Effect of salicylic acid and calcium on mitochondrial functions.

The rapid mitochondrial uptake of calcium followed by slow release in certain pathophysiological states associated with an increase in intracellular calcium, to normalize the cytoplasmic levels of free calcium, provides an important protective mechanism against calcium cellular toxicity. Salicylic acid, an in vivo metabolite of aspirin, inhibits the uptake and enhances the release of calcium by mitochondria, thereby increasing the levels of cytoplasmic free calcium. The Ca2+ induced mitochondrial swelling is enhanced in the presence of salicylic acid and in which turn leads to loss of biosynthesis of ATP. These results suggest that salicylic acid may promote cellular damage in pathophysiological states associated with increase in intracellular free calcium.

Pneumococcal bacteremia in Charleston County, South Carolina. A decade later.

Since nationwide surveillance for pneumococcal bacteremia in the United States is not done, community-based studies are useful alternative methods to monitor trends in this disease. Data on the incidence of pneumococcal bacteremia in Charleston County, South Carolina, from 1974 to 1976, have been used to support cost-effective pneumococcal vaccine programs for the elderly. We reevaluated the incidence of pneumococcal bacteremia in Charleston County in 1986 and 1987 to assess whether earlier estimates remained valid given changes in medical practice. During 1986 and 1987, overall annual incidence of pneumococcal bacteremia in Charleston County was 18.7 per 100,000 (95% confidence limits, 13.7 to 23.6 per 100,000), which represents a 2.3-fold increase over the earlier rate. The increase coincided with a 2.2-fold increase in the annual number of blood cultures processed at four Charleston County hospital laboratories from 1975 to 1987 despite only a 1.1-fold increase in the number of patients discharged from these hospitals. Annualized rates increased 2.3-fold for adults more than or equal to 65 years old to 53 per 100,000 and 4.6-fold for children less than 2 years old to 162 per 100,000. The case-fatality rate of bacteremic patients was 18%, compared with 21% in the earlier study. The case-fatality rate for adults more than or equal to 65 years of age was 44%. Ninety-one percent of adults 19 to 64 years old with bacteremia had underlying medical conditions for which pneumococcal vaccine is recommended; all persons 55 to 64 years old had at least one underlying condition. The marked increases in pneumococcal bacteremia rates detected are likely due to more routine culturing of blood from symptomatic patients with pneumococcal disease. These findings emphasize the need for effective programs promoting use of pneumococcal vaccine in high-risk groups, particularly those more than or equal to 65 years old, and the development of a more immunogenic vaccine for children less than 2 years old.

Reye syndrome: rate of oxidation of fatty acids in leukocytes and serum levels of lipid peroxides.

We examined the oxidation of different chain length fatty acids in the leukocytes and the quantity of lipid peroxides in the plasma of two Reye syndrome patients. We have found that the oxidation of [1-14C] octanoic acid in homogenates of leukocytes from one of the Reye syndrome patients was only 38 percent of the control, whereas oxidation of [1-14C] palmitic and [1-14C] lignoceric acid was slightly increased. The level of lipid peroxides in the serum of both of the Reye Syndrome patients was 4.42 and 3.04 times higher than the control level. These results suggest that impaired oxidation of medium chain fatty acids (octanoic acid) and higher levels of lipid peroxides may contribute to the pathogenesis of cellular toxicity in Reye Syndrome. Reye Syndrome (RS) was first described by Reye et. al. in 1963 and is now recognized as an important cause of morbidity and mortality in infants and children. The clinical course in RS consists of an antecedent viral illness with subsequent encephalopathy and hepatic dysfunction. Laboratory findings in RS include hypoglycemia, hyperammonemia, free fatty acidemia, elevated organic acids and amino aciduria. The ultrastructural findings in RS patients include changes in mitochondria, smooth endoplasmic reticulum morphology, and an increase in the number of peroxisomes. The elevation of serum free fatty acids in RS and their decrease in patients who improve clinically suggests a disturbance in fatty acid metabolism. To understand the role of free fatty acids in the pathogenesis of RS, we examined the levels of lipid peroxides in plasma and catabolism of fatty acids of different chain lengths in leukocytes from RS patients.

Bacteremia in Charleston County, South Carolina.

To describe the epidemiology of bacteremia in a large, well defined population, the authors reviewed medical records for residents of Charleston County, South Carolina, who had bacteria isolated from blood in the period 1974 to 1976. The incidence was 80 cases per 100,000 population per year. The most common organisms were Escherichia coli, Staphylococcus aureus, Klebsiella, and Streptococcus pneumoniae. The incidence was highest for neonates, infants, and those 70 years of age and older with annualized attack rates of 1,864,250, and 446 cases per 100,000 population, respectively. The incidence was 3.2 times higher for blacks than for whites and, within races, appeared to be independent of family income. Twenty-five per cent of patients had no clinically apparent focus of infection, 26% had urinary tract infection, and 17% had pneumonia. Thirty-nine per cent of cases were nosocomial, and 30% of patients died.

Successful immune reconstitution in severe combined immunodeficiency despite Epstein-Barr virus and cytomegalovirus infections.

Cytomegalovirus (CMV) and Epstein-Barr virus (EBV), frequently found in the acquired immune deficiency syndrome (AIDS), have been suspected of contributing to the latter immunodeficiency. The ability of normal HLA-identical sibling bone marrow to reconstitute an 8-month-old infant with severe combined immunodeficiency infected with these two viral agents is of interest. After presentation with severe mucocutaneous candidiasis, cavitary pulmonary disease, nodular cutaneous lesions, and hepatic abscesses containing acid-fast organisms, immunologic studies revealed lymphopenia, 1-3% T cells, and no lymphocyte responses to mitogens. Prior to transplantation, the infant's blood B lymphocytes grew spontaneously in culture, suggesting they were infected with EBV. Indeed, an appropriate antibody response to EBV was detected at 2 months post-transplantation. At 3 weeks postgrafting, neutropenia and cholestatic jaundice developed without other signs of graft versus host disease. Liver biopsy demonstrated CMV but no EBV by DNA hybridization. There was evidence of T- and B-cell function by 2 weeks postgrafting, including vigorous in vivo and in vitro responses to candida. Although the blood lymphocyte T4:T8 ratio was inverted at 2 weeks, it reverted to normal by 6 weeks post-transplantation. All clinical disease resolved by 8 months and karotyping revealed all T and B lymphocytes to be XX. Thus, despite infections with both CMV and EBV, complete immunologic reconstitution was achieved in this, the most severe of all genetically determined immunodeficiency conditions, arguing against these viruses having a major role in the failure of bone marrow transplantation in AIDS.

Role of neutrophil antigen NA1 in an infant with autoimmune neutropenia.

A nontransfused 14-month-old female infant was investigated for persistent neutropenia of eight months' duration, with absolute neutrophil counts ranging from 410 to 935 cu mm. The patient's sera reacted with neutrophils from her own peripheral blood, from normal donors, and from her mother, all these having the neutrophil antigen NA 1, but not with neutrophils from NA 1-negative donors, including the father. The autoantibody was detectable by capillary agglutination and by indirect immunofluorescence techniques but not by complement-dependent cytotoxicity. No antibody was found in the mother's serum. Studies on three occasions showed good correlation between the appearance of circulating autoantibody and the peripheral neutrophil counts. Our observations, together with previously published reports, suggest a possible relationship of NA 1 antigen and the disease susceptibility of NA 1-positive infants to autoimmune neutropenia.

Pneumococcal bacteremia in Charleston County, South Carolina.

To describe the epidemiology of pneumococcal bacteremia in a large population, this study reviewed medical records for residents of Charleston County, South Carolina, who had pneumococci isolated from blood cultures during the period 1974-1976. The overall incidence of documented pneumococcal bacteremia was 8.5 cases per 100,000 population per year. It was highest for those in the first two years of life (35 per 100,000 per year) and those in their sixties (21 per 100,000 per year). The incidence was more than five times higher in blacks than in whites and within races appeared to be independent of socioeconomic status or population density. Seventy-three per cent of the cases occurred in persons with another medical problem. These data on the incidence of documented pneumococcal bacteremia underestimate the true incidence of bacteremia to the extent that blood cultures were not performed under optimal circumstances for all persons with compatible clinical syndromes. The data suggest that certain groups would benefit from vaccination against pneumococcal disease if the vaccines are shown to be safe and effective for these groups.

Congenital dysgranulopoietic neutropenia: clinical, serologic, ultrastructural, and in vitro proliferative characteristics.

Six children with severe congenital neutropenia and repeated life-threatening infections were investigated by examining clinical features and myeloid cell ultrastructure, cytochemistry, and in vitro proliferation. Despite the presence of neutropenia, normal numbers of colony-forming cells (CFC) were present in blood and marrow specimens, and colony-stimulating activities (CSA) from blood cells and serum were normal or slightly increased in all patients. In vitro maturation of the progenitors to neutrophils was also uniformly present in the colonies. No patients had demonstrable antineutrophil antibodies or serum inhibitors of myelopoiesis. Serum lysozyme levels were normal. Ultrastructural and cytochemical studies of directly sampled marrow cells revealed several abnormalities in most neutrophilic myeloid cells from each of the patients consistent with an intrinsic myeloid precursor cell defect. These included (1) the defective synthesis or degeneration of primary granules, (2) an absence or marked decrease of secondary granules in the few late neutrophils observed in the bone marrow, and (3) the presence of autophagy. Phagocytosis of intact myeloid cells with subsequent degeneration was not observed; however, neutrophil debris was evident in phagocytic vacuoles of marrow macrophages. Our demonstration of ultrastructurally dysmorphic neutrophilic granulocytes, intramedullary cell lysis, normal stem cell numbers, and negative serology is comparable to similar observations of erythroid cells from patients with congenital dyserythropoietic anemia. We therefore hypothesize that the dysgranulopoiesis in these children results in neutropenia and propose the descriptive name congenital dysgranulopoietic neutropenia.

Primary amebic meningoencephalitis.

Primary amebic meningoencephalitis a rapidly fatal CNS infection caused by the free-living ameba Naegleria fowleri. The disease is acquired by swimming in fresh water and is being recognized with increasing frequency. Results of early diagnosis and treatment with amphotericin and other drugs suggest therapeutic optimism. Epidemiological surveys have shown the organism to be commonly present in fresh-water lakes in the warmer parts of the world. Prompt recognition and treatment is vital.

X-linked immunodeficiency with increased IgM: clinical, ethnic, and immunologic heterogeneity.

Two cases of immunodeficiency with increased IgM are reported. Patient 1 was a black male 3.5 years old who had recurrent pyogenic infections, failure to thrive, oral thrush, and systemic cryptococcal infection. Patient 2 was a 9-year-old white female who had recurrent cervical abscesses. Serum immunoglobulin determinations by radial immunodiffusion in both patients showed marked depression of IgG and IgA and marked elevation of IgM. A low molecular weight circulating monomeric IgM was demonstrated by immunoelectrophoresis and gel filtration in the second patient; this was not present in the first case. In vitro impairment of cellular immunity was observed in both patients. Administration of dialyzable leukocyte extracts (transfer factor) led to improvement of cell-mediated immunity in patient 1. The etiology of this syndrome apparently has several different genetic bases. These patients demonstrate heterogeneity in genetic, ethnic, immunologic, and other features of the syndrome.

Proteus mirabilis brain abscess in a neonate.

Occasionally a brain abscess has been observed in a neonate. This report presents a unique case of a septic infant who developed a proteus mirabilis brain abscess shortly after birth, which persisted undetected until 21/2 months of age.

Congenital neutropenia. Report of a case and a biorationale for dental management.

Congenital neutropenia is characterized by a marked decrease in or lack of circulating PMN's in children with no prior history of drug intake. The neutropenia is persistent and the clinical course is one of early onset of severe, recurrent, and eventually fatal infections. Bone marrow studies show a maturation arrest of neutrophilic precursors. Because of their greatly increased susceptibility to infection, patients with congenital neutropenia present a difficult dental management problem. A case of congenital neutropenia has been presented, as well as a biorationale for dental treatment. On the basis of reports in the literature, the following recommendations for the management of patients with congenital neutropenia are made: 1. The prevention and control of infection and the interception of dental disease before surgical intervention becomes necessary should be the overriding considerations in the management of patients with congenital neutropenia. 2. The carious breakdown of teeth should be prevented by the daily application of a 0.4 per cent stannous fluoride gel in addition to oral hygiene and limitation of sucrose intake. 3. Periodontal therapy should be palliative only, since alveolar bone loss is progressive despite frequent oral hygiene instruction and prophylaxis. The goal of periodontal therapy for patients with congenital neutropenia should therefore be a decrease in gingival inflammation to make the patient's mouth more comfortable and to slow down alveolar bone loss. Periodontal surgery is contraindicated. 4. Bacteremia and subsequent septicemia should be prevented since a minor infection can become life threatening in patients with congenital neutropenia. The patient should rinse for 30 seconds and the gingival sulci should be irrigated with a phenolated antiseptic mouthwash prior to all dental manipulations of the soft tissue. This will significantly reduce the incidence of bacteremia. 5. Surgery should be avoided if at all possible because of the high risk of post-operative infection. All surgery sholld be performed in the hospital, and the patient should be given antibiotics as determined by his physician. Primary closure should be done with fine polyglycolic acid sutures to reduce the chance of infection. If postoperative infection can be prevented, wound healing will progress normally despite the complete absence of PMN's.

Treating Pseudomonas cepacia meningitis with trimethoprim-sulfamethoxazole.

An infant with neonatal meningitis caused by Pseudomonas cepacia responded promptly to treatment with trimethoprim-sulfamethoxazole (Bactrim) after other abtibiotics had failed. Pseudomonas cepacia has proven to be resistant to most of the commonly used antibiotics.

Mucocutaneous lymph node syndrome.

Mucocutaneous lymph node syndrome represents a series of clinical findings that has been observed primarily in Japanese children. The disease now appears to be migrating to this country. It involves the cervical lymph nodes, the skin, and mucus membranes. Although the course is usually benign and self-limiting, a number of deaths have resulted from coronary artery disease.

Congenital neutropenia: neutrophil proliferation with abnormal maturation.

A child with congenital neutropenia was studied using bone marrow culture and ultrastructural and cytochemical techniques. The patient's marrow cells formed a large number of granulocytic colonies of normal size in culture, and her peripheral blood leukocytes produced adequate colony-stimulating factor. No serum inhibitors were identified. The patient's promyelocytes from direct marrow and culture appeared normal in ultrastructure, and primary granules, contained peroxidase and acid phosphatase activity. Myelocytes and rare segmented neutrophils from direct marrow specimens demonstrated atypical notched nuclei, myelin figures in Golgi lamellae and primary (azurophilic) granules, and no identifiable secondary (specific) granules. These data indicate an intrinsic neutrophil defect which allows normal proliferation of precursor cells, but results in abnormal granulogenesis and apparent inability to form secondary granules.