Of the major autoimmune connective tissue diseases, Sjören's syndrome (SS) is perhaps the least w... more Of the major autoimmune connective tissue diseases, Sjören's syndrome (SS) is perhaps the least well understood. Both primary and secondary forms of SS occur, but their phenotypes are not well defined. No less than 10 sets of diagnostic/classification criteria for SS have been applied since 1965 (1–11), but none have been universally adopted or accepted by the American College of Rheumatology. These criteria have often identified patients with similar clinical features, but not necessarily with a common disease process. There is scant longitudinal data on SS. The absence of recognized classification criteria contributes to delays in diagnosis for individual patients and hampers research into SS due to small sample sizes and heterogeneously diagnosed patient populations. To address these issues, the ongoing Sjören's International Collaborative Clinical Alliance (SICCA) was funded under a US National Institutes of Health contract beginning in 2003. The SICCA project has the goals of 1) designing and implementing an international SS registry for collecting and storing clinical data and biospecimens; 2) developing standardized classification/diagnostic criteria for SS that are universally applicable; and 3) providing these resources for future studies of SS funded by the NIH or comparable agencies.
JAIDS Journal of Acquired Immune Deficiency Syndromes, 2008
To estimate oral disease prevalence among Zimbabwean women by HIV serostatus and CD4 cell count a... more To estimate oral disease prevalence among Zimbabwean women by HIV serostatus and CD4 cell count and to assess accuracy of oral disease diagnoses made by nurses as compared with an oral surgeon. Standardized oral mucosa examinations were performed by trained nurse-examiners and by an oral surgeon among women recruited in Harare, Zimbabwe. A total of 461 women (320 HIV-infected, 141 uninfected) were seen by nurses and an oral surgeon within a 2-week period. Oral candidiasis (OC) was the most common lesion diagnosed in nearly one quarter of HIV-infected women, whereas hairy leukoplakia and Kaposi sarcoma were found in <3%. The prevalence of OC diagnosed by nurses or the surgeon was significantly higher among women with a CD4 count <200 cells/mm than in women with a CD4 count from 200 to 499 cells/mm3 or a CD4 count >499 cells/mm3. The sensitivity of nurse examinations compared with examinations by the oral surgeon among HIV-infected women for the diagnosis of OC was 73%, the specificity was 95%, and the kappa-statistic was 0.71. OC was the most common lesion in HIV-infected women and was strongly associated with a low CD4 cell count. Interexaminer agreement was good for the diagnosis of OC among HIV-infected women. This study suggests that OC may play a role, in combination with other clinical indicators as a marker of disease progression in resource-poor settings.
A multicenter, double-blind, randomized, placebo-controlled clinical trial was conducted to deter... more A multicenter, double-blind, randomized, placebo-controlled clinical trial was conducted to determine the safety and efficacy of thalidomide for treating esophageal aphthous ulceration in persons infected with human immunodeficiency virus (HIV). Twenty-four HIV-infected patients with biopsy-confirmed aphthous ulceration of the esophagus were randomly assigned to receive either oral thalidomide, 200 mg/day, or oral placebo daily for 4 weeks. Eight (73%) of 11 patients randomized to receive thalidomide had complete healing of aphthous ulcers at the 4-week endoscopic evaluation, compared with 3 (23%) of 13 placebo-randomized patients (odds ratio, 13.82; 95% confidence interval, 1.16-823.75;
The epidemiology of HIV-related oral disease in industrialized nations has evolved following the ... more The epidemiology of HIV-related oral disease in industrialized nations has evolved following the initial manifestations described in 1982. Studies from both the Americas and Europe report a decreased frequency of HIV-related oral manifestations of 10-50% following the introduction of HAART (highly active antiretroviral therapy). Evidence suggests that HAART plays an important role in controlling the occurrence of oral candidosis. The effect of HAART on reducing the incidence of oral lesions, other than oral candidosis, does not appear as significant, possibly as a result of low lesion prevalence in industrialized countries. In contrast to other oral manifestations of HIV, an increased prevalence of oral warts in patients on HAART has been reported from the USA and the UK. HIV-related salivary gland disease may show a trend of rising prevalence in the USA and Europe. The re-emergence of HIV-related oral disease may be indicative of failing therapy. A range of orofacial iatrogenic consequences of HAART has been reported, and it is often difficult to distinguish between true HIV-related oral disease manifestations and the adverse effects of HAART. A possible association between an increased risk of oral squamous cell carcinoma and HIV infection has been suggested by at least three epidemiological studies, with reference to the lip and tongue. These substantial and intensive research efforts directed toward enhancing knowledge regarding the orofacial consequences of HIV infection in the industrialized nations require dissemination in the wider health care environment.
The envelope glycoprotein B (gB) coding sequences of two strains of human herpesvirus-(HHVG GS an... more The envelope glycoprotein B (gB) coding sequences of two strains of human herpesvirus-(HHVG GS and 229) were determined by sequencing a 2.5-kb open reading frame adjacent to the DNA polymerase sequence. The deduced primary translation product is 830 amino acids in length and is 964/o conserved between the two divergent strains with no localized hypervariability noted. It contains the expected signal and transmembrane sequence motifs as well as a putative site of protease cleavage. There was 39% amino acid identity with the gB of human cytomegalovirus (CMV, strain AD1 69). HHVG-CMV gB peptide homology was evident through the entire sequence, but was especially strong in the amino-terminal portion of CMV gp55, which contains linear and conformational epitopes recognized by CMV-neutralizing antibodies. All 10 cysteine residues of HHV6 gB match corresponding residues of CMV gB. Sequence data suggest strong structural similarity and possible immunologic cross-reactivity of gB from the two viruses. 523 0042.6822/92 $5.00
Gastroenterology Clinics of North America, Oct 1, 1988
Patients with HIV infection and AIDS frequently experience one or more oral lesions at some time ... more Patients with HIV infection and AIDS frequently experience one or more oral lesions at some time during the course of their disease. Recognition and management of these oral manifestations is an important component of AIDS care.
To test the hypothesis that the anti-apoptotic ability of Epstein-Barr virus (EBV) may result in ... more To test the hypothesis that the anti-apoptotic ability of Epstein-Barr virus (EBV) may result in altered expression of apoptosis-associated proteins in oral hairy leukoplakia (HL), we evaluated HL tissue and normal epithelium for these proteins by immunohistochemistry. Twenty formalin-fixed, paraffin-embedded specimens of HL lesions and six specimens of normal control mucosa were selected from archived tissue specimens. Bcl-2, Bcl-x, Bax and p53 apoptosis-associated proteins were evaluated in immunohistochemically stained tissue sections according to staining intensity and pattern. The percentage of p53-positive basal cells was estimated in sequential fields. Generally, there were only slight differences in the expression of Bcl-2 and Bcl-x proteins in the epithelium of HL and control tissue. The staining for Bcl-2 was weaker in keratinocytes than in putative melanocytes and Langerhans cells. Equivocal diffuse cytoplasmic staining of prickle cells was also noted. Keratinocytes throughout the epithelium stained positively for Bcl-x protein, although upper layers were more weakly stained. The 'balloon' keratinocytes in HL were infrequently positive for Bcl-x. Bax staining in HL differed from that in control tissue in being more heterogeneous. The staining reaction in HL was weak to negative in upper epithelial levels where 'balloon' keratinocytes were located. Weak to moderate nuclear p53 protein staining was detected in a mean of 25.3% of basal keratinocytes in all but one of the HL specimens; weak staining was seen in only two control specimens. We found only slight immunohistochemical evidence that expression of the apoptosis-associated proteins is altered in HL. p53 appears to over-expressed in HL; we speculate that this may be related to up-regulation or stabilization of wild-type p53 protein related to EBV infection.
... al., 1983; Kent et al., 1983; Rothstein et al., 1984a,b). Early studies in animals demonstrat... more ... al., 1983; Kent et al., 1983; Rothstein et al., 1984a,b). Early studies in animals demonstrated that bone bonds directly to hydroxylapatite without intervening fibrous tissue (Boyne and Szutz ... Thesam-ples were fixed in formalin, decalcified, and stained with he-matoxylin and cosin ...
Of the major autoimmune connective tissue diseases, Sjören's syndrome (SS) is perhaps the least w... more Of the major autoimmune connective tissue diseases, Sjören's syndrome (SS) is perhaps the least well understood. Both primary and secondary forms of SS occur, but their phenotypes are not well defined. No less than 10 sets of diagnostic/classification criteria for SS have been applied since 1965 (1–11), but none have been universally adopted or accepted by the American College of Rheumatology. These criteria have often identified patients with similar clinical features, but not necessarily with a common disease process. There is scant longitudinal data on SS. The absence of recognized classification criteria contributes to delays in diagnosis for individual patients and hampers research into SS due to small sample sizes and heterogeneously diagnosed patient populations. To address these issues, the ongoing Sjören's International Collaborative Clinical Alliance (SICCA) was funded under a US National Institutes of Health contract beginning in 2003. The SICCA project has the goals of 1) designing and implementing an international SS registry for collecting and storing clinical data and biospecimens; 2) developing standardized classification/diagnostic criteria for SS that are universally applicable; and 3) providing these resources for future studies of SS funded by the NIH or comparable agencies.
JAIDS Journal of Acquired Immune Deficiency Syndromes, 2008
To estimate oral disease prevalence among Zimbabwean women by HIV serostatus and CD4 cell count a... more To estimate oral disease prevalence among Zimbabwean women by HIV serostatus and CD4 cell count and to assess accuracy of oral disease diagnoses made by nurses as compared with an oral surgeon. Standardized oral mucosa examinations were performed by trained nurse-examiners and by an oral surgeon among women recruited in Harare, Zimbabwe. A total of 461 women (320 HIV-infected, 141 uninfected) were seen by nurses and an oral surgeon within a 2-week period. Oral candidiasis (OC) was the most common lesion diagnosed in nearly one quarter of HIV-infected women, whereas hairy leukoplakia and Kaposi sarcoma were found in <3%. The prevalence of OC diagnosed by nurses or the surgeon was significantly higher among women with a CD4 count <200 cells/mm than in women with a CD4 count from 200 to 499 cells/mm3 or a CD4 count >499 cells/mm3. The sensitivity of nurse examinations compared with examinations by the oral surgeon among HIV-infected women for the diagnosis of OC was 73%, the specificity was 95%, and the kappa-statistic was 0.71. OC was the most common lesion in HIV-infected women and was strongly associated with a low CD4 cell count. Interexaminer agreement was good for the diagnosis of OC among HIV-infected women. This study suggests that OC may play a role, in combination with other clinical indicators as a marker of disease progression in resource-poor settings.
A multicenter, double-blind, randomized, placebo-controlled clinical trial was conducted to deter... more A multicenter, double-blind, randomized, placebo-controlled clinical trial was conducted to determine the safety and efficacy of thalidomide for treating esophageal aphthous ulceration in persons infected with human immunodeficiency virus (HIV). Twenty-four HIV-infected patients with biopsy-confirmed aphthous ulceration of the esophagus were randomly assigned to receive either oral thalidomide, 200 mg/day, or oral placebo daily for 4 weeks. Eight (73%) of 11 patients randomized to receive thalidomide had complete healing of aphthous ulcers at the 4-week endoscopic evaluation, compared with 3 (23%) of 13 placebo-randomized patients (odds ratio, 13.82; 95% confidence interval, 1.16-823.75;
The epidemiology of HIV-related oral disease in industrialized nations has evolved following the ... more The epidemiology of HIV-related oral disease in industrialized nations has evolved following the initial manifestations described in 1982. Studies from both the Americas and Europe report a decreased frequency of HIV-related oral manifestations of 10-50% following the introduction of HAART (highly active antiretroviral therapy). Evidence suggests that HAART plays an important role in controlling the occurrence of oral candidosis. The effect of HAART on reducing the incidence of oral lesions, other than oral candidosis, does not appear as significant, possibly as a result of low lesion prevalence in industrialized countries. In contrast to other oral manifestations of HIV, an increased prevalence of oral warts in patients on HAART has been reported from the USA and the UK. HIV-related salivary gland disease may show a trend of rising prevalence in the USA and Europe. The re-emergence of HIV-related oral disease may be indicative of failing therapy. A range of orofacial iatrogenic consequences of HAART has been reported, and it is often difficult to distinguish between true HIV-related oral disease manifestations and the adverse effects of HAART. A possible association between an increased risk of oral squamous cell carcinoma and HIV infection has been suggested by at least three epidemiological studies, with reference to the lip and tongue. These substantial and intensive research efforts directed toward enhancing knowledge regarding the orofacial consequences of HIV infection in the industrialized nations require dissemination in the wider health care environment.
The envelope glycoprotein B (gB) coding sequences of two strains of human herpesvirus-(HHVG GS an... more The envelope glycoprotein B (gB) coding sequences of two strains of human herpesvirus-(HHVG GS and 229) were determined by sequencing a 2.5-kb open reading frame adjacent to the DNA polymerase sequence. The deduced primary translation product is 830 amino acids in length and is 964/o conserved between the two divergent strains with no localized hypervariability noted. It contains the expected signal and transmembrane sequence motifs as well as a putative site of protease cleavage. There was 39% amino acid identity with the gB of human cytomegalovirus (CMV, strain AD1 69). HHVG-CMV gB peptide homology was evident through the entire sequence, but was especially strong in the amino-terminal portion of CMV gp55, which contains linear and conformational epitopes recognized by CMV-neutralizing antibodies. All 10 cysteine residues of HHV6 gB match corresponding residues of CMV gB. Sequence data suggest strong structural similarity and possible immunologic cross-reactivity of gB from the two viruses. 523 0042.6822/92 $5.00
Gastroenterology Clinics of North America, Oct 1, 1988
Patients with HIV infection and AIDS frequently experience one or more oral lesions at some time ... more Patients with HIV infection and AIDS frequently experience one or more oral lesions at some time during the course of their disease. Recognition and management of these oral manifestations is an important component of AIDS care.
To test the hypothesis that the anti-apoptotic ability of Epstein-Barr virus (EBV) may result in ... more To test the hypothesis that the anti-apoptotic ability of Epstein-Barr virus (EBV) may result in altered expression of apoptosis-associated proteins in oral hairy leukoplakia (HL), we evaluated HL tissue and normal epithelium for these proteins by immunohistochemistry. Twenty formalin-fixed, paraffin-embedded specimens of HL lesions and six specimens of normal control mucosa were selected from archived tissue specimens. Bcl-2, Bcl-x, Bax and p53 apoptosis-associated proteins were evaluated in immunohistochemically stained tissue sections according to staining intensity and pattern. The percentage of p53-positive basal cells was estimated in sequential fields. Generally, there were only slight differences in the expression of Bcl-2 and Bcl-x proteins in the epithelium of HL and control tissue. The staining for Bcl-2 was weaker in keratinocytes than in putative melanocytes and Langerhans cells. Equivocal diffuse cytoplasmic staining of prickle cells was also noted. Keratinocytes throughout the epithelium stained positively for Bcl-x protein, although upper layers were more weakly stained. The 'balloon' keratinocytes in HL were infrequently positive for Bcl-x. Bax staining in HL differed from that in control tissue in being more heterogeneous. The staining reaction in HL was weak to negative in upper epithelial levels where 'balloon' keratinocytes were located. Weak to moderate nuclear p53 protein staining was detected in a mean of 25.3% of basal keratinocytes in all but one of the HL specimens; weak staining was seen in only two control specimens. We found only slight immunohistochemical evidence that expression of the apoptosis-associated proteins is altered in HL. p53 appears to over-expressed in HL; we speculate that this may be related to up-regulation or stabilization of wild-type p53 protein related to EBV infection.
... al., 1983; Kent et al., 1983; Rothstein et al., 1984a,b). Early studies in animals demonstrat... more ... al., 1983; Kent et al., 1983; Rothstein et al., 1984a,b). Early studies in animals demonstrated that bone bonds directly to hydroxylapatite without intervening fibrous tissue (Boyne and Szutz ... Thesam-ples were fixed in formalin, decalcified, and stained with he-matoxylin and cosin ...
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