Nebulized and intraperitoneal ketamine have equivalent antidepressant-like effect in the forced swim and tail suspension tests in mice.

Major depressive disorder (MDD) is a debilitating illness that affects millions of people worldwide. Currently available antidepressants often take weeks to months to reach their full effect, which leads to an increased risk of suicidal behavior in patients with MMD. Intranasally, esketamine has emerged as an alternative to current antidepressants because of its rapid onset and long-lasting effects in patients with MDD. Animal models are useful for the initial pharmacological screening and for a better understanding of the mechanisms underlying the effects of new drugs with potential against MDD. There is a lack of data on alternative routes of drug administration, either oral or injectable, that can be used in preclinical studies. This study aimed to test whether ketamine has antidepressant-like effects in mice when administered via nebulization using a low-cost apparatus. When mice whose depressive-like behavior was induced by corticosterone were treated with nebulized ketamine at concentrations of 1.3, 2.6, and 5.2 mg/mL, immobility was reduced by 38.6 %, 62.0 %, and 61.1 %, respectively, in the forced swimming test (FST) and 43.6 %, 42.1 %, and 57.9 %, respectively, in the tail suspension test (TST). When depression-like behavior was induced by dexamethasone, nebulization with ketamine reduced immobility by 79.7 %, 49.2 %, and 44.4 % in the FST and 80.9 %, 71.4 %, and 80.4 %, respectively, in the TST. When depression-like behavior was induced by the association between dexamethasone and unpredictable chronic mild stress (UCMS) exposure, immobility was reduced by 26.1 %, 55.3 %, and 19.1 % in FST. Mice treated with nebulized ketamine did not show significant changes in the distance covered or in the time spent moving in the open field test. The efficacy of intraperitoneal and nebulized ketamine is equivalent, which shows that nebulization can be an alternative inexpensive route of drug administration for behavioral studies in rodents.

A case report: Hypoxic ischemic encephalopathy & pneumonia in a neonate after SARS-CoV-2 intrauterine transmission.

Severe acute respiratory coronavirus 2 (SARS-CoV-2) is primarily transmitted via respiratory droplet or aerosol route. However, there is mounting evidence for intrauterine transmission. We report on a late preterm infant with suspected intrauterine acquisition of SARS-CoV-2 who experienced birth depression, hypoxic ischemic encephalopathy, multisystem organ involvement, and late onset COVID-19 pneumonia [22].

Investigation of the relaxing effect of a camphor nanoemulsion on rat isolated trachea.

Asthma is a chronic inflammatory disease that targeting lower airways, being characterized by bronchial smooth muscle hyper responsiveness and mucus hypersecretion. Asthma is considered the most common respiratory disease in the world, affecting approximately 235 million individuals. The main therapy sometimes fails to establish clinical improvement in patients, which leads to a constant search for new alternatives. Camphor is a transparent solid monoterpene with a strong aroma, which due to its high lipophilicity is insoluble in water. Nanostructured carrier systems have shown promise as a delivery system for lipophilic compounds such as monoterpenes. Therefore, the objective of this work was to evaluate the relaxant effect of nanoemulsified camphor (NEC), as well as the mechanism of action of that monoterpene, in isolated rat trachea. The results obtained demonstrated that NEC promote relaxation of the isolated rat trachea when smooth muscle contraction was induced by both carbachol (CCh) and KCl, presenting a pCE50 of 2.25 ± 0.27 and 3.30 ± 0.07, respectively. In the presence of dexamethasone (DEXA), tetraethylammonium (TEA), glibenclamide (GLIB), 1H-[1,2,4]-oxadiazole-[4,3,-a]-quinoxaline-1-one (ODQ) and ruthenium red (RR) there was a significant difference in at least one of the evaluated pharmacological parameters, such as concentration-response curves shape, Emax or pCE50. As conclusion, NEC may be involved with ß-adrenergic receptors, channels for K+ sensitive to ATP (KATP) or Channels for K+ opened by Ca2+ (KCa), increase in prostanoids and with receptor channel with transient potential (TRPv). In conclusion, ß-adrenergic receptors, prostanoids, nitric oxide (NO), ATP-sensitive K+ channels (KATP), Ca2+-opened K+ channels (KCa), and transient receptor potential cation channel subfamily V (TRPV) are involved in the relaxing effect of NEC. In addition, the mechanism of action of NEC may be involved with the signal transduction pathway Nitric Oxide/soluble guanylyl cyclase/cGMP/cGMP-activated protein kinase. NEC, therefore, demonstrates spasmolytic activity when presenting tracheal relaxation compared to CCh and KCl contracturants.

Acaricidal efficacy and chemical study of hexane extracts of the leaves of Neoglaziovia variegata (Bromeliaceae) against the tick Rhipicephalus microplus.

The frequent use of acaricides against the tick Rhipicephalus microplus increases the risk of development of resistance. Recent studies have revealed that Neoglaziovia variegata, an indigenous plant species known in Brazil as 'caroá', has a deleterious effect against R. microplus. In the current study, extracts of N. variegata were studied for their possible acaricidal properties. A hexane extract of N. variegata leaves was fractionated in a chromatography column and the fractions were tested in adult tick immersion tests in triplicate using three concentrations (5, 10 and 25 mg/ml). All the fractions had harmful effects on the ticks. However, three fractions were more efficaceous. Phytochemical analysis indicated that stigmast-5-en-3-ol and stigmastanol were most abundant; they might be responsible for the acaricidal effects, making them potentially useful as alternative agents to control the tick R. microplus.

In vitro and in silico studies of 8(17),12E,14-labdatrien-18-oic acid in airways smooth muscle relaxation: new molecular insights about its mechanism of action.

In the field of experimental pharmacology, researchers continuously investigate new relaxant agents of the airway smooth muscle cells (ASMCs), since the pathophysiology of respiratory illnesses, such as asthma, involves hyperresponsiveness and changes in ASMC homeostasis. In this scenario, labdane-type diterpenes, like forskolin (FSK), are a class of compounds known for their relaxing action on smooth muscle cells (SMCs), being this phenomenon related to the direct activation of AC-cAMP-PKA pathway. Considering the continuous effort of our group to study the mechanism of action and prospecting for compounds isolated from natural sources, in this paper, we presented how the diterpene 8(17),12E,14-labdatrien-18-oic acid (LBD) promotes relaxant effect on ASMC, performing in vitro experiments using isolated guinea pig trachea and in silico molecular docking/dynamics simulations. In vitro experiments showed that in the presence of aminophylline, FSK and LBD had their relaxant effect potentiated (EC50 from 1.4 ± 0.2 × 10-5 M to 1.5 ± 0.3 × 10-6 M for LBD and from 2.0 ± 0.2 × 10-7 M to 6.4 ± 0.4 × 10-8 M for FSK) while in the presence of Rp-cAMPS this effect was attenuated (EC50 from 1.4 ± 0.2 × 10-5 M to 3 × 10-4 M for LBD and from 2.0 ± 0.2 × 10-7 to 3.1 ± 1.0 × 10-6 M for FSK). Additionally, in silico simulations evidenced that the lipophilic character of LBD is probably responsible for its stability on AC binding site. LBD presented two preferential orientations, where the double bonds of the isoprene moiety as well as the unique polar group (carboxylic acid) in this compound form important anchoring points. In this sense, we consider that the LBD can interact stabilizing the catalytic dimmer of AC as the FSK, although less efficiently.

New insights on relaxant effects of (-)-borneol monoterpene in rat aortic rings.

The monoterpene alcohol (-)-borneol has many biological effects such as sedative, anti-inflammatory, analgesic, anti-nociceptive, antithrombotic and vasorelaxant effects. Our objective in this study was to investigate the mechanism of action of (-)-borneol and determine its vasorelaxant effect. (-)-Borneol was tested on isolated aortic rings contracted with PE (10-6  m). This study was performed in the absence or in the presence of endothelium, L-NAME (100 µm), indomethacin (10 µm), TEA (1 and 10 mm), 4-AP (1 mm) or glibenclamide (1 mm) to assess the participation of EDRF, nitric oxide, prostanoids and potassium channels on the relaxing effect of (-)-borneol. In this work, (-)-borneol induced a relaxant effect in aortic rings, with and without endothelium, in a concentration-dependent manner. The pharmacological characterization obtained using L-NAME, indomethacin, TEA, 4-AP and glibenclamide demonstrates that the effect of (-)-borneol was modified in the presence of L-NAME, indomethacin and glibenclamide showing that these signal transduction pathways are involved in the relaxing effect of the monoterpene. (-)-Borneol has a vasorelaxant effect that depends on the presence of vascular endothelium, with the participation of nitric oxide and prostanoids. Also, (-)-borneol displayed a direct action on the vascular smooth muscle, greatly dependent on KATP channels.

Red blood cell transfusions increase fecal calprotectin levels in premature infants.

OBJECTIVE: We hypothesized that red blood cell (RBC) transfusions influence intestinal inflammation in very low birth weight (VLBW) infants. We also suspected that hematocrit (Hct) at transfusions and RBC storage time correlate with intestinal inflammation. STUDY DESIGN: VLBW infants, without major congenital defects, intestinal perforation or necrotizing enterocolitis, were enrolled prospectively. Fecal calprotectin (FC) levels were measured from stool samples collected before and after RBC transfusions. Data on Hct and RBC storage time were collected. RESULT: Data from 42 RBC transfusions given to 26 infants revealed that FC levels increased faster than baseline after RBC transfusions (P=0.018) and were higher in multiple-transfused infants (0 to 48 and >48 h post transfusion, P=0.007 and P=0.005, respectively). Lower Hct and RBC storage >21 days correlated with higher FC levels (P=0.044 and P=0.013, respectively). CONCLUSION: RBC transfusions, anemia and prolonged RBC storage were associated with an increase in intestinal inflammation.

The vasorelaxant effect of 8(17),12E,14-labdatrien-18-oic acid involves stimulation of adenylyl cyclase and cAMP/PKA pathway: Evidences by pharmacological and molecular docking studies.

The relaxant effect of 8(17),12E,14-labdatrien-18-oic acid (LBD) was investigated on isolated aortic rings and compared with forskolin (FSK), a standard and potent activator of adenylyl cyclase (AC) with relaxing effect. The presence of potassium channel blockers, such as glibenclamide (ATP-blocker), apamin (SKCa-blocker), charybdotoxin (BKCa-blocker) did not significantly affect either the LBD or FSK concentration-response curves. However, in the presence of 4-aminopyridine (KV-blocker), the relaxant effect for both diterpenes was significantly attenuated, with reduction of its relative potencies. Moreover, the relaxation induced by 8-Br-cAMP, an analog of cAMP, was also significantly attenuated in the same conditions, i.e., in the presence of 4-aminopyridine. The presence of aminophylline, a nonselective phosphodiesterase inhibitor, caused a significant increasing in the potency for both LBD and FSK. On the other hand, the presence of Rp-cAMPS, a selective PKA-inhibitor, significantly attenuated the relaxant effect of LBD. In this work, in the same experimental conditions, both labdane-type diterpenes presented remarkably similar results; FSK, however, presented a higher potency (100-fold) than LBD. Thus, the hypothesis that LBD could be a novel AC-activator emerged. To assess that hypothesis, computational molecular docking studies were performed. Crystallographic structure of adenylyl cyclase/forskolin complex (1AB8) was obtained from RSCB Protein Data Bank and used to compare the modes of interaction of the native ligand and LBD. The computational data shows many similarities between LBD and FSK concerning the interaction with the regulatory site of AC. Taken together, the results presented here pointed to LBD as a novel AC-activator.

Depth of bacterial invasion in resected intestinal tissue predicts mortality in surgical necrotizing enterocolitis.

OBJECTIVE: Up to a third of all infants who develop necrotizing enterocolitis (NEC) require surgical resection of necrotic bowel. We hypothesized that the histopathological findings in surgically resected bowel can predict the clinical outcome of these infants. STUDY DESIGN: We reviewed the medical records and archived pathology specimens from all patients who underwent bowel resection/autopsy for NEC at a regional referral center over a 10-year period. Pathology specimens were graded for the depth and severity of necrosis, inflammation, bacteria invasion and pneumatosis, and histopathological findings were correlated with clinical outcomes. RESULT: We performed clinico-pathological analysis on 33 infants with confirmed NEC, of which 18 (54.5%) died. Depth of bacterial invasion in resected intestinal tissue predicted death from NEC (odds ratio 5.39 per unit change in the depth of bacterial invasion, 95% confidence interval 1.33 to 21.73). The presence of transmural necrosis and bacteria in the surgical margins of resected bowel was also associated with increased mortality. CONCLUSION: Depth of bacterial invasion in resected intestinal tissue predicts mortality in surgical NEC.

The vasorelaxant effect of p-cymene in rat aorta involves potassium channels.

The monoterpenes are the main constituents of most essential oils and p-cymene is a monoterpene commonly found in various species of aromatic herbs, which has been reported for anti-inflammatory, antinociceptive, and antimicrobial activities. However, there is no report concerning its pharmacological activity on the vascular smooth muscle. The aim of current work was to investigate the effects of p-cymene in isolated rat aorta and also study its mechanism of action. In this work, we show that p-cymene has a relaxant effect, in a dose-dependent way, on the vascular smooth muscle, regardless of the presence of the endothelium. Using a nonselective potassium channel blocker, the CsCl, the relaxant effect of p-cymene was attenuated. In the presence of more selective potassium channels blockers, such as TEA or 4-AP, no change in the relaxant effect of p-cymene was evidenced, indicating that BKCa and KV channels are not involved in that relaxant effect. However, in the presence of glibenclamide or BaCl2, KATP and Kir blockers, respectively, the relaxant effect of p-cymene was attenuated. The data presented indicate that p-cymene has a relaxing effect on rat aorta, regardless of the endothelium, but with the participation of the KATP and Kir channels.

Antinociceptive and anti-inflammatory effects of Costus spicatus in experimental animals.

CONTEXT: Costus spicatus Swartz (Costaceae), commonly called "cana-do-brejo'" in Brazil's northeast, is a medicinal plant found in wet coastal forests. In folk medicine an infusion of the aerial parts is taken to treat inflammation and pain. OBJECTIVE: The methanol extract obtained from the leaves of Costus spicatus (MECs) was evaluated for antinociceptive and anti-inflammatory activities. METHODS: Analgesic and anti-inflammatory activities were studied by measuring nociception through acetic acid, formalin, and hot-plate tests, while inflammation was induced by carrageenan. All experiments were conducted with experimental animals. RESULTS AND DISCUSSION: Following oral administration, MECs (100, 200, and 400 mg/kg) significantly reduced the number of writhes (52.8, 43.1, and 55.3%, respectively) in the writhing test and the number of paw licks during phase 1 (61.9, 54.1, and 92.1%) and phase 2 (62.5, 82.9, and 98.1%, all doses) during the formalin test when compared to the control group animals. The reaction time during the hot-plate test was increased significantly and was dose-dependent, whereas pretreatment with naloxone rigorously reduced the analgesic potential of MECs, which suggested participation of the opioid system in the modulation of pain induced by MECs. Such results were unlikely to be provoked by motor abnormality, as MECs-treated mice did not exhibit any performance alteration during the Rota-rod test. The administration of 200 and 400 mg/ kg (i.p.) of MECs exhibited an anti-inflammatory effect during the carrageenan test, which was based on interference with inflammatory mediator synthesis. CONCLUSION: We conclude that MECs has antinociceptive and anti-inflammatory activities in rodents.

O Ácido (8)17,12E,14-labdatrieno-18-óico (labdano302), diterpeno tipo labdano isolado de Xylopia langsdorffiana St. Hil. & Tul. (Annonaceae) relaxa a traquéia isolada de cobaia / The (8)17,12E,14-labdatrien-18-oic acid (labdane302), labdane-type diterpene isolated from Xylopia langsdorffiana St. Hil. & Tul. (Annonaceae) relaxes the guinea-pig trachea

A espécie Xylopia langsdorffiana St. Hil.. & Tul. é popularmente conhecida como "pimenteira-da-terra" no Sudeste do Brasil. A partir do fracionamento do extrato etanólico, obtido das cascas do caule desta espécie, foi isolado um diterpeno tipo labdano, identificado como sendo o ácido 8(17),12E,14-labdatrieno-18-óico, e que neste trabalho é codificado como labdano302. O labdano302 relaxou o tônus basal dos anéis de traquéia isolada de cobaia com um valor de CE50 de 6,7 ± 0,5 x 10-8 M. O diterpeno labdano302 relaxou de maneira dependente de concentração os anéis pré-contraídos com carbacol (10-6 M), tanto na presença (CE50 = 1,4 ± 0,7 x 10-5 M) como na ausência de epitélio funcional (CE50 = 1,5 ± 0,3 x 10-5 M), bem como anéis pré-contraídos com 18 ou 60 mM de KCl, apresentando valores de CE50 de 2,3 ± 0,4 x 10(7) M e 1,8 ± 0,8 x 10-5 M, respectivamente. Este efeito relaxante, sobre as contrações induzidas por 18 mM de KCl, tanto foi significantemente mais potente quanto mais eficaz quando comparado ao efeito sobre as contrações induzidas por 60 mM de KCl. Assim, labdano302 mostra um efeito relaxante em traquéia isolada de cobaia, tanto em seu tônus basal como sob estímulo contrátil, aparentemente sem a participação dos fatores relaxantes derivados do epitélio, contudo com possível participação dos canais de K+.

Xylopia langsdorfiana St. Hil. & Tul. is popularly known as "pimenteira-da-terra" in Southeast of Brazil. The fractionation of the ethanol extract obtained from the stem-bark of this species yielded a labdane-type diterpene identified as 8(17),12E,14-labdatrien-18-oic acid, referred here as labdane302. In this study, we investigated the effect of labdane302 in guinea-pig trachea. labdane302 relaxed the basal tonus of trachea rings with EC50 value of 6.7 ± 0.5 x 10-8 M. The diterpene labdane302 relaxed the pre-contracted rings by carbachol 10-6 M both in the presence (EC50 = 1.4 ± 0.7 x 10-5 M) and absence of functional epithelium (EC50 = 1.5 ± 0.3 x 10-5 M), as well as pre-contracted by KCl 18 mM or 60 mM, presented EC50 values of 2.3 ± 0.4 x 10-7 M and 1.8 ± 0.8 x 10-5 M, respectively. This relaxant effect, upon contractions induced by KCl 18 mM, was more potent as well as more efficient than the one presented with KCl 60 mM pre-contracted rings. The labdane-type diterpene labdane302 shows the relaxant effect in isolated guinea-pig trachea, pre-contracted or upon basal tonus, apparently without participation of epithelium-derived relaxant factors, but apparently involving activation of K+ channels.

Extratos metanólico e acetato de etila de Solanum megalonyx Sendtn. (Solanaceae) apresentam atividade espasmolítica em íleo isolado de cobaia: um estudo comparativo / Methanol and ethyl acetate extracts from Solanum megalonyx Sendtn. (Solanaceae) present spasmolytic activity in guinea-pig ileum: a comparative study

Solanum megalonyx Sendtn. (Solanaceae) é conhecida popularmente por "jurubeba" no Nordeste do Brasil e se apresenta na forma de arbusto. Várias espécies de Solanum apresentam efeito espasmolítico em órgãos isolados. Assim, objetivou-se investigar e comparar o efeito dos extratos metanólico (SM-MeOH) e acetato de etila (SM-AcOEt), obtidos das partes aéreas de S. megalonyx, em íleo isolado de cobaia. SM-MeOH e SM-AcOEt antagonizaram (n = 5) as contrações fásicas induzidas por 1 mM de acetilcolina (logCI50 = 3,2 ± 0,1 e 1,8 ± 0,6 mg/mL, respectivamente) ou de histamina (logCI50 = 2,8 ± 0,5 e 1,7 ± 0,3 mg/mL, respectivamente). SM-MeOH e SM-AcOEt também relaxaram (n = 5) o íleo pré-contraído por 40 mM de KCl (logCE50 = 1,9 ± 0,09 e 1,9 ± 0,1 mg/mL, respectivamente), por 1 mM de histamina (logCE50 = 1,9 ± 0,07 e 1,7 ± 0,08 mg/mL, respectivamente) ou de acetilcolina (logCE50 = 1,9 ± 0,02 e 1,7 ± 0,09 mg/mL, respectivamente) de maneira dependente de concentração e equipotente. Demonstra-se pela primeira vez que S. megalonyx apresenta efeito espasmolítico não seletivo em íleo isolado de cobaia, sugerindo que os extratos podem estar agindo em um passo comum da via de sinalização dos agentes contráteis testados.

Solanum megalonyx Sendtn. (Solanaceae) is known popularly as "jurubeba" in Northeastern Brazil where it can be found as a shrub. Several species of Solanum present spasmolytic effect in several tissues, thus this study was aimed to investigate and compare the effect of the methanol extract (SMMeOH) and ethyl acetate extract (SM-AcOEt), obtained from aerial parts of Solanum megalonyx Sendtn., in guinea-pig ileum. In this work, both SM-MeOH and SM-AcOEt antagonized the phasic contraction induced by acetylcholine 1 mM (logIC50 = 3.2 ± 0.1 and 1.8 ± 0.6 mg/mL) and histamine 1 mM (logIC50 = 2.8 ± 0.5 and 1.7 ± 0.3 mg/mL, respectively) (n = 5), without statistical differences between these values. In another set of experiments, SM-MeOH and SM-AcOEt also relaxed the isolated guinea-pig ileum pre-contracted by KCl 40 mM (logEC50 = 1.9 ± 0.09 and 1.9 ± 0.1 mg/mL, respectively), histamine 1 mM (logEC50 = 1.9 ± 0.07 mg/mL and 1.7 ± 0.08 mg/mL, respectively) or acetylcholine (logEC50 = 1.9 ± 0.02 mg/mL and 1.7 ± 0.09 mg/mL, respectively) (n = 5) in a concentration-dependent and equipotent manner. This study demonstrates for the first time that aerial parts of S. megalonyx present a non-selective spasmolytic effect in guinea-pig ileum, suggesting that the extracts could be acting in a common step of the pathway signaling that leads to contraction induced by the contractile agents tested.

Spasmolytic action of the methanol extract and isojuripidine from Solanum asterophorum Mart. (Solanaceae) leaves in guinea-pig ileum.

Solanum asterophorum Mart. (Solanaceae) is a shrub popularly known as "jurubeba-defogo" in the northeast of Brazil. In the present work, the methanol extract (SA-MeOH, 3750 microg/mL) and isojuripidine (10(-7) - 3 x 10(-4) M), a steroidal alkaloid obtained from S. asterophorum Mart. leaves, inhibited phasic contractions induced by both 1 microM histamine [IC50 = (225.8 +/- 47.4), g/mL and (3.5 +/- 0.8) x 10(-5) M] or 1 microm acetylcholine [IC50 = (112.5 +/- 20.6) microg/mL and (2.3 +/- 0.4) x 10(-5) M] in guinea-pig ileum, respectively. The extract and isojuripidine also relaxed the ileum (SA-MeOH, 1-750 microg/mL, and isojuripidine, 10(-9) - 3 x 10(-4) M) pre-contracted with 1 M histamine [EC50 = (101.1 +/- 17.4) microg/mL and (1.2 +/- 0.3) x 10(-6) M] or 1 microM acetylcholine [EC50 = (136.8 +/- 21.1) microg/mL and (1.9 +/- 0.4) x 10(-6) M] or 40 mm KCl [EC50 = (149.4 +/- 19.5) microg/mL and (1.8 +/- 0.7) x 10(-6) M], respectively, in an equipotent and concentration-dependent manner. This effect is probably due to inhibition of calcium influx through voltage-operated calcium (Ca(v)) channels. To confirm this hypothesis, we evaluated their effect on cumulative CaCl2 curves in depolarizing medium nominally without Ca2+. SA-MeOH (27, 243, 500, and 750 microg/mL) and isojuripidine (3 x 10(-8), 10(-6), 3 x 10(-5), and 3 x 10(-4) M) inhibited the contractions induced by CaCl2, in a concentration-dependent manner. The concentration-response curves to CaCl2, in the presence of SA-MeOH and isojuripidine, were shifted downward in relation to a control curve in a non-parallel manner resulting in reduction of the maximum effect [E(max) = (71.2 +/- 9.2); (57.4 +/- 9.2); (43.8 +/- 3.4); (41.5 +/- 2.4) and (90.6 +/- 4.8); (74.7 +/- 8.7); (66.4 +/- 3.9); (31.3 +/- 4.1)%, respectively]. SA-MeOH and isojuripidine present spasmolytic action in guinea-pig ileum due to a partially blockade of calcium influx through Ca(v) channels.

Ectopic pregnancy from surgical emergency to medical management.

During the past 25 years, the incidence of ectopic pregnancy has progressively increased while the morbidity and mortality have substantially decreased, and the treatment has progressed from salpingectomy by laparotomy to conservative surgery by laparoscopy and more recently to medical therapy. This therapeutic transition from surgical emergency to medical management has been attributed to early diagnosis through the use of sensitive assays for hCG and the high definition of vaginal ultrasound. By using these sensitive diagnostic tools, we are now able to select those patients who are most likely to respond to medical management versus those who are at high risk of rupture and require surgery. Besides being less invasive and associated with significantly lower risks, medical therapy with methotrexate results in significant cost savings, which have been calculated to be approximately $3,000 per treated patient. Our goal is to identify those patients with ectopic pregnancy who are most likely to respond to methotrexate therapy and least likely to develop significant side effects. Recent studies have helped us define the predictors of success with methotrexate treatment in women with ectopic pregnancy. The reported success rates of treating ectopic pregnancy with methotrexate vary from 71% to 100%. The highest success rates have been reported from institutions that have detailed diagnostic and therapeutic protocols, readily available assays for serum hCG levels, high-resolution vaginal probe ultrasound, and support staff that can closely monitor clinical response. The importance of developing specific protocols to create a clinical environment that supports the effective use of medical therapy for ectopic pregnancy is confirmed by the associated cost savings, decreased morbidity, and patient preference. Modern diagnostic advances and minimally invasive treatments coupled with improved success rates for assisted reproductive technologies should reduce the morbidity and mortality associated with ectopic pregnancy and offer the affected couple a much more optimistic outlook for subsequent reproductive potential.

Safe technique for laparoscopic entry into the abdominal cavity.

STUDY OBJECTIVE: To evaluate and compare the safety and efficacy of a new method to enter the abdominal cavity at laparoscopy. DESIGN: (Canadian Task Force classification II-2). SETTING: Referral center for reproductive surgery in a teaching hospital affiliated with a university-based residency program. PATIENTS: Twenty representative women of variable body habitus (body mass index 16.5-39 kg/m2). INTERVENTION: Laparoscopy and laparotomy. MEASUREMENTS AND MAIN RESULTS: We measured the thickness of the abdominal wall at the base of the umbilicus and just below its inferior border. We also measured distances traversed by the Veress needle or cannula from skin to peritoneal cavity at both sites when the piercing instrument was directed at 45- or 90-degree angle from the horizontal plane of the abdominal wall. Finally, we measured distances created between parietal peritoneum and underlying viscera when the abdominal wall was lifted manually or with towel clips placed laterally, 2 cm from the umbilicus and at the edges of the intraumbilical incision. Distances created between parietal peritoneum and underlying viscera while lifting the abdominal wall by each of these three techniques were measured with a calibrated probe inserted through the intraumbilical port and observed with a 5-mm laparoscope from the suprapubic port. These distances were measured before and after carbon dioxide insufflation at 15 mm Hg, as well as before and while inserting the cannula through the abdominal wall. Mean +/- SD thickness of the abdominal wall at the base of the umbilicus and lower border of the umbilicus were 1.4 +/- 0.5 and 3.0 +/- 1.1 cm, respectively (p <0.01). Distances traversed by piercing instruments through the abdominal wall at the umbilicus and lower border of the umbilicus when the angle of insertion was 45 degrees were 1.98 +/- 0.76 and 4.24 +/- 1.53 cm, respectively (p <0.01). Distances were significantly greater when the angle of insertion was 45 degrees rather than 90 degrees. Distances between parietal peritoneum and underlying viscera when the abdominal wall was lifted manually with towel clips 2 cm from the umbilicus, or at the edges of the intraumbilical incision were 3.5 +/-1.14, 5.14 +/- 1.04, and 6.8 +/- 0.94 cm, respectively (p <0.01). When force was applied on the abdomen at cannula insertion, these distances were reduced by 2.1 +/- 0.91, 1.03 +/- 0.32, and zero centimeters, respectively (p <0.01). CONCLUSION: Our technique of inserting the cannula perpendicularly through the base of the umbilicus traverses the shortest distance to the abdominal cavity through the least vascular area of the abdominal wall. Lifting the abdominal wall with towel clips placed at the edges of the intraumbilical incision achieves the greatest distance between parietal peritoneum of the abdominal wall and underlying viscera, thus maximizing the margin of safety in protecting peritoneal organs and retroperitoneal vessels from injury.