Joan E. Lafuze

Overcoming Stigma: Involving Families in Medical Student and Psychiatric Residency Education

ObjectiveThe primary purpose of this article is to present a possible mechanism for increasing communication about psychiatric matters such as diagnoses, treatment, and stigma between the physicians, including psychiatrists, and the families of persons with mental illness through a NAMI presentation.MethodsIncluded are a description of a stigma-reduction presentation to junior medical students; information about an instrument to evaluate pre- and postclerkship student attitudes; and a discussion of consumer and family participation in the education of first-year psychiatric residents.ResultsMoving the NAMI presentation from the freshman year to the junior year rotation and first year resident experience has been more efficacious, possibly because clinically oriented students and medical and psychiatric residents seem more receptive to communication about stigma and the family situation.ConclusionThe educational collaborations between advocacy groups and academia show promise for increasing communication about psychiatric disorders, treatment, and stigma issues between families and psychiatric patients.

In vitro and in vivo effects of treatment by platelet-activating factor on N-formyl-met-leu-phe-mediated responses of polymorphonuclear leucocytes

Two chemoattractants, the peptide N‐formyl‐met‐leu‐phe (FMLP), and the ether phospholipid, platelet activating factor (PAF), each stimulate a variety of in vitro responses in polymorphonuclear leucocytes (PMN). Because often more than one inflammatory mediator is active during inflammation, we determined the effect on PMN of sequential stimulation with these two agents. Before FMLP stimulation, human PMN were exposed to PAF, at concentrations which gave little or no response when administered alone. PAF enhanced FMLP‐elicited superoxide release in a dose‐dependent fashion. Likewise, release of granular lysozyme from the cells was increased in PAF treated cells. Similar treatment with other phospholipids, including the lyso derivation of PAF, failed to produce these effects. Incubation with nordihydro‐guaiaretic acid, an inhibitor of arachidonic acid metabolism, had little effect on the enhancement of lysozyme release by PAF. To determine if enhancing effects by PAF might occur also in vivo, we studied rabbits receiving PAF and/or FMLP intravenously. When rabbits received 0·01 μg PAF (a dose which does not elicit the sustained neutropenia observed with higher doses of PAF) followed by 0·05 μg FMLP the absolute granulocyte count (AGC) dropped at 1 min (46 ± 11% of original value), and continued to fall (24 ± 12% at 10 min). Controls, treated with the suspending fluid for PAF, and then 0·05 μg FMLP, had a similar 1 min AGC value, but at 10 min AGC returned to 65±6·1% (P<0·001 for comparison of 10 min values). Thus PAF pretreatment enhanced FMLP‐elicited granulocytopenia in vivo. Study of in vitro human PMN aggregation revealed that, at certain relative concentrations of PAF and FMLP. aggregation was enhanced. These studies show that both in vitro and in vivo responses of FMLP‐stimulated PMN may be exaggerated by pre‐exposure to PAF.

Vitamin E Attenuates the Effects of FMLP on Rabbit Circulating Granulocytes

Summary: Exposure of circulating rabbit granulocytes to the chemoat-tractant N-formyl-methionyl-leucyl-phenylalanine (FMLP) in vivo results in transient granulocytopenia, hypotension, and car-diorespiratory distress. The effectiveness of vitamin E in attenuating these responses was tested. Vitamin E accelerated the rate of return of granulocytes to the peripheral circulation after FMLP-induced granulocytopeniaand mitigated the hypotension. The reversible adherence of FMLP-stimulated granulocytes to endothelium offers a plausible mechanism to explain the transient granulocytopenia. From in vitro studies it was found that FMLP-activated granulocytes from animals treated with vitamin E showed decreased adherence to cultivated aortic endothelial monolayers when compared with FMLP-activated granulocytes from control animals.

Amniotic basement membrane: a barrier to neutrophil invasion

Polymorphonuclear neutrophils activated by N-formylmethionyl-leucylphenylalanine are able to cross the human amnion as shown by Russo et al. (1981). With the same technique, we added polymorphonuclear neutrophils to either the epithelial or stromal surface of the amnion. The lower compartment of the incubation chamber contained 10(-8) mol/L of N-formylmethionyl-leucylphenylalanine. Of 24 amnion tested, only one showed polymorphonuclear neutrophil permeation. Ultrastructural observations indicated that the basal lamina and the zona reticularis of the basement membrane acted as barriers to polymorphonuclear neutrophil invasion. Recent studies indicate that the basal lamina and the zona reticularis of the basement membrane contain collagen type V. No data support the existence of collagenase of polymorphonuclear neutrophil origin that cleaves collagen type V. If enzymatic degradation of extracellular matrix components play a role in polymorphonuclear neutrophil invasion, it is possible that type V collagen acts as a barrier to polymorphonuclear neutrophil invasion in the human amnion.

Effect of vitamin E on FMLP-induced activation of rabbit polymorphonuclear leukocytes

Granulocytes of vitamin E-treated rabbits were compared to granulocytes from placebo-treated rabbits. Granulocytes were isolated from rabbit peripheral blood by a new method employing Percoll and gelatin sedimentation. Vitamin E-treated cells showed less adherence to rabbit aortic endothelium when stimulated with FMLP. FMLP receptor numbers and affinity were not significantly different. Resting cell surface and baseline transmembrane potential were similar in both cell types. Decrease in cell surface potential with FMLP was comparable in vitamin E- and placebo-treated cells. Vitamin E-treated PMN depolarized more and hyperpolarized more rapidly than placebo cells. Thus vitamin E-treated PMNs show differences in the early events of PMN activation. These may contribute to the lower stimulated adherence observed with vitamin E-treated cells.

Comparison of in vivo effects of intravenous infusion ofN-formyl-methionyl-leucyl-phenylalanine and phorbol myristate acetate in rabbits

Comparison of the physiologic responses in rabbits to the intravenous infusion of two polymorphonuclear neutrophil (PMN) activators,N-formyl-methionyl-leucyl-phenylalanine (FMLP) and phorbol myristate acetate (PMA), has revealed marked differences in kinetics for activation between these agents. FMLP infusion was associated with maximally increased respiratory rates (RR), a maximally decreased mean blood pressure (MBP), and a maximally decreased absolute granulocyte count (AGC), all within the first 5 min after infusion. However, there were no significant differences between RR, MBP, and AGC of FMLP-treated animals and controls, 15 min postinfusion and after. On the other hand, PMA did not cause significant changes in RR or MBP until 30 min and 2 h postinfusion, respectively. Previous work has demonstrated that both FMLP and PMA stimulate the PMN metabolically in vitro via the same respiratory burst enzyme, NADPH oxidase, but that each of these activators demonstrates kinetics which are different from the other. Thus, these data from an in vivo study support previous in vitro findings and offer further evidence that the neutropenia and cardiopulmonary alterations following intravenous infusion of FMLP and PMA may be caused by metabolic activation of the blood PMN.

IN VIVO EFFECTS OF β-CAROTENE ON ACTIVATED NEUTROPHILS

Patients with gram negative sepsis may suffer neutropenia and respiratory distress associated with activation of polymorphonuclear neutrophils (PMN). Infusion with the synthetic analog of the bacterial chemoattractant N-Formyl-Methionyl-Leucyl-Phenylalanine (FMLP) causes a dramatic but transient neutropenia, hypotension and respiratory distress in rabbits. Employing this rabbit model, we have shown previously that pretreatment with vitamin E (vit E) accelerates the return of the absolute granulocyte count (AGC) and mean blood pressure (MBP) toward normal at 10 min but not at 5 min after FMLP infusion. To test the effects of another antioxidant β-carotene (BC) on neutrophil activation in vivo we pretreated rabbits with BC to raise plasma levels (test 1.1±.8ug/ml vs control .05±.06ug/ml p=0.02). When 0.5ug FMLP was administered iv AGC decreased (at 2.5 min % change was 34±1.3 control vs 25±10 test p=ns). By 5 min there was a significantly greater return of PMN to the peripheral circulation in the BC treated animals (% change 39.6± vs 61±5 controls p < 0.04). There was not a significant difference in % change of MBP between test and control animals at any time over the 30 minutes of monitoring. Thus, BC appears to be more effective than vit E in accelerating the return of PMN to the peripheral circulation following activation and may have therapeutic potential in diseases associated with PMN activation.