Effect of pancreatic and leukocyte elastase on hydraulic conductivity in lung interstitial segments.

Elastase-induced changes in flow were used to quantify the degradation of lung interstitial elastin. Degassed rabbit lungs were inflated with silicon rubber via airways and vessels. The lungs were cut into 1-cm-thick sections. Two chambers were bonded to each section to enclose the interstitium surrounding an arterial segment. Flow of albumin solution (0-5 g/dl) between the chambers was followed by that of the albumin solution with 0.25 g/dl pancreatic elastase solution. Driving pressure was 5 cmH(2)0, and mean interstitial pressure was either 0 or 10 cmH(2)O. Elastase caused an increase in flow in approximately 70% of the interstitial segments and a reduction in flow in the remaining segments. The elastase-induced response in flow was independent of both albumin concentration and mean interstitial pressure. Leukocyte elastase (5 units/dl) produced flow responses similar to those of 0.25 g/dl pancreatic elastase. The increased flow of leukocyte elastase was reduced by a subsequent flow with 0.25 g/dl pancreatic elastase but enhanced by a subsequent flow with a 10-fold lower concentration. A change in the order of the elastase flows reversed the concentration-dependent responses. This behavior suggests a complex interaction among the interstitial fibers after degradation by pancreatic and leukocyte elastase. Endogenous elastase-induced increases in interstitial permeability might affect blood-lymph barrier permeability, whereas elastase-induced cessation of flow might be related to the alveolar septal wall destruction observed in emphysema.

Effect of concentration and hyaluronidase on restriction of hetastarch flux through lung interstitial segments.

The transport properties of lung interstitium were studied by measuring the flow of hetastarch solution (2 and 6%) through 1-cm perivascular interstitial segments of rabbit lungs. Hetastarch (10(4)-10(7) Da) solution has a colloid osmotic pressure similar to that of albumin solution. Driving pressure was 5 cm H(2)O and mean interstitial pressure was 0 cm H(2)O. The flows of 2 and 6% hetastarch solutions were measured before (Q(1)) and after (Q(2)) the addition of 0.02% hyaluronidase. Hetastarch molecular distributions in effluent samples were measured by high-performance size-exclusion chromatography (HPSEC) to determine sieving ratio (C(out)/C(in), downstream-to-upstream concentration ratio). Hyaluronidase significantly (P < 0.0004) increased flow sixfold, but the increase in flow (Q(2)/Q(1)) was reduced through the interstitium around smaller vessels. A similar behavior was observed with the flow of albumin solution without and with hyaluronidase. C(out)/C(in) decreased monotonically with molecular weight, was greater with 6% than with 2% (low colloid osmotic pressure) hetastarch, and increased with hyaluronidase. Modeling the transport through uniform pores, equivalent pore radius was 10 and 15 nm with 2 and 6% hetastarch, respectively, and doubled with hyaluronidase. In conclusion, interstitial pores expand in response to an increase in colloid osmotic pressure both before and after tissue degradation by hyaluronidase.

Biliary giardiasis in a patient with human immunodeficiency virus.

A 41-year-old man with human immunodeficiency virus (HIV) (CD4 count, 446/mm3) developed a protracted course of abdominal pain, weight loss, and increasing liver function tests after undergoing a metronidazole treatment regimen for Giardia enteritis. Three months later, endoscopic retrograde cholangiography (ERCP) showed dilated common and intrahepatic bile ducts and luminal irregularities of the common bile duct. Seven months after the onset of his acute diarrhea, a repeat ERCP with aspiration demonstrated many Giardia trophozoites and cysts in the bile and continued structural abnormalities consistent with cholangiopathy. A 10-day course of high-dose intravenous metronidazole did not resolve these signs or symptoms. A gallbladder ultrasound showed a thickened wall. Laparoscopic cholecystectomy led to resolution of abdominal pain and normalization of serum alkaline phosphatase over an 8-month period. Gallbladder histopathology revealed chronic cholecystitis, but no parasites were seen on hematoxylin and eosin staining or with Giardia antigen enzyme immunoassay testing of the gallbladder. The patient refused to undergo a follow-up ERCP, but a right upper quadrant ultrasound and computed tomography of the abdomen were normal.

Selective serotonin reuptake inhibitors and isoniazid: evidence of a potential adverse interaction.

BACKGROUND: Recognizing a potential interaction between isoniazid (INH), a weak monoamine oxidase inhibitor, and serotonin reuptake inhibitors (SSRIs), we assessed medication discontinuation rates in human immunodeficiency virus-infected individuals taking an SSRI, INH, or both. METHOD: We retrospectively reviewed treatment records to determine if patients on an SSRI, INH, or both completed drug therapy in accordance with a treatment plan (e.g., 12 months of INH therapy). Patients on both medications constituted the study group; patients taking either an SSRI or INH alone constituted comparison groups. RESULTS: There were no significant differences between the groups based on age, gender, CD4%, or CD4 count. Seven of the 10 patients (70%) in the study group discontinued therapy, which was significantly greater than the 2 of 14 (14%) in the SSRI group (P = 0.01) and the 4 of 18 (22%) in the INH group (p = 0.02) who discontinued therapy. CONCLUSION: Medication discontinuation rates for patients prescribed an SSRI coincident with INH were significantly higher than for individuals prescribed these medications separately. These differences cannot be accounted for on the basis of age, gender, or CD4%, but they may be attributable to increased side effects caused by interactions between these medications.

Inferior vena cava compression due to massive hydronephrosis from bladder outlet obstruction.

A 71-year-old man presented with acute urinary retention due to benign prostatic hyperplasia and was found to have computed tomography-documented mechanical obstruction of the inferior vena cava (IVC) due to massive hydronephrosis. Obstruction of IVC flow promptly resolved after bladder decompression.

Cutaneous leishmaniasis following local trauma: a clinical pearl.

Cutaneous leishmaniasis is acquired from the bite of an infected sand fly and can result in chronic skin lesions that develop within weeks to months after a bite. Local trauma has been implicated as a precipitating event in the development of skin lesions in patients who have been infected with Leishmania species. Here we report a case series and review the literature on patients who developed cutaneous leishmaniasis after local trauma, which may familiarize clinicians with this presentation.

Antibody-dependent cellular cytotoxicity in HIV type 1-infected patients receiving VaxSyn, a recombinant gp160 envelope vaccine.

Antibody-dependent cellular cytotoxicity (ADCC) activity was measured in 60 human immunodeficiency virus (HIV-1)-infected patients receiving a recombinant gp160 (rgp160) envelope protein of HIV-1(NL4-3) in alum and 64 receiving placebo over a 5-year study period. There was no difference in the percentage of ADCC responders when comparing rgp160-immunized patients (mean, 78.4%) with those receiving placebo alone (mean, 81.5%) at any time point examined. Patients were further divided into progression groups regardless of their vaccine status. ADCC activity was somewhat higher in rapid than in slow-progressing groups, although the number that had detectable ADCC activity was equivalent in each group. ADCC activity of sera from rapid- and slow-progressing groups against primary or laboratory isolate envelopes was similar. This study showed that transcription with rgp160 did not appear to enhance HIV-specific ADCC activity. ADCC activity did not appear to correlate with protection against AIDS in this cohort of HIV-1-infected people.

Immunohistochemistry to identify Leishmania parasites in fixed tissues.

The definitive diagnosis of leishmaniasis currently depends on the identification of characteristic amastigote morphology in tissue, or isolation of promastigotes by culture. Histopathological identification can be difficult, and is variably sensitive; culture is considered "the gold standard", but is not uniformly diagnostic or available. In this study, we compared light microscopic immunohistochemistry (IHC) using a monoclonal anti-Leishmania antibody (G2D10) to standard hematoxylin and eosin (H&E) stain in the diagnosis of Leishmania on skin. Sixty-one archived specimens from patients suspected of being infected with Leishmania were used; 41 of these had leishmaniasis confirmed by culture. Although not statistically significant, both sensitivity and specificity were higher for IHC compared to H&E: 51% (95% CI: 35-67%) compared to 42% (CI: 26-58%; 2p=0.29) for sensitivity, and 100% (CI: 83-100%) compared to 85% (CI: 62-97%, 2p=0.25) for specificity, respectively. Furthermore, because organisms could be diagnosed by IHC at low power (x20-40), this assay was more rapid than H&E, in which parasite morphology could best be identified at oil immersion power. The G2D10 antibody has broad Leishmania species recognition, and offers promise as a simple, rapid diagnostic screen for leishmaniasis. Further study is underway to better characterize this antibody.

The United States military and leishmaniasis.

Leishmaniasis occurs not only in American travelers and military personnel alike but infects a significant portion of the world's population. The US military has made major contributions to the understanding of the complicated epidemiology of this parasite, the development of rapid reliable diagnostic tests, and to the development of safe, more efficient, and more effective treatment of leishmaniasis.

Safety and efficacy of intravenous sodium stibogluconate in the treatment of leishmaniasis: recent U.S. military experience.

The efficacy and toxicity of sodium stibogluconate (SSG) at a dosage of 20 mg/(kg.d) for either 20 days (for cutaneous disease) or 28 days (for visceral, mucosal, or viscerotropic disease) in the treatment of leishmaniasis is reported. Ninety-six U.S. Department of Defense health care beneficiaries with parasitologically confirmed leishmaniasis were prospectively followed for 1 year. One patient was infected with human immunodeficiency virus; otherwise, comorbidity was absent. Clinical cure occurred in 91% of 83 cases of cutaneous disease and 93% of 13 cases of visceral/viscerotropic disease. Adverse effects were common and necessitated interruption of treatment in 28% of cases, but they were generally reversible. These included arthralgias and myalgias (58%), pancreatitis (97%), transaminitis (67%), headache (22%), hematologic suppression (44%), and rash (9%). No subsequent mucosal leishmaniasis was identified, and there were no deaths attributable to SSG or leishmaniasis.

Herpes zoster and lymphopenia associated with sodium stibogluconate therapy for cutaneous leishmaniasis.

A review of 84 patients with cutaneous leishmaniasis treated with sodium stibogluconate (Pentostam) at our institution revealed that three had developed herpes zoster during or shortly after receiving therapy. Because zoster has been associated with depressed cellular immunity, we prospectively followed serial lymphocyte subpopulations in eight patients with cutaneous leishmaniasis who received Pentostam. By day 7 of therapy, the white blood cell count had fallen by a median of 1.15/mm3, the total lymphocyte count by a median of 804/mm3, and the CD4+ lymphocyte count by a median of 306/mm3 (67% of baseline; confidence interval, 52%-78%). An in vitro cell-viability assay demonstrated that Pentostam is not toxic to human mononuclear cells. The administration of Pentostam for the treatment of cutaneous leishmaniasis results in lymphopenia that may be related to the subsequent occurrence of herpes zoster.

Lytic vertebral lesions: an unusual manifestation of AIDS-associated Kaposi's sarcoma.

The differential diagnosis of neovascular skin lesions in patients with AIDS includes Kaposi's sarcoma and bacillary angiomatosis. It has been suggested that the radiographic presence of lytic bone lesions in association with these skin lesions supports a diagnosis of bacillary angiomatosis. We present a case of disseminated Kaposi's sarcoma in which evidence of lytic vertebral disease was seen on computed tomography; the histopathologic characteristics of the osseous lesions are described. Findings of magnetic resonance imaging implied more diffuse marrow involvement. Human immunodeficiency virus-associated osseous manifestations of rochalimaea infection and Kaposi's sarcoma are reviewed.

Systemic sporotrichosis treated with itraconazole.

Amphotericin B is recommended for the treatment of systemic infection caused by Sporothrix schenckii. However, this agent is toxic, its use is frequently followed by relapse, and some isolates of S. schenckii are resistant. Recent studies suggest that newer azole compounds, such as itraconazole, are effective in cutaneous and lymphocutaneous sporotrichosis, but data on their efficacy in systemic infections are scarce. We used itraconazole in the sequential treatment of six patients with systemic sporotrichosis: three with bone and joint disease and three with disseminated infection manifested by subcutaneous nodules. In all six cases, symptoms and signs of infection improved, with resolution of subcutaneous nodules, normalization of imaging studies, cessation of wound drainage, and return of joint mobility and function. No toxicity was noted. One patient with disseminated infection had a relapse while receiving 100 mg of itraconazole daily. The average duration of follow-up was 18 months. Thus itraconazole appears promising for the treatment of systemic sporotrichosis. A dose of at least 200 mg/d appears to be needed to prevent relapse.

Posterior subcapsular cataracts associated with megestrol acetate therapy.

Megestrol acetate, used for eight weeks as an appetite stimulant in a man infected with human immunodeficiency virus, was associated with the development of bilateral posterior subcapsular cataracts. We propose that the glucocorticoid properties of megestrol were contributory. Complicating this association, the patient developed cytomegalovirus retinitis approximately six weeks after the cataracts were recognized.

Predictors of HIV-1 disease progression in early- and late-stage patients: the U.S. Army Natural History Cohort. Military Medical Consortium for Applied Retrovirology.

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/mm3. 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.

Immunization of owl monkeys with a recombinant protein containing repeated epitopes of a Plasmodium falciparum glycophorin-binding protein.

A Plasmodium falciparum glycophorin binding protein (GBP-130) has been implicated in protective immunity to malaria. The gene for GBP-130 encodes a protein containing 11 tandemly repetitive 50 amino acid units. We report an immunization trial in Aotus monkeys using a recombinant DNA protein containing three of these 50 amino acid repeats. When administered with aluminum hydroxide, this antigen induced low levels of antibodies that reacted with the recombinant protein by ELISA and with parasite antigens in immunoblot and immunofluorescence assays, but not by immunoprecipitation. When administered with Freund's complete adjuvant, this antigen induced high levels of antibodies that reacted in ELISA, immunoblot, immunofluorescence, and immunoprecipitation assays. Serum from immunized monkeys did not inhibit parasite growth, and protection from intravenous challenge with P. falciparum-infected erythrocytes was not observed in any experimental group. These results suggest that the repetitive region of GBP-130 is not a useful vaccine candidate.