Conglutinin, mannan-binding protein, and serum amyloid P component concentrations in sera from cows: changes associated with mastitis. To study the roles of conglutinin (Kg), mannan-binding protein (MBP), and serum amyloid P component (SAP) in the protection of cattle against infections, the concentrations of these proteins in the sera from cows with mastitis were determined by sandwich enzyme-linked immunosorbent assays. The Kg and MBP concentrations in the sera from cows with mastitis were much lower than those from uninfected (or clinically healthy) ones, and increased after recovery. No significant difference in the SAP concentrations was found between healthy and infected cows. With the sera from cows experimentally infected with bovine leukemia virus, the Kg concentrations were also lower than those from uninfected ones, whereas the MBP concentrations were not. From these findings, the Kg concentration is suggested to be serologically a possible indicator for clinical diagnosis of treatment for mastitis although both Kg and MBP concentrations were found to decrease in cows with mastitis and to increase after recovery.


Impaired baroreflex control of arterial pressure in WHHL rabbits. The present study was designed to investigate baroreflex control capacity of arterial pressure (AP) in the conscious Watanabe heritable hyperlipidemic (WHHL) rabbit. The control capacity of the baroreflex system was assessed with overall open-loop gain (G). Seven WHHL and 14 normal Japanese white rabbits were chronically implanted two catheters in the aortic arch through the left subclavian and common carotid arteries. A small amount of blood (2 ml/kg, body weight) was rapidly extracted into a syringe via the left common carotid artery in the conscious state. Mean arterial pressure (MAP) was monitored with a catheter-transducer system through the left subclavian artery. The MAP responses to the rapid hemorrhage were averaged 8 times by a computer. G was calculated as G = delta API/delta APS-1, where delta API was an immediate MAP fall after the hemorrhage and delta APS was a steady-state error 1-2 min after the hemorrhage. The values of G in the conscious normal and WHHL rabbits were 7.35 +/- 0.24 and 1.91 +/- 0.29 (mean +/- SE, p < 0.01), respectively. To investigate effects of pentobarbital anesthesia on baroreflex system, the hemorrhage experiment was repeated several times under pentobarbital anesthesia (20 mg/kg, i.v.). The values of G in the anesthetized normal and WHHL rabbits were 6.69 +/- 0.23 and 1.68 +/- 0.34 (mean +/- SE, p < 0.01), respectively. G in the normal and WHHL rabbits did not show any significant change in the presence and absence of pentobarbital anesthesia (p > 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)


Vagal afferent activities and respiratory reflexes during drug-induced bronchoconstriction in the guinea pig. Vagal afferent activities and respiratory reflexes during drug-induced bronchoconstriction were studied in 31 anesthetized, spontaneously breathing or artificially ventilated guinea pigs. Histamine (5, 10, 20 micrograms/kg), ACh (10, 20, 40 micrograms/kg) and endothelin-1 (2 micrograms/kg) were intravenously injected to the animals in order to induce the bronchoconstriction. In spontaneously breathing and vagi intact animals, a considerable respiratory change characterized by rapid-shallow breathing was elicited by histamine. Such respiratory change was abolished by bilateral vagotomy, indicating that the vagal pathway fairly participated in the respiratory change during bronchoconstriction. Indeed, recordings of electrical activities of single vagal afferent nerve fibers from pulmonary stretch and irritant receptors elucidated that the bronchoconstriction by the three drugs markedly influenced these receptor activities. The response of stretch receptors to bronchoconstriction was grouped into four types: two of those types showed a marked increase in their activities and the other two a decrease or no change. Such uneven response was assumed to be derived from heterogenous contraction and aeration among the intrapulmonary small airway. On the other hand, irritant receptors were invariably stimulated by increased transmural pressure during bronchoconstriction. Administration of isoproterenol (20 micrograms/kg) which inhibited the smooth muscle contraction abolished stimulatory effect of the drugs to irritant receptors, suggesting that the effect was due to indirect action through the muscle contraction rather than their direct action to the nerve endings.


Are there M cells in the cecal tonsil of chickens? A unique morphological cell type, "microfold or membranous (M) cell-like cell", was detected electron-microscopically in the cecal tonsil epithelium of the chicken. M cell-like cells possessed a few short microvilli of irregular arrangement and a large number of lymphocytes and macrophages wedged into their basal surfaces. Triticum vulgaris was found to bind to M cell-like cells. With horseradish peroxidase (HRP) treatment, M cell-like cells showed an active HRP uptake just as did the neighbouring usual absorptive epithelial cells. No uptake of colloidal carbon particles from the intestinal lumen was recognized in any part of the intestinal epithelium. These results suggest that M cell-like cells of the chicken possess some M cell-characteristic morphological and histochemical features, but that their active uptake of foreign materials is not so developed as in mammalian M cells.


[Acyl and plasmalogen analogs of platelet activating factor--new lipid cellular bioregulators]. Recent data concerning two structural platelet-activating factor (PAF) analogs-1-O-acyl-2-acetyl-sn-glycero-3-phosphocholine (acyl-PAF) and 1-O-alk-1'-enyl-2-acetyl-sn-glycero-3-phosphocholine (vinyl-PAF) identified in some cells and tissues are reviewed. Isolation, identification, biosynthesis, and metabolism of acyl-PAF and vinyl-PAF are considered. The activity of acyl-PAF and vinyl-PAF towards platelets, leukocytes, isolated myocardium, and ileum as well as its in vivo activity are discussed. The influence of acyl-PAF and vinyl-PAF on PAF platelet interaction, Ca2+ mobilization, and platelet adenylate cyclase activity is considered. It is concluded that similar to PAF, acyl-PAF and vinyl-PAF should be regarded as a family of PAF lipid bioregulators.


[Detection of apoprotein A-1 immunoreactivity in chromatin of rat hepatocytes]. The binding of 125I-labeled lipoproteins to subcellular structures of rat hepatocytes was studied. The protein component of HDL, LDL, and VLDL was found in large and small membranes, nuclei, mitochondria, lysosomes, microsomes, and cell cytosol. The presence in liver nuclear chromatin of proteins immunochemically related to apoA-1 was demonstrated by solid phase immunoenzymatic analysis, dot immunoanalysis, and immunoelectroblotting. The apoprotein A-1 immunoreactivity was detected in transcriptionally inactive total chromatin, transcriptionally active chromatin, and nuclear matrix. The specific apoA-1 immunoreactivity of transcriptionally active chromatin and nuclear matrix was two times as low as that of total and transcriptionally inactive chromatin. Immunoelectroblotting revealed two proteins possessing an apoA-1 immunoreactivity (M(r) 28 and 14 kDa). The 28 kDa protein was found in transcriptionally active chromatin and nuclear matrix, while the 14 kDa one--only in transcriptionally inactive chromatin. the roles of apoproteins in lipid transport to nuclei and the maintenance of chromatin in a transcriptionally active state are discussed.


[Two types of prolactin-binding sites on membranes of cow milk fat globules]. Prolactin (PRL) binding to specific receptors of cow milk fat globular membranes (MFGM) has been studied. The data obtained point to the existence of two PRL-binding sites on cow MFGM. The parameters of PRL binding to lactogenic receptors have been estimated for a two-binding-site model.


[Substrate specificity of phosphoribosyl-aminoimidazole-succinocarboxamide synthetase (SAICAR-synthetase) from Saccharomyces cerevisiae yeast]. The substrate specificity of phosphoribosyl-aminoimidazole-succinocarboxamide-synthetase (SAICAR-synthetase, EC 6.3.2.6) of the yeast Saccharomyces cerevisiae towards a set of carboxyaminoimidazole ribotide (CAIR) analogs with modifications in the imidazole ring, ribose and phosphate moieties, as well as aspartic acid analogs has been studied. It was found, in particular, that: i) the presence of double charged phosphate group, 2'- and 3'-hydroxyl groups in the ribose fragment and of an amino group in the imidazole ring of the CAIR molecule is not the absolute requirement for the enzymatic reaction; ii) 3'-carboxy-1.2.4-triazole analog of CAIR is a competitive inhibitor of the enzyme; iii) 2'-deoxy-CAIR is a substrate for both yeast SAICAR-synthetase and its avian liver and human erythrocyte counterparts. A new method designed to determine the SAICAR-synthetase activity with the help of bifunctional enzymes possessing, in addition to the SAICAR-synthetase activity, also a phosphoribosyl-aminoimidazole-carboxylase activity, is proposed; this method is based on the use of 2'-deoxy-CAIR. Some aspartic acid analogs (L-malic acid, beta-threo-oxy-, and beta-threo-fluoro-aspartic acids and alanosine) are substrates for yeast SAICAR-synthetase. The possible involvement of malate as an alternative substrate for the SAICAR-synthetase reaction in vivo is discussed. The results of a comparative analysis of already established primary structures of yeast, bacterial, human, and chicken SAICAR-synthetases are presented.


[Effect of mevinolin and glycyrrhizinic acid on cholesterol and bile acid metabolism in cultured rabbit hepatocytes]. A comparison of effects of two hypocholesterolemic drugs--mevinolin and glycyrrhizinic acid, on cholesterol and bile acid metabolism in cultured rabbit hepatocytes has been carried out. The following parameters have been determined: i) cholesterol synthesis from [2-14C]acetate; ii) bile acid production from newly synthesized and [4-14C]-labeled HDL2 cholesterol, and, iii) total cholesterol efflux into the incubation medium Mevinolin (0.5 microgram/ml) inhibited [2-14C] acetate incorporation into cholesterol by more than 90%. Conversely, glycyrrhizinic acid did not influence cholesterol synthesis even when used at high (100 micrograms/ml) concentrations but stimulated the conversion of endogenous (by 37%) and exogenous (by 18%) cholesterol into bile acids and increased, in addition, the proportion of bile acids in the total sterol pool released from hepatocytes into the incubation medium. At the same time, mevinolin used at 0.5 microgram/ml decreased the bile acid production by endogenous (by 27%) and exogenous (by 40%) cholesterol. The data obtained suggest that glycyrrhizinic acid exerts hypocholesterolemic action by stimulation of cholesterol conversion into bile acids without any effect on cholesterol synthesis. As for mevinolin, it has a cholesterol-suppressing effect via a mechanism of cholesterol synthesis inhibition only.


[Comparative study of the features of protein composition of human aorta tunica media]. A preliminary two-dimensional map of human aorta tunica media proteins comprising 280 polypeptide fractions has been constructed. Individual protein fractions were characterized in terms of molecular masses and relative electrophoretic mobility; the resulting values were stored in the "protein" data base. Using co-electrophoresis, the positions of certain tunica media proteins (light chains, myosin, tropomyosin, actin, albumin) was determined. The two-dimensional map was used to compare tunica media proteins with their human cardiac muscle counterparts.


[Activation of Na/H exchange by thrombin in peritoneal mast cells]. Using the fluorescent probe, BCECF, the changes in intracellular pH (pHi) in rat peritoneal mast cells were studied. alpha-Thrombin (0.1 nM) induced biphasic changes in pHi which consisted in a temporary decrease in pH with its subsequent steady increase due to the Na/H exchange activation which was inhibited by EIPA and controlled by extracellular Na+. The biphasic changes in pHi induced by DIP-alpha-thrombin (0.1 pM-1 nM), a catalytically inactive form with an intact recognition site, were similar to those of alpha-thrombin, whereas beta/gamma-thrombin (10-1000 pM), a catalytically active form characterized by structural disturbances in the recognition site, was able to induce only the initial phase of acidification. The thrombin recognition site modulators, alpha 1-thymosin and heparin, blocked the ability of the enzyme to induce the alkalinization of pHi. Nigericin stimulated the Na/H-exchange in mast cells. The rate of the Na/H-exchange activation determined with nigericin, decreased with an increase in the alpha-thrombin dose from 0.1 pM up to 10 nM. Activation of protein kinase C (PKC) in mast cells by PMA used at 1 nM and 10 nM led to the alkalinization of the cytoplasm as a result of the Na/H-exchange activation blocked by EIPA. The PKC inhibitor, H-7, suppressed the pHi increase induced by both PMA and alpha-thrombin. The alpha-thrombin-induced acidification of the cytoplasm was completely blocked by SITS in Ca(2+)-free media, whereas in media with Ca2+ SITS inhibited the pHi decline. Acidification of the cytoplasm by thrombin seems to be due to both Ca2+ influx and activation of Cl- fluxes. It is concluded that the observed activation of the Na/H-exchange by thrombin is induced by a cascade of intracellular reactions involving PKC.


[Hydrolysis of prolactin by a serine proteinase from mammary gland secretory cell mitochondria]. Mitochondrial proteinase isolated from secretory cells of the mammary gland of lactating rats able to hydrolyze 125I-labeled and native prolactin (PRL) has been studied. The enzyme represents a serine proteinase and is localized in the inner mitochondrial membrane. The molecular mass of the enzyme is 17-18 kDa, pH optimum is at 8.0-9.0. Partial purification of the enzyme has been carried out. The Km constant for 125I-PRL is equal to 10(-6) M, that for 2% hemoglobin is 1.2 x 10(-4) M. Analysis of products of rat and ovine PRL hydrolysis by proteinase using high performance liquid chromatography and PAAG electrophoresis revealed the formation of large-size fragments of the hormone. A possible role of proteinase in the mechanism of PRL action on mammary gland tissues is discussed.


Morphometric analysis of sciatic nerve and its main branches in the rabbit. In the rabbit the myelinated fibres with the largest diameter originating from the sciatic nerve distribute mainly into the peroneal nerve, even though there is no difference in the density of myelinated fibres of the representative unit between the sciatic nerve and its branches. The distribution of the myelinated fibre diameters is unimodal in the sciatic nerve, but bimodal both in the peroneal and tibial nerves. The quotient axon diameter/fiber diameter (g ratio) shows a different trend between the sciatic nerve and the branches originating from it. Except for the peroneal nerve, the increase of the axon calibre corresponds to the reduction of the relative myelin sheath thickness and therefore to the reduction of internodal distance. The results show that the sciatic nerve and its terminal branches in the rabbit have morphometrical characteristics that are peculiar and differ from those of the other rodents.


The oxytocin positive elements in the hypothalamic magnocellular nuclei of rats treated with histamine. The oxytocin positive elements of the hypothalamic supraoptic (SON) and paraventricular (PVN) nuclei, were instigated in 160 male rats through immunohistochemical, morphometric and statistical methods. The rats subdivided into five groups: 20 control rats; 20 rats treated with physiological saline intraperitoneal via (ip); 20 rats treated with physiological saline intracerebroventricular via (icv); 20 histamine (HA) treated rats, ip; and 20 HA treated rats, icv. Some labeled nerve cells appear, mainly, in the lateral part of the SON and the PVN of the control animals. These neurons have central nucleus and oxytocin positive cytoplasmic granulations. After the treatment with physiological saline, ip or icv, no alterations were observed. In HA treated rats, icv, numerous neurons and pathways were observed strongly labeled. Large droplets appear in the SON and in the PVN of these animals. In HA treated rats, ip, the oxytocin positive material is similar to that observed in the control rats. The morphometric and statistical studies confirm these findings. The results are discussed in this paper.


Influence of chick or quail embryonic testes on the reproductive system of the quail embryo. The reproductive system of female quail embryo undergoes masculinization under the influence of chick and quail embryonic testis grafted into an extraembryonic coelom. Müllerian ducts undergo regression. The left gonad transforms into an ovotestis and the right gonad either does not develop or transforms into a small testis. Testicular chick or quail graft does not affect the development of the cortical ovarian-like region in the left testis of male hosts. In some quail testicular grafts developing in female quail hosts cortical region is retained longer than normally.


Characterization of the nuclear receptors of triiodothyronine (T3) by immunocytochemistry under electron microscopy. By immunocytochemical methods, using colloidal gold particles coupled to antibodies, it is possible to label the occupied nuclear T3 receptors and observe them by electron microscopy. We carried out some experiments to validate these methods by testing the absence of non-specific binding of the antibodies to subcellular structures different from the T3 receptors. So, we have verified that the number of occupied T3 receptors in tissues from normal rats is lower in kidney cells than in heart and liver ones, a finding which is an agreement with data reported by others. The occupation of the receptors increases after T3 administration and decreases by triiodothyroacetic acid (Triac) administration to the rats, due to the displacement of T3 from the receptors with the latter. Our results are similar to those of the other authors using radioactive tracers. Non-specific binding was not detected. The occupied T3 receptors labelled with colloidal gold particles are located most commonly in the hetero/euchromatin interface. From our results we conclude that the colloidal gold particles observed by electron microscopy specifically label occupied T3 receptors, and the determination of the thyroid status at cellular level can be achieved using electron microscopy after labelling the receptors by immunocytochemistry with colloidal gold particles coupled to antibodies.


Selective species specificity of tumor necrosis factor for toxicity in the mouse. The selective cytotoxic activity of tumor necrosis factor (TNF) on many transformed human or murine cell lines is (almost) not species-specific. There are, however, a limited number of biological assay systems such as gene induction in murine thymoma cells and the murine thymocyte proliferation assay, in which recombinant murine (rm) TNF, but not recombinant human (rh) TNF is active. We have now investigated the possible species specificity of the lethality-inducing properties of TNF in the mouse. When administered alone, only rmTNF, but not rhTNF caused lethality. This difference was not due to a different endotoxin contamination or to a different pharmacokinetic behavior. When a sensitizing agent, galactosamine, was added, the species specificity was abolished. We have shown previously that similar conclusions could be drawn for at least some of the antitumor mechanisms of TNF. We conclude that to mimic the two major phenomena caused by endotoxin administration, viz. lethality and antitumor effect, two distinct signals are needed. In mice, rmTNF can provide both, while rhTNF needs another agent (a sensitizer) to cause systemic toxicity. The results are discussed with respect to recent findings showing that, in the mouse, rhTNF can only bind to the TNF-R55 receptor type, while rmTNF can bind both to the TNF-R55 and TNF-R75 receptor types.


Glycosylation of the interleukin-1 receptor type I is required for optimal binding of interleukin-1. The two types of cell surface receptors for interleukin-1 (IL-1) are glycoproteins that contain N-glycosidic chains on their extracellular portions. To determine the role of glycosylation of the IL-1 receptor type I (IL-1RtI) in the binding and function of IL-1, we used four plant lectins and glycosidase treatment on two different T-cell lines (EL4-6.1 and D10S) and expressing high number of binding sites for IL-1. The lectins wheat germ agglutinin, phytohemagglutinin, and concanavalin A inhibited in a dose-response manner the IL-1-induced proliferation of D10S cells. Binding of IL-1 was blocked and radioactive IL-1 was displaced from these cells by these lectins. Specific sugars (GlcNAc, NeuAc, Gal-GlcNAc-Man, Man, or alpha-MeMan) did not themselves affect IL-1 binding but reversed the blocking effects of the lectins. The two cell lines differed in their responses to the lectin-mediated inhibition of IL-1 binding. Digestion by N-glycosidase significantly decreased the capacity of cells to bind IL-1, and reduced by approximately 20,000 D the M(r) of the IL-1RtI. Neuraminidase and O-glycanase treatment did not alter the binding of IL-1 to D10S or EL4-6.1 cells. This study demonstrates that glycosylation of the extracellular domain of the IL-1RtI is due to N-linked carbohydrates, that the degree of glycosylation can vary in cells of different lineage, and that this N-linked glycosylation appears to be essential for optimal binding and activity of IL-1 to its type I receptor.


Tumor recognition and lytic competence of IL-2-activated lymphocytes: regulation of both antibody-independent and -dependent cellular cytotoxicity via P75 IL-2 receptor. Fc receptor-positive lymphocytes (FcR+) contain lymphokine-activated killer cell (LAK) precursors that in response to IL-2 develop potent antitumor cytotoxicity. These FcR+ cells are also capable of antibody-dependent cytotoxicity (ADCC), which can be detected using fresh human peripheral blood lymphocytes (PBL) directed to murine targets, however, PBL-mediated ADCC to human tumors usually is very low, requiring a stimulation of the PBL, which also can be accomplished with IL-2. Using human melanoma tumor target cells, with and without the 14G2a monoclonal antibody, we examined in parallel the role of p75 IL-2 receptor for regulation of the induction of both LAK and ADCC forms of antitumor cytotoxicity. Enrichment of FcR+ cells from fresh peripheral blood by elutriation and flow cytometry, followed by varying periods of IL-2 culture, revealed a differential kinetics of activation. ADCC was detectable after PBL exposure to IL-2 for as short as the 4 h cytotoxicity assay, while LAK activation required more than 24 h of exposure. Elimination of the FcR+ cells by magnetic bead depletion from large granular lymphocyte populations (LGL) resulted in a loss of both LAK and ADCC. Addition of antibody known to block the binding of IL-2 to the p75 molecule of the IL-2 receptor complex (Mik-beta 1) to activation cultures at zero time resulted in abrogation of both cytotoxicities. These results suggest that differentiation and maturation of the ADCC effectors occurs in response to IL-2 via the p75 molecule, as also does LAK activation.(ABSTRACT TRUNCATED AT 250 WORDS)


The immunomodulatory role of IFN-alpha or maltose-stabilized IFN-alpha on T-cell activation. The effects of human interferon-alpha (IFN-alpha) or maltose-stabilized IFN-alpha (MS-IFN-alpha) on IL-2 production by PHA- or anti-CD3 mAb-stimulated MOLT 16 cells, a human leukemic T cell line, were studied. MS-IFN-alpha is an IFN-alpha-containing powder in which maltose was used as an excipient, and has been shown to have a positive effect on human immunodeficiency virus (HIV)-infected patients. In this study, MS-IFN-alpha powder was dissolved in a culture medium and used for the experiments. IL-2 production by PHA- or anti-CD3 mAb-stimulated MOLT 16 cells was augmented by coculturing with IFN-alpha or MS-IFN-alpha. The augmentation of IL-2 production by IFN-alpha or MS-IFN-alpha was completely abrogated by rabbit anti-IFN-alpha antibody. We have previously shown that IL-2 production by PHA-stimulated MOLT 16 cells is augmented by coculturing with IL-1. Furthermore, IL-2 production by PHA-stimulated MOLT 16 cells was also augmented by human TNF-alpha in a dose-dependent manner. The TNF-alpha-induced augmentation was completely abrogated by rabbit anti-TNF-alpha antibody. Interestingly, both IFN-alpha and MS-IFN-alpha synergized with rIL-1 alpha or TNF-alpha resulting in IL-2 production being augmented far more effectively than either cytokine alone.(ABSTRACT TRUNCATED AT 250 WORDS)


Comparative tissue distribution of 125I- and U-14C-labeled recombinant human interleukin-2 in the rat. The distribution of recombinant human interleukin-2 (rhIL-2) after intravenous administration of 125I- or U-14C-labeled rhIL-2 is reported in the major organs of the rat. Five minutes after the administration of U-14C-labeled rhIL-2, the radioactivity had been rapidly cleared from the plasma, while 38% of the dose was found in the kidneys, confirming that the major site of clearance for rhIL-2 is the kidney. After 1 h, a large fraction of the radioactivity had disappeared from the kidney and was found in the carcass. When the same experiments were carried out with 125I-labeled rhIL-2, comparable distribution results were obtained: Preferential accumulation of 125I radioactivity (37.4%) was found in the kidney at 5 min after iv administration of 125I-labeled rhIL-2. One hour after dosing 125I label was predominantly present in the carcass (46%) and skin (15%). Similar percentages of the dose of 125I or 14C radioactivity were present in other organs or tissues. The present study indicates a similar distribution of the radiolabel in selected tissue and organs regardless of whether 14C or 125I was employed.


Modulation of the posthemorrhage bacterial polysaccharide antigen-specific antibody response by interleukins 2 and 4. Abnormalities in immune response play a major role in the increased susceptibility to infection after hemorrhage and trauma. Several studies have shown decreased release in vitro of interleukin-2 (IL-2) following blood loss. To better define in vivo the interactions between T and B cells, as well as the effects of treatment with the T cell-derived cytokines IL-2 and IL-4, mice were injected with concanavalin A at predetermined times posthemorrhage, and the percentages and numbers of splenic plasma cells producing antibody to the bacterial polysaccharide antigen levan (from Aerobacter levanicum) were determined. Decreased numbers and percentages of levan specific splenic plasma cells were found in animals treated with concanavalin A both immediately and 2 to 4 days after hemorrhage. Treatment in vivo with recombinant IL-2, but not IL-4 or anti-IL-2 receptor antibodies, following blood loss was able to increase the numbers of levan specific plasma cells to levels as high or higher than those found in normal, unhemorrhaged animals, but was unable to affect the decreased percentage of levan specific splenic plasma cells. These results suggest that the use in vivo of IL-2 may restore bacterial antigen specific antibody responses to normal levels after blood loss.


Ontogeny of intestinal lipid and lipoprotein synthesis. Despite increasing evidence that the fetal intestine produces apoproteins, there is limited knowledge about its ability to absorb fat. The present study focused on the intracellular processing of lipid formation and transport by lipoproteins in the developing fetus. Explants of fetal jejunum (14-20 weeks) were maintained in serum-free organ culture for 42 h with [14C]-oleate. Esterified lipids extracted from the tissue showed an abundance of phospholipids (PL; 54-77%), while those harvested from the medium displayed a predominance for triglycerides (TG; 68-73%). Only a minor percentage of radioactivity was recovered in cholesterol ester (CE) from the tissue (1.8-2.5%) or medium (1.3-2.5%). Separation of PL by thin-layer chromatography revealed a prevalence of phosphatidylcholine followed by phosphatidylethanolamine. Over the fetal period studied a trend towards increase was noted in TG, CE and most of the PL classes but not phosphatidylcholine. In parallel, we observed a progressive increase in these lipoprotein fractions produced by the fetal intestine during development, i.e., chylomicrons, very low-density lipoproteins and high-density lipoproteins. Our data stress not only the ability of the fetal intestine to absorb fat, but also the ontogenetic changes of lipid and lipoprotein synthesis.


Measurement of total bodywater volume with deuterated water in newborn infants. D2O and H2(18)O are often used as tracers for the determination of total body water (TBW). For newborn infants, the commonly used noninvasive method has not been validated. In this study TBW was calculated from D2O concentrations in blood and compared with TBW calculated from D2O concentrations in urine. TBW calculated from all urine portions voided at least 6 h after D2O administration on average was 1.0% lower. TBW calculated from only three urine portions voided 6, 12, and 24 h after D2O administration was 0.6% (mean) lower compared to TBW calculated from D2O concentrations in blood. This study indicates that the noninvasive method to measure TBW can be considered a reliable method when used in newborn infants.


GTP-dependent protein(Gs) activity in preterm infants. In a previous study, we showed a renal resistance to PTH in preterm infants during their 1st week of life. We proposed it could explain early neonatal hypocalcemia. Such renal resistance is well known in type 1 pseudohypoparathyroid patients and is explained by a defect of stimulatory GTP-dependent protein (Gs). To determine if functional immaturity in the Gs protein could be involved in PTH resistance, we studied 27 newborn babies: 7 full-term and 20 preterm babies. Biological activity of the Gs unit was determined on days 1, 3 and 10 after delivery by bioassay. No correlation was found between the Gs unit activity and either gestation or birth weight at these dates. Eight infants had hypocalcemia and their Gs unit activity did not differ from those with normocalcemia. Furthermore, we showed that the Gs unit is active from 29 weeks of gestation. We conclude that the Gs protein appears not to be involved in the pathophysiology of early renal resistance to PTH and therefore in early neonatal hypocalcemia.


Ovine maternal and fetal glomerular atrial natriuretic factor receptors: response to dehydration. In pregnancy, dehydration produces marked effects on maternal and fetal body water homeostasis including an increase in fetal urinary sodium concentration and excretion. To examine the role of fetal plasma atrial natriuretic factor (ANF) and glomerular ANF receptors in dehydration-induced natriuresis, we compared plasma ANF levels and glomerular ANF binding characteristics in dehydrated and control maternal and fetal sheep. Mean (+/- SEM) maternal and fetal plasma ANF levels in control animals (n = 9) at 132-136 days gestation were 37 +/- 3 pg/ml and 138 +/- 20 pg/ml, respectively. Although mean ANF receptor maximum binding capacities (Bmax) were significantly higher in maternal than in fetal glomeruli (83 +/- 11 vs 34 +/- 12 fmol/mg protein, respectively), the dissociation constants (Kd) for ANF binding were not different (2.7 +/- 0.6 and 3.7 +/- 1.7 x 10(-10) M, respectively). In an additional 9 animals studied after 63 +/- 4 h of water deprivation, maternal plasma ANF levels were significantly lower than in the control group (14 +/- 4 vs. 37 +/- 3 pg/ml), maternal glomerular ANF receptor Bmax values were significantly higher (732 +/- 203 vs. 83 +/- 11 fmol/mg protein), and Kd values were six-fold higher (17.0 +/- 7.1 vs. 2.7 +/- 0.6 x 10(-10) M), although this difference was only marginally significant (p = 0.06). In contrast to the adult, there was a small, nonsignificant decrease in plasma ANF levels and no difference in Bmax or Kd values between the dehydrated and euhydrated fetal animals.(ABSTRACT TRUNCATED AT 250 WORDS)


Effect of hypoxia on renal prostaglandin E2 production in human and rat neonates. Effect of hypoxia on renal prostaglandin E2 (PGE2) production was shown in asphyxic newborn infants and experimental hypoxic rats. In asphyxic infants, at postnatal day 1, the urinary excretion of PGE2 in severe asphyxia (1.00 +/- 0.19 pg/kg/min, n = 10) was lower than that of the mild asphyxia (2.15 +/- 0.18 pg/kg/min, n = 10) or normal newborn infants (2.65 +/- 0.25 pg/kg/min, n = 8) (p less than 0.01). The urinary excretion of PGE2 was inversely correlated with the urinary N-acetyl-beta-D-glucosaminidase (r = -0.84, p less than 0.01). The urine volume in mild asphyxia (0.04 +/- 0.005 ml/kg/min) was higher in comparison to normal newborn infants (0.026 +/- 0.002 ml/kg/min) (p less than 0.01), but had no correlation with the urinary excretion of PGE2. In experimental hypoxic rats, the renal PGE2 concentration increased from 0.19 +/- 0.02 ng/mg protein to the maximum level of 0.59 +/- 0.03 ng/mg protein at 10 min of hypoxia. The renal PGE2 concentration then decreased to the minimum level (0.105 +/- 0.02 ng/mg protein) at 24 h after 20 min hypoxia. The renal ATP rapidly decreased during 20 min hypoxia, and gradually increased to 55.1 +/- 6.2 nmol/mg protein at 24 h after 20 min hypoxia, which recovered only about 60% of the control level. It seems likely that renal PGE2 does not play a major role in diuresis in mild birth asphyxia and that severe birth asphyxia suppresses the renal PGE2 production in early neonatal period.(ABSTRACT TRUNCATED AT 250 WORDS)


Effect of dexamethasone on antioxidant enzymes in fetal rat lungs and kidneys. To determine if an enhancement in the fetal antioxidant enzyme (AOE) system by maternal dexamethasone (DEX) is specific to organ and dose, the lung and kidney of pups, whose mother received DEX (0.2 or 2 mg/kg) twice, were obtained on days 19 and 20 of gestation. Low-dose DEX increased the four AOE in the day-19 lung, but not in day-20 lung. High-dose DEX decreased the copper-zinc superoxide dismutase (SOD) and glutathione peroxidase in the lungs. Thus, the DEX-induced maturation of lung AOE is dependent on dose and timing. DEX enhanced the four AOE in the day-19 kidney at both doses. In the day-20 kidney, DEX enhanced the manganese SOD at the low dose and also catalase at the high dose, suggesting that DEX accelerates the maturation of kidney AOE as well.


Intestinal development and fatty acid binding protein activity of newborn pigs fed colostrum or milk. Newborn pigs (n = 20) were gavage-fed sow's colostrum, defatted colostrum, milk, defatted milk or a 5% lactose solution over 24 h in order to evaluate effects on growth and functional differentiation of small intestine. Colostrum-fed pigs had greater (p less than 0.01) mucosal mass in the proximal half of the small intestine than did the milk- or lactose-fed groups. Total fatty acid binding protein (FABP) activity and FABP activity per mg DNA in proximal intestines of colostrum-fed pigs exceeded that for the lactose group. FABP activities (per g mucosa or mg soluble protein) were greater (p less than 0.01) in the proximal segments of small intestines of pigs fed whole versus the corresponding defatted secretion. These results indicate that the feeding of colostrum specifically augments perinatal intestinal growth and differentiation as manifested by increased cellular hypertrophy and FABP activity. Milk lipid and unidentified factor(s) enriched in colostrum are inducers of intestinal FABP activity.


Hemodynamic effects of continuous negative extrathoracic pressure and continuous positive airway pressure in piglets with normal lungs. The hemodynamic effects produced by continuous positive airway pressure (CPAP) and continuous negative extrathoracic pressure (CNEP) of 4 and 8 cm H2O were compared in 8 normal, spontaneously breathing piglets. Arterial blood gases and hemodynamic measurements were obtained before and during CPAP and CNEP of 4 and 8 cm H2O. CPAP 8 cm H2O and CNEP 8 cm H2O produced significant increases (p less than 0.01) in PaO2 from baselines 76 +/- 3 to 85 +/- 3 and 77 +/- 4 to 85 +/- 3 mm Hg, respectively. No significant changes occurred in PaCO2 or cardiac index, except during CPAP 8 cm H2O [38 +/- 1 to 44 +/- 2 mm Hg (p less than 0.05) and 376 +/- 30 to 330 +/- 30 ml/kg/min (p less than 0.05), respectively]. During CPAP of 4 cm H2O, significant increases occurred in mean right atrial pressure (Pra) (2.1 +/- 0.3 to 3.3 +/- 0.4 mm Hg; p less than 0.01), left ventricular end-diastolic pressure (LVEDP) (2.8 +/- 0.4 to 3.7 +/- 0.3 mm Hg; p less than 0.01), and mean pulmonary artery pressure (Ppa) (12.9 +/- 0.8 to 15.1 +/- 0.8 mm Hg; p less than 0.01). CPAP of 8 cm H2O produced marked increases in Pra (2.1 +/- 0.2 to 4.9 +/- 0.7 mm Hg; p less than 0.01), LVEDP (2.7 +/- 0.5 to 4.5 +/- 0.4 mm Hg; p less than 0.01) and Ppa (12.8 +/- 0.8 to 17.7 +/- 0.6 mm Hg; p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)


Urinary and plasma epidermal growth factor levels are decreased in neonates with intrauterine growth retardation and in their mothers. Epidermal growth factor (EGF) concentrations in urine and plasma samples collected from pregnant women and neonates were measured by RIA. The EGF concentration of the first voided urine was higher in appropriate-for-date (AFD) neonates (33.9 +/- 23.0 ng/mg creatinine) than in those with intrauterine growth retardation (IUGR; 23.5 +/- 7.7 ng/mg creatinine, p less than 0.05) and heavy-for-date (19.8 +/- 5.2 ng/mg creatinine, p less than 0.05) neonates. The urinary EGF concentration of pregnant women showed no marked changes throughout pregnancy. Urinary EGF concentrations of women with AFD fetuses (45.9 +/- 31.2 ng/mg creatinine) did not differ significantly from those of women with diabetes (39.9 +/- 26.8 ng/mg creatinine) or women with multiple fetuses (44.6 +/- 30.6 ng/mg creatinine). However, women with IUGR fetuses showed lower urinary EGF concentrations (13.8 +/- 7.4 ng/mg creatinine, p less than 0.05) than women with AFD fetuses. Maternal and fetal platelet-poor plasma EGF concentrations at delivery were lower in the IUGR group (mother: 2.62 +/- 0.38 ng/ml, fetus: 2.16 +/- 0.07 ng/ml, respectively, p less than 0.05 and p less than 0.005) than in the AFD group (mother: 3.34 +/- 0.64 ng/ml, fetus: 3.24 +/- 0.93 ng/ml). In the IUGR group, the EGF concentration in fetal blood was always lower than that in maternal blood (p less than 0.05), although the AFD groups showed no such difference. These data suggest that EGF levels are closely related to fetal growth.


Developmental changes of glutamate dehydrogenase activity in rat liver mitochondria and its enhancement by branched-chain amino acids. The developmental changes of glutamate dehydrogenase activity in the fetal and neonatal rat liver were investigated, as well as the effects of branched-chain amino acids on this enzyme. Hepatic glutamate dehydrogenase activity showed a marked increase at the end of the fetal period and peaked on the 5th day of neonate at approximately 3 times higher than the adult level. Glutamate dehydrogenase was activated by leucine, isoleucine, and valine in this order when they were added to isolated intact liver mitochondria in vitro. The enhancement of enzyme activity was more marked in fetal rats than in adults. In contrast, when branched-chain amino acids were added after disrupting the mitochondrial membrane by sonication, only leucine slightly activated glutamate dehydrogenase, while isoleucine and valine slightly inhibited its activity. Our findings suggest that glutamate may be actively synthesized in the developing rat liver mitochondria and then transaminated to other nonessential amino acids for protein synthesis, and that increased intramitochondrial branched-chain amino acid concentrations may enhance glutamate dehydrogenase activity. This anabolic metabolism will contribute to the fetal growth and development.


Urodilatin and atrial natriuretic peptide are present in the urine of healthy neonates and young infants. Urine sampling has been proposed as noninvasive monitoring of plasma atrial natriuretic peptide (ANP) in neonates, assuming urine contains only filtered plasma ANP. Recently, urodilatin, another natriuretic peptide, which is cross-reactive to ANP in the ANP radioimmunoassay (ANP-RIA), has been isolated from the urine of adults. We studied the urine of healthy term neonates and young infants for the presence of urodilatin. In all urine samples, we found three peaks of ANP-RIA-reactive material: the first one in the position of urodilatin, the second one coeluting with synthetic ANP and a third late eluting peak, possibly containing degradation products. The physiological significance of these findings remains to be investigated.


Some animal models for the study of perinatal asphyxia. Much of our current understanding concerning the pathophysiology of perinatal brain disorders has evolved from animal studies over the past three decades. Fetal and neonatal nonhuman primate, pregnant sheep, lamb, puppy, piglet and immature rodents, all have been important animal models for perinatal brain research. Although no model can be considered 'perfect' in reflecting the variety and complexity of human brain pathology, the investigator must assess the merits and limitations of each model within the framework of the research questions being asked. A variety of experimental designs have been used over the years and variations of particular interest are the animal age, the method of producing brain insult and the procedures used for evaluating outcomes. Most models relating to the study of intracranial hemorrhage, cerebral blood flow and cerebral energy metabolism have generally been acute preparations. Some important long-term survival models have also been developed in recent years for the study of hypoxic-ischemic encephalopathy. The latter include the nonhuman primate, piglet, sheep and immature rat models. In this article, I have reviewed some important animal models used in perinatal brain research with emphasis on those relating to perinatal asphyxia and intracranial hemorrhage.


Effect of glucose on perinatal hypoxic-ischemic brain damage. Investigations suggest that hyperglycemia superimposed on hypoxia-ischemia or cerebral ischemia accentuates brain damage in adult experimental animals and humans. Such does not appear to be the case in immature animals. The present review discusses fundamental differences in immature and adult brain metabolism which account for the age-specific paradox. Based on currently available data, it is recommended that glucose supplementation not be curtailed during labor and delivery of asphyxiated human infants; on the contrary, glucose therapy might substantially reduce hypoxic-ischemic brain damage.


Brain injury in the premature infant--current concepts of pathogenesis and prevention. Brain injury in the premature infant and, particularly, the prevention of that injury is an enormous problem. With modern neonatal intensive care, approximately 85% of very low birth weight infants survive, and of these survivals, approximately 5-15% exhibit major spastic motor deficit, grouped under the rubric, 'cerebral palsy', and an additional 25-50% exhibit less prominent developmental disabilities, particularly school failure.


Ischaemia of the preterm brain.

Ischaemia of the preterm brain. Much has been learned about the diagnosis and prognosis of periventricalar leucomalacia during the past 10 years. The understanding of its causation, however, has not advanced much. Still, the candidate for the principal role is focal ischaemia in the particularly vulnerable regions of the brain. It has been difficult to provide direct supportive evidence for this hypothesis. It has not been possible to define a threshold for (global) cerebral blood flow (CBF) under which brain damage or electrical dysfunction occurs. Three hypothetical explanations for the lack of clear relation between global CBF and electrical brain activity of the preterm infant must be examined more closely: (1) the very low levels of CBF are adequate, (2) global CBF does not reflect the perfusion of the white matter, or (3) acute white-matter ischaemia does not result in cerebro-electrical dysfunction. In view of the practical importance, more research is indicated.


Perinatal pharmacology and cerebral blood flow. Many of the drugs used in neonatal intensive care units might impede cerebral blood flow, thereby increasing the risk of intraventricular hemorrhage and periventricular leukomalacia. Our studies focussed on sick preterm neonates who were treated with the following drugs: caffeine (20 mg/kg i.v., as caffeine citrate); phenobarbital (loading dose: 20 mg/kg); indomethacin (0.2 mg/kg/dose, every 12 h three doses), and synthetic surfactant (Exosurf; 50 mg/kg = 5 ml/kg intratracheally). All of the drugs studied, except indomethacin, had no adverse effect on cerebral hemodynamics.


Intrauterine blood flow and postnatal neurological development in growth-retarded fetuses. Intrauterine growth retardation (IUGR) is associated with abnormal neuro-developmental outcome. Aortic blood flow velocity waveforms have been shown to predict fetal distress in IUGR. Fetal aortic blood flow velocity waveforms were correlated to neuro-developmental performance at 7 years of age. Results suggest that abnormal fetal aortic blood flow velocity waveforms are associated with neuro-developmental impairment.


Cerebral function in the growth-retarded fetus and neonate. Intrauterine growth retardation is associated with increased risks for permanent neurological disabilities. A series of studies was undertaken to elucidate whether fetal growth retardation causes a primary perturbation of brain function and development and whether an increased vulnerability for periods of oxygen lack exists. In two groups of neonates who were small for gestational age (SGA) evoked potentials were investigated. A high frequency of abnormal recordings were obtained in SGA babies. SGA babies had significantly longer latency periods for the primary evoked potentials than appropriately grown controls. In guinea pigs and rats growth retardation was induced by reducing the placental blood flow during late gestation. Growth retarded guinea pups demonstrated a considerable reduction of the ability to retain normal somatosensory evoked response during hypoxia compared to appropriately grown littermates. Growth retarded rat fetuses exhibited marked changes of the monoamine metabolism in the brain inasmuch as basal levels of serotonin and its main metabolite were low while an inappropriate acceleration of the serotonin synthesis rate took place during hypoxia. The tissue concentrations of aspartate were also significantly lower in growth retarded fetuses than normally grown littermates. Finally, lipid peroxidation was assessed. During adequate oxygenation no difference was observed when lipid peroxidation was assessed. During adequate oxygenation no difference was observed when lipid peroxidation in brain tissue of growth retarded and appropriately grown fetuses was compared but during mild-moderate hypoxia lipid peroxidation was significantly more intense in the growth retarded group.(ABSTRACT TRUNCATED AT 250 WORDS)


Doppler ultrasound and the neonatal cerebral circulation: methodology and pitfalls. Doppler ultrasound is a popular technique for investigating the haemodynamics of the neonatal cerebral circulation. Different types of instrumentation are available of which a duplex scanner is a suitable choice for spot measurements, whilst a simple continuous wave directional Doppler may be better for long-term monitoring purposes. Doppler signals may be obtained from many arterial and venous sites within the neonatal brain, but most measurements are made from the anterior or middle cerebral arteries. It is usual to process the Doppler signal to obtain an envelope waveform which may represent either mean velocity or maximum velocity, although the latter has some distinct advantages. The zero-crossing detector used for early studies is unsuitable for use with Doppler signals. Changes in the shape of the velocity waveform may be quantified using different methods, of which the so-called resistance index is the most popular. It is also possible to make absolute velocity measurements, although these cannot be converted to flow because it is not possible to measure the diameter of neonatal cerebral vessels. There is considerable controversy as to whether the diameter of the vessels at the sites of ultrasound insonation can be affected by factors such as blood pressure and arterial gases, but it is unlikely that any such changes could invalidate the basic findings of Doppler studies. With care and attention to detail, Doppler ultrasound provides a valuable window on the neonatal cerebral circulation.


Hemodynamic foundation of umbilical arterial Doppler waveform analysis. This paper reviews various in vitro and in vivo studies which have been conducted to investigate the influence of central and peripheral circulatory factors on the Doppler indices. These studies indicate that the Doppler indices are affected by both central and peripheral hemodynamics. Of the central factors, the heart rate influences the indices predominantly through the variations during the diastolic phase of the cardiac cycle. This was confirmatory of the clinical findings. Of the other central factors, cardiac contractility may not affect the rising slope of the Doppler waveform. Regarding the peripheral hemodynamics, both in vitro and in vivo studies confirm that the indices reflect the changes in the peripheral resistance; however, opposition to flow in a pulsatile flow can be adequately described only by impedance. Initial in vivo and in vitro studies demonstrate that the indices correlate well with the impedance parameters. However, this is true only when the central circulation remains stable.


Near infrared spectroscopy. Investigation and assessment of perinatal brain injury. Near-infrared spectroscopy is a new technique for noninvasive monitoring of tissue oxygenation and haemodynamics. Quantitative measurements can be made of oxyhaemoglobin, deoxyhaemoglobin, oxidized cytochrome and various haemodynamic indices. This technique is likely to prove increasingly valuable for: cot-side monitoring brain oxygenation and haemodynamics in babies; investigating the mechanisms of damage to the brain; according the results of treatment; and assigning long-term prognosis.


The dexamethasone suppression test in children and adolescents: a review and a controlled study. Dexamethasone Suppression Test (DST) studies conducted in children and adolescents are reviewed, together with factors hypothesized to explain discrepancies in rates of DST nonsuppression across studies. These factors are then examined in a controlled study of 27 adolescents with major depressive disorder (MDD) and 34 normal controls (NC). Subjects were given 1 mg of dexamethasone at 11:00 PM, and the following day serum samples for cortisol were collected each hr from 8 AM to 11 PM through an indwelling catheter. There were no significant differences found between the MDD and NC subjects on any postdexamethasone cortisol measure. Further, cortisol suppressors and nonsuppressors were not distinguished by any of the hypothesized factors identified from the review, including inpatient status, presence of suicidality, endogenous features, psychotic symptoms, or prior history of MDD. Questions about the appropriateness of the 1 mg dose of dexamethasone (currently the standard dose used with adolescents) are raised, together with a discussion of the effects of stress on DST findings.


Changes in middle cerebral artery velocity after marijuana. Velocity of blood flow in the middle cerebral artery was measured with transcranial Doppler flowmeter before, during, and 1 hr after smoking a marijuana cigarette and a placebo cigarette during two separate visits to the laboratory. Ten healthy, right-handed male volunteers with a history of marijuana smoking took part in the study. The participants were drug-free for a minimum of 3 mo before the project. During the experiment, blood pressure, pulse rate, and end tidal levels of carbon dioxide were continually monitored. Marijuana smoking was associated with a significant increase in middle cerebral artery velocity. Although marijuana smoking was associated with increased pulse rate, the changes in blood velocity and pulse rate followed different time courses. Marijuana smoking was not associated with significant changes in blood pressure or end tidal carbon dioxide.


The morphology of lipopigment in rat Purkinje neurons after chronic acetyl-L-carnitine administration: a reduction in aging-related changes. The aging-related accumulation of neuronal lipopigment is considered to be cellular debris from processes of renewal of cellular constituents, but it can also reflect cell damage and certain diseases. Acetyl-L-carnitine (AC) has been reported to reduce some morphological and behavioral associations of brain aging and the present study investigated the effects of 37 weeks of AC administration on lipopigment in rat Purkinje neurons. Lipopigment was identified by fluorescence microscopy and the area enclosed by an outline of each discrete region of lipopigment was measured. Acetyl-L-carnitine was associated with a significant (p = 0.05) reduction in the number of discrete lipopigment regions and there was a significant (p = 0.001) association of AC administration with numbers of lipopigment regions in various size categories. As AC administration was associated with a reduction in some of the aging-related morphological changes in lipopigment, this compound is a candidate for evaluation as a long-term prophylactic agent for the adverse effects of cerebral aging.


An olfactory-limbic model of multiple chemical sensitivity syndrome: possible relationships to kindling and affective spectrum disorders. This paper reviews the clinical and experimental literature on patients with multiple adverse responses to chemicals (Multiple Chemical Sensitivity Syndrome-MCS) and develops a model for MCS based on olfactory-limbic system dysfunction that overlaps in part with Post's kindling model for affective disorders. MCS encompasses a broad range of chronic polysymptomatic conditions and complaints whose triggers are reported to include low levels of common indoor and outdoor environmental chemicals, such as pesticides and solvents. Other investigators have found evidence of increased prevalence of depression, anxiety, and somatization disorders in MCS patients and have concluded that their psychiatric conditions account for the clinical picture. However, none of these studies has presented any data on the effects of chemicals on symptoms or on objective measures of nervous system function. Synthesis of the MCS literature with large bodies of research in neurotoxicology, occupational medicine, and biological psychiatry, suggests that the phenomenology of MCS patients overlaps that of affective spectrum disorders and that both involve dysfunction of the limbic pathways. Animal studies demonstrate that intermittent repeated low level environmental chemical exposures, including pesticides, cause limbic kindling. Kindling (full or partial) is one central nervous system mechanism that could amplify reactivity to low levels of inhaled and ingested chemicals and initiate persistent affective, cognitive, and somatic symptomatology in both occupational and nonoccupational settings. As in animal studies, inescapable and novel stressors could cross-sensitize with chemical exposures in some individuals to generate adverse responses on a neurochemical basis. The olfactory-limbic model raises testable neurobiological hypotheses that could increase understanding of the multifactorial etiology of MCS and of certain overlapping affective spectrum disorders.


Platelet and whole blood serotonin content in depressed inpatients: correlations with acute and life-time psychopathology. Platelet or whole blood serotonin content did not differ significantly in patients with major depression compared to healthy controls, but within the patient group, platelet serotonin levels correlated negatively with severity of depression (r = -0.49, p = 0.007). Levels were 39% lower in patients who had made a suicide attempt compared to nonattempter patients (47.2 +/- 27.3 versus 77.6 +/- 41.7 ng/10(8) platelets, p = 0.04). Conversely, comorbid borderline personality disorder (85.3 +/- 41.5 ng/10(8) platelets) was associated with 31% greater platelet serotonin content than nonborderline patients (58.9 +/- 31.1 ng/10(8) platelets) and 27% greater than healthy controls (62.4 +/- 19.8 ng/10(8) platelets). A pronounced seasonal variation in whole blood and platelet serotonin content was found in both patients and controls, largely due to lower levels in summer. Excluding cases tested in the summer abolished the statistically significant differences in patients with and without comorbid borderline personality disorder (BPD). Nevertheless, BPD attempters had lower serotonin levels than BPD nonattempters but higher serotonin levels than non-BPD attempters. Current hostility and a life-time history of aggression were positively correlated with platelet serotonin content (r = 0.44, p = 0.04 and r = 0.41, p = 0.06). This study provides evidence for an association between lower platelet serotonin content and depression and suicidal behavior, and association of higher platelet serotonin content and comorbid borderline personality disorder and behavior traits such as aggressivity.


Clozapine in the treatment of dysphoric mania. Seven patients with bipolar disorder, characterized by dysphoric mania with psychotic features and chronic disability, refractory to standard treatments and anticonvulsants, all showed marked symptomatic and functional improvement when given the atypical antipsychotic clozapine. During follow-up over 3-5 years, most of the patients sustained substantial gains in psychosocial function; and of the six patients remaining on clozapine, no further hospitalizations were needed. This remarkable improvement in a severely ill group of patients suggests that clozapine may have utility in the treatment of bipolar disorder as well as schizophrenia.


Exercise tolerance in panic disorder patients. Sixteen panic patients and fifteen normal controls performed submaximal exercise testing on a bicycle ergometer. Only one patient subject panicked. Biochemical, physiological, and psychological data showed similar exercise tolerance in both patients and controls. Exercise-induced distress and lactate increment do not appear to cause panic attacks.


The contribution of constructional accuracy and organizational strategy to nonverbal recall in schizophrenia and chronic alcoholism. The Rey-Osterrieth complex figure was used to assess the separate influences of the constructional accuracy and the organizational strategy employed while copying the figure on the later, incidental recall of the figure. We tested a model, which hypothesized that subjects who copied the main framework of the figure holistically would be more likely to achieve good copy accuracy scores and to reproduce the figure more accurately at recall than subjects who used a piecemeal approach during copy. Subjects included 68 detoxified, chronic alcoholics (ALC), 28 patients with schizophrenia (SZ), and 69 normal control subjects (NCS). The results showed that the ALC and the SZ groups, on average, had lower accuracy and strategy scores at copy than did the NCS group, and furthermore, that the combined contributions of copy accuracy and copy strategy accounted for group differences at recall. A path analysis revealed that, for all three groups, copy strategy had a significant direct effect on copy accuracy. Moreover, copy accuracy and copy strategy made independent contributions to recall accuracy within the ALC and NCS groups; by contrast, within the SZ group, copy strategy made an independent contribution to recall performance but copy accuracy did not. These results suggest that (1) organizational strategy can influence constructional accuracy at both copy and recall; (2) copy accuracy and strategy have the potential to influence recall independently; and (3) the recall deficit in ALC could be attributed to abnormalities in both accuracy and strategy at copy, whereas in SZ it could be attributed only to strategy abnormalities. The deficits observed on the complex figure test in the ALC and SZ were primarily nonmnemonic and were related to ability in figure construction and organizational strategy.


Sympathoadrenomedullary activity in the neuroleptic malignant syndrome. Many clinical features of the neuroleptic malignant syndrome suggest that sympathetic nervous system hyperactivity is involved in the pathophysiology of this disorder. Only a few studies have examined levels of catecholamines or their metabolites in patients with NMS; results so far have been inconclusive. In the present study urinary catecholamine metabolites obtained during the course of NMS were studied with respect to frequently reported signs and symptoms of NMS. The principal findings are that (1) elevated urinary catecholamines and metabolites are a frequent but inconstant feature of NMS; (2) it is likely that sympathetic nervous system hyperactivity contributes to the picture of fulminant NMS; and (3) the role of the adrenal medulla in producing excess catecholamines during NMS is uncertain.


Effect of 12-hour infusion of naloxone on mood and cognition in normal male volunteers. The effects of a 12-hour naloxone infusion on mood, cognition, and plasma cortisol levels were evaluated in eight normal subjects. The dosage used was a 10 mg dose plus 7 mg/hr (total = 94 mg). Naloxone induced a significant rise in serum cortisol and also induced cognitive impairment, as shown by increased choice reaction time, reduced ability to recall the order of letters and numbers, and reduced accuracy of spatial orientation. The rise in cortisol induced by naloxone was significantly correlated with the rise in the Profile of Mood Scale (POMS) score, indicative of dysphoria. Finally, performance on the spatial orientation task was highly negatively correlated with the peak POMS score after naloxone. From these data and previous studies it is concluded that opioid receptors of low sensitivity to naloxone may mediate a common mechanism regulating the pituitary-adrenal axis' mood, and cognitive function during stress. Personality traits may account for the large individual variability reported in previous studies.


Low plasma gamma-aminobutyric acid levels in male patients with depression. Plasma levels of gamma-aminobutyric acid (GABA) were significantly lower in males with primary unipolar major depressive disorder than in healthy controls. Although the difference in means between control and symptomatic depressed patient groups was small, the distribution of plasma GABA in the depressed patients was markedly different from controls. Forty percent of depressed patients had plasma GABA levels below those of controls. Plasma GABA levels correlated positively with duration of illness, and negatively with age at onset of the mood disorder and the total Endogenomorphic Symptom Score on the Hamilton Rating Scale. Plasma GABA levels may be a biochemical marker of vulnerability to depression, as opposed to a consequence of the illness. A low GABA condition in depression fits and complements the prevailing biogenic amine hypotheses of depression.


Asterixis induced by carbamazepine therapy. There are very few reports about asterixis as a side effect of treatment with psychopharmacologic agents. In this report we present four patients treated with a combination of different psychotropic drugs, in whom asterixis was triggered either by adding carbamazepine (CBZ) to a treatment regimen, or by increasing its dosage. Neither dosage nor serum levels of CBZ were in a higher range. We consider asterixis to be an easily overlooked sign of neurotoxicity, which may occur even at low or moderate dosage levels, if certain drugs as lithium or clozapine are used in combination with CBZ.


Lipids in psychological research: the last decade. We review the recent literature examining lipid changes during stressful experiences, and the psychological and constitutional differences that influence lipid levels at rest and that may modulate lipid response to stress. Mild forms of chronic or episodic stress are apparently not associated with alterations in lipids and lipoproteins, but severe forms of real or perceived stress do appear to alter lipid levels. Acute laboratory stress is frequently associated with short-term alterations in lipids and lipoproteins, but the significance of these changes is unclear. Several individual characteristics, such as heightened neuroendocrine or autonomic reactivity to stressors, Type A component behavior, and other aspects of personality, appear to be associated with an atherogenic lipid profile. Stress may influence lipid concentrations and metabolism through a variety of physiological and behavioral mechanisms, but none have been clearly elucidated. Future research should concentrate on understanding these mechanisms.


Serum lipids, neuroendocrine and cardiovascular responses to stress in healthy Type A men. This study examined the relationship between serum lipid activity in healthy Type A men and cardiovascular and neuroendocrine responses to a behavioral stressor, mental arithmetic. Assessment of blood lipids included measures of total cholesterol (TC), low density lipoprotein cholesterol (LDLC), high density lipoprotein cholesterol (HDLC), and serum triglycerides. Cardiovascular (blood pressure and heart rate) and neuroendocrine (epinephrine, norepinephrine and cortisol) responses were recorded before (rest), during (stress) and after (recovery) the mental arithmetic test. Diastolic blood pressure, mean arterial pressure and, to a lesser extent, systolic blood pressure levels at rest, during stress, and at recovery correlated positively with TC levels. In addition, both diastolic and mean arterial pressure were positively correlated with the ratio of TC to HDLC and with triglycerides during stress and recovery. Heart rate did not correlate with any lipid measure. Cardiovascular stress-reactivity calculated as change from rest to stress did not correlate significantly with any lipid measure. Plasma norepinephrine during stress correlated positively with triglycerides; a similar trend was observed for the TC/HDLC ratio. Plasma cortisol at rest and during stress correlated positively with the TC/HDLC ratio and serum triglycerides, and negatively with HDLC. Plasma norepinephrine reactivity calculated as change from rest to stress correlated negatively with HDLC and positively with triglycerides. In addition, cortisol reactivity was positively correlated with triglycerides. It is suggested that the mechanisms mediating Type A behavior and coronary heart disease may include increased cardiovascular and neuroendocrine responses as well as unfavorable lipid profiles.


Time effects on event-related brain potentials and vigilance performance. A review of the literature showed that in vigilance or oddball tasks, changes over time in event-related potentials (ERPs) and performance measures often seem to be unrelated, but a number of studies had some shortcomings. In the present study a visual vigilance experiment was carried out, in which single-trial ERPs and performance data of 40 males were obtained. A relationship between time trends in behavioral and ERP measures was found: an early P3 amplitude and response latency (RT) showed an inversely varying relation over time. Analysis of covariance showed that the two linear trends tap the same aspect of processing: both trends became insignificant when adjusted for common variance. A negative correlation between mean values of P3 amplitude and RT rather than for change scores has been observed in previous studies, but has been ignored in the literature. However, correlations with RT have also been reported for other ERP deflections. Although there were several correlations between mean scores, most time-induced changes in ERP parameters appeared to be unrelated to worsening performance, for which several explanations are advanced. The ERP results do not support the hypothesis that a decrement in performance is caused by increasing difficulty discriminating targets from nontargets. A gradual decline in effort or resources allocated to the task might be an alternative explanation of performance deterioration. However, an effort-hypothesis cannot easily be tested. Effort is often invoked post hoc, and has previously been associated with many ERP components. The relationship between ERPs and the signal detection measures "sensitivity" d' and "response bias" beta is discussed.


[A prospective study on temporary and permanent sensation disorders after oral surgical measures in the lateral mandibular area]. Postoperative disturbances of sensory nerve function after dentoalveolar surgery imply forensic problems. Also the indication of microsurgical reconstruction will be discussed in these cases as well. Both questions can only be seen on the background of data material concerning those nerve complications. Therefore a clinical prospective study on functional disturbances of the inferior alveolar as well as the lingual nerve after dentoalveolar surgery in 1.107 cases was undertaken. Concerning the inferior alveolar nerve 2.2% of temporary functional disturbances were assessed while 1.4% of temporary functional disturbances for lingual nerve were found. Complete restoration of sensory function was found three months postoperatively in 20% of these cases and six months postoperatively in the remaining patients.


[Initial clinical experiences with the photodynamic therapy (PDT) of oral cavity carcinomas]. Photodynamic therapy (PDT) is based on the selective accumulation of photosensitizing agents in tumor tissues. Activation of the photosensitizer with ligh of suitable wavelength leads to tumor destruction preserving healthy tissues. 13 carcinomas stage T1 and T2 of the oral cavity in men were treated. Necroses of a depth from 1.5 to 6 mm occurred regularly. Therefore photodynamic therapy seems to be suitable to treat small, superficial cancers of the oral cavity, especially, if the tumors are multilocated.


[The use of the T-Scan system in occlusal diagnosis]. The present study examines the T-Scan reproduction system used in occlusal diagnosis. The system represents a major technical innovation in functional diagnostics. Nevertheless, various aspects of it still require improvement. Amplifying or confirming the results of previous studies, the following observations are intended to indicate how the system might be improved, and how it can be reliably used at present: The reproduction afforded by the sensor as situated in the mouth is insufficient. Exact reproduction of the topography of the occlusal contacts is not possible. Reproducibility of the temporal sequence of the contacts is slight. The registering of dental functional movements can give rise to errors of interpretation. Threshold values for the registration of contact points in the system's pressure mode are uneven. The relative reproduction of different impressions is unreliable. Since in the system's pressure-mode early contacts cannot be distinguished from strong physiological contacts, in clinical practice the former must first be identified using the time-mode.


[The effect of the interocclusal space on temporomandibular recordings. A study with the use of the Stereognathograph PC]. 1536 recordings of the condylar movement of 32 patients were made by means of the Stereognathograph PC. The test persons performed mediotrusive and protrusive movements. These movements were recorded with tooth contact and with increased interocclusal space, with and without the clinician's supportive guidance. The objective of the study was to analyse the effects of increased interocclusal space on the recording of the condylar path. Statistical evaluation showed that neither procedure has any real advantage over the other. Both, the occlusal tray as well as the paraocclusal tray may, depending on clinical situation of the ligaments, lead to erroneous recordings. The reproducibility of the recording of the condylar path is only slightly decreased by increased interocclusal space. Considering, however, the amount of work involved in each procedure, the occlusally fixated tray should probably be given preference, when there is no intention of recording occlusal guided movements.


[Mandibular positions in complete dentures according to the calotte principle]. A total of 37 patients was provided with complete dentures according to the calotte system. Two groups were formed with regard to the arrangement of the anterior teeth. After a mean period of wear amounting to 13 months different positions of the mandible were recorded in 21 patients under the guidance of a central bearing point and in occlusion. Patients with an arrangement of the anterior teeth free of interferences in excursive movements exhibited a significantly lower distance habitual occlusion/retruded position than subjects with an overlap limiting sagittal freedom. Therefore, an arrangement of the anterior teeth integrated into the calotte complex respectively free of interferences in eccentric positions is to be preferred.


[Microbiological studies of self-disinfecting alginate impression materials]. Using microbiologically experimental methods and observations corresponding to praxis the efficiency of the addition of antiseptics to alginate is evaluated. The addition of chlorhexidine to the alginate leads to a considerable reduction of the amounts of germs, but an one hundred percent disinfection of the alginates is not always performed. An influence of the alginate materials and the water quality on the antimicrobial efficacy of chlorhexidine has been proved. The always occurring contamination of the impression tray rules out a complete stopping of infection between the patient and the laboratory staff.


[A clinico-histological study for the diagnosis and classification of spontaneous periodontal diseases in the dog]. Using standardized investigation methods periodontal parameters were proved for diagnostic application of spontaneous periodontal diseases in dogs. The diseases are classified in gingivitis simplex, g. granulomatosa, g. ulcerosa, g. hyperplastica, g. desquamativa, juvenile periodontitis, rapidly progressive p. and chronic p. This proposal can be used for further investigations in experimental dentistry and for therapeutic purposes in veterinary dentistry.


African-American women and abortion: a neglected history. The history of African-American women's efforts to control their fertility is largely unknown. From slavery to the present, the growth rate of the African-American population has been cut in half. Demographers and historians frequently attribute this change to external factors such as poverty, disease, and coerced birth control, rather than the deliberate agency of African-American women. This essay assembles a brief historical record of the ways African-American women have sought to control their fertility through the use of abortion and birth control. It also examines the activism of African-American women in the establishment of family planning clinics and in defense of abortion rights.


Correlates of health insurance coverage: evidence from the Midwest. The Midwest is often overlooked in national studies of health insurance status. We analyzed the economic and social characteristics of uninsured and underinsured individuals and households in a Midwestern state using both bivariate and multivariate techniques. As in much of the country, economic factors, particularly income and employment, were most significant in accounting for insurance coverage. Unexpectedly, rural and urban residents were equally likely to lack insurance. Results indicate that in rural areas, underinsurance may be a greater problem than uninsurance, and that income-based health insurance is more effective than employer-provided plans in reaching all Americans.


The relationship between primary care and life chances. Many researchers criticize clinical medicine for its failure to improve mortality rates. But in their critiques, few distinguish primary care from expensive, high-technology specialized care. This research is concerned with the empirical relationship between the availability of health services resources (i.e., primary care, specialty care, hospital beds) and certain "life chances," as measured by overall and disease-specific mortality rates, and life expectancy. The model shows a significant direct association between primary care and favorable mortality outcomes, though the same does not hold true for variables such as hospital beds or physician specialists. There should be greater emphasis on prevention-oriented primary care as a mechanism for health improvement and cost control.


Antibiotic-associated diarrhea.

Antibiotic-associated diarrhea. Diarrhea is clearly one of the most common side effects encountered with antimicrobial treatment. Virtually all drugs with an antibacterial spectrum of activity have been implicated, although there are definite differences in associated incidence rates that appear to depend on spectrum of activity and pharmacokinetic properties. Most cases of antibiotic-associated diarrhea can be classified in two categories: cases in which Clostridium difficile is implicated and cases in which no putative agent or recognized pathophysiological mechanism is clearly established. This review is intended to provide management guidelines for patients with diarrhea that occurs in association with antibacterial agents.


Neurobrucellosis: clinical and therapeutic features. Eighteen patients with neurobrucellosis are described. Eleven patients had meningitis alone or with papilledema, optic neuropathy, or radiculopathy. Four patients had meningovascular complications manifested by stroke or intracerebral hemorrhage from a presumed mycotic aneurysm. Two patients had parenchymatous dysfunction, including a child who had a cerebellar syndrome without evidence of direct infection of the central nervous system. One patient presented with polyradiculopathy. Twelve of 16 patients had pleocytosis; none had cell counts greater than 419 x 10(6)/L. Most patients had hypoglycorrhachia and elevated levels of protein in the cerebrospinal fluid (CSF). Results of an agglutination test for Brucella in serum were positive for all patients. Six of 16 patients had positive blood cultures, and four of 14 had positive CSF cultures. Antimicrobial treatment included concurrent administration of two or more of the following drugs: streptomycin, tetracycline (or doxycycline), rifampin, and trimethoprim-sulfamethoxazole. Eleven patients fully recovered. Five patients were left with residual neurological deficits. Four of these patients suffered permanent hearing loss, one of whom also had significant loss of vision in one eye. One elderly senile patient with meningovascular brucellosis remained in a vegetative state despite receiving antimicrobial therapy for 6 months. One patient died due to rupture of a mycotic aneurysm within 7 days of initiation of therapy. One other patient was treated after sustaining an intracerebral hemorrhage, but this patient's condition was diagnosed only after discharge.


Atypical papulovesicular rash due to infection with Rickettsia conorii. We present an unusual case of Rickettsia conorii infection that was associated with cutaneous papulovesicular lesions on a patient who had returned from the bushveld of South Africa. The lesions were diffusely scattered across the trunk, extremities, and both palms. Several recent reports have documented similar papulovesicular or pustulovesicular rashes that occurred on travelers returning from southern Africa. These rashes resemble the lesions of rickettsialpox. Evidence suggests that these atypical exanthems may be due to variant strains of R. conorii or to an unusual host response to infection with this organism; thus, infection with R. conorii should be included in the list of diseases that cause poxlike lesions.


Rhinoceros' rhinorrhea: cause of an outbreak of infection due to airborne Mycobacterium bovis in zookeepers. Seven of 24 zookeepers exposed to a Southern white rhinoceros infected with Mycobacterium bovis were presumably infected via aerosols generated in the cleaning of the barn for the rhinoceros. All demonstrated conversion by the intermediate-strength purified-protein-derivative skin test, but none had clinical illness. In certain occupational settings like zoos and abattoirs, exposure to M. bovis may be an occupational hazard, and routine periodic tuberculin screening should be performed.


Comparison of mycobacterial lymphadenitis among persons infected with human immunodeficiency virus and seronegative controls. Lymphadenitis is a common extrapulmonary manifestation of mycobacterial disease in persons with human immunodeficiency virus (HIV) infection. We compared the clinical, mycobacterial, and diagnostic characteristics of mycobacterial adenitis in 11 HIV-seropositive and 29 HIV-seronegative patients. Ninety-three percent of the HIV-seronegative patients and 54% of the HIV-seropositive patients were foreign-born. In contrast to the HIV-seronegative patients, seropositive patients were more likely to be febrile and have negative purified protein derivative skin tests and abnormal chest roentgenograms. Sputum samples were rarely diagnostic in either group. Mycobacterium tuberculosis was the most commonly isolated organism in both groups, although United States-born patients with HIV infection were more likely to be infected with nontuberculous mycobacteria. In contrast to results for seronegative patients, fine-needle aspiration was usually diagnostic in the HIV-seropositive population, especially in those at risk for M. tuberculosis infection. Similarly, the rate at which smears were positive for acid-fast bacilli was significantly higher in the HIV-seropositive group, a circumstance suggesting a higher burden of organisms in this population. Finally, although preceding opportunistic infections were uncommon in the HIV-seropositive group, both tuberculous and nontuberculous adenitis were associated with advanced immunosuppression.


Antibiotic susceptibility profiles of 941 gram-negative bacteria isolated from septicemic patients throughout Canada. The Canadian Study Group. The choice of antimicrobial therapy for the treatment of bacteremia is often empirical and based on the knowledge of antibiotic susceptibility profiles of the most common bacteria causing such infections. It therefore is crucial to survey the susceptibility of bacteria causing sepsis. This study examines the susceptibility profiles of 941 gram-negative bacteria, isolated from septic patients in 10 Canadian hospitals, to 28 antimicrobial agents. Among the isolates, 30 different species were represented; Escherichia coli dominated, representing 52.5% of isolates. More than 50% of all bacteria were resistant to ampicillin. Only 67% of the E. coli isolates were susceptible to ampicillin, while 30% of all strains were resistant to ticarcillin. Of the cephalosporins, ceftazidime and cefoperazone/sulbactam were the agents to which isolates were the most susceptible (90%). Only 51% of the E. coli strains were susceptible to cephalothin, while 91% were still susceptible to cefazolin. A total of 93% and 98% of the strains were susceptible to aztreonam and imipenem, respectively. Aminoglycosides were highly active against most isolates, in general in the following order: netilmicin greater than tobramycin greater than gentamicin greater than amikacin. Tobramycin was the most active against Pseudomonas aeruginosa. Nearly all isolates were susceptible to the quinolones. Tolerance (MBC/MIC ratio, greater than or equal to 32) was rarely observed. This survey of the susceptibility of gram-negative bacteria causing sepsis provides valuable information for implementing the chemotherapy for gram-negative septicemia and demonstrates that several older and newer agents, alone or in combination, can be used as adequate initial therapy for gram-negative sepsis in Canada.


Epidemiology of blastomycosis in a region of high endemicity in north central Wisconsin. The clinical and epidemiologic features of 73 patients with laboratory-confirmed blastomycosis who were identified over an 11-year period in North Central Wisconsin are presented. Pulmonary disease was the sole manifestation in 77% of patients. More than one-half of all patients had symptoms that included fever, cough, weight loss, night sweats, and pleuritic chest pain. Virtually all were previously healthy, and most did not have an outdoor occupation. However, 82% of these patients lived or had visited within 500 m of rivers or associated waterways. The majority experienced the onset of symptoms between December and April. The estimated mean annual incidence rate of infection for Vilas County was 40.4 cases per 100,000 persons, and that for the largest city in the county was 101.3 cases per 100,000 persons. Several areas with an exceptionally high incidence of the infection were observed. We suggest that, in regions where blastomycosis is hyperendemic, clinical disease is most often pulmonary and occurs in immunocompetent individuals and that residence near an ecological focus may be a greater risk factor for acquisition of blastomycosis than is occupation.


Acute pubic osteomyelitis in athletes.

Acute pubic osteomyelitis in athletes. Three cases of pubic osteomyelitis in athletes are reported. The clinical presentation in each case was acute groin, hip, or perineal pain; fever; chills; inability to bear weight; and pubic symphysis tenderness. Since radiographic changes in the pubic bone can be delayed, a high index of suspicion is required by the clinician. Although Staphylococcus aureus is the dominant pathogen in pubic osteomyelitis, it is recommended that the diagnosis be established by culture of blood or pubic bone aspirate so that specific therapy can be instituted quickly.


Phaeohyphomycosis due to Exophiala species: clinical spectrum of disease in humans. Phaeohyphomycosis caused by Exophiala species is an unusual infection, but it has been reported with increasing frequency as immunosuppressive therapy has become more widespread and laboratory methods for diagnosis have improved. To our knowledge, the first case of subcutaneous phaeohyphomycosis due to Exophiala jeanselmei in a cardiac transplant patient is presented, and previously reported cases of exophiala infection are reviewed. This patient was successfully managed with surgical excision of the lesion and combination therapy with amphotericin B and 5-fluorocytosine.


Unusual manifestations of Yersinia enterocolitica infections diagnosed using novel methods. We report the cases of two patients who had infections due to Yersinia enterocolitica. The first patient exhibited chronic recurrent fever, hepatic and splenic granulomas, and bone marrow abnormalities, and the second patient presented with enterocolitis with leukocytoclastic vasculitis of the skin. Cultures and agglutination titers were negative. Indirect immunofluorescence techniques with use of serotype-specific antisera and antisera to Yersinia outer-membrane proteins (Yops) were applied to biopsy specimens, and immunoblotting techniques for determining class-specific circulating antibodies to Yops were used for demonstrating these unusual manifestations of Y. enterocolitica infections.


Concepts on the use of liposomal antimicrobial agents: applications for aminoglycosides. Liposomes are microscopic lipid vesicles consisting of one or more concentric phospholipid bilayers enclosing discrete aqueous spaces. Liposomes provide an apparently nontoxic biological delivery system for hydrophobic and hydrophilic drugs. With few exceptions liposomal antimicrobial drugs are administered intravenously, although other routes have been investigated. Intravenously administered, conventionally prepared vesicles are rapidly cleared from the blood principally by phagocytic cells of the mononuclear phagocyte system (MPS), in particular by macrophages located in the liver (Kupffer's cells) and spleen. The expectation that liposomes would provide a new form of drug carrier capable of diverse physiological selectivity has not been realized. The low endocytotic capacity of many cell types and the inability of liposomes to transverse continuous vascular endothelia have prevented the active targeting of non-MPS tissues with liposomes. Despite their well-documented toxicity and the development of new antimicrobial classes, aminoglycosides continue to have an important antimicrobial role. The encapsulation of aminoglycosides into liposomes may reduce the toxicity associated with the multiple daily administration often required for patients with normal renal function. In addition, the encapsulation of aminoglycosides alters their pharmacokinetics, increases t1/2 and area under the curve, decreases Vd and Cpmax, and causes a shift in drug accumulation from the kidney to other organs, thus potentially reducing nephrotoxicity. Studies demonstrate improved outcome for intracellular infections treated with liposomal aminoglycosides vs. free aminoglycosides. Unresolved questions include what role liposomal aminoglycosides have in the treatment of extracellular infection and whether their sustained release action will promote resistance.


Pyomyositis in North America: case reports and review. We report two cases and review the characteristics of pyomyositis. The courses of patients who presented with pyomyositis at the Maricopa Medical Center (Phoenix) are detailed. Ninety-eight reported cases over the last 20 years in North America, found through a MEDLINE search, are summarized. Infection with the human immunodeficiency virus (HIV) may predispose the patient to pyomyositis. The onset is usually insidious with progression to large purulent collections and significant morbidity. The diagnosis is frequently suggested by findings of imaging studies. Staphylococcus aureus is responsible for most cases in tropical areas but is less frequently associated with cases in North America. Since infection with HIV predisposes patients to bacterial infections, pyomyositis will occur more frequently in this patient population. Increased awareness of the disease will improve management. Following aspiration or surgical drainage, therapy with broad-spectrum empirical antibiotics may be considered initially in the treatment of pyomyositis.


Maternal-fetal transmission of human immunodeficiency virus: a review of possible routes and cellular mechanisms of infection. The prevalence of human immunodeficiency virus (HIV) infections among children is increasing in a manner that closely follows the spread of the disease among women. Despite the fact that in utero transmission via the placenta is though to play a major role in the spread of HIV to the pediatric population, little is known about the timing, route(s), and cellular mechanisms by which maternal-fetal transmission occurs. This review attempts to use a developmental and cellular approach to assess the available clinical and laboratory data pertaining to maternal-fetal HIV transmission. While much of this review focuses on the role of the placenta, particularly the placental trophoblast, on the transmission of HIV, potential routes of infection during early development are also discussed. Clinical studies indicate that the placental trophoblast can be infected with HIV but have shed no light on how the virus gains entry to this tissue. While some laboratory studies confirm that trophoblast cells and placental macrophages can be infected with HIV in vitro, many studies are difficult to interpret because of inadequate characterization of the placental cells used. The role of CD4 in the infection of trophoblast remains controversial and clearly warrants a systematic examination. It is also apparent that viral tropism has not received enough attention and more studies using different strains of HIV are required. Thus, several basic questions remain to be answered before strategies to prevent maternal-fetal transmission of HIV can be developed.


Tuberculosis of the breast as a presenting manifestation of AIDS. Tuberculous infections of the breast are considered rare in the developed world. We describe a case of mammary tuberculosis in a woman who was not initially known to be seropositive for the human immunodeficiency virus (HIV) and who was thought to have a pyogenic breast abscess. This uncommon presentation of extrapulmonary tuberculosis as an AIDS-defining condition highlights the necessity for performing mycobacterial smears and cultures in such cases when patients are at risk for HIV infection.


Central venous catheter sepsis caused by unusual Gordona (Rhodococcus species: identification with a digoxigenin-labeled rDNA probe. We describe central line sepsis caused by Gordona (Rhodococcus) species in two patients, which complicated receipt of long-term total parenteral nutrition at home. Species identification was attempted by conventional biochemical analysis and analysis of polymorphisms in the ribosomal RNA genes with use of a digoxigenin-labeled rDNA probe. Using these techniques, we identified our first patient's isolate as Gordona terrae. The isolate from our second patient was biochemically atypical and could not be reliably matched to any of the recognized Gordona (Rhodococcus) species. To our knowledge, these patients are the first to have been reported with systemic infection caused by Gordona (Rhodococcus) species. The first patient's infection resolved after 6 weeks of intravenous therapy with vancomycin with the catheter left in situ; however, infection in the second patient required catheter removal for cure. These cases show that immunocompetent patients receiving long-term parenteral nutrition may develop central line infections with these unusual species of microorganisms.


Isolated pulmonary aspergillar infection in cardiac transplant recipients: case report and review. The optimal type and duration of antifungal therapy for localized aspergillosis in cardiac transplant recipients is unclear. We report the case of a patient who had persistent invasive pulmonary aspergillosis despite prolonged treatment with amphotericin B. A combined approach using antifungal therapy and surgery appears effective for localized pulmonary disease. Aspergillar infection in solid organ transplant recipients is reviewed.


Biliary concentrations of fluconazole in a patient with candidal cholecystitis: case report. A patient with acute cholecystitis due to Candida albicans and Candida parapsilosis was treated with a percutaneous cholecystostomy and daily intravenous fluconazole. Fluconazole levels in serum and bile were measured by gas chromatography. Fluconazole levels in the bile were equal to those in the blood for the first 8 hours after a dose and were slightly higher than serum levels after that. Bile levels after an oral dose of fluconazole were 15% higher than levels achieved after intravenous administration of the drug. The infection was cured after 2 weeks of treatment. This experience suggests that sufficient fluconazole is excreted in the bile to be effective for treatment of biliary infections due to susceptible yeasts.


Meningitis due to Prototheca wickerhamii in a patient with AIDS. The first documented case of algal meningitis due to Prototheca wickerhamii is reported in a patient with AIDS. The initial CSF culture yielded only Cryptococcus neoformans. P. wickerhamii was isolated on four subsequent lumbar punctures. The patient died, and at autopsy the alga was isolated from leptomeninges over the brain and about the spinal cord. Histologic sections from numerous locations of the brain revealed masses of cryptococci and prototheca.


An unusual case of false-positive serology for the human immunodeficiency virus: report from the heterosexual HIV transmission study. A man was found to have a repeatedly positive enzyme immunoassay (EIA) that was confirmed by a western blot with six positive bands. He was told that he was seropositive for the human immunodeficiency virus (HIV), but subsequent EIAs were negative and western blots were either negative or indeterminant. All other HIV-related studies were unrevealing, and no explanation for the false-positive result was found. We have not absolutely eliminated the possibility of mislabeled specimens, but we believe this to be unlikely. The possibility, albeit infrequent, of concomitant false-positive EIAs and western blots should be kept in mind when formulating public policy with regard to HIV testing.


Lymphocutaneous Nocardia brasiliensis infection acquired from a cat scratch: case report and review. Nocardia brasiliensis is a bacterium that is most commonly found in the soil. Traumatic inoculation of N. brasiliensis into the skin is the most typical mode of acquisition of infection due to this organism. To the best of my knowledge, I report the first case of lymphocutaneous N. brasiliensis disease from a penetrating cat scratch of the skin, thereby establishing cats as vehicles for the transmission of this infection. Treatment with penicillin produced a rapid resolution of all signs and symptoms of infection. The efficacy of penicillin against the N. brasiliensis isolate recovered from this patient was highly unusual. In general, penicillin has limited therapeutic value since these organisms elaborate beta-lactamase. Sulfonamides remain the drugs of choice for the treatment of these infections. These soil-borne organisms are most likely carried on the claws of cats and may establish infection after percutaneous inoculation. A high index of suspicion for N. brasiliensis soft-tissue infection is required since a delayed or missed diagnosis may be associated with progressive local disease and/or widespread disseminated infection.


Adenovirus pneumonia with severe sequelae in an immunocompetent adult. Notable complications from adenovirus pneumonia in healthy adults are rare. We report a well-documented case of adenovirus type 3 infection in a previously well adult woman that resulted in severe pulmonary complications as well as self-limited ocular, hepatic, and gastrointestinal abnormalities.