Unusual Localisation for Onychomatricoma on the 5th Toenail: A Case Report and Review of the Literature.

Onychomatricoma is a rare and benign tumour of the nail matrix but originates rarely from the ventral portion of the proximal nail fold. This tumour is characterised by fingerlike projections that invade the nail plate. This lesion, of unknown aetiology, is typically asymptomatic with slow progression. Localisation on the finger is the most frequently described. We report the case of a 68-year-old woman who has an onychomatricoma in an unusual location, the fifth toe of the left foot. Due to its clinical appearance, the tumour can be confused with and treated as onychomycosis. However, if it is resistant to an oral antifungal well behaved treatment, one must consider onychomatricoma diagnosis.

Early and specific diagnosis of seropositivity to HIVs by an enzyme-linked immunosorbent assay using env-derived synthetic peptides.

We describe and evaluate the sensitivity and specificity of an enzyme-linked immunosorbent assay (ELISA) using a 22-amino-acid peptide corresponding to the carboxy-terminal end of HIV-1 gp120 and two 30-amino-acid long cyclic peptides including the two vicinal cysteines present on HIV-1 gp41 and on HIV-2 gp36. This test was evaluated. Data obtained with the Western blot (WB) and the peptide-based ELISA on a first panel composed of sera from 547 patients attending a specialized outpatient clinic (high-risk population) are in perfect agreement; moreover, 39 samples that had falsely been found positive with a viral lysate-based ELISA were not detected by peptide-based ELISA. The second panel was composed of 309 sera which were difficult to resolve using both WB and viral lysate-based ELISA. Using the peptide-based ELISA, 134 were found clearly positive and 173 clearly negative; only two were falsely positive. Finally, sera from 16 individuals examined at the time of seroconversion gave high absorbancy readings even if they were weakly reactive by WB (weak gp160 band). This test is thus highly sensitive and specific, and capable of detecting early seroconversion. It is also instrumental in clearly defining samples that are found indeterminate in the WB, and consequently it avoids the unnecessary follow-up required when a false-positive result is obtained using viral lysate-based ELISA.

A phase I/II dose-escalation study of herpes simplex virus type 1 thymidine kinase "suicide" gene therapy for metastatic melanoma. Study Group on Gene Therapy of Metastatic Melanoma.

We performed a dose-escalating phase I/II study of retrovirus-mediated herpes simplex virus type 1 thymidine kinase (HSV-1-TK) suicide gene therapy for metastatic melanoma. HSV-1 TK expression, which specifically sensitizes transduced and bystander cancer cells to ganciclovir (GCV) toxicity, was mediated by one (four patients, first dose step) to three (four patients, second dose step) injections of "M11" retrovirus vector-producing cells in melanoma cutaneous nodules. After a 7-day period allowed for cancer cell transduction, GCV was administered for 14 days. Safety was assessed by clinical and laboratory evaluations, and efficacy was assessed by tumor measurements and histology. M11 doses ranged from 76 to 1247 x 10(6) cells. Treatment-related adverse events were mild and transient, limited to inflammatory skin reactions at injection and fever on repeated injections. Plasma GCV was in the active range (>0.2 microg/ml); transgene was detected by polymerase chain reaction in three of six patients; treated tumor size was moderately affected under GCV as compared with untreated tumors, although 2 weeks after GCV administration important (>50%) treated-tumor necrosis was evidenced on histology in three of eight patients. All patients showed disease progression on long-term follow-up. Thus, M11-mediated HSV-1 TK gene therapy was well tolerated over a wide dose range. The limited tumor response is likely to be related to poor gene transfer efficiency. However, necrosis following GCV administration in transduced tumors indicates a potential for treatment efficacy.

Disseminated Penicillium marneffei infection associated with human immunodeficiency virus: a report of two cases and a review of 35 published cases.

Penicillium marneffei, a dimorphic fungus that is endemic in southeast Asia, causes deep-seated infection in humans and rodents. About 20 cases have been reported among the local populations of China, Thailand, and Hong Kong, and 35 cases have now been described in patients infected with the human immunodeficiency virus (HIV). We present a review of the literature and report two additional cases. Both immunocompromised and apparently immunocompetent hosts tend to develop disseminated, symptomatic infection. HIV-infected patients having travelled to southeast Asia and presenting with fever, skin lesions, hepatomegaly, adenopathies, or lung disease should be investigated for Penicillium marneffei infection. The diagnosis is based on the demonstration of the organism in clinical specimens. Treatment with amphotericin B or itraconazole is generally successful, but maintenance therapy is warranted for patients with an underlying immunodeficiency.

Low-rate emergence of thymidine analogue mutations and multi-drug resistance mutations in the HIV-1 reverse transcriptase gene in therapy-naive patients receiving stavudine plus lamivudine combination therapy.

OBJECTIVES: Mutations usually associated with zidovudine exposure have been observed in zidovudine-naive patients treated by stavudine in combination. These mutations were named thymidine analogue mutations (TAMs). This fact, combined with phenotypical and biochemical findings provided additional evidence for cross-resistance between zidovudine and stavudine. A recent genotypic study in naive patients receiving stavudine/didanosine combination showed emergence of TAMs and a multidrug-resistance mutation (MDR), Q151M, in 36 and 10% of cases, respectively. Stavudine plus lamivudine is one of the most used binucleoside associations in the antiretroviral combinations. The objective of this study was to assess the genotypic changes in the HIV-1 reverse transcriptase (RT) gene in antiretroviral-naive patients treated by stavudine plus lamivudine. METHODS: We analysed the RT gene of 44 HIV-1 patients, naive of antiretroviral therapy, who were treated for 24 or 48 weeks with stavudine/lamivudine. RESULTS: At the end of the follow-up, all patients acquired the lamivudine-associated mutation M184V. Only two subjects (4.5%) developed a TAM (T215Y; M41L), one subject developed a V75T/A mutation and one subject developed the particular MDR pattern F116Y, Q151M. CONCLUSIONS: Our study clearly demonstrated that naive subjects treated with stavudine/lamivudine for 24-48 weeks selected a low rate of TAMs and MDR Q151M. One hypothesis explaining these results could be the development of the M184V mutation.

Clinical and spectroscopic improvement in HIV-associated cognitive impairment.

To assess the impact of highly active antiretroviral therapy (HAART) on AIDS-associated cognitive impairment, 22 patients with AIDS with (n = 11) and without (n = 11) cognitive deficit were evaluated clinically and by MRS every 3 months for 9 months. Nineteen patients were on HAART at study entry, 21 after 2 months. Cognitively impaired patients presented with a subcorticofrontal deficit and decreased N-acetyl-aspartate in frontal white matter. These clinical and metabolic abnormalities reversed partially on HAART, whereas they remained within normal limits in cognitively unimpaired patients.

Capillary microscopy during eosinophilic fasciitis in 15 patients: distinction from systemic scleroderma.

PURPOSE: Eosinophilic fasciitis (EF) is a newly recognized syndrome that bears much discussion in regard to its distinction from progressive systemic sclerosis (PSS). In vivo microscopic examination of the nailbed capillaries has elicited the description of a characteristic vascular pattern seen in PSS dermatomyositis, and mixed connective tissue disease. To clarify the capillaroscopic aspects of this syndrome and to seek criteria distinguishing it from PSS, we performed nailbed capillary microscopy in 15 patients with EF and compared the results of this examination with those in 98 patients with PSS and those in 75 normal control subjects. PATIENTS AND METHODS: The diagnosis of EF was made in 15 patients aged 25 to 69 years (average 43 years) who had an acute course, with painful edema and subcutaneous sclerotic induration sparing the extremities. There was a peripheral hypereosinophilia in all 15 patients. Twelve underwent muscle or deep cutaneous biopsy, including the fascia. Nine of these had fascial thickening, and an inflammatory cell infiltrate was observed in eight. The diagnosis of PSS was made in 98 patients, according to the usual criteria. Seventy-five normal control subjects were examined. All the capillaroscopic examinations were performed by one observer. RESULTS: None of the patients in the EF group had a scleroderma-like capillaroscopic pattern. Thirteen had normal results of capillary microscopy. Two had a nonspecific organic microangiopathic picture. In the group of 98 patients with PSS, 89 had numerous megacapillaries (p less than 0.001), seven had a nonspecific organic microangiopathic pattern, and two had normal findings (p less than 0.001). In the whole group of 75 control subjects, the features were normal. CONCLUSION: Our results show a clear distinction between the results of capillary microscopy in cases of EF and PSS. The normal pattern in EF seems to be another argument for its differentiation from PSS.

Efficacy of intravenous gammaglobulin therapy in chronic refractory polymyositis and dermatomyositis: an open study with 20 adult patients.

PURPOSE: Polymyositis and dermatomyositis are inflammatory muscular diseases of unknown cause. Many interventions are available to treat patients with these conditions including corticosteroids, immunosuppressive drugs, plasmapheresis, and total body irradiation. However, these therapies are not always effective, and they may be associated with certain serious side effects. An attempt was made to evaluate the efficacy of polyvalent intravenous immunoglobulin (IVIG) in patients with polymyositis or dermatomyositis refractory to traditional treatment. PATIENTS AND METHODS: Twenty patients (16 women and 4 men; mean age 43 [16 SD] years), 14 with chronic refractory polymyositis and six with dermatomyositis, received high doses of IVIG because of the failure of traditional treatments (prednisone [19], methotrexate [10], azathioprine [6], cyclophosphamide [3], cyclosporine [3], chlorambucil [1], plasmapheresis [8], lymphopheresis [1], and total body irradiation [1]). In one patient with positive results on picornavirus serologic testing, IVIG was the first treatment choice. IVIG therapy was given with prednisone in 15 patients, with methotrexate in six patients, and with plasmapheresis in one patient. There were no changes in treatment in the 2 months before the introduction of IVIG therapy and no increases in dose during this treatment. Preparations of polyvalent human intravenous gammaglobulins with increased intact immunoglobulin G were used. Thirteen patients received 1 g/kg daily for 2 days each month, and seven patients received 0.4 g/kg daily for 5 days each month. The mean duration of treatment was 4 months. RESULTS: Clinical assessment, which consisted of the measurement of proximal muscle power, and biochemical studies were carried out before each treatment period. Significant clinical improvement was noted in 15 of the 20 patients. Mean muscle power estimated for the 20 patients before and after IVIG therapy was statistically significantly reduced (p less than 0.01). Eighteen patients showed biochemical improvement, and two patients with normal initial serum creatine kinase levels showed clinical improvement. Mean creatine kinase levels for the 20 patients during IVIG therapy showed a statistically significant decrease from the first IVIG perfusions (p less than 0.01). Side effects of IVIG therapy were noted in four patients; however, these effects were mild. During IVIG therapy, steroid doses were significantly reduced from the second or the third IVIG infusion (p less than 0.05). CONCLUSION: IVIG is an efficacious new therapy for polymyositis and dermatomyositis and should play a role in the treatment of these diseases, replacing or reducing steroid and immunosuppressive medications.

Relationship between anti-p24 antibody levels and p24 antigenemia in HIV-infected patients.

We studied the influence of HIV p24 antigen immune complexing with anti-p24 antibodies on the assessment of their respective levels in HIV-positive sera. ELISAs were used to evaluate anti-p24 antibody levels and p24 antigenemia, with or without acid dissociation. Observations include the following: (1) p24 antigenemia usually coexisted with low anti-p24 levels; (2) the p24 antigen concentration inversely correlated with anti-p24 antibody levels; and (3) acid dissociation increased the percentage of p24 antigen-positive sera, mostly when anti-p24 was low. In contrast, (1) antigenemia and antibodies varied independently in antiretroviral-treated AIDS patients, undetectable p24 antigen coexisting then with low anti-p24; (2) after acid dissociation, antigen was still undetectable in 83% of sera with high antibody levels, and in 20% with low antibody levels; and (3) acid dissociation did not increase low anti-p24 levels. Whereas the first set of observations indicates that p24 antigen and anti-p24 antibodies can be engaged in immune complexes, the second set indicates that p24 antigen and antibodies were not inevitably linked in such complexes: they may actually be indicative of two distinct biological phenomena.

Influence of age at infection on human immunodeficiency virus disease progression to different clinical endpoints: the SEROCO cohort (1988-1994). The Seroco Study Group.

METHOD: The influence of age at infection on progression of human immunodeficiency virus (HIV) disease to different clinical endpoints was studied among 393 HIV-seropositive adults selected from the French SEROCO cohort; follow-up lasted from January 1988 to November 1994. Selected patients had a known date of infection and were enrolled shortly after seroconversion. Age-associated risk ratios (RR) were estimated using the Cox model (age fitted as a continuous variable and RR expressed for each 10-year increment after adjustment for symptomatic primary infection and sexual preference). RESULTS: Age had a weak influence on progression from the date of infection to the first category B event (crude RR = 1.15; adjusted RR = 1.09; 95% confidence interval [CI]: 0.89-1.36) but a marked influence on progression from the first category B to the first category C event (crude RR = 1.95; adjusted RR = 1.97; 95% CI: 1.37-2.79). Similar results were obtained after adjustment for the CD4+ cell count at enrollment. A qualitative CD4+ cell defect could explain the influence of age, but this remains to be confirmed. CONCLUSION: Age at infection should be included in the definition of CD4+ cell count thresholds for clinical management and treatment initiation. Risk factors for progression should be assessed according to the different clinical endpoints.

[Cognitive disorders in AIDS: clinical, virological and neuroradiological features]. / Troubles cognitifs du SIDA: aspects cliniques, virologiques et neuroradiologiques.

HIV-associated neurocognitive disorders are mainly reported during the late stages of the disease, in deeply immunosuppressed patients Clinically, they present as a subcortical cognitive impairment, dominated by reduced psychomotor speed and memory deficit. Encephalic magnetic resonance imaging shows in most cases a diffuse leucoencephalopathy, and there is often a poor correlation between clinical status and neuroradiological findings. The diagnostic and prognostic value of HIV load in blood and cerebrospinal fluid is currently under investigation. Finally, the efficacy of new antiretroviral drugs on HIV dementia remains uncertain.

[Anonymous and free-of-charge detection of human immunodeficiency virus infection. 20-months' experience at a center]. / Dépistage anonyme et gratuit de l'infection par le virus de l'immunodéficience humaine. Expérience d'un centre pendant 20 mois.

The results of 20 months' activity of the anonymous and free-of-charge detection centre of the Pitié-Salpêtrière hospital group, Paris, concerning human immunodeficiency virus infection (HIV) are presented. During that period, 3,480 persons consulted and 3,332 anonymous questionnaires were filled and returned: 20.5 percent of the subjects were homosexuals, 6.5 percent were drug-addicts and 73 percent were non drug-addict heterosexuals; 31 percent used condoms. A total of 3,398 blood samples were collected; 232 sera were positive or undetermined for HIV-1 and/or HIV-2 by the ELISA method; 132 Western Blot tests confirmed the positivity for HIV-1 but not for HIV-2. The overall serum positivity was 4 percent; 18.3 percent of drug-addicts, 9.5 percent of homosexuals and 0.9 percent of heterosexuals were HIV positive. Among seropositive subjects, 51 percent were homosexuals, 27 percent were drug-addicts, 4 percent were homosexual drug-addicts and 18 percent were heterosexuals (43 percent of these had had multiple partners); condoms were used by 59 percent of HIV positive subjects. The percentage of HIV positive subjects in our series was lower than that estimated in populations at risk (drug-addicts 50 percent, homosexuals 32 percent); it was similar to the percentages found in other detection centres (5 to 6 percent). Most seropositive patients belong to the category of persons who are the first to be struck by HIV. The heterosexual population is relatively spared, but most of the recent seroconversions have occurred in this group.

[Oxidative stress in 29 HIV seropositive patients. Two-year results of a double-blind trial of diethyldithiocarbamate versus placebo]. / Stress oxydatif chez 29 sujets séropositifs. Résultats à 2 ans d'une étude en double insu diéthyldithiocarbamate versus placebo.

Among 29 seropositive subjects who had participated in the HIV 87 therapeutic trial (Mérieux laboratories), the oxidative stress was evaluated at 24 months in 16 treated with diethyldithiocarbamate (dithiocarb) and in 13 who had received the placebo. No significant difference was found between these two groups, whereas the existence of an oxidative stress has been confirmed in seropositive subjects compared with controls.

[Anonymous and free-of-charge centers for screening for HIV infection. Results of 30 months of activity in Public Assistance in Paris hospitals]. / Centres de dépistage anonyme et gratuit du VIH. Bilan de 30 mois de fonctionnement à l'Assistance publique--Hôpitaux de Paris.

The results of 30 months of activity of anonymous and free-of-charge HIV detection centres in Paris hospitals are presented. During this period (April 1988 to December 1990), 15805 subjects were seen. This population accounts for about 11 percent of all French anonymous and free detection centres in 1990, and for 26 percent of the number of subjects consulting in detection centres of the same type. Risk factors could be listed in 8132 consulting subjects: 73 percent were heterosexuals and not drug-addicts; 19.5 percent were homo- or bisexuals; 6 percent were drug-addicts; 0.6 percent were both homosexuals and drug-addicts; 29 percent of the 7806 persons questioned about their use of condoms stated that they used them often or always. A total of 15271 blood samples were taken. The percentage of seropositivity was 4.73 percent with a significant fall from 5.87 percent in 1988 to 4.38 percent in 1990; 23.4 percent of homosexual drug-addicts, 17.6 percent of heterosexual drug-addicts, 9.3 percent of homo- or bisexuals and 1.3 percent of heterosexuals were seropositive. In the seropositive population, 46.4 percent were homo- or bisexuals, 29.8 percent were drug-addicts, 19.7 percent were heterosexuals and 3.7 percent were homosexual drug-addicts. Three subjects had been contaminated by blood transfusion. The percentage of seropositive subjects in our study was superior to the mean found in other anonymous and free detection centres (4.73 percent versus 3 percent in 1990), this probably reflecting the high prevalence of the infection in the Paris region. The seropositive subjects usually belonged to the categories primarily affected by the HIV. The percentage of seropositivity in our drug-addicts (17.6 percent) was much lower than that usually reported in French drug-addicts (30 to 40 percent).