Selective vulnerability of unmyelinated fiber Schwann cells in nerves exposed to local anesthetics

When peripheral nerves of experimental rats are exposed to local anesthetics, distinctive and reproducible pathologic changes occur involving the perineurial sheath and endoneurial contents. Application of intermediate strength concentrations of the local anesthetics, 2-chloroprocaine, lidocaine, etidocaine, and intermediate or high concentrations of procaine to the surface of rat sciatic nerves resulted in the following changes. By 48 hours, the perineurial sheath exposed to the drug was disrupted and became permeable to granulocytes which infiltrated the subjacent endoneurium in conjunction with edema formation in the endoneurial interstitium. Application of 10% procaine to exposed nerve resulted in extensive demyelination. The most striking pathologic change occurring with either intermediate or high doses was accumulation of lipid droplets in Schwann cells, a phenomenon that occurred often in myelin-producing Schwann cells but much less frequently in unmyelinated fiber Schwann Cells. Lipid accumulation appears to be one of several reactive changes that affect Schwann cells of myelinated fibers and is dose-dependent. On the other hand, while reactive changes were infrequently seen in unmyelinated fiber Schwann cells, these cells appeared more susceptible to injury as shown by electron microscopy. Injury to Schwann cells by local anesthetics is temporary because these cells can replicate quickly. Autoradiographic studies of thymidine incorporation 1 week after procaine administration to the sciatic nerve showed intense proliferation of Schwann cells, but no such activity in controls. These findings support the view that their neurotoxic properties may account in some part for the function of local anesthetics, that Schwann cells of small unmyelinated fibers are more vulnerable to these agents than those of myelinated fibers, and that destruction of their supporting cells is followed by vigorous mitotic activity in the endoneurium.     

Identification of very early lymphoid precursors in bone marrow and their regulation by estrogen

Estrogen is a negative regulator of lymphopoiesis and provides an experimental tool for probing relationships between lymphocyte precursors and stem cells. We found that expression of lymphocyte-associated genes and immunoglobulin (Ig) gene rearrangement occurred before CD45R acquisition. Lymphoid-restricted progenitors that were Lin(-)IL-7R alpha(+)c-kit(lo)TdT(+) (lineage marker(-), interleukin receptor 7 alpha(+), c-kit(lo) and terminal deoxynucleotidyl transferase(+)) were selectively depleted in estrogen-treated mice; within a less differentiated Lin-c-kit(hi) fraction, functional precursors of B and T, but not myeloid, cells were also selectively depleted. TdT and an Ig heavy chain transgene were detected within a hormone-regulated Lin(-)c-kit(hi)Sca-1(+)CD27(+)Flk-2(+)IL-7R alpha(-) subset of this multipotential progenitor population. Identification of these extremely early lymphoid precursors should facilitate investigation of the molecular mechanisms that control lineage-fate decisions in hematopoiesis.     

Renovaskuläre Hypertonie

Zusammenfassung In der vorliegenden Untersuchung wurde das postoperative Blutdruckverhalten bei 35 Patienten mit renovaskulärer Hypertonie untersucht: 17 Patienten mit fibromuskulärer Dysplasie (FMD) und 18 mit arteriosklerotischen Gefäßwandveränderungen (ASS).Patienten mit FMD waren im Mittel jünger (31,8 Jahre), zeigten eine kürzere Hypertonieanamnese (1,8 Jahre) und waren prävalent weiblich (82%), während Patienten mit ASS deutlich älter waren (48,2 Jahre), eine längere Hypertoniedauer (2,6 Jahre) zeigten und bevorzugt männlich (78%) waren.In beiden Gruppen zeigte das intravenöse Pyelogramm einen vergleichbar hohen Anteil positiver Befunde (FMD=64%, ASS=61%).Postoperativ waren in der Gruppe mit FMD 47% (n=8) geheilt, 47% (n=8) gebessert und nur 6% (n=1) der Patienten geringgradig gebessert. Die vergleichbaren Werte für die Gruppe mit ASS betrugen 28, 55 und 17%. Für das Gesamtkollektiv war folglich ein guter Operationserfolg (geheilt und gebessert) in 88,5% der Fälle zu beobachten. Patienten mit ASS und postoperativ nur geringgradiger Besserung (n=3) zeigten eine auffallend lange Hypertonieanamnese (7,0±1,4 Jahre).Bei allen Patienten wurde präoperativ die seitengetrennte Bestimmung der Renin-Aktivität (PRA) im Nierenvenenblut durchgeführt und aus den Werten die PRA-Quotienten (PRA betroffene/nicht betroffene Seite) errechnet. Bei 27 Patienten wurde die Bestimmung 15 und 30 min nach intravenöser Stimulation mit 40 mg Furosemid wiederholt. PRA-Quotienten von 1,5 wurden als signifikant bezeichnet.Bei 31 Patienten mit einseitiger renovaskulärer Hypertonie wurde die Höhe des PRA-Quotienten zum postoperativen Blutdruckverhalten korreliert. Dabei zeigte sich zwischen der Gruppe der postoperativ Geheilten und der der postoperativ Gebesserten kein signifikanter Unterschied im mittleren PRA-Quotienten. Ferner ließen sich für das Gesamtkollektiv der 31 Patienten mit einseitiger renovaskulärer Hypertonie unter Ausgangs- und Stimulationsbedingungen keine signifikanten Korrelationen zwischen Höhe der PRA-Quotienten und postoperativem Blutdruckabfall ermitteln.Unsere Ergebnisse unterstützen nicht die weit verbreitete Ansicht, daß sich die seitengetrennte Bestimmung der PRA im Nierenvenenblut als Parameter für den zu erwartenden Operationserfolg bei Patienten mit einseitiger renovaskulärer Hypertonie eignet. Die Methode kann deshalb nach unserer Ansicht nicht mehr als obligater Bestandteile der präoperativen Diagnostik der renovaskulären Hypertonie empfohlen werden.     

Transitions to parenthood: his,hers, and theirs

This study explores marital processes that may underlie the apparent decline in satisfaction with marriage in partners becoming parents for the 1st time. The study assessed 47 couples expecting a 1st child and 15 couples not yet decided about having a child at pretest, post 1 (6 months post partum of 9 months after pretest) and post 2 (18 months postpartum or 21 months after pretest). Questionnaires examined: 1) psychological sense of self; 2) partners' role arrangements and communication; 3) parenting ideology; 4) perceptions of the family of origin; and 5) social support and life stress, including parents' work patterns. Parenthood seems to bring more change, and more negative change, in each of the 5 domains of family life that were investigated for comparable couples not having a 1st child experience over a similar period of time. Quantitative data support this conclusion in 4 of the 5 domains (individuals sense of self, marital, parent-child, and outside the family). Interview data suggest that new parents' relationships with their families of origin also undergo change at this time. Although shifts within domains often showed patterns similar to change in overall satisfaction with the marriage, the connection between the 2 was not linear and direct, especially for women. Men and women in transition to parenthood become increasingly different from one another; the results suggest that increased gender differentiation accompanying the transition to parenthood is a factor in accounting for marital satisfaction decline.     

Experimental determination of the kinetics of calcium-binding with chondroitin sulphate and the effects of uric acid on this process

Summary The calcium-binding kinetics of chondroitin sulphate C (CS) have been determined using equilibrium analysis including ⁴⁵Ca. There is a linear relationship between the extent of the Ca binding and the concentration of CS present. 1 mol CS disaccharide unit binds 0.757 mol Ca. Scatchard plots of the data have revealed a single constant of dissociation (K _D =1429). In the presence of urate ions, and dependent on the pH value, the ability of CS to bind Ca may be impaired by as much as 31%. These measurements have supported the theory that urate ions interact with the GAGs in urine.     

Changing Levels of Social Engagement with Gay Men Is Associated with HIV Related Outcomes and Behaviors: Trends in Australian Behavioral Surveillance 1998–2020

Archives of Sexual Behavior - Changes to how gay, bisexual, and other men who have sex with men (GBM) connect with each other and with their communities have implications for HIV prevention. Social...     

Decreased accumulation of endogenous brain-derived neurotrophic factor against constricting sciatic nerve ligatures in streptozotocin-diabetic and galactose-fed rats

Anterograde and retrograde trafficking of brain-derived neurotrophic factor (BDNF) was examined in streptozotocin-diabetic and galactose-fed rats by measuring accumulation of endogenous neurotrophin proximal and distal to two constricting sciatic nerve ligatures and by direct injection of radiolabeled neurotrophin into the sciatic nerve. Compared to controls, accumulation of endogenous BDNF proximal and distal to the ligatures as well as basal levels in non-ligated nerve segments were decreased in streptozotocin-diabetic and galactose-fed rats. Neither streptozotocin diabetes nor galactose intoxication affected the amount of 125I-labeled BDNF retrogradely transported to the DRG after injection into the sciatic nerve. These results suggest that reduced anterograde and retrograde accumulations of BDNF in experimental diabetes are not a result of impaired capacity for receptor-mediated transport.     

Cardiovascular parameters and scoring systems in the evaluation of response to therapy in sepsis and septic shock

Summary In 47 medical and postoperative ICU patients with 57 episodes of sepsis and septic shock, cardiovascular parameters including systemic vascular resistance (SVR), cardiac index (CI), stroke volume index (SVI), left ventricular stroke work index (LVSWI) as well as six scoring systems (APACHE II, Elebute, Goris, HIS, SAPS and SSS) were studied regarding their usefulness in the assessment of disease progression and evaluation of response to supplemental sepsis therapy (immunoglobulins, plasmapheresis). Among the hemodynamic parameters, only a prompt SVR improvement significantly discriminated between ultimate survivors and nonsurvivors. Thus, an increase in SVR (>160 dyn*cm^–5*sec, within days 0 to 4, persisting for >24 hours) can serve as a prognostically validated response criterion (responders/non-responders: 26/31; mortality: 27% vs. 77%). Non-invasively, the APACHE II score was best suited (specificity: 88%, sensitivity: 67%) to classify hemodynamically defined responders to supplemental sepsis treatment (score-reduction 4 on day 4 after onset of therapy).

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Herz-Kreislauf-Parameter und Score-Systeme in der Beurteilung des Therapieerfolges bei Sepsis und septischem Schock

Zusammenfassung Bei 47 internistischen sowie postoperativen Intensivpatienten mit insgesamt 57 Episoden von Sepsis und septischem Schock wurden Herz-Kreislauf-Parameter inklusive systemischer Gefäßwiderstand (SGW), Herzindex, Schlagvolumenindex und linksventrikulärer Schlagarbeitsindex sowie sechs Score-Systeme (APACHE II, Elebute, Goris, HIS, SAPS und SSS) in ihrer Wertigkeit zur Beurteilung des Krankheitsverlaufes sowie des Ansprechens auf additive Sepsistherapie (Immunglobuline, Plasmapherese) untersucht. Von den hämodynamischen Parametern diskriminierte nur der — prompt nachweisbare — Anstieg des SGW signifikant zwischen letztlich überlebenden und nicht überlebenden Patienten. Ein Anstieg des SGW (>160 dyn*c^m–5*s innerhalb von vier Tagen, länger als 24 Stunden anhaltend) kann somit als prognostisch validiertes Responder-Kriterium dienen (Responder/Non-Responder: 26/31; Letalität: 27% vs. 77%). Nichtinvasiv erwies sich der APACHE II Score (Kriterium: Score-Abfall 4 bis zum Tag 4 nach Therapiebeginn) zur Klassifizierung der hämodynamisch definierten Therapie-Responder bei additiver Sepsistherapie am besten geeignet (Spezifität: 88%, Sensitivität 67%).