Association of circulating receptor Fc gamma RIII-positive monocytes in AIDS patients with elevated levels of transforming growth factor-beta.

Monocytes in the circulation of normal individuals express two receptors for the constant region of immunoglobulin, Fc gamma RI and Fc gamma RII. In contrast, we have observed that AIDS monocytes express significant levels of a third Fc gamma R, Fc gamma RIII (CD16), which is normally associated with activation or maturation of the monocyte population. By dual-fluorescence analysis using a monoclonal antibody specific for Fc gamma RIII (MAb 3G8), 38.5 +/- 3.2% of the LeuM3 (CD14)-positive monocytes in AIDS patients were CD16 positive as compared to 10.4 +/- 1.0% for healthy individuals (n = 29; P less than 0.005). Furthermore, AIDS monocytes expressed Fc gamma RIII-specific mRNA which is expressed minimally or not at all in control monocytes. As a recently identified inducer of Fc gamma RIII expression on blood monocytes, transforming growth factor-beta (TGF-beta) was found to be elevated in the serum and/or plasma of AIDS patients. Moreover, incubation of normal monocytes with AIDS serum or plasma induced CD16 expression which correlated with serum TGF-beta levels (r = 0.74, P less than 0.001) and was inhibited with a neutralizing antibody to TGF-beta. Thus, the increased CD16 expression on peripheral blood monocytes in AIDS patients may be the consequence of elevated circulating levels of the polypeptide hormone TGF-beta.

Flavimonas oryzihabitans (Pseudomonas oryzihabitans; CDC group Ve-2) bacteremia in the immunocompromised host.

Flavimonas oryzihabitans, known previously as Pseudomonas oryzihabitans, and a member of the Centers for Disease Control group Ve-2, is a gram-negative organism that has rarely been implicated as a human pathogen. Flavimonas oryzihabitans appears to be a soil and saprophytic organism that survives in moist environments and is indigenous to rice paddles. To our knowledge, only seven cases of human infection caused by this organism have been reported; they involved four patients with bacteremia and three patients with peritonitis who were receiving continuous ambulatory peritoneal dialysis. In this report, we describe three immunocompromised patients with catheter-associated bacteremia: a patient with cancer, a patient with acquired immunodeficiency syndrome, and a patient with sickle cell disease. There is emerging clinical evidence that F oryzihabitans should be recognized as an organism that is capable of causing human disease, particularly in immunocompromised patients and with the increased usage of permanent catheters.

Syphilitic hepatitis in HIV-infected patients: a report of 7 cases and review of the literature.

BACKGROUND: A recent resurgence of primary and secondary syphilis has been observed in certain population groups, particularly among persons infected with human immunodeficiency virus (HIV). Liver involvement is an infrequently recognized complication of early syphilis, with no previous reports among HIV-infected patients. METHODS: We describe 7 cases of syphilitic hepatitis in HIV-positive individuals and review the literature. RESULTS: At our institutions, all patients presented with a rash consistent with secondary syphilis. Each case was characterized by a conspicuous increase in serum alkaline phosphatase level (mean level +/- standard deviation, 905 +/- 523.6 IU/L) and milder elevations in serum transaminase levels. The mean CD4+ absolute T cell count was 317 cells/mm3, and the median rapid plasma reagin (RPR) titer was 1 : 128. There was a significant correlation between higher CD4+ cell counts and the RPR titers (R=0.93; P=.002). Symptomatic resolution and biochemical improvement, particularly a significant decrease in serum alkaline phosphatase levels (P=.02), occurred following antibiotic therapy. CONCLUSIONS: Hepatic dysfunction is not uncommon in HIV-infected persons and is attributable to multiple causes. In the appropriate clinical setting, syphilitic hepatitis is an easily diagnosed and reversible etiology of liver dysfunction. The recognition of this entity will prevent unnecessary evaluation of abnormal liver enzyme levels in HIV-positive patients.

Serum calcitonin precursors in sepsis and systemic inflammation.

High serum levels of the calcitonin (CT) prohormone, procalcitonin (pro-CT), and its component peptides occur in systemic inflammation and sepsis. Using two different assays, we undertook a prospective study to determine the utility of serum precalcitonin peptides (pre-CT) as markers in this condition. Twenty-nine patients meeting criteria for the systemic inflammatory response syndrome were studied daily in two intensive care units. Sera were collected, and APACHE II scores were determined until recovery or death. All patients had markedly elevated serum pre-CT. Prognostically, peak values were the most important. The highest values portended mortality, and a lower level could be ascertained below which all patients survived. Peak pre-CT levels were significantly higher in patients with infection documented by blood cultures than in those patients with no documented infection from any source (P < 0.05). Mature CT remained normal or only moderately elevated. Compared with the serum pre-CT levels, receiver operating characteristic curve analysis revealed that the APACHE II scores, although more cumbersome, were better overall predictors of mortality. Thus, pre-CT is an important serum marker for systemic inflammatory response syndrome and is predictive of outcome. It also provides data concerning the presence of severe infection and may prove to be clinically useful for proactive patient care.

Hemophilus influenzae septic arthritis in adults. A report of four cases and a review of the literature.

The clinical and diagnostic features of 29 adult patients with H. influenzae septic arthritis are reviewed. Twelve men and 17 women ranging in age from 22 to 82 years developed the infection. H. influenzae septic arthritis is an acute, febrile disease with a mean duration of symptoms before diagnosis of 4 days. Fifteen patients had monoarticular arthritis, 6 with an infected knee. Polyarticular involvement, with a range of 2 to 9 joints, was diagnosed in 14 patients. Nineteen patients had concurrent extraarticular sites of infection, including meningitis, pneumonia, pharyngitis, sinusitis, conjunctivitis, and cellulitis. Twenty-two of 29 patients had predisposing factors for infection, including ethanolism, trauma, rheumatoid arthritis, systemic lupus erythematosus, diabetes mellitus, splenectomy, multiple myeloma, lymphoma, gout, and acquired common variable hypogammaglobulinemia. Characteristic synovial fluid findings included purulent, greenish fluid, elevated WBC count, and gram-negative pleomorphic microorganisms. Treatment for these patients included antibiotic therapy, most often ampicillin and chloramphenicol, and joint drainage by repeated arthrocentesis or arthrotomy. A favorable outcome was reported in 25 of 29 patients. Hemophilus influenzae septic arthritis should be suspected in adults who are immunocompromised and have a concurrent extraarticular source of infection.

Exacerbation of dideoxycytidine-induced neuropathy with dideoxyinosine.

Dideoxycytidine (ddC) and dideoxyinosine (ddI) are nucleoside derivatives that exhibit antiretroviral activity against the human immunodeficiency virus (HIV). Both of these agents are under active investigation as potential therapies for patients with HIV infection. In addition, both drugs may be obtained for HIV-infected individuals who cannot tolerate zidovudine. A major focus of the research effort involving these agents has been to define their toxicities. Both agents may cause peripheral neuropathy. We wish to report a patient who developed severe neuropathy following the administration of ddI that was given shortly after the patient was removed from a clinical trial of ddI. The rapid development of toxicity indicates that this side effect is additive or synergistic for these agents.

Effect of lithium carbonate in HIV-infected patients with immune dysfunction.

Ten homosexual men received oral lithium carbonate at doses that maintained their serum lithium concentrations between 0.5 and 1.5 mEq/L. Prior to treatment all patients had HIV isolated from PHA-activated peripheral blood lymphocytes (PBLs) using a quantitative antigen-capture enzyme-linked immunosorbent assay (ELISA) assay for detection, and had an absolute number of CD4 (helper) lymphocytes of less than 300/mm3. Eight of 10 patients developed symptoms of drug toxicity requiring discontinuation of the drug in 7 patients. Two patients completed only 4-5 weeks of lithium therapy, and 5 patients received 7-8 weeks. All patients remained culture positive for HIV during the trial, and viral titers as measured by the antigen capture assay were unchanged or increased. There were no significant changes in the absolute number of CD4 lymphocytes, CD4/CD8 ratio, or phytohemagglutinin (PHA) or tetanus toxoid induced proliferative responses. There was a significant decrease in mixed lymphocyte reaction (MLR). Lithium carbonate demonstrated no immunorestorative or antiviral activity when given in therapeutic doses. Drug toxicity limited therapy in the majority of patients.

Clinical, virologic, and immunologic effects of combination therapy with ribavirin and isoprinosine in HIV-infected homosexual men.

We evaluated the clinical, immunologic, and virologic effects of oral treatment with ribavirin and isoprinosine for up to 3 months in asymptomatic, HIV-culture-positive homosexual men. Fifteen consecutive men received isoprinosine 4 g/day (1 g q.i.d.), and 800 (9 men) or 1,200 mg/day (6 men) of ribavirin. Five men in each ribavirin dosage group completed at least 2 months of treatment. No unexpected toxicities were observed. Eight minor HIV-related events occurred in six men while on study. All men remained HIV-positive, and time to positive culture decreased by at least 4 days in three men from each treatment group. Serum p24 levels did not change in two men who were p24 antigenemic and received 800 mg/day of ribavirin. Treatment was associated with a generalized lymphopenia affecting all lymphocyte subsets including CD4, which was partially reversible 1 month after stopping treatment. Most of the men remained anergic on DTHS skin testing. No improvements were noted in in vitro lymphoproliferative responses to antigens or in NK cell activity (which decreased significantly in the 1,200 mg/day ribavirin group). Although well tolerated at the doses employed, the combination of ribavirin and isoprinosine produced an unexpected generalized lymphopenia and did not exhibit HIV-suppressive or immunorestorative effects.

Prevalence of cardiac abnormalities in human immunodeficiency virus infection.

The prevalence of cardiac abnormalities in the spectrum of human immunodeficiency virus (HIV) infection is unknown. Sixty consecutive HIV-infected patients were studied using echocardiograms, electrocardiograms (50 patients) and ambulatory electrocardiographic monitoring (43 patients). Group A (25 patients) were seropositive but pre-AIDS, whereas group B (35 patients) had AIDS and included 24 with an active opportunistic infection (group B1) and 11 without it (group B2). Abnormalities were identified in 32 of 60 patients (53%) and were more frequent in group B (23 of 35, 66%) than in group A (9 of 25, 36%, p less than 0.05) but independent of active opportunistic infection (15 of 24, 62%, in group B1 vs 8 of 11, 73%, in group B2). Echocardiographic abnormalities were identified in 21 of 60 patients (35%), including 7 of 25 (28%) in group A vs 14 of 35 (40%) in group B (difference not significant), and 7 of 24 (29%) in group B1 vs 7 of 11 (64%) in group B2 (difference not significant). Those patients with an absolute CD4 lymphocyte count less than or equal to 100/mm3 had a higher prevalence of echocardiographic abnormalities (12 of 22) than those with CD4 counts greater than 100/mm3 (1 of 14, p less than 0.01). Left ventricular dilation or hypokinesis was identified in 14 of 60 patients (23%), including 4 of 25 (16%) in group A and 10 of 35 (29%) in group B. Electrocardiographic abnormalities were seen in 22 of 50 patients (44%) including 5 of 18 (28%) in group A and 17 of 32 (53%) in group B (difference not significant).(ABSTRACT TRUNCATED AT 250 WORDS)

Ultrastructural markers in circulating lymphocytes of subjects at risk for AIDS.

One hundred random lymphocytes in each of 168 buffy coat preparations from 59 subjects at risk for AIDS (50 homosexuals, 7 hemophiliacs, and 2 combined, all with T4:T8 ratios of less than or equal to 1.2) were screened for the presence of ultrastructural markers, "tubuloreticular structures" (TRS), and "test tube and ring-shaped forms" (TRF). Twenty-six (44%) of the subjects were TRS positive (71 specimens) and 12 (20%) were TRS/TRF positive (34 specimens). TRF were only observed in TRS-positive specimens. There was an inverse relationship between the incidence and abundance of markers and the T4:T8 ratios, i.e., mean T4:T8 +/- SE for TRS-negative, TRS-positive, and TRS/TRF-positive subjects were 0.59 +/- 0.05, 0.42 +/- 0.05, and 0.19 +/- 0.06, respectively. Markers were present for as long as 16 months before AIDS was diagnosed in four subjects and before the appearance of features suggestive of AIDS in two others. The assessment of TEM markers in peripheral blood lymphocytes is a simple method for screening at-risk subjects in whom AIDS is likely to develop.

Listeria monocytogenes sepsis and small cell carcinoma of the rectum: an unusual presentation of the acquired immunodeficiency syndrome.

A 26-year-old male homosexual initially presented with Listeria monocytogenes sepsis and a small cell carcinoma of the rectum. His subsequent course included esophageal candidiasis, Pneumocystis carinii pneumonia, and severe T-lymphocyte abnormalities on immunologic testing, consistent with the acquired immunodeficiency syndrome (AIDS). This represents the first case of AIDS associated with this unusual tumor and Listeria infection.

Thymosin in the early diagnosis and treatment of high risk homosexuals and hemophiliacs with AIDS-like immune dysfunction.

PIP: The adnormal levels of thymosin alpha 1 in acquired immunodeficiency syndrome (AIDS) patients, depressed T-cell function, thymus pathology, and the restoration of T-cell function by thymosin fraction 5 (TF5) lend support to the hypothesis that the thymus plays a central role in AIDS. The thymosin alpha 1 assay may provide a means of identifying symptomatic carriers of AIDS. This paper summarizes the current status of diagnostic studies with thymosin alpha 1 in AIDS and reports the 1st clinical trial with thymosin in subjects with AIDS-like immune dysfunction. Serum samples from intravenous drug abusers, homosexuals, and Haitians with AIDS have revealed thymosin alpha 1 levels at least 2 standard deviations from the mean of controls without AIDS. Preliminary data from a pilot study in homosexuals and hemophiliacs at high risk for AIDS suggest that the administration of TF5 may be effective in reconstituting some T-cell mediated specific immune functions, including cell-medicated lympholysis (CML) and the mixed lymphocyte response (MLR), and enhancing the lectin-induced production of T-cell growth factor. On the other hand, TF5 has failed to have any effects on the T4/T8 ratio, absolute lymphocyte counts, or natural killer cell activity.^ieng

Candida vertebral osteomyelitis: report of three cases and a review of the literature.

We have recently treated three patients with Candida vertebral osteomyelitis. In each patient there was at least one characteristic prodromal condition, including trauma, multiple antibiotics following bowel surgery, and acute nonlymphocytic leukemia. All patients were treated successfully with amphotericin B. Based on our findings and a review of the literature, we would recommend a 1.0-1.2 gm total dosage of amphotericin B. Alternative therapeutic choices such as 5FC and/or ketoconazole, under specific clinical conditions, have been successfully employed. However, cure can best be confirmed by post-treatment biopsy.

Peptococcaceae bacteremia.

Bacteremia with Peptococcaceae is an uncommon clinical manifestation of infection with this family of microorganisms. A 20-month review of 12 patients with bacteremic infections due to anaerobic gram-positive cocci revealed that obstetrical patients during the peripartum period constitute the group at greatest risk for the development of such infections. Eight of the 12 patients were young women hospitalized on the obstetrical service. Seven patients had postpartum endometritis and one patient had chorioamnionitis. The remaining four patients include a single patient each with pylephlebitis and microabscesses of the liver, ascending cholangitis, thoracic empyema, and necrotizing soft-tissue infection. Bacteriologic identification of the microorganisms revealed the following: Peptostreptococcus micros (5 patients), Peptostreptococcus asaccharolyticus (5 patients), Peptostreptococcus magnus (1 patient), and Peptococcus species (1 patient). Eleven of the 12 patients received appropriate antibiotic therapy. All patients did well and there were no major sequelae.

Paratyphoid orchitis.

A case of pyogenic orchitis due to infection with Salmonella enteritidis ser. Paratyphi B is discussed. Unlike previously reported cases of Salmonella orchitis, this patient developed infection by bacteremic spread and not by direct extension from the epididymis. Therapy with chloramphenicol resulted in an excellent clinical response.

Treatment of silastic catheter-induced central vein septic thrombophlebitis.

Two patients with surgically implanted right atrial silastic catheters for home hyperalimentation developed central vein septic thrombophlebitis. Initial treatment including removal of the catheter and antibiotic therapy was unsuccessful and both patients had persistent fever and bacteremia. A clinical and microbiologic response occurred when anticoagulation therapy with heparin was added to the treatment regimen. Although a surgical approach has been emphasized in patients with peripheral vein suppurative thrombophlebitis, anticoagulation therapy may be a useful alternative in the treatment of patients with central vein infection.

Diagnosis of intra-abdominal abscesses. A review.

Intra-abdominal abscess, resulting either from primary intraperitoneal disease or as a complication of surgery, remains a serious problem with high patient mortality if not treated early and adequately. The initial attempt at diagnosis rests on strong clinical evidence supported by nonspecific laboratory findings. The most helpful advance over conventional x-ray studies has been the advent of noninvasive imaging techniques such as ultrasonography or computed tomography. Radioisotopic scanning with gallium or indium makes possible a generalized survey of the peritoneal cavity, but only after a delay from the time of injection. Ultrasonography is somewhat limited in utility, particularly in the left subphrenic space, and CT scanning remains the technique with highest resolution. These noninvasive imaging techniques also have the potential for directed percutaneous catheter drainage.

Disseminated talc granulomatosis. An unusual finding in a patient with acquired immunodeficiency syndrome and fatal cytomegalovirus infection.

The association of disseminated magnesium silicate talc granulomatosis and acquired immunodeficiency syndrome is reported in a male homosexual who used intravenous drugs and who died of overwhelming cytomegalovirus (CMV) infection. Autopsy findings included widespread deposition of talc crystals in the lungs, liver, lymph nodes, bone marrow, and spleen. Typical CMV inclusions were seen in the lungs, kidneys, adrenal glands, gastrointestinal tract, and right eye. There was no evidence of malignancy. Analysis of peripheral blood neutrophil function revealed impaired chemotaxis and chemokinesis, but opsonophagocytosis had remained normal. The CMV infection in the small bowel was extensive and resulted in severe destruction of the muscularis propria and neural plexi, leading to marked dilatation and persistent diarrhea. The terminal course was marked by intractable hypotension, pneumonitis, and malnutrition, which could be attributed respectively to CMV involvement of the adrenal glands, lungs, and small bowel. The etiology and possible role of systemic talc granulomatosis in the development of immunosuppressive illness is reported herein.