A retrospective review of 61 patients with antiphospholipid syndrome. Analysis of factors influencing recurrent thrombosis

BACKGROUND: Antiphospholipid syndrome (APS) is a disorder of recurrent venous or arterial thrombosis, pregnancy losses, and thrombocytopenia. Recurrent thrombosis has particularly adverse effects on patients prognosis. The factors that influence recurrence and management techniques that prevent these events remain controversial. To add further insight regarding predisposing factors and the prevention of thrombotic recurrence, 61 well-characterized patients with APS were followed up for a median time of 77 months. METHODS: A retrospective cohort study was conducted in which the following factors were examined to determine their influence on thrombotic recurrence: primary vs secondary syndrome; the presence of hypertension, hyperlipidemia, diabetes, or smoking; patient age, sex, and race; pregnancy and oral contraceptives use; and treatment with warfarin sodium, warfarin plus aspirin, aspirin alone, prednisone, or no treatment. RESULTS: There was no difference between patients with primary and secondary APS with respect to recurrent arterial (55% vs 38%, respectively) or recurrent venous (47% vs 50%, respectively) thrombotic events. In all patients with APS, white race (P = .02) was associated with recurrent arterial events. Venous thrombosis occurred during pregnancy or in the postpartum period in 16 (30%) of 53 women and in 8 women taking oral contraceptives. Recurrent arterial and venous thromboses were significantly decreased with prophylactic warfarin use when compared with prednisone use or no treatment. Recurrences were infrequent in patients with prothrombin ratios of 1.5 to 2.0. CONCLUSIONS: Treatment with warfarin was most effective in preventing recurrent arterial and venous thrombosis. Pregnancy and the use of oral contraceptives or prednisone may also influence recurrence.     

A retrospective analysis of nitric oxide inhalation in patients with severe acute lung injury in Sweden and Norway 1991-1994

BACKGROUND: Patients with severe acute lung injury (ALI) have been treated compassionately on doctors' initiative with inhaled nitric oxide (INO) in Sweden and Norway since 1991. In 1994 the previously used technical grade nitric oxide was replaced by medical grade nitric oxide. METHODS: We have carried out a retrospective data collection on all identified adult patients treated with INO for >4 h during the period 1991-1994 focusing on safety aspects and patient outcome. We used the following exclusion criteria (1) Age <18 years, (2) Simultaneous treatment with extracorporeal removal of CO2 (3) NO inhalation period <4 h, (4) Incomplete or missing patient charts, (5) Use of INO in order to treat pulmonary hypertension following cardiac surgery, with little or no acute lung injury. RESULTS: Inclusion criteria were met by 56 out of 73 identified patients. Mean age was 48+/-19 years and the median duration of INO treatment was 102 h. PaO2/FIO2 ratio at start of treatment was 85 +/- 33 mm Hg with a lung injury score (LIS) of 3.2+/-0.8. The aetiology of the lung injury was pneumonia (n= 27), sepsis (n=12) and trauma (n=8). Survival to hospital discharge was 41% and survival after 180 d was 38%. Three serious adverse events were identified, two from technical failures of the INO delivery device and one withdrawal reaction necessitating slow weaning from INO. No methaemoglobin values >5% were reported during treatment. CONCLUSION: The overall mortality did not differ dramatically from historical controls with high mortality. Only a randomised study may determine whether INO as an adjunct to treatment alters the outcome in severe ALI. One cannot at present advocate the routine use of INO in patients with ALI outside such studies.     

Adolescents'' experiences of anger in a residential setting

The most common types of psychiatric diagnoses linked with substance abuse or dependence in women are defined and discussed. A framework is described to facilitate the nurse provider's understanding of the various relationships psychiatric symptoms can have to substance-using patterns. Guidelines are provided to assist the nurse in identifying problems of dual diagnoses and providing care to women with dual diagnoses in general care settings.     

Monocyte tissue factor expression and ongoing complement generation in ventricular assist device patients

BACKGROUND: Ongoing complement activation in patients with a ventricular assist device may contribute to observed hemostatic abnormalities and cellular aggregation by mediating leukocyte and platelet activation, formation of leukocyte-platelet conjugates, and the tissue factor pathway of coagulation. METHODS: Blood from 30 patients was collected before ventricular assist device implantation and during the implantation period. Plasma levels of thrombin-antithrombin III complexes, C3a, and SC5b-9 were measured by commercial enzyme-linked immunosorbent assay. Flow cytometry was used to measure circulating monocyte tissue factor expression and circulating monocyteplatelet and granulocyte-platelet conjugates. RESULTS: Thrombin-antithrombin III complex level and monocyte tissue factor expression peaked in the early postoperative period, with maxima occurring on postoperative days 5 and 3, respectively. Levels of C3a and SC5b-9 remained dramatically elevated over normal values for the duration of the study (6 and 5 times upper normal, respectively). Levels of monocyte-platelet conjugates were normal before implantation, decreased during the first 4 postoperative days, and then increased and remained elevated. Levels of granulocyte-platelet conjugates were elevated over the normal range before implantation and remained elevated from postoperative days 3 to 21. A positive correlation was found between levels of SC5b-9 and granulocyte-platelet conjugates (Spearman R=0.66; p < 0.001), and between levels of C3a and thrombin-antithrombin III complex (Spearman R=0.13; p=0.021). CONCLUSIONS: The data suggest a model in which complement mediates formation of leukocyte-platelet aggregates and may indirectly contribute to thrombin generation through monocyte tissue factor expression.     

Building bridges between families and nursing home staff: the Partners in Caregiving Program

Prostaglandins are natural fatty acid derivatives with diverse physiological effects, including immune function and the control of cell growth. While the action of prostaglandins in the induction of stress proteins in vertebrate cells is well documented, their functions in invertebrate cells have been poorly investigated. The purpose of the present study was to investigate the effect of prostaglandin A1 (PGA1; 0.25, 1.25 and 12.5 micrograms/ml) on protein synthesis during the growth of Aedes albopictus cells. We found that PGA1 stimulates the synthesis of several polypeptides with molecular masses of 87, 80, 70, 57, 29, 27 and 23 kDa in Aedes albopictus cells. When the proteins induced by PGA1 and those induced by heat treatment were compared by polyacrylamide gel electrophoresis, PGA1 was found to induce the stress proteins. The HSP70 family and the low-molecular weight polypeptides (29 and 27 kDa, respectively) were induced by PGA1 in the lag phase. We also observed that PGA1 is able to induce a 23-kDa polypeptide independently of the growth phase of the cell.     

Neutralization of IL-12 demonstrates the existence of discrete organ-specific phases in the control of Leishmania donovani

Aspergillus nidulans grows by apical extension of multinucleate cells called hyphae that are subdivided by the insertion of crosswalls called septa. Apical cells vary in length and number of nuclei, whereas subapical cells are typically 40 microm long with three to four nuclei. Apical cells have active mitotic cycles, whereas subapical cells are arrested for growth and mitosis until branch formation reinitiates tip growth and nuclear divisions. This multicellular growth pattern requires coordination between localized growth, nuclear division, and septation. We searched a temperature-sensitive mutant collection for strains with conditional defects in growth patterning and identified six mutants (designated hyp for hypercellular). The identified hyp mutations are nonlethal, recessive defects in five unlinked genes (hypA-hypE). Phenotypic analyses showed that these hyp mutants have aberrant patterns of septation and show defects in polarity establishment and tip growth, but they have normal nuclear division cycles and can complete the asexual growth cycle at restrictive temperature. Temperature shift analysis revealed that hypD and hypE play general roles in hyphal morphogenesis, since inactivation of these genes resulted in a general widening of apical and subapical cells. Interestingly, loss of hypA or hypB function lead to a cessation of apical cell growth but activated isotropic growth and mitosis in subapical cells. The inferred functions of hypA and hypB suggest a mechanism for coordinating apical growth, subapical cell arrest, and mitosis in A. nidulans.     

On choosing a detergent for solution NMR studies of membrane proteins

Acne is a common condition seen routinely by both primary care physicians and dermatologists. Most patients have no underlying pathology and respond to traditional treatment; others, however, require more individualized evaluation and aggressive therapy. New information regarding the pathogenesis and treatment of acne is now available. This update discusses the proper evaluation of early childhood acne, the emergence of Propionibacterium acnes resistance, and the rare but serious side effects occasionally seen with minocycline. Advances in the topical treatment of acne, the use of oral contraceptives in acne, and the use and efficacy of isotretinoin are also addressed.     

Cytochrome P450 1A-like proteins expressed in the islets of Langerhans and altered pancreatic beta-cell secretory responsiveness

1. The cytochrome P450 (CYP) mixed-function oxidase system is widely distributed in body tissues and plays a key role in the metabolism of endogenous and exogenous compounds. Little attention has been paid to the expression of the system in the islets of Langerhans. The current study has examined the expression and potential role of the CYP1A family within the islets of Langerhans of control and 3-methylcholanthrene (3-MC)-induced Wistar rats. 2. CYP1A expression within pancreatic slices and islets from 3-MC-induced and control rats demonstrated that CYP1A-like protein levels were induced by 3-MC pretreatment (25 mg kg-1 day-1; i.p. for 3 days). 3. Effects of 3-MC-induction on beta-cell secretory responsiveness were investigated by use of rat collagenase-isolated islets. Insulin release from control islets incubated with 3 mM glucose (basal) was 1.4 +/- 0.2 ng/islet h-1 (mean +/- s.e.mean, n = 7). Incubation with 16.7 mM glucose, 25 mM KCl, 100 microM arachidonic acid, or 100 microM carbachol caused a 4.4, 7.0, 4.0 and 4.2 fold, respectively, increase in insulin release (P < 0.001). Forskolin (2 microM), or phorbol 12-myristic 13-acetate (10 nM) potentiated glucose-stimulated insulin release 1.2 and 1.6 fold (P < 0.01) whereas adenalin (1 microM) caused a 76% inhibition (P < 0.01). 4. Islets from 3-MC pretreated animals displayed similar responsiveness to all agents tested except arachidonic acid, carbachol and forskolin. Insulin release in response to arachidonic acid and carbachol was enhanced 5.2 and 5.0 fold, respectively, by 3-MC pretreatment (P < 0.001 compared to control islets incubated with 3 mM glucose); the effect of forskolin on insulin output was significantly decreased (20%; P < 0.01) compared to control islets. 5. 3-MC pretreatment did not cause any significant differences in food intake, plasma glucose or total islet insulin content. Incubation of islets with 3-MC in vitro (1 microM - 10 mM) did not affect basal or glucose-stimulated insulin release. 6. These data suggest that CYP1A-like protein expression within the pancreatic islets of Langerhans is inducible and may have a role in the alteration of pancreatic beta-cell secretory responsiveness.     

Structural requirements for peptidic antagonists of the corticotropin-releasing factor receptor (CRFR): development of CRFR2beta-selective antisauvagine-30

Different truncated and conformationally constrained analogs of corticotropin-releasing factor (CRF) were synthesized on the basis of the amino acid sequences of human/rat CRF (h/rCRF), ovine CRF (oCRF), rat urocortin (rUcn), or sauvagine (Svg) and tested for their ability to displace [125I-Tyr0]oCRF or [125I-Tyr0]Svg from membrane homogenates of human embryonic kidney (HEK) 293 cells stably transfected with cDNA coding for rat CRF receptor, type 1 (rCRFR1), or mouse CRF receptor, type 2beta (mCRFR2beta). Furthermore, the potency of CRF antagonists to inhibit oCRF- or Svg-stimulated cAMP production of transfected HEK 293 cells expressing either rCRFR1 (HEK-rCRFR1 cells) or mCRFR2beta (HEK-mCRFR2beta cells) was determined. In comparison with astressin, which exhibited a similar affinity to rCRFR1 (Kd = 5.7 +/- 1.6 nM) and mCRFR2beta (Kd = 4.0 +/- 2.3 nM), [DPhe11,His12]Svg(11-40), [DLeu11]Svg(11-40), [DPhe11]Svg(11-40), and Svg(11-40) bound, respectively, with a 110-, 80-, 68-, and 54-fold higher affinity to mCRFR2beta than to rCRFR1. The truncated analogs of rUcn displayed modest preference (2- to 7-fold) for binding to mCRFR2beta. In agreement with the results of these binding experiments, [DPhe11, His12]Svg(11-40), named antisauvagine-30, was the most potent and selective ligand to suppress agonist-induced adenylate cyclase activity in HEK cells expressing mCRFR2beta.     

Principles of ex ovo competitive exclusion and in ovo administration of Lactobacillus reuteri

The data that have been presented indicate that the in ovo use of competitive exclusion (CE) agents is feasible for both chickens and turkeys. However, there are many pitfalls that await the use of in ovo application of CE agents, including the use of nonspecies-specific intestinal microbes and the use of harmful proteolytic, gas-producing and toxin-producing intestinal microbes. Of the potential CE agents that have posthatch application, only Lactobacillus reuteri has been shown to be safe and effective in terms of not affecting hatchability and in having a prolonged effect in the hatched chick or poult. Lactobacillus reuteri administration in ovo increases its rate of intestinal colonization and decreases the colonization of Salmonella and Escherichia coli in both chicks and poults. Additionally, mortality due to in-hatcher exposure to E. coli or Salmonella is reduced with in ovo L. reuteri. Use of antibiotics in ovo may preclude the use of co-administered CE agents, but Gentamicin and L. reuteri are a compatible mixture when administered in ovo in separate compartments. Nevertheless, the intestinal morphology can be affected by both the CE agent and by antibiotics. Lactobacillus reuteri both in ovo and ex ovo will increase villus height and crypt depth, and Gentamicin in ovo causes a shortening and blunting of the villus. Both Gentamicin and L. reuteri in ovo suppress potentially pathogenic enteric microbes, but with diminished antibiotic effects shortening and blunting of the intestinal villi does not correct itself. Goblet cell numbers increase significantly on the ileum villus of chicks treated with Gentamicin in ovo, and this is presumably due to the increase in potentially pathogenic bacteria in the intestinal tract. Diminishing antibiotic effects posthatch would then negatively affect the absorption of nutrients and reduce growth at least in a transitory manner. Thus, L reuteri administration in ovo singly or in combination with Gentamicin followed by L reuteri via drinking water or feed appears to have potential to control many enteric pathogens in poultry. Additional work in the use of in ovo CE cultures is mandated because there is a world-wide movement to reduce antibiotic use in poultry due to increased microbial resistance to antibiotics. Use of naturally occurring intestinal bacterial cultures, either in mixed culture or as single well-defined cultures, has potential for immediate use in the poultry industry.