Sensory motor neuropathy associated with AIDS.

Clinical, laboratory, and pathologic observations in six patients with sensory motor peripheral neuropathy associated with the acquired immunodeficiency syndrome (AIDS) are presented. Blood and urine testing failed to reveal other causes for peripheral neuropathy. Distinctive CSF findings included elevated human immunodeficiency virus-specific indices. Peripheral nerve pathology confirmed the results of electrodiagnostic studies and revealed axonal loss and demyelination. Epineurial and endoneurial mononuclear infiltrates were present in three patients, and in one with early neuropathy, retroviral-like particles were present in peripheral nerve axoplasm. The findings indicate that in some patients with AIDS, neuropathy may be the direct result of a viral insult, although the causes are likely multifactorial.

The effect of Pseudomonas aeruginosa cytotoxin and toxin A on human polymorphonuclear leukocytes.

After exposure to cytotoxin or toxin A of Pseudomonas aeruginosa, the ultrastructure of resting and phagocytosing human polymorphonuclear leukocytes (PMNL) and of cells of P. aeruginosa strain 1348A was studied by transmission (TEM) and scanning (SEM) electronmicroscopy, and by light microscopy (LM) after histochemical staining of cytoplasmic granules. Cytotoxin caused marked clumping and destruction of PMNL, pyknotic nuclear changes with bleb formation, and release of cytoplasmic granules; phagocytosis was markedly diminished. In contrast, after exposure to toxin A, PMNL phagocytosed actively, but their cytoplasmic pseudopodia were markedly irregular and their nuclei pyknotic. Colloidal-gold-labelled cytotoxin showed an affinity for the cytoplasmic membranes, nuclei and granules of PMNL. Cytotoxin had no apparent effect on cells of P. aeruginosa strain 1348A but there was polar separation of the cytoplasmic membrane in bacteria exposed to toxin A. Cytotoxin and toxin A appear to be important in the pathogenesis of infections caused by P. aeruginosa.

Comparison of the effect of three adrenal corticosteroids on human granulocyte function against Pseudomonas aeruginosa.

The effect of hydrocortisone, methylprednisolone, and dexamethasone on the phagocytic and bactericidal capabilities of normal human granulocytes (PMN) was studied under previously described optimal conditions for Pseudomonas aeruginosa, PA 1348A. At hydrocortisone and methylprednisolone concentrations of 1,000 micrograms/ml, delayed phagocytosis was clearly observed, whereas dexamethasone 400 micrograms/ml had no effect on phagocytosis. The bactericidal effect of PMN on PA 1348A was significantly reduced by all three corticosteroids at highest concentrations (p less than 0.05). However, the effect of methylprednisolone was greatest and that of dexamethasone was least evident, 25% and 10% reduction in PMN bactericidal activity, respectively. Following exposure to the highest concentrations of corticosteroids, TEM observations correlated well with the PMN functional assays. While the observations of PMN and bacteria in controls, hydrocortisone, and dexamethasone preparations were similar, evidence for incomplete phagocytosis, lack of vacuole coalescence, minimal disruption of bacterial cell walls, and dividing bacteria in phagosomes were evident in methylprednisolone preparations. These PMN functional and TEM observations suggest that of the three corticosteroids studied, methylprednisolone appears most deleterious to the PMN phagocytic and bactericidal activity.

Benign monoclonal IgAK gammopathy associated with polyneuropathy and dysautonomia.

The first case of benign IgAK monoclonal gammopathy associated with peripheral neuropathy is described. Dysautonomia is an unusual, yet prominent, manifestation of neuropathy in this patient. Electrodiagnostic testing and nerve biopsy were compatible with demyelination and axonal loss. Myelin sheath, perineural, and endoneural interstitial tissue fixation of anti-IgA and anti-kappa light chains was demonstrated by direct immunofluorescence microscopy. Absorption studies utilizing human peripheral nerve myelin resulted in complete removal of the paraprotein band. Analytic procedures with myelin-associated glycoprotein and gangliosides, however, were negative. Based on these findings, an alternative etiology for this neuropathy is hypothesized.

Effects of Pseudomonas aeruginosa cytotoxin on human serum and granulocytes and their microbicidal, phagocytic, and chemotactic functions.

The effect of Pseudomonas aeruginosa cytotoxin on human granulocytes (PMNs) and pooled human serum was studied by hemacytometer counts, phagocytic, bactericidal, and chemotaxis assays, and by transmission electron microscopy. The optimal assay conditions for phagocytosis of 75Se-labeled P. aeruginosa 1348A included 20% pooled human serum and a ratio of one PMN to between 10 and 20 bacteria. For the bactericidal assay, 20% pooled human serum and a ratio of one PMN to between one and five bacteria were used. Chemotaxis of PMNs was studied by agarose gel technique with 10(-7) M f-Met-Leu-Phe or 0.01 to 35 micrograms of cytotoxin per ml as a chemoattractant. The degree of PMN destruction was dependent on cytotoxin concentrations and PMN exposure time to cytotoxin. Virtually complete PMN lysis was observed after a 2-h exposure to 6 to 10 micrograms of cytotoxin per ml. PMN exposure to 2 micrograms of cytotoxin per ml for as long as 2 h had no adverse effect on phagocytosis. PMN exposure to greater than or equal to 4 micrograms of cytotoxin per ml for 2 h demonstrated a significant decrease in the percentage of bacteria killed. The results of experiments designed to separate cytotoxin effect on PMN lysis from the effect on PMN bactericidal capacity showed that there is an effect of cytotoxin on PMN bactericidal function. PMN exposure to 4 micrograms of cytotoxin per ml for 30 min caused a significant decrease in PMN migration. Cytotoxin had no chemoattractant qualities or effect on pooled human serum as studied by chemotaxis and phagocytosis assays. Although a cytotoxin concentration of greater than or equal to 2 micrograms/ml was required to demonstrate PMN ultrastructural changes observed in transmission electron microscopy studies, at a concentration of 0.1 microgram/ml, cytotoxin caused an impairment in the integrity of the PMN membrane, allowing a low-molecular-weight substance (ruthenium red) to enter into the cytoplasm. Cytotoxin may be an important factor in the pathogenesis and in the high mortality rate of patients with P. aeruginosa infections.

Hairy-cell leukemia: induction of complete remission with pentostatin (2'-deoxycoformycin).

Two men with advanced but previously untreated B cell hairy-cell leukemia were treated with low doses of pentostatin (2'-deoxycoformycin) in intermittent courses. There was prompt clearance of hairy cells from the blood, regression of splenomegaly and lymphadenopathy, and correction of anemia, thrombocytopenia, and granulocytopenia. Side effects were tolerable and myelosuppression was not observed. Both patients achieved complete remission documented by bone marrow aspiration and biopsy and radionuclide scans of liver and spleen. They remain in complete remission nine and six months, respectively, after their last treatment. Pentostatin (Warner-Lambert, Ann Arbor, Mich) is highly active in hairy-cell leukemia and merits more extensive evaluation in this disease. A woman with hairy-cell leukemia has begun treatment with pentostatin, and at ten weeks there is disappearance of gross splenomegaly and clearance of hairy cells from the blood. Bone marrow studies have not yet been repeated.

The spleen: a correlative overview of normal and pathologic anatomy.

The human spleen, an organ of unique anatomic and functional importance, is the largest component of the reticuloendothelial system, with direct interposition between systemic and portal circulation, and yet the morphologic correlates of its various functions remain somewhat mysterious. The contributions of transmission and scanning electron microscopy to the understanding of splenic structure have been considerable. They have helped clarify the three fundamental sites of structural alteration and specialization that are defined and discussed: 1) the white pulp with its two variable components--the lymphoid follicle and periarteriolar sheath--which, with the marginal zone of the red pulp, is the primary site of lymphoproliferative activity; 2) the cords of the red pulp, the functionally slow component of the splenic circulation, which sequester senescent or structurally altered red cells and effect their removal by means of scavenging macrophages (and which may be secondarily involved by the accumulation of platelets or certain types of leukemic cells, resulting in chronic cordal distention, or by the accumulation of collagen in fibrocongestive splenomegaly); and 3) the splenic sinuses, the unique structure of which determines that only healthy red cells with normally plastic and flexible membranes pass through to the venous circulation. Abnormal transiting cells such as sickle cells frequently clog the apertures to these sinuses. Direct arteriocapillary sinus terminations provide the anatomic basis for a fast component of the red pulp circulation, the existence of which was questioned for many years and the extent of which is still unknown in pathologic states.

Acute inhibition of intestinal lipid transport by Pluronic L-81 in the rat.

Lymph fistula rats were used to determine the acute effects of the hydrophobic surfactant, Pluronic L-81, on lipid transport by the small bowel. Animals were infused intraduodenally with a lipid emulsion containing [3H]triolein and Pluronic L-81, and the rate of intestinal transport of absorbed lipid into lymph was studied using liquid scintillation spectrometry. With this technique, various dose levels of Pluronic L-81 were analyzed for a possible inhibitory effect on lipid transport. Also, the rate at which this agent produced inhibition of intestinal lipid transport was determined. Results were correlated with electron microscopic studies of jejunal enterocytes and lipoprotein particles recovered in intestinal lymph. Infusion of Pluronic L-81 at a rate of 0.25 mg/h had no effect, but infusion at 0.5 and 1 mg/h produced a dramatic reduction in lipid transport by the small bowel. The rate of inhibition of lymphatic lipid output was rapid, with a t1/2 of 69 min for the 0.5 mg/h dose and 35 min for the 1 mg/h dose. This inhibition of lipid transport was associated with marked mucosal accumulation of lipid as demonstrated by radiochemical and morphological data. By electron microscopic analysis, only very low-density lipoprotein-sized particles were transported into lymph by enterocytes exposed to an effective dose of Pluronic L-81. It is concluded that small amounts of Pluronic L-81 produce a striking inhibition in the intracellular transport of chylomicron-sized particles, thereby blocking secretion of chylomicrons by the enterocytes. Furthermore, this action is very rapidly produced by effective doses of this agent.

Polymyositis in Kaposi syndrome.

Polymyositis in association with Kaposi sarcoma occurred in a 60-year-old black man. Muscle biopsy revealed prominent plasmacytic and eosinophic inflammatory infiltration resembling the myopathy of Sjögren's syndrome. Nonspecific changes were seen by electron microscopy of post mortem muscle. The myopathy could be interpreted as a remote effect of neoplasm.