Success rate of type 1 tympanoplasty: a comparative study.

OBJECTIVES: This study aimed to compare graft take rate after tympanoplasty between adults and paediatric patients, cartilage and fascia grafts, and overlay and underlay techniques. METHODS: Data were analysed in groups according to the technique (underlay vs overlay), age (paediatric patients vs adults) and graft (cartilage vs temporalis fascia). The main outcome measures were full graft take and the incidence of complications. RESULTS: A total of 198 patients (208 ears) were included. Overall, full graft take was achieved in 200 ears (96 per cent). The success rate was higher in adults compared with paediatric patients (97.5 per cent vs 92.25, respectively) but the difference was insignificant. Similarly, higher but insignificant graft take rate was found in the cartilage group compared with fascia group (98.6 per cent vs 94.9 per cent, respectively). CONCLUSION: All cases of overlay tympanoplasty had full graft take (success rate 100 per cent). In the underlay group, successful graft take was achieved in 154 cases (95 per cent). This difference was statistically insignificant.

Hearing results after stapedotomy for otosclerosis: comparison of prosthesis variables.

OBJECTIVE: To evaluate the influence of different piston variables on hearing following stapedotomy. METHODS: Data were analysed in groups according to: piston material (titanium vs fluoroplastic), shaft diameter (0.4 mm vs 0.5 mm) and crimping style (manual crimping vs self-crimping). Pre- and post-operative average air-bone gap, air-bone gap difference, success rate and operative time were evaluated. RESULTS AND CONCLUSION: Fifty-one patients (58 ears) were included. A post-operative air-bone gap of 10 dB or lower was achieved in 44 cases, with a success rate of 75.9 per cent; 52 cases (89.7 per cent) had an air-bone gap of 20 dB or lower. The success rate was higher, but not significantly, in fluoroplastic than in titanium pistons (85 per cent vs 70 per cent). Pistons with shaft diameters of 0.5 mm and 0.4 mm had success rates of 79 per cent and 72 per cent, respectively. No significant differences were found for any audiometric parameters. There were no significant differences between manual crimping and self-crimping pistons in terms of audiometric results or success rate.

Mast cells/basophils in the peripheral blood of allergic individuals who are HIV-1 susceptible due to their surface expression of CD4 and the chemokine receptors CCR3, CCR5, and CXCR4.

A population of metachromatic cells with mast cell (MC) and basophil features was identified recently in the peripheral blood of patients with several allergic disorders. This study now shows that these metachromatic cells express on their surface the high-affinity IgE receptor (FcepsilonRI), CD4, and the chemokine receptors CCR3, CCR5, and CXCR4, but not the T-cell surface protein CD3 and the monocyte/macrophage surface protein CD68. This population of MCs/basophils can be maintained ex vivo for at least 2 weeks, and a comparable population of cells can be generated in vitro from nongranulated hematopoietic CD3(-)/CD4(+)/CD117(-) progenitors. Both populations of MCs/basophils are susceptible to an M-tropic strain of human immunodeficiency virus 1 (HIV-1). Finally, many patients with acquired immunodeficiency syndrome have HIV-1-infected MCs/basophils in their peripheral blood. Although it is well known that HIV-1 can infect CD4(+) T cells and monocytes, this finding is the first example of a human MC or basophil shown to be susceptible to the retrovirus. (Blood. 2001;97:3484-3490)

Neuro-brucellosis in children.

Brucellosis is an infection caused by gram negative cocobacilli (Brucellae). Presentation is usually non-specific and diagnosis depends on high index of suspicion. Nervous system involvement in children is rare as only 47 cases were reported until 1998. We are reporting two patients with neurobrucellosis. The first case was an 8-year-old boy who presented with papillodeoma, and neck stiffness of one month duration. Cerebrospinal fluid pressure was 360mm/water, protein 0.63gm/dl, and cerebrospinal fluid sugar/serum sugar 0.2/4.7mmol. Brucella titer was high in serum and cerebrospinal fluid. The second case was a 3-year-old girl with congenital hydrocephalus, with history of fever, loss of weight, and abdominal cyst around the distal end of ventriculo-peritoneal shunt tube. Brucella mellitenesis was isolated from cerebrospinal fluid and blood. Both cases were treated successfully by 3 antibiotics for 8-12 week.

The level of HIV infection of macrophages is determined by interaction of viral and host cell genotypes.

The outcome of HIV infection in vivo and in vitro depends on the interaction of viral and cellular genotypes. Analysis of infection of blood monocyte-derived macrophages by primary HIV strains shows that approximately one-third of 32 isolates was consistently high-replicating, one-third was consistently low-replicating, and one-third was dependent on the donor of the macrophages (i.e., variable). HIV isolates from patients with AIDS showed enhanced replication within macrophages and predominant use of CCR5 for entry, although 13% did use CXCR4. Tissue isolates from brain and CSF showed an enhanced ability to infect 1-day-old monocytes compared with blood isolates from patients with AIDS. The ability of primary isolates to infect neonatal or adult monocytes maturing into macrophages or placental macrophages correlated directly with the extent of CCR5 expression. Studies of macrophages from pairs of identical twins and unrelated donors showed genetic control over CCR5 expression, which was independent of the CCR5delta32 genotype. Furthermore, these studies showed a marked host-cell genetic effect on the variable primary HIV strains. Although CCR5 was essential for the entry of most primary isolates, it was not the essential "bottleneck" determining productivity of infection. The location of this bottleneck in the HIV replication cycle differs according to viral strain and host-cell donor, but it was exerted before the stage of reverse transcription in 80-90% of cases. Such host-cell genetic factors may affect viral load in vivo where macrophages are the predominant target cells.

Persistent CCR5 utilization and enhanced macrophage tropism by primary blood human immunodeficiency virus type 1 isolates from advanced stages of disease and comparison to tissue-derived isolates.

Viral phenotype, tropism, coreceptor usage, and envelope gene diversity were examined in blood isolates collected from 27 individuals at different stages of human immunodeficiency virus type 1 (HIV-1) disease and tissue derived isolates from 10 individuals with AIDS. The majority (89%) of blood and all tissue HIV-1 isolates from all stages of infection were non-syncytium inducing and macrophage (M) tropic. Tropism and productive infection by HIV isolates in both monocytes and monocyte-derived macrophages (MDM) increased in advanced disease (HIV tropism for monocytes, 1 of 6 from categories I and II versus 11 of 21 [P = 0.05] from category IV and II [CD4 < 250]; and high-level replication in MDM, 1 of 6 from categories I and II versus 16 of 21 from categories IV and II [P = 0. 015]). There was a high level of replication of blood and tissue isolates in T lymphocytes without restriction at any stage. Overall, the level of replication in MDM was 5- to 10-fold greater than in monocytes, with restriction in the latter occurring mainly at entry and later stages of replication. Only three blood isolates were identified as syncytium inducing, and all had a dualtropic phenotype. There was a significant increase of HIV envelope gene diversity, as shown by a heteroduplex mobility assay, in advanced disease; this may partly underlie the increase of HIV replication in MDM. Unlike blood isolates (even those from patients with advanced disease), tissue isolates displayed greater similarities (90%) in productive infection between MDM and monocytes. The majority (87%) of all isolates, including those from patients with advanced disease, used CCR5, and only 5 of 37 isolates showed expanded coreceptor usage. These results indicate that in the late stage of disease with increasing viral load and diversity, CCR5 utilization and M-tropism persist in blood and tissue and the replicative ability in macrophages increases. This suggests that these characteristics are advantageous to HIV and are important to disease progression.

Definition of the stage of host cell genetic restriction of replication of human immunodeficiency virus type 1 in monocytes and monocyte-derived macrophages by using twins.

Using identical (ID) twins, we have previously demonstrated that host cell genes exert a significant impact on productive human immunodeficiency virus (HIV) infection of monocytes and macrophages (J. Chang et al., J. Virol. 70:7792-7803, 1996). Therefore, the stage in the replication cycle at which these host genetic influences act was investigated in a study using 8 pairs of ID twins and 10 pairs of sex- and age-matched unrelated donors (URDs). In the first phase of the study, blood monocytes and monocyte-derived macrophages (MDM) of ID twins and URDs were infected with 15 HIV type 1 strains. Four well-characterized primary isolates and HIV-BaL were then examined in more detail. The host cell genetic effect in MDM was exerted predominantly prior to complete reverse transcription, as the HIV DNA level and p24 antigen levels were concordant (r = 0.91, P = 0.0001) and similar between the pairs of ID twin pairs (r = 0.96, P = 0.0001) but discordant between URD pairs (r = 0.11, P = 0.3) in both phases of the study. To further examine genetic influence on viral entry, we examined the proportion of CCR5 membrane expression on MDM. As expected, there was wide variability in proportion of MDM expressing CCR5 among URDs (r = 0. 58, P = 0.2); however, this variability was significantly reduced between ID twin pairs (r = 0.81, P = 0.01). Differences in viral entry did not necessarily correlate with CCR5 expression, and only very low levels of CCR5 expression restricted HIV entry and production. In summary, the host cell genetic effect on HIV replication in macrophages appears to be exerted predominantly pre-reverse transcription. Although CCR5 was necessary for infection, other unidentified host genes are likely to limit productive infection.

CCR5 expression correlates with susceptibility of maturing monocytes to human immunodeficiency virus type 1 infection.

The chemokine receptor CCR5 and to a lesser extent CCR3 and CCR2b have been shown to serve as coreceptors for human immunodeficiency virus type 1 (HIV-1) entry into blood- or tissue-derived macrophages. Therefore, we examined the expression of the chemokine receptors CCR1, CCR2b, CCR3, CCR5, and CXCR4 as RNAs or as membrane-expressed antigens in monocytes maturing into macrophages and correlated these results with the susceptibility of macrophages to HIV-1 infection, as measured by their concentrations of extracellular p24 antigen and levels of intracellular HIV DNA by quantitative PCR. There was little change in levels of CCR1, CCR2b, and CCR5 RNAs. CCR3 RNA and surface antigen were undetectable throughout maturation of adherent monocytes over 10 days. CXCR4 RNA and membrane antigen were strongly expressed in newly adherent monocytes, but their levels declined at day 7. The amounts of CCR5 RNA remained stable, but the amounts of CCR5 antigen increased from undetectable to peak levels at day 7 and then declined slightly at day 10. Levels of susceptibility to laboratory (HIV-1BaL) and clinical strains of HIV-1 showed parallel kinetics, peaking at day 7 and then decreasing at days 10 to 14. The concordance of levels of HIV DNA and p24 antigen suggested that the changes in susceptibility with monocyte maturation were at or immediately after entry and correlated well with CCR5 expression and inversely with CXCR4 expression.

HIV infection of macrophages and pathogenesis of AIDS dementia complex: interaction of the host cell and viral genotype.

AIDS dementia complex (ADC) develops in only a third of HIV-infected patients who progress to AIDS. Macrophages and microglial cells are the major cellular sites of productive HIV replication in brain. Using 11 blood isolates of HIV from asymptomatic patients there was marked variation in tropism and the level of productive infection in recently adherent monocytes and monocyte-derived macrophages cultured in vitro. However, less variation was seen with 19 blood isolates from advanced HIV infection and 11 postmortem tissue isolates from brain, cerebrospinal fluid, spleen, and lung. Newly adherent monocytes expressed CCR5 in all seven patients tested, consistent with their susceptibility to infection but not explaining the above variability. There is, also marked regional variability in neuropathology in the brain of patients with ADC. We have demonstrated that there was marked variation in the V3 sequences of HIV clones from different regions of the cortex of a patient with ADC, suggesting independent evolution of HIV replication in brain. Furthermore, production of the neurotoxin quinolinic acid from HIV-infected macrophages varied, depending on the host and source of HIV isolate. Hence variations in viral genotype, production by infected macrophages, and subsequent toxin production may contribute to the variability in neuropathology between individuals and between different regions of the brain in the same individual.