Release of some trace metals from disposable coils during hemodialysis.

In a previous study, we demonstrated that certain disposable coils are contaminated with zinc and release substantial quantities of zinc during hemodialysis, producing high postdialysis plasma zinc concentrations. The present investigation was undertaken to monitor plasma and dialysis fluid zinc and copper throughout dialysis and to estimate plasma zinc and copper uptake. Aluminum, cadmium, and lead release from coils was also determined. Venous plasma, arterial plasma, and coil chamber fluid were sampled periodically during dialysis; the trace metal concentrations were determined by flame atomic absorption spectrophotometry. Release of considerable quantities of zinc from the coils into the dialysis fluid, with uptake into the patient's plasma, was found. Approximately one-half of the plasma zinc uptake occurred within the first 45 min. Coils from different lots released significantly (p less than 0.001) different quantities of zinc. Plasma uptake of zinc ranged from 3.2 mg to 23.0 mg, with a mean (+/-SD) of 15.0 +/- 6.1 mg. Copper release and uptake was low. No detectable release of lead, cadmium, or aluminum was observed. The results suggest that zinc release from disposable dialysis coils should be assessed before recommending that hemodialysis patients receive zinc supplements.

Elevated plasma zinc concentrations in renal dialysis patients.

It has been suggested that hemodialysis patients might benefit from zinc supplements. However, little attention is given to the trace element content of renal dialysis fluids or to contamination of such fluids with trace metals. Pre- and postdialysis plasma copper and zinc concentrations of patients at two hospital dialysis units were measured by atomic absorption spectrophotometry. The plasma zinc concentration increased substantially in 34 of 37 patients as a result of dialysis. Measurement of dialysate zinc concentrations after primary source of zinc. Because of the possibility of zinc toxicity, zinc nutritional status should be carefully evaluated before recommending zinc supplementation for dialysis patients. Uremic patients dialyzed with certain disposable Cuprophan-membrane coils receive substantial quantities of zinc during dialysis; other Cuprophan-membrane coils tested released negligible quantities of zinc.

Zinc and immunocompetence in the elderly: baseline data on zinc nutriture and immunity in unsupplemented subjects.

Zinc nutriture and immune function were studied in 100 subjects, age 60-89 yr. Mean (+/- SD) zinc concentrations found were 84.8 +/- 15.5 micrograms/dL (13.0 +/- 2.4 microM) for plasma, 1.04 +/- 0.24 micrograms (0.016 +/- 0.004 mumol)/10(9) cells for erythrocytes, 4.06 +/- 1.85 micrograms (0.062 +/- 0.028 mumol)/10(9) cells for mononuclear cells, 3.91 +/- 1.77 micrograms (0.060 +/- 0.027 mumol)/10(9) cells for polymorphonuclear leukocytes, 0.53 +/- 0.39 micrograms (0.0081 +/- 0.0060 mumol)/10(9) cells for platelets, and 222 +/- 101 micrograms (3.39 +/- 1.54 mumol)/g for hair. Zinc ingestion was below the RDA in more than 90% of study subjects. The incidence of anergy to a panel of seven skin test antigens was 41%; responses to these antigens were significantly associated with the plasma zinc concentration. Subjects with depressed lymphocyte responses to mitogens had significantly lower platelet and significantly higher mononuclear cell zinc concentrations than those with normal responses.

Zinc and immunocompetence in elderly people: effects of zinc supplementation for 3 months.

One hundred and three apparently healthy elderly subjects age 60-89 y were randomly assigned to one of three treatments: placebo, 15 mg zinc/d, or 100 mg Zn/d for 3 mo. Plasma Zn was significantly increased only in the 100 mg Zn group. Zn concentrations in erythrocytes, platelets, mononuclear cells, and polymorphonuclear leukocytes were not significantly increased by any treatment. None of the treatments significantly altered delayed dermal hypersensitivity (DDH) to a panel of seven recall antigens or in vitro lymphocyte proliferative responses (LPR) to mitogens and antigens. Fifteen subjects had initially poor lymphocyte proliferative responses that improved in 14 of these individuals during the study; this was not due to Zn supplementation but might have been caused by one or more components of a vitamin-mineral supplement administered to all study subjects.

Status of selected nutrients and progression of human immunodeficiency virus type 1 infection.

BACKGROUND: Immune function is highly dependent on nutritional status because the large mass and high rate of cellular turnover of the immune system make it a major user of nutrients. Furthermore, nutrient requirements may be increased during acute and chronic infections, including HIV-1 infection. OBJECTIVE: The current study was designed to assess relations among HIV-1 progression and 11 nutritional and demographic variables. DESIGN: The participants were 106 HIV-infected outpatients and 29 uninfected control subjects (n = 89 men and 46 women; age range: 35-57 y). The HIV-infected subjects represented a broad range of disease progression. RESULTS: We found lower concentrations of plasma and erythrocyte magnesium and of erythrocyte reduced glutathione beginning early in the course of HIV-1 infection. Significantly decreased hematocrit and increased serum copper concentration developed only late in the course of the disease. Statistically significant univariate associations were found between the CD4(+) T lymphocyte count and hematocrit, plasma magnesium concentration, and plasma zinc concentration. The lowest erythrocyte magnesium concentrations occurred in HIV-infected subjects who consumed alcoholic beverages. Independent variables that were significant joint predictors of CD4(+) cell count in multiple regression analyses were hematocrit and plasma free choline and zinc concentrations. These 3 factors together explained 43% of the variability in CD4(+) cell counts. CONCLUSION: The results provide evidence that compromised nutritional and antioxidant status begin early in the course of HIV-1 infection and may contribute to disease progression.

Primary lymphoma of the central nervous system in children with acquired immunodeficiency syndrome.

Three children with acquired immunodeficiency syndrome and primary lymphoma of the CNS are described. All three children had clinical signs of focal mass lesions and progressive neurologic deficits. In one child the deterioration was extremely rapid. New lesions appeared on serial CT scans every few days, simulating an infectious process and leading to death within 3 weeks. Results of neuroradiologic studies in these patients demonstrated multicentric lesions that were often periventricular. On CT scans, the lesions were hyperdense before contrast and were enhanced with contrast medium. Double-dose delayed contrast CT scans and magnetic resonance imaging studies were more sensitive in indicating additional lesions. Histologically, all three tumors were B cell neoplasms; two lymphomas were large cell type, whereas one was small cell, noncleaved (Burkitt-like). Primary CNS lymphoma occurred with an incidence of 1/26 (4%) in our autopsy series and 3/100 (3%) of all pediatric cases of human immunodeficiency virus-type 1 infection, living and dead, that have been seen at the Children's Hospital of New Jersey. By comparison, opportunistic and reactivated latent CNS infections were less common in this same population and never appeared clinically as mass lesions. Therefore, in our experience, primary lymphoma is the most common cause of focal or multifocal mass lesions in the brains of children with acquired immunodeficiency syndrome. This tumor may be radiosensitive. In most cases, early biopsy is probably necessary to establish the diagnosis.

Neurologic manifestations of human immunodeficiency virus infection in children.

This report describes the neurologic manifestations of 36 children with human immunodeficiency virus (HIV) infection. In this cohort, in 16 of 21 children with acquired immunodeficiency syndrome (AIDS), three of 12 children with AIDS-related complex, and one of three asymptomatic seropositive children, a progressive encephalopathy developed. Neurologic signs were often detected early but tended to worsen coincident with progression of the immunodeficiency. The presence of progressive encephalopathy correlated with the absence of serum neutralizing antibodies to HIV and with a poor, usually fatal, outcome. The incubation period from initial HIV infection in the perinatal period to the onset of progressive encephalopathy varied from 2 months to 5 years. Intrablood-brain barrier synthesis of HIV-specific antibodies was demonstrated in eight of 14 children with AIDS and AIDS-related complex, indicating active brain infection with HIV. In three cases this was unassociated with progressive neurologic signs. Unique neuropathologic findings in children who died with HIV infection further suggest that the progressive encephalopathy is the result of primary and persistent infection of the brain with this retrovirus. These findings broaden the spectrum of HIV infection in children and have important implications for the development of antiviral therapy.

Older children and adolescents living with perinatally acquired human immunodeficiency virus infection.

OBJECTIVE: To describe the clinical, immunologic, and psychosocial characteristics of children living with perinatally-acquired human immunodeficiency virus (HIV) infection beyond the age of 9 years. METHODS: This is a descriptive cohort study of 42 surviving perinatally infected children older than 9 years followed at the Children's Hospital Acquired Immunodeficiency Syndrome (AIDS) Program (part of a university-based inner city medical center) as of June 1993. The study is based on medical record data of clinical, immunologic, and psychosocial parameters. RESULTS: The cohort includes 20 boys and 22 girls with a mean age of 136 months. The mean age at diagnosis of HIV infection was 88 months, and 59.5% were asymptomatic at the time of diagnosis. Currently, after a mean follow-up period of 48 months from diagnosis, 23.8% remain asymptomatic, 19.1% have non-AIDS-defining HIV-related symptoms, and 57.1% have AIDS; 85.7% of the cohort did not develop HIV-related symptoms until after 48 months of age (late-onset prolonged survivors). There was an average annual decline of 71.4 CD4+ cells/microL in the cohort from the ages of 7 to 16 years, and 21.4% have a current CD4+ lymphocyte count of greater than 500 cells/microL, 28.6% between 200 and 500 cells/microL, and 50% less than 200 cells/microL; 76% are orphaned as a result of maternal death, with the majority of the cohort (60%) cared for by extended family members. Disclosure of diagnosis has occurred in 57.1%. The vast majority of the cohort (76%) are attending regular school, with the remainder in special education. CONCLUSIONS: Although close to one quarter of the children and adolescents ages 9 to 16 years living with perinatally acquired HIV infection described in this cohort remain asymptomatic and have a relatively intact immune system, the remainder are living with significant HIV-related symptoms, many of which are chronic in nature and have an impact on daily living. The children in this cohort had both significant immunologic deterioration and symptomatic disease progression during the mean follow-up period of 48 months from the time of diagnosis with HIV infection.

Persistent human immunodeficiency virus type 1 antigenemia in children correlates with disease progression.

In a longitudinal study, human immunodeficiency virus type 1 (HIV-1) antigen (HIV-Ag) was measured in serum specimens from 54 children with HIV-1 infection followed for a median duration of 17 months. The persistent detection of free HIV-Ag in a group of 25 children was associated with clinical deterioration in 22 (88%) and a mortality of 52%, whereas the persistent nondetection of free HIV-Ag in a group of 18 children was associated with clinical deterioration in five (28%) and a mortality of 11% during the period of observation. Nine children had transient HIV-1 antigenemia and two children converted from HIV-Ag negative to positive during the study. Free HIV-Ag levels varied inversely with antibody reactivity to viral core proteins p24 and p17 determined by Western immunoblot, suggesting either the formation of immune complexes or a balance between viral expression and the host immune response. Five mother-infant pairs were studied for HIV-Ag expression in the perinatal period. In three of these pairs, both mother and infant were HIV-Ag negative, in one pair the mother had high levels of HIV-Ag and the infant was HIV-Ag negative. In the remaining mother-infant pair, the neonate became HIV-Ag positive but the mother was HIV-Ag negative prepartum and postpartum. These data suggest that HIV-Ag probably does not cross the placenta and that the detection of free HIV-Ag in the offspring of a HIV-1 infected mother most likely indicates viral infection.(ABSTRACT TRUNCATED AT 250 WORDS)

Lead poisoning--one approach to a problem that won't go away.

A reduction in sources of environmental lead exposure has resulted in substantial declines in mean blood lead concentrations of all age groups in the United States. However, some segments of the population continue to have unacceptable levels of lead exposure and elevated blood lead concentrations. In addition, virtually all residents of industrialized countries have bone lead stores that are several orders of magnitude greater than those of our preindustrial ancestors. Recent studies suggest that these skeletal lead stores adversely affect health and can contribute to reduced birth weights, aggressive behavior in children, and anemia, hypertension, and kidney disease in adults. Evidence is described that demonstrates that an increase in dietary calcium consumption can reduce lead absorption and toxicity from exogenous and endogenous lead exposure. A relatively inexpensive and effective way to reduce the substantial morbidity that will result from widespread lead exposure is by fortification of a variety of foods with low levels of calcium. This approach can complement other efforts to prevent lead exposure and reduce lead toxicity.

Dilated cardiomyopathy in children with acquired immunodeficiency syndrome: a pathologic study of five cases.

Clinicopathologic features with special reference to the heart are presented in five fatal cases of acquired immunodeficiency syndrome (AIDS) in children. Three children showed clinical evidence of cardiovascular compromise or congestive heart failure. Autopsy was performed in all cases. The enlarged heart showed biventricular dilatation with grossly unremarkable valves and coronary arteries and absence of mural thrombi. Microscopic examination of the heart revealed primarily myopathic abnormalities with hypertrophy of the myocardium and only rare foci of sparse inflammatory infiltrate. The pathogenesis of dilated cardiomyopathy in these children with AIDS is not known. Infection, immunologic factors, anemia, deficiency of nutritional factor(s), and longer survival may be related to the pathogenesis. Pediatricians should be alert to the possibility of cardiac involvement in pediatric AIDS.

Pathologic pulmonary findings in children with the acquired immunodeficiency syndrome: a study of ten cases.

Lung tissue and tissue from the lymphoreticular system obtained at open biopsy and/or autopsy were studied in ten children with the acquired immunodeficiency syndrome (AIDS). One or both parents of nine of the children had AIDS or risk factors for AIDS. The remaining child had hemophilia. The following pulmonary lesions were seen: 1) diffuse alveolar damage (DAD), 2) Pneumocystis carinii and/or cytomegalovirus pneumonitis, 3) lymphoid interstitial pneumonitis (LIP), and 4) desquamative interstitial pneumonitis (DIP). Combinations of such factors as mechanical ventilation, oxygen therapy, and opportunistic infection played a role in the pathogenesis of DAD. Opportunistic infections were related to the defective cell-mediated immunity in these children. The clinical, epidemiologic, immunologic, and pathologic features of the thymuses of these patients indicate that the immune deficiency was unlikely to have been of congenital origin. The immunologic abnormalities may also have been related to the pathogenesis of LIP and DIP. Neither LIP nor DIP has been described in adults with AIDS. Open lung biopsy is of practical importance in the diagnosis and treatment of pulmonary disease in children with AIDS.

Conduction system in children with acquired immunodeficiency syndrome.

Six children died of acquired immunodeficiency syndrome (AIDS), four of them females, ages 7 months, 13 months, 2 years 8 months, and 4 years; and two of them males, aged 2 1/2 and 7 years. They were born to IV drug-addicted parents. The conduction system (CS) and the entire heart were studied by serial section. In all cases the heart was hypertrophied and enlarged; one had total thrombotic occlusion of the right coronary artery with extensive infarction of the ventricular septum. Vascular changes also were found in all hearts, involving small arteries, arterioles, and venules. In the arteries, they involved the intima, media, and adventitia, and perivascular areas in a degenerative and inflammatory process. The elastic tissue was especially affected. A nonspecific myocarditis was present in four cases and epicarditis in all. Changes in the summit of the ventricular septum were present in four cases, consisting of increased fibrosis and arteriolosclerosis. The CS changes varied in location, showing either vasculitis, myocarditis, or fragmentation of the bundle with lobulation and fibrosis. The changes in the conduction system were not as severe as the changes in the surrounding myocardium. In one case the ECG was abnormal, showing left hemiblock. This corresponded to the finding of fibrosis, vacuolization of cells, and space formation in the left bundle branch.

Pregnancy complicated by heroin addiction.

During a 5-year time span, 118 addicted women gave birth to viable infants. These patients were subject to an increased incidence of complicating medical problems as well as many obstetric problems leading to maternal or fetal risk. The obstetrician should be aware of the possibility of addiction and its effects on pregnancy, and when possible, appropriate management should be initiated. Intensive care of the neonate must be begun as soon as possible.

Pathologic appraisal of the thymus gland in acquired immunodeficiency syndrome in children. A study of four cases and a review of the literature.

We studied the entire thymus gland by step-serial sections in four fatal cases of acquired immunodeficiency syndrome (AIDS) in children. The location, configuration, and blood vessels of the thymus gland were normal. The weight was reduced. There was severe depletion of both lymphocytes and Hassall's corpuscles. Because of the normal location, configuration, and blood vessels and the seemingly less severe lymphocytic depletion than is seen in congenital immunodeficiency syndromes and because of the clinical and epidemiologic features, we concluded that this syndrome in children represents AIDS. We postulated that the epithelial cells of the Hassall's corpuscles may be the primary site of thymic injury in AIDS.

Thymus biopsy in children with acquired immunodeficiency syndrome.

Thymic biopsy was done at the time of open lung biopsy in 11 children with acquired immunodeficiency syndrome (AIDS). Precocious involution, involution mimicking dysplasia designated as dysinvolution, and thymitis characterized by lymphomononuclear or plasmacytic infiltration, medullary lymphoid follicles, or medullary multinucleated giant cells were seen. Thymic biopsy is helpful in distinguishing AIDS from certain congenital immunodeficiency disorders. The three different types of thymic lesions may represent progression and/or different expressions of thymic epithelial injury in children with AIDS.

Congenital acquired immunodeficiency syndrome and congenital toxoplasmosis: pathologic support for a chronology of events.

We report a case of congenital acquired immunodeficiency syndrome (AIDS) with congenital opportunistic toxoplasmosis. The thymic histopathology was that seen in childhood AIDS cases and not that seen in primary congenital toxoplasmosis. The toxoplasma infection was selectively localized to the brain and the serum titers were paradoxically low as reported in most adult cases of AIDS with secondary infection by the parasite. These findings strongly suggest that the infection by the human immunodeficiency virus (HIV) preceded the toxoplasma infection in the fetus.

Plasma zinc and copper in primary and secondary immunodeficiency disorders.

Plasma copper and zinc concentrations were measured in 58 patients with a laboratory-confirmed primary or secondary immunodeficiency. Patients with severe combined immunodeficiency, collagen vascular disease with depressed cell-mediated immunity, and acquired or congenital acrodermatitis enteropathica had mean plasma zinc concentrations substantially below the lower limit of normal. In contrast, patients with primary humoral and polymorphonuclear leukocyte defects had normal plasma zinc concentrations. Patients with primary polymorphonuclear leukocyte defects had a mean plasma copper concentration substantially above the upper limit of normal. Those subjects with primary humoral immunity defects also had significantly elevated plasma copper concentrations in comparison to controls. Plasma copper concentrations in patients with severe combined immunodeficiency or acrodermatitis enteropathica were normal. Cutis laxa patients had low plasma zinc and copper concentrations. These data demonstrate that zinc and copper homeostasis are altered in come immunodeficiency disorders and may be important factors in host defenses. Since it is known that cellular immunity is impaired by zinc deficiency, patients with primary and secondary immunodeficiency states with appropriately documented mild or severe zinc deficiency should receive zinc supplements.

Blood product acquired HIV infection in children.

The medical community needs to ensure safety of blood and blood products. Blood bankers have instituted rigid criteria for exclusion of potential donors in high risk categories. Institution of HIV testing would appear to make blood products safer although the complete elimination of HIV contaminated blood and blood products may not be possible. The ELISA test is excellent for screening but misses approximately 1 in 200 (0.5%) HIV infected donors. Donor-screened, heat-treated factor VIII products appear to be quite effective in protecting the hemophilia population. However, we must continue to search for methodologies and techniques which will further guarantee blood product safety. The following methodologies have been suggested and warrant strong consideration: Vigilance in exclusion of potential high risk donors. Newer methodologies for retrovirus screening including the use of other surrogate markers. Institution of screening for HTLV-I and other retroviruses with attention to population surveillance for newer agents. Institution of cleaner methods of extracting specific blood components by monoclonal antibody techniques and DNA methodologies. For hemophiliacs, development of recombinant DNA products which by-pass the need for plasma derived clotting factors. It is predicted that such products should become available for use in about two years. In the interim, all clotting factors used should be donor-screened and virus-inactivated (by heat treatment, detergent washing and/or other newer methodologies). For the blood recipient, programs allowing for self donation prior to elective surgery and designated donors should be implemented. Although such programs may be logistically difficult, they should be given high priority.(ABSTRACT TRUNCATED AT 250 WORDS)