Transmyocardial laser revascularization combined with intramyocardial endothelial progenitor cell transplantation in patients with intractable ischemic heart disease ineligible for conventional revascularization: preliminary results in a highly selected small patient cohort.

OBJECTIVE: Transmyocardial laser revascularization for angina relief and intramyocardial autologous endothelial progenitor cell injection for neoangiogenesis may offer a new treatment strategy for patients with intractable ischemic heart disease. METHODS: Transmyocardial laser revascularization and intramyocardial injection of bone marrow-derived CD133+ cells was performed in six highly symptomatic patients. Transmyocardial laser channels were created and isolated CD133+ cells were injected intramyocardially. All patients were followed up for a minimum of 6 months postoperatively. RESULTS: One patient died shortly after the operation due to refractory heart failure. In the five survivors, CCS class improved as well as left ventricular ejection fraction. Left ventricular end-diastolic volume and myocardial perfusion varied between the patients. All patients described a considerable improvement in quality of life postoperatively. Repeated 24-hour Holter monitoring revealed no significant arrhythmias. CONCLUSIONS: In this small patient cohort, intramyocardial CD 133+ cell injection combined with transmyocardial laser revascularization led to an improvement in clinical symptomatology in all patients and in left ventricular function in 4 out of 5 patients, with an unclear effect on myocardial perfusion. Caution is advised when employing this therapy in patients with severely depressed left ventricular function.

Antiviral effect and ex vivo CD4+ T cell proliferation in HIV-positive patients as a result of CD28 costimulation.

Because stimulation of CD4+ lymphocytes leads to activation of human immunodeficiency virus-type 1 (HIV-1) replication, viral spread, and cell death, adoptive CD4+ T cell therapy has not been possible. When antigen and CD28 receptors on cultured T cells were stimulated by monoclonal antibodies (mAbs) to CD3 and CD28 that had been immobilized, there was an increase in the number of polyclonal CD4+ T cells from HIV-infected donors. Activated cells predominantly secreted cytokines associated with T helper cell type 1 function. The HIV-1 viral load declined in the absence of antiretroviral agents. Moreover, CD28 stimulation of CD4+ T cells from uninfected donors rendered these cells highly resistant to HIV-1 infection. Immobilization of CD28 mAb was crucial to the development of HIV resistance, as cells stimulated with soluble CD28 mAb were highly susceptible to HIV infection. The CD28-mediated antiviral effect occurred early in the viral life cycle, before HIV-1 DNA integration. These data may facilitate immune reconstitution and gene therapy approaches in persons with HIV infection.

Rates of p24 antigenemia and viral isolation in comparable white and black HIV-infected subjects. Military Medical Consortium for Applied Retroviral Research.

OBJECTIVE: To determine the relative frequencies of HIV-1 p24 antigen and culture positivity in white and black patients. DESIGN: Volunteers in the US military's HIV natural history study were 46% white, 44% black, 7% Hispanic and 3% other. Focusing on the comparable groups of whites and blacks, a retrospective analysis was performed of the results of virologic assays collected over a 2-year period. METHODS: p24 antigen was quantitated in sera with and without immune complex dissociation (ICD); viral isolation was performed by coculture of peripheral blood mononuclear cells. RESULTS: Results of the two virologic assays were very similar in the two racial groups, both overall and after stratification by CD4 cell count. As reported previously, the concentration of serum immunoglobulin G was found to be greater in black than white subjects. In contrast to results with ICD, sera tested without ICD resulted in differing (higher) rates of antigenemia in whites than blacks (P = 0.002). CONCLUSIONS: The frequencies of p24 antigen and culture positivity were found to be independent of race. Previously observed racial differences in antigen positivity were likely to be due to more extensive antibody binding in blacks than in whites.

Gentamicin and tobramycin Kinetics.

Eighty-two hospitalized adult patients were randomized to treatment with gentamicin or tobramycin. Serum levels were compared to computer-derived mathematically predicted levels to evaluate predictability of gentamicin and tobramycin serum levels. When comparable dosages were used mean peak gentamicin levels (4.87 micrograms/ml) did not differ from those after tobramycin (4.31 micrograms/ml). Seventy-three percent of patients had peak levels after gentamicin greater than 4.0 micrograms/ml compared to 46% after tobramycin. Factors purported to influence predictability of aminoglycoside serum levels were examined. In 46 of 74 patients whose actual body weight was 10 to 35 kg less than estimated ideal body weight levels after both drugs were lower than predicted. Serum levels were also lower than predicted in 7 of 11 patients with ascites, 6 of 7 patients receiving carbenicillin therapy, and 17 of 29 patients who had pneumonia. Neither hematocrit nor temperature appeared to influence predictability of serum levels. A comparison of methods used to obtain computer-derived predicted levels showed that ideal body weight provided the most accurate prediction. Differences between predicted and measured levels were established when calculations were based on actual body weight (P = 0.009) or on surface area (P = 0.003 for peak and 0.023 for trough levels).

Sources of variability in repeated T-helper lymphocyte counts from human immunodeficiency virus type 1-infected patients: total lymphocyte count fluctuations and diurnal cycle are important.

The study objective was to determine the causes and magnitude of absolute CD4 (T4) count variation in human immunodeficiency virus type 1 (HIV-1)-infected (+) adult males. We conducted a prospective, blinded, and controlled study of 22 adult military male outpatients, including 16 HIV(+) [12 in Walter Reed stage (WR-) 1 through 5, 4 in WR-6 (AIDS)], and 6 HIV seronegative (-) healthy controls. Ten CD4+ cell counts were drawn within a 3-day interval from each patient at the following times: 0800, 1200, 1600, and 2200 h on day 1; and 0800, 1200, and 1600 h on days 2 and 3. A significant CD4+ cell count diurnal increase of 59 cells/mm3 was detected between 0800 h and 2200 h from the WR-1-5 patients (p = 0.018), although this diurnal change was significantly blunted (p = 0.028) as compared with the 506 cells/mm3 CD4+ cell count diurnal increase observed from the HIV(-) healthy controls. The coefficients of variation [CV = (standard deviation/average) x 100] of the three daily 0800 h CD4 cell counts from each patient were 15 (median) and 19 (average) for the WR-1-5 patient group. Blood leukocyte counts, differential fractions of lymphocytes, and total lymphocyte counts contributed more to the observed CD4+ cell count variability than did the CD4% measurements [CV = 7.5 (median), 11 (average)] obtained from flow cytometry. We conclude that the large fluctuations that we observed in repeated CD4+ cell counts in HIV(+) patients can be explained in part by CD4+ cell count diurnal cycle and in part by high variability in total lymphocyte counts.(ABSTRACT TRUNCATED AT 250 WORDS)

Dermatologic manifestations of parasitic diseases.

The skin being exposed to the environment is commonly the portal of entry for parasites. Infections with parasites characteristically produce cutaneous lesions as well as systemic disease in humans. In the past, parasitic diseases were limited to their endemic areas. With the relative ease of worldwide travel, however, they are appearing with increasing frequency in the United States and other developed countries. This article describes the characteristic cutaneous findings of parasitic diseases that physicians in the United States may encounter in their medical practice.

Molluscum contagiosum. Ultrastructural evidence for its presence in skin adjacent to clinical lesions in patients infected with human immunodeficiency virus type 1. Military Medical Consortium for Applied Retroviral Research.

BACKGROUND AND DESIGN: Molluscum contagiosum in acquired immunodeficiency disease, although not life threatening, is often a marker of late-stage disease and may lead to disfiguring cutaneous lesions. Although most current therapy results in at least temporary clearing of individual lesions, lesions frequently recur and new lesions arise. Examination of hematoxylin-eosin-stained histologic sections in two patients showed changes suggestive of viral infection in the epidermis 0.5 cm and 1 cm lateral to obvious clinical lesions. These areas were clinically free of any lesions. Both routine histopathologic examination and ultrastructural examination were performed in two patients infected with human immunodeficiency virus type 1 (HIV-1) and three non-HIV-1-infected patients. RESULTS: All patients showed histologic changes diagnostic of molluscum contagiosum. In addition, the sections from HIV-1-infected patients showed areas of acanthosis, hyperkeratosis, and nuclear atypia. Electron microscopy of these areas revealed rare viral organisms in these areas. Similar acanthotic, hyperkeratotic areas were not seen in the biopsy specimens from the non-HIV-1-infected patients and no viral particles were found in the epidermis around the lesions. CONCLUSION: Viral structures consistent with molluscum contagiosum are present within the clinically normal epidermis around lesions of molluscum contagiosum in some HIV-1-infected patients. This may explain the large number of lesions seen in these patients and the difficulty in controlling the spread and recurrence of molluscum contagiosum in HIV-1-infected patients.

Iontophoresis of vinblastine into normal skin and for treatment of Kaposi's sarcoma in human immunodeficiency virus-positive patients. The Military Medical Consortium for Applied Retroviral Research.

BACKGROUND: Patients who test positive for human immunodeficiency virus type 1 (HIV-1) and who have disfiguring and/or painful cutaneous lesions of Kaposi's sarcoma (KS) may not be candidates for systemic chemotherapy and/or immunotherapy. Intralesional vinblastine sulfate, as a single-agent chemotherapeutic drug, has been used with some success to treat KS in patients who are HIV-1 positive. However, some patients may not tolerate the pain associated with injection of vinblastine. Transcutaneous iontophoresis of vinblastine was evaluated for therapy of KS in HIV-1-infected patients. Prior to therapy of patients, we iontophoresed vinblastine into the normal skin of volunteers who were not infected with HIV-1 to document the clinical and histologic features that occurred. OBSERVATIONS: Iontophoresis produced a localized erythematous papular eruption in non-HIV-infected volunteers but not in HIV-1-infected patients. Histologic changes in the biopsy specimens taken from non-HIV-infected volunteers consisted primarily of scattered necrotic keratinocytes and a mild to moderate superficial lymphohistiocytic infiltrate. Thirty-one lesions of KS were treated with partial to complete clearing and symptomatic improvement. CONCLUSION: Clinical and histologic features of iontophoresed normal skin suggest an immunologic mechanism of action. Iontophoresis of vinblastine for KS is well tolerated and results in symptomatic improvement as well as varying degrees of clearing of the lesions.

Inflammatory linear verrucous epidermal nevus in patients with positive results of tests for human immunodeficiency virus 1.

Inflammatory linear verrucous epidermal nevi are rare lesions that have many similarities to psoriasis on histologic examination, and are resistant to therapy. The two lesions reported occurred in patients with positive results of tests for human immunodeficiency virus 1 and showed features consistent with psoriasis. Results of tests for immunohistochemical markers were also consistent with previous findings and expected staining patterns in lesions of psoriasis. Our findings suggest that inflammatory linear verrucous epidermal nevi represent a clonal dysregulation in growth, probably secondary to an inflammatory stimulus. Since human immunodeficiency virus 1 has been associated with onset and exacerbation of psoriasis, perhaps this virus or another secondary infection associated with human immunodeficiency virus 1 infection could also play a role in the onset of this rare lesion.

Bacterial meningitis following Pantopaque myelography. A case report and literature review.

A case of acute bacterial meningitis following Pantopaque myelography is reported, and the literature reviewed pertaining to this uncommon but potentially fatal complication. A positive Gram's stain is most helpful in differentiating bacterial from chemical meningitis. Treatment of the meningitis before and after determination of its cause is described. Preventive steps include removal of Pantopaque from the subarachnoid space immediately at the conclusion of fluoroscopy, and observance of strict sterile technique during myelography, including use of face masks.