Maternal and fetal parameters in pregnant woman undergoing tocolysis with nifedipine / Parâmetros maternos e fetais em gestante submetida a tocólise com nifedipina

Abstract Objectives: to evaluate the effects of nifedipine with tocolysis under maternal and fetal parameters. Methods: a cohort study with 40 pregnant women admitted at a high-risk pregnancy ward to inhibit premature labor between September/2010 to May/2012. Nifedipine was used as a 20mg sublingual attack dose and maintained 20mg every six and eight hours orally. The variables of the analysis were fetal heart rate (FHR), maternal heart rate (MHR), systolic blood pressure (SBP) and diastolic blood pressure (DBP), and amniotic fluid index (AFI). All the variables were evaluated prior to administrating nifedipine and approximately after 6 hours and every 24 hours, until hospital discharge. Results: there were no modification of the FHR (p=0.48) and the SBP (p=0.29). The MHR increased after 24 hours, but with no statistical difference (p=0.08), returning to similar levels as at admission within 48 hours. The DBP decreased at 6 (p=0.04) to 72 hours, being stable afterwards. The AFI decreased significantly at 24, 48 and 72 hours. Conclusions: the use of high doses of nifedipine with tocolysis causes a decrease of the maternal's diastolic blood pressure and consequently decreases the amniotic fluid index, but probably without any clinical repercussions.

Resumo Objetivos: avaliar os efeitos da nifedipina utilizada na tocólise sobre os parâmetros maternos e fetais. Métodos: estudo de coorte incluindo 40 gestantes admitidas na enfermaria de alto risco para inibição do trabalho de parto prematuro entre setembro/2010 a maio/2012. Utilizou-se a nifedipina sublingual na dose de ataque de 20mg e uma manutenção de 20mg por via oral a cada seis e oito horas. As variáveis avaliadas foram os batimentos cardio-fetais (BCF), frequência cardíaca materna (FCM), pressão arterial sistólica (PAS) e diastólica (PAD) e índice de líquido amniótico (ILA). Todas as variáveis foram avaliadas antes da administração da nifedipina e aproximadamente após 6h e cada 24h até alta hospitalar. Resultados: não houve modificação dos BCF (p=0,48) e da PAS (p=0,29). A FCM aumentou após 24h, mas sem significância estatística (p=0,08) retornando a níveis similares ao da admissão com 48h. A PAD diminuiua partir de 6h (p = 0,04)até 72h, mantendo-se constante. O ILA diminuiu significativamente em 24h, 48h e 72h. Conclusão: a utilização de altas doses de nifedipina para tocóliseocasio na diminuição dos níveis pressóricos diastólicos maternos e consequentemente diminuição do ILA, mas provavelmente sem repercussões clínicas.

Impact of topical nifedipine on wound healing in animal model (pig) / Impacto da nifedipina tópica na cicatrização de feridas em modelo animal (porco)

Abstract Background The human skin is an extremely sophisticated and evolved organ that covers the whole body. External agents or the patient's own diseases can cause skin injuries that can challenge healthcare professionals and impose high social, economic and emotional costs. Objectives To evaluate the impact of topical nifedipine on skin wound healing, specifically on polymorphonuclear cells, vascular proliferation, and collagen. Methods We used three pigs, and created eight injuries in the dorsal region of each animal. We applied 1%, 10%, and 20% concentration nifedipine creams to four of the wounds in animals 1, 2, and 3 respectively and treated the other twelve wounds with saline solution 0.9% only. We analyzed the presence of polymorphonuclear cells, vascular proliferation, and collagen at six different times (days 1, 3, 7, 14, 21, and 28). Results The evaluation of polymorphonuclear levels showed mild cell activity at all times in the control group, while in the nifedipine groups, marked levels were more frequent at all times during the experiment. There was a 4.84-fold increase in the chance of marked vascular proliferation (p = 0.019) and, at the same time, a decrease in collagen formation (OR 0.02 / p = 0.005) in animal 3. Conclusions Topical NFD may have an impact on skin wound healing mechanisms. Our study showed that polymorphonuclear cells and vascular proliferation increased. We also demonstrated that collagen formation decreased. Therefore, topical NFD may have a positive impact on skin wound healing. Additional studies are needed to confirm our results.

Resumo Contexto A pele humana é um órgão extremamente sofisticado e evoluído que cobre todo o corpo. As lesões cutâneas podem ser causadas por agentes externos ou pelas próprias doenças do paciente, e podem representar um desafio para os profissionais de saúde com altos custos sociais, econômicos e emocionais. Objetivos Avaliar o impacto da nifedipina tópica na cicatrização de feridas cutâneas, especialmente em relação a polimorfonucleares, proliferação vascular e colágeno. Métodos Utilizamos três porcos e realizamos oito ferimentos na região dorsal de cada animal. Aplicamos as concentrações de nifedipina creme a 1%, 10% e 20% para os animais 1, 2 e 3, respectivamente, sendo que, em quatro ferimentos, aplicamos o creme e, nos outros quatro ferimentos, apenas soro fisiológico a 0,9%. Analisamos a presença de polimorfonucleares, proliferação vascular e colágeno em seis momentos diferentes (dias 1, 3, 7, 14, 21 e 28). Resultados A avaliação dos níveis polimorfonucleares mostrou atividade celular discreta em todos os momentos no grupo controle, enquanto nos grupos nifedipina, os níveis marcados foram mais frequentes em todos os momentos do experimento. Houve aumento de 4,84 vezes na chance de uma produção marcada (p = 0,019) da proliferação vascular e, ao mesmo tempo, diminuição da formação do colágeno (odds ratio, OR 0,02; p = 0,005) no animal 3. Conclusões A nifedipina tópica pode ter impacto no mecanismo de cicatrização cutânea. Nosso estudo mostrou que há aumento dos polimorfonucleares e da proliferação vascular. Além disso, há diminuição da formação do colágeno. Assim, a nifedipina tópica pode ter impacto positivo na cicatrização das feridas cutâneas. Estudos adicionais são necessários para confirmar nossos resultados.

Progesterona vaginal combinada con nifedipino en la prevención de parto pretermino con cervix corto / Vaginal progesterone combined with nifedipine in The prevention of pretermine labor with short cervix

Objetivo: evaluar los efectos de la progesterona vaginal combinada con nifedipino en comparación al uso único de Nifedipino en la amenaza de parto pretérmino en gestantes entre 24-34 semanas con longitud cervical ≤ a 25 mm en el Hospital Materno Infantil Germán Urquidi. Método: se realizó un estudio de cohorte, prospectivo, comparativo y analítico. Es un diseño de dos grupos (comparativos) donde la selección de pacientes se hizo de acuerdo a criterios de inclusión y exclusión, se evaluaron 231 pacientes. Resultados: el 67% de las pacientes que usaron progesterona más nifedipino resolvieron el evento de Amenaza de Parto Pretérmino en la primera hora en comparación al 50% de las pacientes que usaron solo nifedipino. Con la combinación de progesterona y nifedipino se controló en 1 hora el episodio de Amenaza de Parto Prematuro entre las 24 a 34 semanas de gestación, con el uso único de nifedipino, desde las 32 - 34 semanas existe un promedio de 2 horas en sobrepasar el episodio. Con solo nifedipino como tocolítico, el 80% de los pacientes verificaron parto a los 5 días. Solamente el 20% lograron sobrepasar los 10 días de latencia. La combinación progesterona y nifedipino logro que el 30% de las pacientes alcanzaran una latencia entre los 21-30 días, La edad gestacional al nacimiento con la combinación progesterona y Nifedipino alcanza en un 80% una edad menor o igual a 37 semanas 6 días. Conclusiones: La combinación de Progesterona vaginal más nifedipino, mejora sustancialmente el pronóstico neonatal en todos los resultados obtenidos, el uso único de nifedipino tiene menores efectos beneficiosos en esta investigación.

Objective: evaluate the effects of Vaginal Progesterone combined with nifedipine compared to the single use of nifedipine in the threat of preterm delivery in pregnant women between 24-34 weeks with cervical length ≤ 25mm in the Hospital Materno Infantil Germán Urquidi. Method: a prospective, comparative and analytical cohort study was conducted. It is a design of two groups (comparative) where the selection of patients was made according to inclusion and exclusion criteria, we evaluated 231 patients. Results: the time to exceed the Preterm Childbirth episode, 67% of the patients who used progesterone plus nifedipine resolved the event within the first hour compared to 50% of patients who used only nifedipine. With the combination of progesterone and nifedipine, the episode of Premature Birth Threat between 24 and 34 weeks of gestation was controlled within 1 hour, with the sole use of nifedipine, from 32-34 weeks there is an average of 2 hours in excess of episode. With only nifedipine as tocolytic, 80% of the patients verified delivery at 5 days. Only 20% were able to exceed 10 days of latency. The combination progesterone + nifedipine achieved that 30% of the patients reached a latency between 21-30 days, Gestational age at birth with the combination progesterone + nifedipino reaches 80% an age less than or equal to 37 weeks 6 days. Conclusions: the combination of vaginal progesterone plus nifedipine substantially improves the neonatal prognosis in all the results obtained, the use of nifedipine alone has less beneficial effects in this investigation.

A Case of Severe Coronary Spasm Associated with 5-Fluorouracil Chemotherapy

Cardiotoxicity associated with 5-fluorouracil (FU) is an uncommon, but potentially lethal, condition. The case of an 83-year-old man with colon cancer who developed chest pain during 5-FU infusion is presented. The electrocardiogram (ECG) showed pronounced ST elevation in the lateral leads, and the chest pain was resolved after infusion of nitroglycerin. A coronary angiogram (CAG) revealed that the patient had significant atherosclerosis in the proximal left circumflex artery. Coronary artery spasm with fixed stenosis was considered, and a drug-eluting stent was implanted. After 8 hours, the patient complained of recurring chest pain, paralleled by ST elevation on the ECG. The chest pain subsided after administration of intravenous nitroglycerin followed by sublingual nifedipine. Repeated CAG showed patency of the previous stent. This case supports the vasospastic hypothesis of 5-FU cardiac toxicity, indicating that a calcium channel blocker may be effective in the prevention or treatment of 5-FU cardiotoxicity.

Nitroglicerina transdérmica versus nifedipina oral para inibição do trabalho de parto prematuro: ensaio clínico randomizado / Transdermal nitroglycerin versus oral nifedipine administration for tocolysis: a randomized clinical trial

OBJETIVO: comparar a efetividade da nitroglicerina transdérmica com a nifedipina oral na inibição do trabalho de parto prematuro. MÉTODOS: foi realizado um ensaio clínico com 50 mulheres em trabalho de parto prematuro, randomizadas em dois grupos, 24 para nifedipina oral (20 mg) e 26 para nitroglicerina transdérmica (patch 10 mg). Foram selecionadas as pacientes com gestação única, entre a 24ª e 34ª semanas e diagnóstico de trabalho de parto prematuro. Foram excluídas pacientes com malformações fetais e com doenças clínicas ou obstétricas. As variáveis analisadas foram tocólise efetiva, tempo necessário para tocólise, frequência de recorrência, progressão para parto prematuro e efeitos colaterais. RESULTADOS: a eficácia da tocólise nas primeiras 12 horas foi semelhante entre os grupos (nitroglicerina: 84,6 por cento versus nifedipina: 87,5 por cento; p=0,5). A média do tempo para tocólise também foi semelhante (6,6 versus 5,8 horas; p=0,3). Não houve diferença entre os grupos quanto à recorrência de parto prematuro (26,9 versus 16,7 por cento; p=0,3) e nem na frequência de parto prematuro dentro de 48 horas (15,4 versus 12,5 por cento; p=0,5). Entretanto, a frequência de cefaleia foi significativamente maior no grupo que usou nitroglicerina (30,8 versus 8,3 por cento; p=0,04). CONCLUSÕES: a nitroglicerina transdérmica apresentou efetividade semelhante à nifedipina oral para inibição do trabalho de parto prematuro nas primeiras 48 horas, porém com maior frequência de cefaleia.

PURPOSE: to compare the effectiveness of transdermal nitroglycerin with oral nifedipine in the inhibition of preterm delivery. METHODS: a clinical essay has been performed with 50 women in preterm delivery, randomly divided into two groups, 24 receiving oral nifedipine (20 mg), and 26, transdermal nitroglycerin (10 mg patch). Patients with a single gestation, between the 24th and the 34th weeks and diagnosis of preterm delivery were selected. Women with fetal malformation and clinical or obstetric diseases were excluded. The variables analyzed were: effective tocolysis, time needed for tocolysis, recurrence frequency, progression to preterm delivery, and side effects. RESULTS: tocolysis efficacy in the first 12 hours was similar between the groups (nitroglycerin: 84.6 percent versus nifedipine: 87.5 percent; p=0.50). The time average time needed for tocolysis was also similar (6.6 versus 5.8 hours; p=0.30). There was no difference between the groups, concerning the recurrence of preterm delivery (26.9 versus 16.7 percent; p=0.30), and neither in the rate of preterm delivery within 48 hours (15.4 versus 12.5 percent; p=0.50). Nevertheless, the cephalea rate was significantly higher in the Nitroglycerin Group (30.8 versus 8.3 percent; p=0.04). CONCLUSIONS: transdermal nitroglycerin has presented similar effectiveness to oral nifedipine to inhibit preterm delivery in the first 48 hours, however with higher cephalea frequency.

Nimodipine is more effective than nifedipine in attenuating morphine tolerance on chronic co-administration in the rat tail-flick test.

Opioids, when co-administered with L-type calcium channel blockers (L-CCBs) show morphine like higher antinociceptive effect. This antinociceptive effect has been further investigated using a different experimental paradigm. The effect of two different L-CCBs (nifedipine and nimodipine) on morphine-induced antinociception was studied by the tail-flick test (40 min after morphine administration) in adult Wistar rats. A fixed-dose of nimodipine or nifedipine (2 mg/kg, once daily) was combined with a fixed dose of morphine (10 mg/kg, twice daily) for 10 days. Co-administration of L-CCBs significantly increased the antinociceptive effect of morphine, even 12 hr after administration. Also, nimodipine was more effective than nifedipine. Nimodipine was further studied using a higher and escalating doses of morphine (20-30 mg/kg twice daily for 14 days). Nimodipine increased the antinociceptive effect of morphine in the latter part of the study (days nine to fourteen) though significant difference was observed on 11th evening and 12th morning. No obvious adverse effects were observed in the present study. The results show for the first time that nimodipine is more effective than nifedipine and that these L-CCBs continue to be effective, even 12 hr after administration in the tail-flick test.

Safety and efficacy of oral nifedipine versus terbutaline injection in preterm labor.

OBJECTIVE: To compare the safety and tocolytic efficacy of oral nifedipine with intravenous terbutaline for the management of threatened preterm labor. MATERIAL AND METHOD: Pregnant women between 24 and 36 completed weeks of single gestation with preterm labor were randomized to either oral nifedipine (n=20) or intravenous terbutaline (n=20) treatment. Nifedipine (immediate released capsule) 10 mg was crushed and swallowed, 10 mg every 20 minutes was allowed if necessary with a maximum 40 mg in the first hour. After that 20 mg nifedipine every 4 hours was given, up to 72 hours. Terbutaline was initially infused with the rate 10 g/min with an increment 5 microg/min every 10 minutes if required, until 25 microg/min was reached. Once the contractions had stopped for 2-6 hours, the patients were switched to subcutaneous injection with 0.25 mg terbutaline every 4 hours for 24 hours. The main safety outcome was the changes in maternal diastolic blood pressure from baseline and 1 hour after starting the treatment (deltaDBP(1hr)). Secondary outcomes were the efficacy to delay delivery > or =48 hours and 7 days, the adverse events and the birth outcomes. RESULTS: deltaDBP(1hr) was greater in the terbutaline group than that in the nifedipine group with no statistically significant difference. Hypotension (defined as BP < or = 90/60 mmHg) was found in one patient of the nifedipine group and two patients of the terbutaline group. Seventeen and 14 patients in the nifedipine group and 15 and 12 patients in the terbutaline group had delayed delivery > or =48 hours and 7 days, respectively. Mothers in the nifedipine group experienced fewer side effects than those in the terbutaline group. Maternal heart rate, at I hour after starting the treatment, increased significantly higher in the terbutaline group than in the nifedipine group. Birth outcomes were measured in all nifedipine group patients, but in only 16 of the terbutaline group patients. Six mothers in each group delivered after 37 weeks. Intraventricular hemorrhage (IVH) occurred in three babies (gestational aged 25, 29 and 37 weeks) born to mothers treated with terbutaline. In one baby, IVH related to trauma resulted from the delivery procedure. CONCLUSION: The safety and efficacy of nifedipine compares with that of terbutaline for treatment of preterm labor.

The Relationship Between the Acute Changes of the Systolic Blood Pressure and the Brachial-Ankle Pulse Wave Velocity

BACKGROUND: The brachial-ankle pulse wave velocity (baPWV) is a useful parameter to assess arterial stiffness. However, it is difficult to evaluate arterial stiffness in hypertensive patients because the baPWV is affected by the blood pressure itself. This study was designed to estimate the relationship between the change of the blood pressure parameters and the baPWV (delta baPWV) when hypertensive patients were subjected to an acute reduction of blood pressure. METHODS: Thirty patients with essential hypertension and whose blood pressure was higher than 140/90 mmHg were enrolled. In all the patients, the blood pressure and baPWV were measured using an automatic waveform analyzer with the patients at a resting state. When the reduction of blood pressure was more than 10 mmHg after sublingual administration of nifedipine 10 mg, then the blood pressure and baPWV were measured again in the same manner and then they were compared with the baseline values. Spearman's correlation and multiple linear regression tests were performed to estimate the relationship between the change of the blood pressure parameters (delta SBP, delta DBP, delta MAP and delta PP) and the delta baPWV. RESULTS: The baPWV was significantly decreased shortly after the administration of nifedipine (1903.6+/-305.2 cm/sec vs. 1716+/-252.0 cm/sec, respectively, p<0.01). The delta baPWV was correlated with the delta SBP (r=0.550, p<0.01), delta DBP (r=0.386, p<0.05), delta MAP (r=0.441, p<0.05), and delta PP (r=0.442. p<0.05). On the multiple regression analysis, the delta SBP was the only significant variable for predicting the delta baPWV, and the linear equation was delta baPWV=8.7 x SBP-48. CONCLUSIONS: The baPWV is affected by the systolic blood pressure level to a large degree and careful attention must be paid to the blood pressure level when evaluating arterial stiffness with using the baPWV.

Influência da nifedipina no bloqueio neuromuscular produzido pelo atracúrio e pelo cisatracúrio: estudo em preparações nervo frênico-diafragma de rato / Influence of nifedipine on the neuromuscular block produced by atracurium and cistracurium: study in rat phrenic-diaphragmatic nerve preparation

JUSTIFICATIVA E OBJETIVOS: Os bloqueadores de canais de cálcio podem interagir com bloqueadores neuromusculares potencializando seus efeitos. Os estudos sobre essa interação mostram resultados controversos. Em alguns estudos essas drogas produziram bloqueio neuromuscular, ou contratura, ou nenhum efeito sobre as respostas musculares esqueléticas foi evidenciado. O estudo avaliou, em diafragma de rato, os efeitos da nifedipina sobre a resposta muscular e sua possível interação com os bloqueadores neuromusculares. MÉTODO: Foram utilizados 25 ratos, com peso entre 250 e 300 g sacrificados sob anestesia com pentobarbital (40 mg.kg -1) por via intraperitonial. A preparação foi montada de acordo com a técnica descrita por Bulbring. O diafragma foi mantido sob tensão, ligado a um transdutor isométrico e submetido à estimulação indireta de 0,1 Hz de freqüência. As contrações do diafragma foram registradas em fisiógrafo. Para avaliação dos efeitos das drogas na transmissão neuromuscular, estas foram adicionadas isoladamente ou associadas à preparação, nas seguintes concentrações: nifedipina (4 µg.mL-1); atracúrio (20 µg.mL-1); cisatracúrio (3 µg.mL-1). Nas preparações nervo frênico-diafragma avaliaram-se: 1) a amplitude das respostas do músculo diafragma à estimulação indireta, antes e 45 minutos após a adição da nifedipina e dos bloqueadores neuromusculares isoladamente e após a associação das drogas; 2) os efeitos da nifedipina nos potenciais de membrana (PM) e potenciais de placa terminal em miniatura (PPTM). RESULTADOS: A nifedipina empregada isoladamente não alterou a amplitude das respostas musculares, mas aumentou significativamente a atividade bloqueadora neuromuscular do atracúrio e do cisatracúrio. Não alterou o potencial de membrana e ocasionou aumento inicial na freqüência dos PPTM, seguido de bloqueio. CONCLUSÕES: A nifedipina na concentração empregada potencializou o bloqueio neuromuscular produzido pelo atracúrio e cisatracúrio. Estudos eletrofisiológicos demonstraram ação pré-sináptica e ausência de ação despolarizante sobre a fibra muscular.

Effects of angiotensin converting enzyme inhibitor on renal function in patients of membranoproliferative glomerulonephritis with mild to moderate renal insufficiency.

AIM: To determine the effect of enalapril, angiotensin-converting-enzyme inhibitor (ACE-I) on progression of renal insufficiency in primary membranoproliferative glomerulonephritis with mild to moderate renal insufficiency. METHOD: Thirty patients with histopathologically proved MPGN having hypertension (grade I and II of JNC-VI criteria of hypertension) and mild to moderate impairment of renal function (creatinine clearance varying from 30-80 ml/min, significant albuminuria and serum creatinine 1.2-3.0 mg/dl) were initially treated with diuretics and 3-blockers to bring down BP < 140/90 mm Hg. These patients were then randomly divided into three groups of 10 each, group I--Control; group II--Nifedipine and group III--Enalapril. In group II and III Nifidepine 30 mg/day and in group III Enalapril 10 mg/day respectively were added in addition and treatment was continued for nine months. These patients were followed up monthly for drug efficacy, side effects and any adverse drug reaction. RESULTS: Out of 30, 28 patients completed the study. At the end of nine months of treatment the patients of control group revealed significant increase in serum creatinine (1.65 +/- 0.38 to 2.17 +/- 0.31 mg/dl), blood urea (34.0 +/- 3.9 to 40.0 +/- 3.1 mg/dl), and 24 hours albuminuria (3.6 +/- 0.6 to 4.2 +/- 0.6 gm) and decrease in creatinine clearance (60.3 +/- 13.3 to 37.5 +/- 11.8 m/min); however, in enalapril group there was decrease in serum creatinine (1.72 +/- 0.45 to 1.24 +/- 0.58 mg/dl), blood urea (34.6 +/- 4.7 to 28.1 +/- 6.7 mg/dl) and 24 hours albuminuria (3.3 +/- 1.0 to 1.6 +/- 1.1 gm) and increase in creatinine clearance (56A +/- 15.8 to 77.1 +/- 23.5 ml/min). The patients on nifedipine showed statistically nonsignificant changes in creatinine clearance, blood urea and serum creatinine; while albuminuria increased from 3.0 +/- 1.3 to 3.9 +/- 0.4 gm/24 hours (p < 0.01). The blood pressure was well controlled in all patients. None of the patient had side effects leading to withdrawal of drugs. No adverse drug reaction was noted. CONCLUSION: ACE-I (enalapril) provided protection against the progression of renal insufficiency in patients of MPGN having hypertension with mild to moderate renal impairment. The renoprotective effects of ACE inhibitor (enalapril) is associated with substantial decrease in albuminuria.

Evaluation of anti-atherosclerotic and vasculoprotective effect of long acting nifedipine in patients after PTCA.

The anti-atherosclerotic and vasculoprotective effect of long acting nifedipine (nicardia retard 20) was evaluated on patients undergoing percutaneous transluminal coronary angioplasty (PTCA). This was a randomised, controlled, prospective clinical trial. A total of 30 patients fulfilling inclusion criteria were divided randomly in 2 groups of 15 each. One group was given long acting nifedipine while other group did not receive long acting nifedipine. The rest of the treatment was similar for both the groups. Clinical and angiographic parameters were evaluated regularly for a period of one year. The group receiving long acting nifedipine showed 20% restenosis as against 33% in group not receiving long acting nifedipine. Thus, from this trial, it can be concluded that long acting nifedipine can reduce the progress of reocclusion and thus demonstrates the anti-atherosclerotic and vasculoprotective action.

Endothelial dysfunction: therapy revisited (brief excerpts) (round table discussion on 18/01/2001 at Mumbai).

Indians have highest incidence of coronary heart disease. Here it occurs much more prematurely. Endothelial dysfunction has been increasingly recognised as an early event for the development of various cardiovascular disease. Long acting nifedipine has a definite role to play in reversing endothelial dysfunction.

Síndrome de exceso aparente de mineralocorticoides por déficit de 11 ß hidroxiesteroide deshidrogenasa / A syndrome of apparent mineralocorticoid excess associated with a deficiency of 11 ß-hydroxysteroid dehydrogenase

An 11-year old girl was seen in 1981 with hypokalemia, low renin, low aldosterone, and severe hypertension. A medical adrenalectomy with dexamethasone and aminoglutethimide, and the blockade of mineralocorticoid receptors with spironolactone improved her condition, but the blockade of glucocorticoid receptors with RU-486 worsened it. An aldosterone infusion induced no changes. A sister was born in 1982 with similar findings. Both patients had an impaired ability to convert cortisol to cortisone after an oral load of 200 mg cortisol. In urine, an elevated ratio for metabolites of cortisol to metabolites of cortisone was found. These data suggested a defect in the activity of renal 11ß-hydroxysteroid dehydrogenase. Both parents were asymptomatic, phenotypically normal and non-consanguineous. Their urinary metabolites of cortisol and cortisone were normal before and after stimulation with ACTH. However, the mother reached a peak plasma cortisone concentration 3 SD below the mean reached by normal subjects after an oral 200-mg cortisol load, a fact that suggests that this test could be used to detect heterozygotes. The genetic studies revealed a homozygous mutation on exon 3 of the HSD11K gene, which by substituting TGC for CGC changes Arg 213 for Cys and induces a loss of 84 percent of the enzymatic activity in transfected cells. Both unrelated parents had the same heterozygous mutation. Both patients have been treated with dexamethasone but have also required spironolactone. The older sister has also required high doses of nifedipine to lower her blood pressure. After 19 years of follow-up, the older sister has become normotensive and normokalemic under therapy, and reached a final height of 140 cm at age 17. The younger sister has increased her mean blood pressure at a rate of 1 mm Hg per year, in spite of treatment. Her final height is 143.5 cm

Crisis de esclerodermia renal: rol de la vasculopatía esclerodérmica en la inducción de fibrosis cutáneo-visceral en dos casos / Renal scleroderma crisis: role of sclerodermic vasculopathy in the induction of cutaneous and visceral fibrosis: report of 2 cases

Although fibrosis and vasculopathy coexist in most patients with progressive systemic sclerosis, it is not clear if these events are the result of an unique etiologic factor or if one is consequence of the other. We report two cases of progressive systemic sclerosis that evolved to a renal scleroderma crisis. A 36 years old female presented with a Sjögren syndrome and painful subcutaneous nodules whose biopsy showed perivascular lymphocytic infiltration, perivascular thickening and normal skin. The ESR was 100 mm/h. She developed an hypertensive crisis and progressive renal failure, followed by a rapidly evolving progressive systemic sclerosis. The patient died in the course of this crisis. A 32 years old female with a progressive systemic sclerosis refractory to D-penicillamine treatment, receiving cyclosporin, presented a renal scleroderma crisis, that was successfully treated, with complete recovery of renal function. We highlight the different evolution of these cases, probably due to an early diagnosis and a better experience in the management of this condition

Valoración de tres fármacos para el manejo no parenteral de las crisis hipertensivas / Evaluation of three drugs for non-parenteral management of hypertension crises

Antecedentes. Las crisis hipertensivas son la complicacion aguda más frecuente de la hipertensión arterial esencial. Objetivo. comparar la eficacia y seguridad de nifedipina, dinitrato de isosorbide y captopril en el control de las urgencias hipertensivas mayores. Material y métodos. En un estudio longitudinal, comparativo y abierto, se evaluaron 60 pacientes con crisis hipertensiva divididos al azar en tres grupos de 20 pacientes cada uno; el grupo A recibió 10 mg sublinguales de nifedipina, el grupo B 2.5 mg de isosorbide en aerosol en dos disparos de 1.25 mg cada uno, y el grupo C recibió 25 mg de captopril sublingual en dosis única. En ambos grupos se realizó un electrocardiograma (ECG) inmediatamente antes y 30 minutos después de la administración del fármaco. Resultados. Los 20 pacientes que recibieron nifedipina mostraron una disminución significativa de las cifras de presión arterial (190/115 a 153/86 mmHg) (g < 0.005), así como los 20 pacientes con isosorbide (187/121 a 151/91 mmHg) (p<0.005), mientras que solamente pacientes con captopril controlan la presión arterial (193/115 a 158.5/92 mmHg) (p<0.005) y tres no respondieron. Dos pacientes que recibieron nifedipina tuvieron isquemia subepicárdica en el ECG acompañada de datos clínicos de angor, todos los pacientes tuvieron elevación significativa de la frecuencia cardiaca (p< 0.002). Tres pacientes con isosorbide tuvieron datos de angos en el ECG previo, que mejoró con la administración del fármaco y disminución significativa de la frecuencia cardiaca (p< 0.005). En el grupo C ambos ECG fueron normales, sin cambios importantes en la frecuencia cardiaca. Conclusiones. Nuestros resultados muestran un estrecho límite de seguridad de la nifedipina en estos pacientes que pueden favorecer daño por isquemia tisular, una eficacia parcial del captopril que pueden favorecer daño hipertensivo, y una respuesta favorable al isosorbide, lo que constituye como una alternativa eficaz y segura en pacientes con crisis hipertensiva

Prazosin GITS vs sustained release nifedipine in patients with hypertension and abnormal lipid profile: a randomized, controlled, multicenter study. Madras Hypertension Study Group.

OBJECTIVE: To compare the long-term antihypertensive efficacy, tolerability, and metabolic effects of prazosin GITS and a sustained release (SR) preparation of nifedipine. DESIGN: Randomized, controlled, multicenter study of 26 weeks duration. SETTING: Office practices of 24 physicians in Chennai, Tamil Nadu, India. PATIENTS: Males and females, aged 30 to 70 yrs, with hypertension of JNC V stage 1 or 2 at the end of a 2-week placebo run-in period, and an abnormal lipid profile. Sufficient number of patients recruited so that at least 60 complete the entire study. INTERVENTIONS: Prazosin GITS (Minipress XL, 2.5-5 mg once daily) or sustained release nifedipine (Nicardia Retard 10-20 mg twice daily) for upto 6 weeks, continued upto 24 weeks in those showing a pre-defined response (SBP and/or DBP normalized, or DBP fall of at least 10 mm Hg with actual value of DBP < 95 mm Hg). Patients allocated to either of the two interventions by randomization. OUTCOME MEASURES: Percent patients showing pre-defined BP response at week 6; percent patients with DBP < 90 mm Hg, SBP < 140 mm Hg, and both; percent patients with DBP fall > or = 10 mm Hg; mean fall in BP among those receiving treatment for 24 weeks; mean change in blood glucose and serum lipids at the end of weeks 8, 16, and 24 of treatment; frequency and intensity of adverse events judged probably or definitely related to the drug. RESULTS: 54 patients randomized to prazosin GITS group and 52 to nifedipine SR group. Of these, 39 in prazosin GITS group (M 23, F 16; mean age-50. 6 yr, SEM 1.66) and 36 in nifedipine SR group (M 20, F 16; mean age-52.3 yr, SEM 1.71) completed the study. Percent patients with DBP < 90 mm Hg at 24 weeks: prazosin GITS--100%, nifedipine SR--100%; SBP < 140 mm Hg: prazosin GITS--94.9%, nifedipine SR--91.7%; both DBP < 90 mm Hg and SBP < 140 mm Hg: prazosin GITS--92.3%, nifedipine SR--91.7%; percent patients with DBP fall of 10 mm Hg or more at 24 weeks: prazosin GITS--76.9%, nifedipine SR--83.3%. The mean fall in the systolic and diastolic blood pressure from the end-of-placebo-phase values to all the other time points was comparable in the 2 groups. Treatment with prazosin GITS did not produce any statistically or clinically significant change in the metabolic parameters at the end of 24 weeks, while with nifedipine SR there was a significant increase in the serum LDL values at 24 weeks (p = 0.009). Adverse events probably or definitely related to the drug: prazosin GITS--1.9%, nifedipine SR--2.1%. CONCLUSION: Both drugs were equally effective and well tolerated. While prazosin GITS was neutral on serum lipids, use of nifedipine SR was associated with a significant increase in serum LDL cholesterol at the end of 24 weeks.

Empleo de la asociacion digoxina-nifedipina en el tratamiento de ancianos con cardiopatia hipertensiva / Use of nifedipine-digoxine association in the treatment of old people with hypertensive cardiopathy

Se realiza un estudio sobre la eficacia de la asociacion digoxina-nifedipina en el tratamiento de ancianos con cardiopatia hipertensiva (CPH). La muestra esta constituida por 25 pacientes geriatricos egresados del servicio de medicina interna del Hospital Universitario "Julio Trigo", con el diagnostico confirmado de CPH. Se indico a cada paciente tratamiento con digoxina (0.25 mg) una tableta diaria y nifedipina (10 mg) una tableta cada 8 horas a partir del segundo dia de ingreso; se reaizo seguimiento durante 8 semanas de manera clinica y por examenes complementarios. Solo 2 pacientes no mejoraron la sintomatologia de insuficiencia cardiaca y 1 presento sintomas de intoxicacion digitalica, 24 de los 25 pacientes controlaron sus cifras de tension arterial. Se concluye que la asociacion digoxina - nifedipina a dosis terapeutica en el tratamiento de los pacientes estudiados reulto una opcion terapeutica eficaz dada su buena respuesta clinica y la baja frecuencia de complicaciones