BACKGROUND:Cutaneous Leishmania major has affected many travelers including military personnel in Iraq and Afghanistan. Optimal treatment for this localized infection has not been defined, but interestingly the parasite is thermosensitive.METHODOLOGY/PRINCIPAL FINDINGS:Participants with parasitologically confirmed L. major infection were randomized to receive intravenous sodium stibogluconate (SSG) 20mg/kg/day for ten doses or localized ThermoMed (TM) device heat treatment (applied at 50 degrees C for 30 seconds) in one session. Those with facial lesions, infection with other species of Leishmania, or more than 20 lesions were excluded. Primary outcome was complete re-epithelialization or visual healing at two months without relapse over 12 months. Fifty-four/56 enrolled participants received intervention, 27 SSG and 27 TM. In an intent to treat analysis the per subject efficacy at two months with 12 months follow-up was 54% SSG and 48% TM (p = 0.78), and the per lesion efficacy was 59% SSG and 73% TM (p = 0.053). Reversible abdominal pain/pancreatitis, arthralgias, myalgias, headache, fatigue, mild cytopenias, and elevated transaminases were more commonly present in the SSG treated participants, whereas blistering, oozing, and erythema were more common in the TM arm.CONCLUSIONS/SIGNIFICANCE:Skin lesions due to L. major treated with heat delivered by the ThermoMed device healed at a similar rate and with less associated systemic toxicity than lesions treated with intravenous SSG.CLINICAL TRIAL REGISTRATION:ClinicalTrials.gov NCT 00884377.

The overlay removable partial denture (ORPD) is a treatment option for restoring the dentition of patients with significant loss of occlusal vertical dimension (OVD). 1 Graser G.N. Rogoff G.S. Removable partial overdentures for special patients. Dent Clin North Am. 1990; 34: 741-758 PubMed Google Scholar Articles on this topic have described the use of a provisional occlusal device (POD) to evaluate OVD in terms of function and esthetics. 2 Graser G.N. Rogoff G.S. Overdentures for acquired and congenital anomalies: 2. Partial overdentures. Int J Prosthodont. 1990; 3: 361-367 PubMed Google Scholar , 3 Keng S.B. Treatment of temporomandibular joint dysfunction with a visible light-cured resin overlay denture: a case report. Quintessence Int. 1996; 27: 105-109 PubMed Google Scholar , 4 Windchy A.M. Morris J.C. An alternative treatment with the overlay removable partial denture: a clinical report. J Prosthet Dent. 1998; 79: 249-253 Abstract Full Text Full Text PDF PubMed Scopus (27) Google Scholar , 5 Pavarina A.C. Machado A.L. Vergani C.E. Giampaolo E.T. Overlay removable partial dentures for a patient with ectodermal dysplasia: a clinical report. J Prosthet Dent. 2001; 86: 574-577 Abstract Full Text Full Text PDF PubMed Scopus (26) Google Scholar , 6 Del Castillo R. Lamar Jr., F. Ercoli C. Maxillary and mandibular overlay removable partial dentures for the treatment of posterior open-occlusal relationship: a clinical report. J Prosthet Dent. 2002; 87: 587-592 Abstract Full Text Full Text PDF PubMed Scopus (8) Google Scholar , 7 Ganddini M.R. Al-Mardini M. Graser G.N. Almog D. Maxillary and mandibular overlay removable partial dentures for the restoration of worn teeth. J Prosthet Dent. 2004; 91: 210-214 Abstract Full Text Full Text PDF PubMed Scopus (23) Google Scholar , 8 Sakar O. Beyli M. Marsan G. Combined prosthodontic and orthodontic treatment of a patient with a Class III skeletal malocclusion: a clinical report. J Prosthet Dent. 2004; 92: 224-228 Abstract Full Text Full Text PDF PubMed Scopus (6) Google Scholar , 9 Guttal S. Patil N.P. Cast titanium overlay denture for a geriatric patient with a reduced vertical dimension. Gerodontology. 2005; 22: 242-245 Crossref PubMed Scopus (14) Google Scholar In these reports the authors describe mounting the refractory cast and waxing the occlusal portion of the ORPD using a centric relation (CR) record. The POD was not directly used for articulation and fabrication of the ORPD.

To the Editor: Musher (March 27 issue)1 points out that adenoviruses have caused large outbreaks among military recruits, but additional comment is needed. Adenoviruses do cause epidemics in young adults.2–5 Before vaccination, adenovirus-associated acute respiratory disease affected up to 10 percent of recruits and was responsible for nearly 70 percent of respiratory disease.3 Implementation of an adenovirus-vaccination policy in the military in 1971 resulted in a dramatic reduction in the occurrence of adenovirus-associated acute respiratory disease, but the manufacturer stopped producing the vaccines in 1995.3 Since then, a substantial number of outbreaks of adenovirus infection have occurred.3–5 Administration . . .

The recommended treatment for cutaneous leishmaniasis is pentavalent antimony at a dosage of 20 mg/kg/day for 20 days. Some studies conducted in locales in which Leishmania is endemic have suggested that shorter courses of treatment may be as efficacious. We conducted a randomized, double-blind, placebo-controlled study of 10 versus 20 days of sodium stibogluconate (SSG) in United States military personnel who contracted cutaneous leishmaniasis while serving overseas; 19 patients received SSG for 10 days (and placebo for 10 days), and 19 patients received SSG for 20 days. Cure rates were 100% (19 of 19 patients) in the 10-day group and 95% (18 of 19 patients) in the 20-day group. Side effects were more common among patients who received 20 days of therapy. In this group of otherwise healthy young adults, SSG at a dosage of 20 mg/kg/day for 10 days appears to have been therapeutically equivalent and less toxic than the standard 20-day course.

We report the results of a longitudinal study of RNA splicing patterns in 31 early-stage human immunodeficiency virus disease patients with an average follow-up time of 3 years. Eighteen patients showed no evidence for disease progression, whereas 13 patients either showed a > or = 50% reduction in baseline CD4 count or developed opportunistic infections. Levels of unspliced, tat, rev, and nef mRNAs in peripheral blood mononuclear cells were measured by a reverse transcriptase-quantitative, competitive PCR assay. Viral RNA was detected in all patients at all time points. All 13 rapid progressors had viral RNA loads that were > or = 1 log unit greater than those of the slow progressors. In addition, seven of the rapid progressors showed a reduction of more than threefold in the ratio of spliced to unspliced RNA over the 3 years of follow-up. Conversely, two slow progressors with intermediate levels of viral RNA showed no splicing shift. These results confirm earlier observations that viral RNA is uniformly expressed in early-stage patients. We further show that cellular RNA viral load is predictive of disease progression. Importantly, the shift from a predominately spliced or regulatory viral mRNA pattern to a predominately unspliced pattern both is associated with disease progression and adds predictive utility to measurement of either RNA class alone.

Many reagents and techniques have been used for delayed-type hypersensitivity (DTH) skin testing in the evaluation of HIV-infected patients, resulting in varied interpretation of the utility of DTH skin testing in this population. We report the development of a simple algorithm for selection of DTH antigens and the clinical relevance of DTH skin testing in HIV disease. Antigens and concentrations for testing were first evaluated in a demographically matched, HIV-negative, immunologically healthy population. The testing scheme was then applied to the HIV population of interest for 5 years at several clinical sites. The antigens and concentrations selected resulted in 100% reactivity to two or more antigens in the HIV-negative cohort. Anergy is thus a distinct immunologic abnormality. Although some correlation (r2 = 0.6) of skin test reactivity and CD4 cell count was found in a cohort of HIV-infected individuals, anergy was found to be independently predictive of the development of symptomatic late-stage disease (Walter Reed Stage 6), AIDS, or death. This stepwise evaluation of skin testing and reagents has led to the modification of the skin testing protocol by defining the minimum number of antigens required and establishing the independent prognostic role of DTH skin testing in the evaluation of HIV-infected patients. The addition of mumps (40 CFU/ml), tetanus (1:10), and candida (1:10) to the purified protein derivative (PPD) skin test provides the critical controls to evaluate the status of PPD skin test in HIV-infected individuals as well as to provide a useful and prognostic clinical immunology evaluation.

Many reagents and techniques have been used for delayed-type hypersensitivity (DTH) skin testing in the evaluation of HIV-infected patients, resulting in varied interpretation of the utility of DTH skin testing in this population. We report the development of a simple algorithm for selection of DTH antigens and the clinical relevance of DTH skin testing in HIV disease. Antigens and concentrations for testing were first evaluated in a demographically matched, HIV-negative, immunologically healthy population. The testing scheme was then applied to the HIV population of interest for 5 years at several clinical sites. The antigens and concentrations selected resulted in 100% reactivity to two or more antigens in the HIV-negative cohort. Anergy is thus a distinct immunologic abnormality. Although some correlation (r2 = 0.6) of skin test reactivity and CD4 cell count was found in a cohort of HIV-infected individuals, anergy was found to be independently predictive of the development of symptomatic late-stage disease (Walter Reed Stage 6), AIDS, or death. This stepwise evaluation of skin testing and reagents has led to the modification of the skin testing protocol by defining the minimum number of antigens required and establishing the independent prognostic role of DTH skin testing in the evaluation of HIV-infected patients. The addition of mumps (40 CFU/ml), tetanus (1:10), and candida (1:10) to the purified protein derivative (PPD) skin test provides the critical controls to evaluate the status of PPD skin test in HIV-infected individuals as well as to provide a useful and prognostic clinical immunology evaluation.

HIV-infected individuals in both early and late stages of HIV disease were evaluated over 2 years to assess temporal trends and determinants of disease progression. The Walter Reed (WR) staging system was used to categorize patients into an early-stage cohort (WR Stages 1 and 2. N = 1183) and a late-stage cohort (WR Stage 5, N = 260) based on the initial clinical evaluation. Progression was defined as the occurrence of Stage 5 disease or beyond for the early cohort and Stage 6 disease or beyond for the late cohort. The cumulative incidence of progression was 15.7% (137 events) for the early-stage cohort, and 53.7% (85 events) for the late-stage cohort. Baseline CD4+ T lymphocyte (T4) count was the most significant marker of progression: 26% of WR Stage 1 or 2 patients with T4 lymphocytes below 500/mm3 progressed, compared with 12% with T4 lymphocytes at or above 500/m3. In late-stage individuals, 83% with T4 lymphocytes under 200/mm3 progressed, compared with 27% with T4 lymphocytes at or above 200/mm3. Older age was associated with progression in both early-and late-stage groups. Differences in the rates of disease progression were not significant between blacks and whites or between men and women. Two-year rates of progression among the late-stage patients dropped from 78 to 47% between 1986 and 1988. This contrasted with progression rates in the early-stage cohort, which remained stable: 18% for those entering follow-up in 1986 and 17% for those entering follow-up in 1988. These data indicate a significant slowing of HIV disease progression rates and mortality rates among individuals with late-stage disease that is temporally associated with the increased availability and use of therapies. With control of T4 lymphocyte count, age, and calendar time, neither gender nor race was significantly associated with progression in either early-or late-stage patients.

HIV-infected individuals in both early and late stages of HIV disease were evaluated over 2 years to assess temporal trends and determinants of disease progression. The Walter Reed (WR) staging system was used to categorize patients into an early-stage cohort (WR Stages 1 and 2. N = 1183) and a late-stage cohort (WR Stage 5, N = 260) based on the initial clinical evaluation. Progression was defined as the occurrence of Stage 5 disease or beyond for the early cohort and Stage 6 disease or beyond for the late cohort. The cumulative incidence of progression was 15.7% (137 events) for the early-stage cohort, and 53.7% (85 events) for the late-stage cohort. Baseline CD4+ T lymphocyte (T4) count was the most significant marker of progression: 26% of WR Stage 1 or 2 patients with T4 lymphocytes below 500/mm3 progressed, compared with 12% with T4 lymphocytes at or above 500/m3. In late-stage individuals, 83% with T4 lymphocytes under 200/mm3 progressed, compared with 27% with T4 lymphocytes at or above 200/mm3. Older age was associated with progression in both early-and late-stage groups. Differences in the rates of disease progression were not significant between blacks and whites or between men and women. Two-year rates of progression among the late-stage patients dropped from 78 to 47% between 1986 and 1988. This contrasted with progression rates in the early-stage cohort, which remained stable: 18% for those entering follow-up in 1986 and 17% for those entering follow-up in 1988. These data indicate a significant slowing of HIV disease progression rates and mortality rates among individuals with late-stage disease that is temporally associated with the increased availability and use of therapies. With control of T4 lymphocyte count, age, and calendar time, neither gender nor race was significantly associated with progression in either early-or late-stage patients.

Background. Despite multiple antiviral humoral and cellular immune responses, infection with the human immunodeficiency virus (HIV) results in a progressively debilitating disease. We hypothesized that a more effective immune response could be generated by post-infection vaccination with HIV-specific antigens.Methods. We performed a phase I trial of the safety and immunogenicity of a vaccine prepared from molecularly cloned envelope protein, gp160, in 30 volunteer subjects with HIV infection in Walter Reed stage 1 or 2. The vaccine was administered either on days 0, 30, and 120 or on days 0, 30, 60, 120, 150, and 180. HIV-specific humoral and cellular immune responses were measured; local and systemic reactions to vaccination, including general measures of immune function, were monitored.Results. In 19 of the 30 subjects both humoral and cellular immunity to HIV envelope proteins increased in response to vaccination with gp160. Seroconversion to selected envelope epitopes was observed, as were new T-cell proliferative responses to gp160. Response was associated with the CD4 cell count determined before vaccination (13 of 16 subjects [81 percent] with > 600 cells per milliliter responded, as compared with 6 of 14 [43 percent] with less-than-or-equal-to 600 cells per milliliter; P = 0.07) and with the number of injections administered (87 percent of subjects randomly assigned to receive six injections responded, as compared with 40 percent of those assigned to three injections; P = 0.02). Local reactions at the site of injection were mild. There were no adverse systemic reactions, including diminution of general in vitro or in vivo cellular immune function. After 10 months of follow-up, the mean CD4 count had not decreased in the 19 subjects who responded, but it had decreased by 7.3 percent in the 11 who did not respond.Conclusions. This gp160 vaccine is safe and immunogenic in volunteer patients with early HIV infection. Although it is too early to know whether this approach will be clinically useful, further scientific and therapeutic evaluation of HIV-specific vaccine therapy is warranted. Similar vaccines may prove to be effective for other chronic infections.

Eighty-two patients with audible clicking were evaluated and treated with splints made by using arthrographic assistance. In the course of this study, it became apparent that the later the opening click, the earlier the closing click. It was not always possible to auscultate or palpate either an opening or a closing click in many patients with arthrographic findings of disk displacement with reduction. Since the opening click was the only audible sound in some patients, clinical judgment alone cannot be used to replace the displaced disk at an optimal mandibular position. The elimination of the opening click does not always signify recapture of the disk. Maxillomandibular and incisal relationships limit the amount of protrusion possible to recapture the displaced disk.

Splint therapy for mandibular repositioning is an accepted method of treatment for patients with temporomandibular joint pain and dysfunction. An accurate method of registering the optimal mandibular position on the basis of meniscocondyle relationships depicted on arthrographs is described.

One leishmanial stock was isolated from a Phlebotomus duboscqi female captured in Baringo District, Kenya, and others from papular lesions that developed at sites where this sandfly had fed on a man. When characterized by cellulose acetate electrophoresis (eight enzymes examined), these isolates proved to be identical to known Leishmania major strains from man and a rodent (Arvicanthis sp.) and different from L. donovani and L. adleri, which also occur in Baringo. This is the first case of human cutaneous leishmaniasis caused by L. major reported from Kenya.

Diffuse cutaneous leishmaniasis is characterized by multiple nonulcerative skin lesions. Histologically, these lesions are dominated by vacuolated, heavily infected macrophages, with only a few lymphocytes present. A unique focus of diffuse cutaneous leishmaniasis is present in the Dominican Republic. We studied four patients with this disease. None had a delayed reaction to leishmanial antigen on skin tests. The total numbers of lymphocytes and T cells were normal. None of these patients had a lymphocyte-proliferation response to leishmanial antigens, although their responses to other antigens were normal. Adding indomethacin to cultures or decreasing the number of adherent cells by passage of cells over nylon wool reconstituted the lymphocyte responses to leishmanial antigens. Thus, our studies demonstrate that patients with diffuse cutaneous leishmaniasis have a selective anergy to leishmanial antigen, and that an adherent suppressor cell is one mechanism by which this selective immunosuppressive state is modulated.