTIVE: To evaluate 1) polymorphic inactivation of azathioprine by thiopurine methyltransferase and 2) clinical toxicity. DESIGN: Prospective cohort study. SETTING: Two rheumatology units. PATIENTS: 67 patients for whom azathioprine was prescribed as second-line therapy for rheumatic disease. MEASUREMENTS: Polymerase chain reaction-based assays were used to detect mutations in thiopurine methyltransferase. The primary end point was discontinuation of azathioprine therapy because of toxicity. RESULTS: Six of 67 patients (9%) were heterozygous for mutant thiopurine methyltransferase alleles. Five of the 6 patients discontinued therapy within 1 month of starting treatment because of low leukocyte counts. The sixth patient did not adhere to treatment. Patients with wild-type thiopurine methyltransferase alleles received therapy longer than did patients with mutant alleles (median duration of therapy, 39 weeks [range, 6 to 180 weeks] and 2 weeks [range, 2 to 4 weeks], respectively; P = 0.018). CONCLUSION: Analysis of thiopurine methyltransferase genotype is a quick way to identify patients at risk for acute toxicity from azathioprine.     

Retroviral transfer of CPP32beta gene into malignant gliomas in vitro and in vivo

Malignant gliomas are highly aggressive neoplasms that are very resistant to current therapeutic approaches, including irradiation, chemotherapy, and immunotherapy. To improve the prognosis, it is absolutely essential to explore novel modalities of treatment. Recently, we have demonstrated that interleukin 1beta-converting enzyme (ICE), a mammalian homologue of the Caenorhabditis elegans cell death gene ced-3, induces apoptotic cell death in malignant glioma cells. To date, ICE and ICE-like proteases (the ICE family), such as Ich-1L, CPP32beta, Mch2alpha, and Mch3alpha, have been shown to mediate apoptosis in some cells. The purpose of this study is to determine whether the ICE gene family functions as a useful tool for the treatment of malignant glioma cells through induction of apoptosis. The transient transfection assays showed that CPP32beta and Mch2alpha genes induced apoptotic cell death in malignant glioma cells more effectively than did the ICE, Ich-1L, and Mch3alpha genes. To improve the efficiency of gene transfer into malignant glioma cells, we constructed the retroviral vectors containing the ICE gene family. The retroviral transfer of CPP32beta or Mch2alpha gene effectively induced apoptosis in malignant glioma cells in vitro. Furthermore, treatment of tumors grown in mice with retrovirus containing CPP32beta significantly inhibited growth of the tumors through induction of apoptosis. The retroviral transfer of CPP32beta or Mch2alpha, therefore, may be a novel and promising approach for the treatment of malignant glioma, an invariably fatal tumor.     

Nasal carriage of staphylococcus aureus and epidemiology of surgical-site infections in a Sudanese university hospital

Surgical site infections (SSI) due to Staphylococcus aureus among 256 male and 158 female patients (mean age, 28 years) undergoing elective surgery at the Soba University Hospital (Khartoum, Sudan) were studied. During an 11-month study period all patients were analyzed for nasal carriage of S. aureus at the time of admission. Follow-up of the development of SSI proceeded until 4 weeks after the operations. In addition, nasal swabs were obtained periodically during the same period from 82 members of the staff. In order to discriminate autoinfection from cross infection, bacterial isolates were typed by random amplification of polymorphic DNA (RAPD), pulsed-field gel electrophoresis (PFGE) of DNA macrorestriction fragments, and restriction fragment length polymorphism analysis of the protein A and coagulase genes. Preoperative cultures revealed the presence of S. aureus in the noses of 98 patients (24%). The overall number of postsurgical wound infections in the entire group was 57 (14%), 24 of which were due to S. aureus. Only 6 of the 98 nasal S. aureus carriers suffered from wound infections by the same species. In these six cases the infecting strain could not be genetically discriminated from the nasal inhabitant, substantiating autoinfection. However, nasal carriage of S. aureus is not a significant risk factor for the development of SSI in this setting (6 of 98 patients with autoinfection versus 18 of 316 patients [414 - 98 patients] with cross infection; P = 0.81), most probably due to the fact that noncarriers are at a significant and relatively large risk for acquiring an independent S. aureus SSI. The other S. aureus strains causing SSI showed a high degree of genetic heterogeneity, demonstrating that it is not an epidemic strain that is causing the SSI. Among the staff personnel screened, 47.4% did not carry S. aureus in the nose at any time during the study period, whereas 13. 2% persistently carried a single strain in the nose. Another 39.5% could be classified as intermittent carriers. When strains derived from staff personnel were genetically typed, it was demonstrated that most of the strains represented genetic variants clearly differing from the isolates causing SSI. On the other hand, possible cross colonization among staff personnel and even cross infection from staff personnel to patients or from patient to patient were demonstrated in some cases, but epidemic spread of a single strain or a few clonally related strains of S. aureus could be excluded.