Proton pump inhibitor therapy reverses endoscopic features of fibrosis in eosinophilic esophagitis.

BACKGROUND: Long-standing inflammation leads to esophageal remodeling with stricture formation in patients with eosinophilic esophagitis (EoE). The ability of proton pump inhibitors (PPI) to reverse endoscopic features of fibrosis is still unknown. OBJECTIVE: To investigate the effect of a short course of PPI treatment in reducing endoscopic findings indicative of esophageal fibrosis in EoE patients. METHODS: Cross-sectional analysis of the EoE CONNECT registry. Patients who received PPI to induce EoE remission were evaluated. Endoscopic features were graded using the EoE Endoscopic Reference Score (EREFS), with rings and strictures indicating fibrosis. Results were compared to those from patients treated with swallowed topic corticosteroids (STC). RESULTS: Clinico-histological remission was achieved in 83/166 adult patients treated with PPI (50%) and in 65/79 (82%) treated with STC; among responders, 60 (36%) and 57 (72%) patients respectively achieved deep histological remission (<5 eosinophils/hpf). At baseline, mean±SD EREFS was lower in patients treated with PPI compared to those who received STC (p < 0.001). Short term treatment significantly reduced EREFS scores in patients treated either with PPI or STC as well as rings and strictures. Among patients treated with PPI, deep histological remission (<5 eosinophils/hpf) provided further reduction in total EREFS score. CONCLUSION: Effective PPI therapy for EoE significantly reduced endoscopic esophageal fibrosis in the short term.

Anti-corticosteroids combined therapy for treatment of chronic central serous chorioretinopathy / Terapia combinada de anti-corticosteroides para o tratamento da coriorretinopatia serosa central

Abstract The therapeutic impact is described with the combined use of two medications with different anti-corticosteroid actions in the clinical resolution of a patient with chronic central serous chorioretinopathy.

Resumo Descrevemos nesse artigo o impacto terapêutico do uso combinado de duas medicações anti-corticosteroides com diferentes mecanismos de ação, na resolução clínica de um paciente com coriorretinopatia serosa central crônica.

Avaliação da ministração de corticosteroides em situações de suspeita de parto pré-termo iminente: um estudo de coorte retrospectivo em um centro terciário / Evaluation of corticosteroid administration in situations of suspected imminent preterm delivery: a retrospective cohort study in a tertiary centre

ResumoOBJETIVOA ministração antenatal de um ciclo único de corticoterapia está recomendada a mulheres grávidas entre a 24 e a 34 semanas com risco de parto prematuro. O efeito máximo é atingido quando os corticosteroides ministrados entre 24 horas e 7 dias antes do parto. O objetivo deste estudo foi avaliar a ocorrência de parto nos sete dias após corticoterapia nas principais situações obstétricas com risco de parto pré-termoMÉTODOSEstudo de coorte retrospectivo incluindo 209 grávidas internadas em risco de parto pré-termo submetidas a tratamento com corticosteroides para maturação pulmonar fetal. O estudo foi realizado entre janeiro de 2012 e março de 2014 e um hospital universitário. O desfecho principal avaliado foi o número de mulheres que tiveram parto no prazo de 7 dias após a ministração antenatal de corticosteroides. Foram definidos dois grupos de acordo com o motivo para iniciar corticosteroides: ameaça de parto pré-termo (Grupo APPT) e outras indicações para corticoterapia (Grupo RPPT). Foi efetuada uma análise de sobrevivência de Kaplan-Meier e um valor p<0,05 foi considerado estatisticamente significativoRESULTADOS46,4% (n=97) das mulheres grávidas tiveram parto nos 7 dias após a ministração de corticosteroides. Parto em 7 dias ocorreu mais frequentemente no grupo RPPT, em comparação com o grupo APPT (57,3 versus 42,4%, p=0,001). Foi detectada uma diferença estatisticamente significativa entre a curva de sobrevivência para os grupos APPT e RPPT, com um hazard ratio para parto até 7 dias 1,71 vezes maior para o grupo RPPT (IC95% 1,23-2,37; p<0,001)CONCLUSÃOPode-se concluir que a probabilidade de um evento (nascimento dentro de 7 dias após corticoterapia) é menor no grupo de grávidas internadas no contexto de ameaça de parto pré-termo do que por outras indicações. A utilização de corticosteroides em grávidas internadas por suspeita de trabalho parto pré-termo deverá ser alvo de uma rigorosa avaliação clínica.

AbstractPURPOSEThe administration of a single-course antenatal corticosteroid treatment is recommended for pregnant women between 24 and 34 weeks with risk of premature birth. The maximum effect is achieved when antenatal corticosteroids are administered between 24h and 7 days before delivery. The objective of this study was to evaluate the occurrence of birth within seven days of corticosteroid therapy in major obstetric situations with risk of preterm birthMETHODSRetrospective cohort study including 209 pregnant women hospitalized in risk of preterm delivery, submitted to corticosteroid therapy for fetal lung maturation. The study was carried out between January 2012 and March 2014 at a university hospital. Main outcome measure was the number of women who delivered within 7 da ys after antenatal corticosteroid administration. Two groups were defined according to the reason for starting corticosteroids: threatened preterm labour (Group APPT) and other indications for corticosteroid therapy (Group RPPT). A Kaplan-Meier survival analysis was performed and a p value <0.05 was considered statistically significant.RESULTS46.4% (n=97) of pregnant women gave birth in the seven days following corticosteroid administration. Delivery within 7 days occurred more frequently on group 2 in comparison to group 1 (57.3 versus42.4%; p=0.001). There is a statistically significant difference between the survival curve for groups 1 and 2, with a hazard ratio for delivery within 7 days 1.71 times higher for group 2 (95%CI 1.23-2.37; p<0.001)CONCLUSIONIt can be concluded that the probability of an event (birth within 7 days after corticosteroids) is smaller in the group of pregnant women admitted in the context of threatened preterm labor than for other indications. The use of corticosteroids in pregnant women admitted for suspected preterm labor should be subject to rigorous clinical evaluation.

Parto pré-termo com e sem rotura prematura de membranas: características maternas, obstétricas e neonatais / Premature labour with or without preterm premature rupture of membranes: maternal, obstetric and neonatal features

OBJETIVO: Avaliação das caraterísticas maternas, obstétricas e neonatais nos partos pré-termo (PPT) associados ou não à rotura prematura de membranas pré-termo.MÉTODOS: Estudo retrospetivo de gestações de feto único, com um parto pré-termo, entre 2003 e 2012. Critérios de inclusão: a ocorrência de parto associado ou não à rotura prematura de membranas pré-termo. Critérios de exclusão: partos motivados por comorbidades fetal e/ou maternas (iatrogênicos); e processos não disponíveis ou incompletos para consulta. Foram comparadas caraterísticas entre os dois grupos de PPT: PPT espontâneo (PPTe)versusrotura prematura de membranas pré-termo (RPM-PT), tendo sido utilizados na análise estatística os testes Kolmogorov-Smirnov, Levene, χ2, t de Student e Mann-Withney.RESULTADOS: Dos 2.393 partos pré-termo de feto único, foram analisados 1.432, dos quais 596 foram espontâneos (PPTe) e 836 foram associados à RPM-PT. Das variáveis analisadas, os fatores socioeconômicos foram sobreponíveis em ambos os grupos. Foram mais frequentes no grupo PPTe (p<0,001) a multiparidade (50,7 versus40,3%), os antecedentes obstétricos de PPT (20,8 versus10,2%), o comprimento cervical (18,2 versus27,2 mm), o baixo índice de massa corpórea (IMC) (23,4 versus24,3 kg/m2) e a elevação dos marcadores infecciosos como a Proteína C reativa (2,2 versus1,2 mg/L) e os leucócitos (13,3 versus12,4x109). O desfecho neonatal, em termos de comorbilidade, foi mais adverso no grupo PPTe, sobretudo à custa de piores resultados neurológicos (4,7 versus2,8%, p<0,001).CONCLUSÕES: Os mecanismos etiológicos do PPT, com ou sem RPM-PT, são bastante complexos. Das várias caraterísticas analisadas no nosso estudo, apenas o baixo IMC, a multiparidade com PPT anterior, o comprimento cervical foram os piores parâmetros infeciosos que foram predominantes no grupo PPTe. Esse último grupo mostrou ainda piores resultados perinatais sobretudo neurologicamente.

PURPOSE: Evaluation of maternal, obstetrics e neonatal features in both spontaneous preterm births (PTB) with or without preterm premature rupture of membranes (PPROM).METHODS: Retrospective study of single fetus pregnancies with PTB between 2003 and 2012. Inclusion criteria: PTB associated with ou without PPROM. Exclusion criterias: PTB by medical indication due to fetal/maternal disease and all non accessible or incomplete clinical files. Different characteristics were compared between two groups of PTB: spontaneous PTB without PPROM (sPTB) versusPPROM. Kolmogorov-Smirnov, Levene, χ2, t Student and Mann-Withney tests were used for statistical analysis.RESULTS: From 2,393 PTB of single fetus, 1,432 files were analysed, from which 596 were sPTB and 836 PPROM. The socioeconomic conditions were similar in both groups. Multiparity (50.7versus40.3%), personal history of previous PTB (20.8 versus10.2%), cervical length (18.2 versus27.2 mm), lower body index mass (23.4 versus24.3 kg/m2) and higher infectious parameters (Protein C Reactive: 2.2 versus1.2 mg/L; Leukocytes: 13.3 versus12.4x109) were more frequent in PBTs (p<0,001). Neonatal outcomes, specially neurologic outcomes (4.7 versus2.8%, p<0,001), were worst in PBTs.CONCLUSION: PTB with or without PPROM has a complex etiology. From all evaluated features in our study, only maternal thinness, multiparity with a previous PTB, the cervical length and worst systemic infections parameters were significant in sPTB. This group also showed worst neonatal outcomes, specially on neurological outcomes.

Clinical comparison between brachytherapy of 0.5 ％ loteprednol etabonate eye drops and long-term therapy of 0.1％ fluorometholone eye drops after LASEK / 中华实验眼科杂志

Background Conventional corticosteroid therapy after laser epithelial keratomileusis (LASEK) is topical application of 0.1％ fluorometholone eye drops for 4 months,but this therapy increases the ocular hypertension risk and leads to poor compliance in patients.It is necessary to explore a safe and effective brachytherapeutic drug.Objective This study was to compare the clinical outcomes between the brachytherapy of 0.5％ loteprednol etabonate eye drops and the long-term therapy of 0.1％ fluorometholone eye drops after LASEK.Methods Clinical data were retrospectively analyzed from 208 right eyes in 208 mild and moderate myopia patients who received LASEK at Peking University Third Hospital from 2009 to 2013.The eye drops of 0.5％ loteprednol etabonate was used 6 times daily since operation day until postoperative day 5,and 4 times daily for a week,and then tapered for three consecutive weeks in 104 eyes of the loteprednol group after LASEK,and 0.1％ fluorometholone eye drops was applied topically 4 times daily for initial one month and then tapered for three consecutive months in another 104 eyes in the fluorometholone group after LASEK.Corneal epithelial healing time was compared between the two groups by recording the wearing duration of corneal contact lens.Noncontact intraocular pressure (lOP) was detected and corrected 5 days,2 weeks,1 month and 3,6 months after LASEK.Haze was scored based on the criteria of Cheng under the slit lamp microscope and apparently optometry was performed 1 month and 3,6 months after LASEK.Results The number of eyes removed corneal contact lens in 5,6 and 7 days after LASEK was not significantly different between the loteprednol group and the fluorometholone group (x2 =1.180,P =0.554).No considerable differences were seen in the eye numbers with the equivalent spherical lens (absolute value) ≤0.5 D in 1 month,3months and 6 months after LASEK (Z=-1.028,P=0.304;Z=-0.398,P=0.691;Z=-0.445,P=0.656).In the fifth days after surgery,the median corrected IOP was 13.52 mmHg and 13.12 mmHg in the loteprednol group and the fluorometholone group,respectively,showing a significant difference between them (Z =-1.985,P =0.047),but no significant differences were found in IOP in 2 weeks,1 month and 3 months,6 months after surgery between the two groups (all at P＞0.05).IOP elevated (postoperative IOP-preoperative IOP ≥ 5 mmHg) after LASEK in 5 eyes in the loteprednol group and 4 eyes in the fluorometholone group (x2 =0.116,P =0.733).In 1 month after surgery,the number of eyes in different grades of haze was significantly decreased in the loteprednol group compared with the fluorometholone group (x2=13.506,P=0.009),however,there was no significant differences in haze grading in postoperative 3 months and 6 months between the two groups (x2 =2.199,P =0.699;x2 =1.154,P =0.562).Conclusions Brachytherapy of 0.5％ loteprednol etabonate eye drops appears to have a similar effect in antiinflammation and inhibition of haze to the long-term therapy of 0.1％ fluorometholone eye drops after LASEK.Furthermore,topical application of 0.5％ loteprednol etabonate eye drops dose not increase the risk of ocular hypertension.

Uso antenatal de corticosteróide e evolução clínica de recém-nascidos pré-termo

Resumen Objetivo: descrever a freqüência de utilização de corticosteróide antenatal e a evolução clínica dos recém-nascidos pré-termo. Métodos: estudo observacional prospectivo tipo coorte de todos os neonatos com idade gestacional entre 23 e 34 semanas nascidos na Rede Brasileira de Pesquisas Neonatais entre agosto e dezembro de 2001. Os prontuários médicos foram revistos, as mães entrevistadas e os pré-termos acompanhados. A análise dos dados foi realizada com o teste do qui-quadrado, t de Student, Mann-Whitney, ANOVA e regressão logística múltipla, com nível de significância de 5%. Resultados: avaliaram-se 463 gestantes e seus 514 recém-nascidos. As gestantes tratadas tiveram mais gestações prévias, consultas de pré-natal, hipertensão arterial e maior uso de tocolíticos. Suas crianças apresentaram melhores escores de Apgar no 1º e 5º minutos, menor necessidade de intervenção na sala de parto e menor SNAPPE II. Nasceram com maior peso e idade gestacional, receberam menos surfatante exógeno, ventilação mecânica e oxigenoterapia. Após regressão logística, o uso pré-natal de corticosteróides manteve de forma independente o efeito protetor para as condições de nascimento e para a diminuição do tempo de ventilação mecânica e esteve associado com aumento na ocorrência de sepse neonatal. Conclusão: o uso do corticosteróide antenatal foi associado a melhor atendimento pré-natal. As crianças nasceram em melhores condições e tiveram melhor evolução, porém com maior risco de infecção.

Summary Objectives: to describe the use of antenatal corticosteroid and clinical evolution of preterm babies. Methods: an observational prospective cohort study was carried out. All 463 pregnant women and their 514 newborn babies with gestational age ranging from 23 to 34 weeks, born at the Brazilian Neonatal Research Network units, were evaluated from August 1 to December 31, 2001. The data were obtained through maternal interview, analysis of medical records, and follow-up of the newborn infants. Data analysis was performed with the use of chi-square, t Student, Mann-Whitney, and ANOVA tests and multiple logistic regression, with level of significance set at 5%. Results: treatment was directly associated with the number of prenatal visits, with maternal hypertension and with the antenatal use of tocolytic agents. Babies from treated pregnant women presented better Apgar scores at the 1st and 5th minute, reduced need for intervention in the delivery room and lower SNAPPE II. They were born with higher birth weight, longer gestational age and needed less surfactant use, ventilation, and oxygenation time. After multiple logistic regression, the use of antenatal corticosteroid independently improved birth conditions, decreased ventilation time, being related to increased occurrence of neonatal sepsis. Conclusions: the use of corticosteroid was associated with better prenatal care and birth conditions, better preterm evolution but higher risk of infection.

Prolactin changes in maternal plasma following termination by vacuum curettage and the effect of bromocriptine treatment on these changes.

To study the prolactin secretion and its dependence on the sex steroid concentrations during pregnancy, we measured the circulating prolactin, oestradiol-17 beta, progesterone and testosterone levels following vacuum curettage for termination of early pregnancy in 10 normal women and in 10 other women whose prolactin levels had been lowered with bromocriptine treatment. In normal women, anaesthesia and vacuum curettage led to consistent and significant (p < 0.01) rises in prolactin levels between 0.5 to 5 hours after abortion. This increase was not seen in women treated with bromocriptine whose prolactin level of 8.6 +/- 1.4 ng/ml (mean +/- SE) before abortion was lower than that of 29.6 +/- 6.4 ng/ml found in normal women. The oestradiol and progesterone concentrations decreased rapidly but similarly in both groups of patients following the evacuation of the uterus, whereas the testosterone level did not change significantly. These results indicate: (i) vacuum curettage stimulates prolactin secretion, (ii) the prolactin-stimulating effect of stress appears to be stronger than the prolactin-suppressing effect of postabortal oestradiol and/or progesterone declines, and (iii) bromocriptine blocks the stress-induced prolactin rise.

PIP: To study the prolactin secretion and its dependence on the sex steroid concentrations during pregnancy, we measured the circulating prolactin, estradiol-17beta, progesterone and testosterone levels following vacuum curettage for termination of early pregnancy in 10 normal women and in 10 other women whose prolactin levels had been lowered with bromocriptine treatment. In normal women, anesthesia and vacuum curettage led to consistent and significant (p 0.01) rises in prolactin levels between 0.5 to 5 hours after abortion. This increase was not seen in women treated with bromocriptine whose prolactin level of 8.6 + or - 1.4 ng/ml (mean + or - SE) before abortion was lower than that of 29.6 + or - 6.4 ng/ml found in normal women. The estradiol and progesterone concentrations decreased rapidly but similarly in both groups of patients following the evacuation of the uterus, whereas the testosterone level did not change significantly. These results indicate: 1) vacuum curettage stimulates prolactin secretion; 2) the prolactin-stimulating effect of stress appears to be stronger than the prolactin-suppressing effect of postabortal estradiol and/or progesterone declines; and 3) bromocriptine blocks the stress-induced prolactin rise.

Prevention of postoperative adhesions.

PIP: Recent laboratory and clinical studies concerning the pathogenesis and prophylaxis of postoperative peritoneal adhesions are reviewed. Since the late 19th century there have been several clinical and experimental observations demonstrating that peritoneal defects usually fail to heal with adhesion formation. Instead, mesothelization takes place, producing a surface indistinguishable from the original. This occurs from the base of the defect, meaning large defects heal as quickly as smaller defects. In a study conducted in rats (Ellis), it was noted that areas reperitonealized under tension developed adhesions while similar peritoneal defects left unrepaired and suture controls placed loosely in peritoneum usually healed without adhesions. These findings were confirmed by Buckman and coworkers who discovered that plasminogen activator activity was normally present in the mesothelium and submesothelial blood vessels of peritoneum. 2 other peritoneal insults known to induce adhesion formation are infection and foreign body contamination. Theoretically, it seems possible to reduce adhesion formation by taking the following steps: 1) reducing the initial inflammatory reaction and subsequent exudate release; 2) inhibiting coagulation of this exudate; 3) promoting the removal of fibrin deposition; 4) mechanically separating fibrin-covered surfaces; and 5) inhibiting fibroplastic proliferation. Adhesions continue to be a frequent sequelae of pelvic surgery despite the use of meticulous surgical technique. Although dextran solutions appear promising, their clinical value is unconfirmed.^ieng

Serum alpha-fetroprotein concentration in adult patients under corticoid, estroprogestative or androgen therapy.

The serum alpha-fetoprotein concentration was measured by radioimmunoassy in 41 women with or without hormonal contraception, 21 patients with rheumatoid arthritis given corticosteroids or not, and 6 patients under androgen therapy for aplastic anemia. None of these therapies induced any significant variation of the serum alpha-fetoprotein level. More extensive studies are needed to investigate the possible effect of these hormones on the metabolism of this protein at a cellular level.

PIP: Serum alpha-fetoprotein concentration was measured by radioimmunoassay in 41 women with or without hormonal contraception, 21 pateints with rheumatoid arthritis given corticosteroids or untreated, and 6 patients under androgen therapy for aplastic anemia. The various therapies were ineffective in inducing any change in alpha-fetoprotein level. Future research should focus on the metabolism of this protein at a cellular level in the presence of these hormones.

Steroids in the treatment of clinical septic shock.

A prospective (Part I) and a retrospective (Part II) study were used to determine the safety and efficacy of corticosteroids in the treatment of septic shock. In Part I, 172 consecutive patients in septic shock admitted over an 8-year period were treated with either steroid or saline: 43 received dexamethasone (DMP), 43 received methylprednisolone (MPS), and 86 received saline. The study was double-blind and randomized, and the three groups were compared for age, severity of shock, presence of underlying disease, and year of study. In the 86 saline-treated patients, the mortality rate was 38.4% (33/86); in the steroid-treated patients, it was 10.4% (9/86). With MPS the mortality rate was 11.6% (5/43), and with DMP it was 9.3% (4/43). Thus, overall mortality was significantly less in the steroid-treated group than in the control group. Further, there was no significant difference in mortality rate between the DMP- and the MPS-treated patients. In Part II, 328 patients were studied retrospectively. One-hundred sixty were treated without steroid, and 168 were treated with either DMP or MPS. Again, the two groups of patients were compared for severity of shock, underlying disease, age, and year of study. Mortality among patients treated without steroid was 42.5% (68/160) and among patients treated with steroid was 14% (24/168); there was no significant difference in mortality rate between DMP- and MPS-treated patients. In Parts I and II combined, complications occurred in 6% of steroid-treated patients with no significant difference between DMP- and MPS-treated groups.

PIP: A 2-part study, prospective and retrospective, was conducted to determine the safety and efficacy of corticosteroids in the treatment of septic shock. In part 1, 172 consecutive patients in septic shock admitted over an 8-year period were treated with either steroid or saline: 43 received (DMP) dexamethasone; 43 received (MPS) methylprednisolone; and 86 received saline. The study was double-blind and randomized, and the 3 groups were compared for age, severity of shock, presence of underlying disease, and year of study. In the 86 saline-treated patients, the mortality rate was 38.4% (33/86); in the steroid-treated patients, it was 10.4% (9/86). With MPS the mortality rate was 11.6% (5/43), and with DMP it was 9.3 (4/43). Thus, overall mortality was significantly less in the steroid-treated group than in the control group. Further, there was no significant difference in mortality rate between those treated with DMP and MPS. In part 2, 328 patients were studied retrospectively. 168 were treated without steroid, and 168 were treated with either DMP or MPS. Again, the 2 groups of patients were compared for severity of shock, underlying disease, age, and year of study. Mortality among patients treated without steroids was 42.5% (68/160) and among patients treated with steroids was 14% (24/168). There was no significant difference in mortality rate between DMP- and MPS-treated patients. In parts 1 and 2 combined, complications occurred in 6% of steroid-treated patients with no significant difference between DMP- and MPS-treated patients.

[Post-pill syndrome]. / Sindrome pos-pilula.

PIP: In a survey of 993 patients complaining of sterility and infertility, 365 were found to suffer from ovulatory disorders, and 133 of the latter were taking oral contraceptives. The patients were subjected to the following tests: basal temperature (monophasic curve in 33.08% of the cases), cervical mucus (negative crystallization in 40.60%), endometrium biopsy (Proliferative in 45.11%), and vaginal cytology (anovulatory pattern in 16.53% of the cases). Laparoscopy was used in 35 cases and biopsy of the ovaries in 18. After treatment with various drugs (such as cyclophenyl, clomiphene, human menopausal gonadotropin, human chorionic gonadotropin, estrogen, progestogen, corticoids, oral contraceptives), improvements were obtained in 82.93% of the cases with respect to basal temperature (from monophasic to biphasic), in 90.90% for cervical mucus (positive crystallization), in 35.28% for endometrium biopsy (from proliferative to sectretory), and in 42.86% for vaginal cytology (from anovulatory to ovulatory pattern). 45 pregnancies were obtianed. It is conluded that oral contraceptives can inhibit ovulation after suspending treatment, irrespective of its duration, especially in women previously suffering from menstrual disorders. The overall incidence of this syndrome is low, and it is generally reversible. It is desirable, however, to identify the women exposed to high risk of its occurrence, should the patient desire to stop the contraceptive treatment and have more children.^ieng

The benefits of corticosteroids in endotoxic shock.

The experiments reported here were undertaken to study the effects of pharmacological doses of corticosteroids administered alone or in conjunction with prolonged (12-hour) assisted circulation in 22 dogs subjected to LD50-60 Escherichia coli endotoxin. The most striking findings were lengthened survival time, higher cardiac output, decreased fluid requirement, and minimal evidence of pulmonary congestion or injury in the animals treated with steroids only. Unexplained mesenteric infarction prematurely terminated the experiments in animals undergoing assisted circulation. The benefits of corticosteroids in experimentally induced endotoxic shock are clearly demonstrated in these experiments. Further studies are needed to clarify the supportive role of assisted circulation in endotoxic shock and to determine any possible advantage of hypothermia over normothermia during its course.

PIP: 22 adult mongrel dogs were divided into 4 groups: 1) controls (fluid balanced after endotoxin injection); 2) steroid only administered (methylprednisolone sodium succinate (30 mg/kg, after endotoxin injection); 3) steroids and assisted circulation (normothermal); and 4) assisted circulation (hypothermia). The most striking finding was the lengthened survival time of Group 2 animals. 4/6 lived for 48 hours following a mean lethal dose of E. coli endotoxin, whereas only 2/6 in Group 1 survived for this period; none of 10 in Groups and 3 and 4. 2 Group 4 animals survived the period of perfusion but died of unknown causes, and 1 Group 3 animal developed sustained braducardia, hypotension, and cardiac arrest soon after cessation of cardiac assistance. The most consistent difference between Groups 1 and 2 was the decreased amount of fluids required by the Group 2 animals to maintain an adequate systemic arterial pressure during the observation period. Features also of interest noted were the higher cardiac outputs and the minimal evidence of pulmonary congestion or injury in the animals treated with steroids only. Results clearly demonstrate the beneficial value of pharmcological doses of corticosteroids in experimentally induced endotoxic shock.

Effects of cortisone acetate, methylprednisolone and medroxyprogesterone on wound contracture and epithelization in rabbits.

Standardized flank wounds were made on 20 rabbits divided into the following five groups: Group 1 served as controls, Group 2 were given cortisone acetate 6.25 mg/kg/day (I.M.), Group 3--methylprednisolone (Solu-Medrol) 1 mg/kg/day, Group 4--medroxyprogesterone (Depo-Provera) 35 mg/kg/day, Group 5--methylprednisolone 1 mg/kg/day and medroxyprogresterone 35 mg/kg/day. Wound contracture and epithelization was measured by planimetry of photographs taken twice weekly; weekly weights were recorded, and the maturation phase of wound healing followed in the control and methylprednisolone groups. All three steroids prolonged the latent phase of wound healing, slowed the rate and decreased the total amount of contracture. Cortisone showed the most inhibition of wound contracture and was the only steroid to inhibit epithelization suggesting it may have a slightly different or more potent mode of action. When the methylprednisolone group was followed for seven weeks on daily injections, the maturation phase of wound healing was inhibited, and this inhibition persisted during the next nine weeks after the drug was withdrawn. Only the control and the medroxyprogesterone group gained weight. Combining medroxyprogesterona and methylprednisolone resulted in the severest weight loss of 20% with a 60% mortality.

Vasopressors for treating shock.

PIP: Shock must be treated by correcting the cause, for any treatment of hypotension or shock, as such, is only an adjunctive measure; but the hemodynamic manifestations also need treatment. Vasopressors are helpful and effective under the right circumstances. Unless the blood volume is normal, the use of drugs that block the sympathetic nervous system (e.g., phenoxybenxamine) can be extremely hazardous and hasten death. However, the effect of adrenergic blocking drugs in endotoxic shock and other types of toxic shock is still to be determined; use of such drugs should be considered experimental until the results have been studied more extensively. Clinically, the most common forms of vascular shock are associated with blood loss, myocardial infarction, and endotoxemia. Characteristic hemodynamics of each situation are presented tabularly, and the physicians need to understand the differences is emphasized. The pharmacology of vasopressors, relating primarily to hemodynamic considerations and the response to vasopressors when severe reduction in blood pressure is associated with the shock syndrome is discussed. Drugs that stimulate the adrenergic receptors in the heart and blood vessels, with the exception of isoproteronol, are commonly referred to as vasopressors. The adrenergic stimulators may be classified into 3 groups: alpha (phenylephrine hydrochloride), beta (epinephrine), and alpha-beta (l-norepinephrine). Because alpha stimulators do not usually increase cardiac output, alpha-beta and beta-adrenergic stimulators are generally the most useful for treating shock. Routine use of adrenergic stimulators with the exclusion of other therapies, however, is generally unwarranted.^ieng

Prolonged over-suppression syndrome.

PIP: The syndrome of postpill amenorrhea was investigated retrospectively by studying records of diagnosed cases of amenorrhea (1300) treated or confirmed at the Mayo Clinic. Data are taken from records dating to 1960 (low use of contraceptives) and terminate in 1971. 12 cases are reviewed which were diagnosed as prolonged oversuppression syndrome. No particular oral contraceptive formulation was implicated. 4 of 12 patients had had irregular menstrual cycles before oral contraceptive therapy; whereas 8 had had regular cycles. Bioassay of urinary gonadotropins were consistently in the mid-low normal limits (only 1 determination was available for each patient); some patients had been radioimmunoassayed (single assay) for other pituitary hormones: LH (luteinizing hormone) was at normal basal levels and FSH (follicle stimulating hormone) was also in the normal range. Concentrations of total circulating estrogens were in low or subnormal range in each case. 4 cases had associated galactorrhea, which was attributed to exogenous steroid suppression of the prolactin-inhibiting center of the pituitary. Clomiphene citrate was used to restore functions of the hypothalamic-pituitary axis, and of the 8 receiving clomiphene, 5 responded and 2 conceived.^ieng

Postoperative intraperitoneal adhesions: a double-blind assessment of their prevention in the monkey.

PIP: The effect of combined antihistamine and corticosteroid therapy and the effect of dextran on recurrent intraperitoneal adhesion formation were evaluated in 43 monkeys, all of which had been previously used for reproductive tract studies, and, hence, were suffering from adhesion formation to some degree. In a double-blind manner, the monkeys were randomly divided into 3 experimental groups. 1 group received saline injections before and after lysis surgery followed by introduction of saline solution in the peritoneum during surgery. Group 2 was treated with saline injections, as Group 1, except that dextran solution was introduced into the peritoneal cavity. In Group 3, a combined dexamethasone/promethazine therapy was administered before, during, and after surgery. In all of these monkeys, the degree of adhesion reformation after adhesion lysis surgery was essentially the same in all 3 groups. Rather, careful surgical technique was vastly more important than use of corticosteroids or antihistamines as prophylactic measures.^ieng

Should corticosteroids be used in shock?

PIP: This paper analyzes the available information on the possible mechanisms of corticosteroid action relevant to the correction of shock. Though shock may occur in a number of diseases, the pathophysiological common denominator is inadequate tissue perfusion, and its metabolic consequences: decreased pH, PO2, PCO2, and sodium, and increased lactic acid, potassium, magnesium, fatty acids, ketone bodies, and amino acids. The 4 proposed useful mechanisms of action of corticosteroid for shock treatment are: 1) Corticosteroids are required for normal cardiac function, and their cradiovascular effects are both intropic and vascular (i.e., enhance effects of catecholamines and provide an adrenergic blockade); 2) Corticosteroids stabilize membranes, enhancing the integrity of capillaries and affecting lysosomal membrane stability; 3) they improve tissue metabolism; and 4) catecholamines may also be useful in terms of their other mechanisms of action, which include the prevention of tissue breakdown and direct detoxification of endotoxin. The toxicity and administration of corticosteroids are discussed, and it is pointed out that the only benefit from corticosteroids demonstrated in experimental situations occurred when large doses (more than 300 mg, some up to 1-2 gm., of hydrocortisone or equivalent) were given at the earliest possible decision point and well before extremis, but the authors claim to be in no position to recommend specific agents or dosage regimens for clinical use.^ieng

Therapeutic effects of corticosteroids in septic shock.

PIP: After a brief summary of the pathophysiology of gram-negative septic shock, a laboratory animal experiment testing the therapeutic efficacy of corticosteroids in such shock cases is presented. Healthy adult mongrel dogs were injected intravenously with 2 mg/kg of E. coli endotoxin to produce endotoxin shock. Overall, the survival of untreated animals was 17% and this was not significantly altered by volume replacement with either Ringers or dextran solution. With treatment (dexamethasone phosphate or methylprednisolone succinate) administered intravenously, in addition to volume replacement, survival increased to 70% of endotoxin-shocked dogs. However, hydrocortisone succinate did not improve survival. The precise mechanism by which the efficacious agents worked is unclear, though both clearly did significantly lower total peripheral vascular resistance. The type of fluid replacement used did not affect the enhanced survival found with dexamethasone phosphate or methylprednisolone succinate.^ieng

Septic shock (endotoxic shock).

PIP: The pathophysiology, clinical aspects, medical, and surgical management of endotoxin shock are reviewed. In the primate, the pathophysiology of endotoxin shock is contributed to by selective vasopasm, disseminated intravascular coagulation, and reduced myocardial response to sympathetic stimuli. Studies in the baboon measured various parameters of hemodynamics and coagulation, catecholamines, and some biochemical changes following the injection of a single bolus of endotoxin. Hemodynamic studies pointed to the kidney as a primary target organ. Coagulation changes included alterations in factor XII and XIII (and others) and plasminogen. Deposition of fibrin was also noted. Neurohormonal studies using tritiated norepinephrine showed a sharp rise in catecholamines 3 minutes after injection of endotoxin followed by a return to normal within 120 minutes, confirming the role of vasopasm in reducing renal perfusion early in shock. Prevention of septic shock is the best way to eradicate the extremely high reported mortality rates; infected abortion, chorioamnionitis, and pyelonephritis should all be warning signals. Methods of monitoring the patient in septic shock with special attention to blood pressure, central venous pressure, blood volume changes, and urinary output are discussed. Early surgical intervention and the proper use of vasomotor drugs and corticosteroids enhance patient survival.^ieng