Peripartum cardiomyopathy: a selenium disconnection and an autoimmune connection

BACKGROUND: Increased incidence and prevalence of peripartum cardiomyopathy (PPCM) have been documented in the Hospital Albert Schweitzer (HAS) District of Haiti. Although the basis for this increased incidence of PPCM remains unclear, there is growing evidence for an underlying autoimmune process. One potential risk factor for increased autoreactivity is a micronutrient deficiency. In Africa, low plasma selenium (Se) level has been reported as a possible risk factor for PPCM. This report details results of initial studies to test the hypothesis that plasma levels of Se and/or other micronutrients may be related to PPCM risk in this population. METHODS: Under the direction of the Institutional Review Board (HAS Ethics Committee) and with informed consent, levels of Se and other micronutrients were measured in plasma samples obtained from PPCM mothers and parity-matched control mothers from the HAS District of Haiti. RESULTS: Mean plasma Se level in 18 PPCM patients was 110 ng/ml (range 67-145) compared to mean plasma Se level in 34 control mothers of 121 ng/ml (range 98-172) (P=0.1748). These levels are substantially greater than those reported for pediatric patients with Keshan cardiomyopathy, which can be prevented by Se prophylaxis. No deficiency or significant difference was found in any other micronutrient tested (Vitamin A (retinol), Vitamin B(12), Vitamin C, Vitamin E, and B-Carotene) for these PPCM and control mothers. CONCLUSION: Although there are several possible mechanisms by which Se could play a role in the pathobiology of PPCM, there is no evidence that Se deficiency is a cause of PPCM or a risk factor for the development of PPCM in this district of Haiti. The results of this investigation indicate that future studies of PPCM in this population should focus on other potential etiologic and risk factors.     

Bilateral cryptorchidism with bilateral inguinal hernia and retrovesical mass in an infertile man: single-stage laparoscopic management

A 30-year-old married man presented with the complaint of inability to procreate. Examination revealed bilateral nonpalpable testes and bilateral inguinal hernia. Ultrasonography of the abdomen could not locate the testis; instead, a hypoechoic 5 x 5-cm mass was found behind the bladder. A CT scan of the abdomen revealed the right testis near the right inguinal canal. The left testis could not be identified beside the soft tissue mass. The patient was taken for diagnostic as well as therapeutic laparoscopy. The testis on the right was found just proximal to the internal inguinal ring, and right orchidopexy was done. The left testis was small and rudimentary; hence, orchidectomy was done. Bilateral laparoscopic herniorrhaphy was carried out with polypropylene mesh by fixing it intracorporeally to the pubic bone, Cooper's ligament, inguinal ligament, and conjoint tendon. Subsequently, the retrovesical mass was excised and retrieved by dilating the umbilical port site. The operative time was 3.5 hours with minimal blood loss. The postoperative period was uneventful, and the patient was discharged after 24 hours. The histopathology examination of the retrovesical mass showed an extragonadal germ cell tumor compatible with seminoma.     

Metabolic basis of ethanol-induced hepatic and pancreatic injury in hepatic alcohol dehydrogenase deficient deer mice.

Alcoholic liver disease (ALD) and alcoholic pancreatitis (AP) are major diseases causing high mortality and morbidity among chronic alcohol abusers. Neutral lipid accumulation (steatosis) is an early stage of ALD or AP and progresses to inflammation and other advanced stages of diseases in a subset of chronic alcohol abusers. However, the mechanisms of alcoholic steatosis leading to ALD and AP are not well understood. Chronic alcohol abuse impairs hepatic alcohol dehydrogenase (ADH, a major enzyme involved in ethanol oxidative metabolism) and facilitates nonoxidative metabolism of ethanol to fatty acid ethyl esters (FAEEs, nonoxidative metabolites of ethanol). These esters are implicated in the pathogenesis of various alcoholic diseases and shown to cause hepatocellular and pancreatitis-like injury. Ethanol exposure is known to increase synthesis of FAEEs by several-fold in the livers and pancreata of rats pretreated with hepatic ADH inhibitor. Therefore, studies were undertaken to evaluate hepatocellular and pancreatic injury in hepatic ADH-deficient (ADH(-)) deer mice versus ADH-normal (ADH(+)) deer mice fed ethanol (4% wt/vol) via Lieber-DeCarli liquid diet for 60 days. A significant mortality was found in ethanol-fed ADH(-) deer mice (11 out of 18) versus ADH(+) deer mice (1 out of 16); most of the deaths occurred during the first 2 weeks of ethanol exposure. The surviving animals, sacrificed at the end of 60th day, showed distinct changes in hepatic and pancreatic histology and several-fold increases in nonoxidative metabolism of ethanol in ethanol-fed ADH(-) versus ADH(+) deer mice. Extensive vacuolization with displacement or absence of nucleus in some hepatocytes, and significant increase in hepatic neutral lipids were found in ethanol-fed ADH(-) versus ADH(+) deer mice. Ultrastructural changes showed perinuclear space, edema, presence of apoptotic bodies and disintegration, and/or dilatation of endoplasmic reticulum (ER) in the pancreata of ethanol-fed ADH(-) deer mice. FAEE levels were significantly higher in ADH(-) versus ADH(+) deer mice, approximately four-fold increases in the livers and seven-fold increases in the pancreata. Ethyl esters of oleic, linoleic, and arachidonic acids were the major FAEEs detected in ethanol-fed groups. The role of FAEEs in pancreatic lysosomal fragility is reflected by higher activity of cathepsin B (five-fold) in ethanol-fed ADH(-) versus ADH(+) deer mice. Although the present studies clearly indicate a metabolic basis of ethanol-induced hepatic and pancreatic injury, detailed dose- and time-dependent toxicity studies in this ADH(-) deer mouse model could reveal further a better understanding of mechanism(s) of ethanol-induced hepatic and pancreatic injuries.     

Unrecognized peripartum cardiomyopathy in Haitian women.

OBJECTIVE: Haitian women have a high relative incidence of clinical presentation with peripartum cardiomyopathy (PPCM): an incidence estimated at one case per three hundred live births, a ten-fold occurrence compared to American women. Our objective has been to test the hypothesis that some Haitian women may have a forme fruste of PPCM while still without clinical symptoms. METHOD: A preliminary case-control study was conducted at the Hospital Albert Schweitzer (HAS), Deschapelles, Haiti, in which 25 apparently healthy postpartum women, without cardiovascular symptoms and with a normal cardiovascular clinical examination, were selected from a consecutive list of obstetrical deliveries and screened by echocardiography for left ventricular dysfunction. RESULT: Four out of 25 patients (16%) had asymptomatic left ventricular dysfunction that subsequently evolved towards either improvement or deterioration. Supporting evidence for the existence of asymptomatic left ventricular dysfunction or forme fruste PPCM is presented. A hypothetical schema of the pathophysiology of PPCM explains how a latent phase of variable duration may exist prior to onset of detectable clinical heart failure. CONCLUSION: Screening Haitian women during the last month of pregnancy or in the early postpartum period may help to detect asymptomatic left ventricular dysfunction. Early detection and treatment of PPCM in a known high risk population could lead to improvements in maternal and fetal mortality and morbidity.     

Randomized, open-label, phase III study of a 28-day oral regimen of eniluracil plus fluorouracil versus intravenous fluorouracil plus leucovorin as first-line therapy in patients with metastatic/advanced colorectal cancer.

PURPOSE: To compare the efficacy and tolerability of eniluracil (EU)/fluorouracil (5-FU) with that of 5-FU/leucovorin (LV) as first-line therapy for patients with metastatic/advanced colorectal cancer. PATIENTS AND METHODS: This multicenter, randomized, open-label, phase III study (FUMA3008) conducted in the United States and Canada compared the safety and efficacy of EU/5-FU (11.5 mg/m(2)/1.15 mg/m(2) twice daily for 28 days every 35 days) with that of intravenous 5-FU/LV (425 mg/m(2)/20 mg/m(2) once daily for 5 days every 28 days) in patients with previously untreated metastatic colorectal cancer. Overall survival (OS) was the primary end point. RESULTS: A total of 981 patients were randomized and 964 patients received treatment (485 EU/5FU, 479 5FU/LV). Survival for EU/5-FU was not statistically equivalent (but not statistically inferior) to that for 5-FU/LV (hazard ratio, 0.880; 95% confidence interval [CI], 0.75 to 1.03). Median duration of survival was 13.3 months in the EU/5-FU group and 14.5 months in the 5-FU/LV group. Median duration of progression-free survival for EU/5-FU was statistically inferior to that of the control group (20.0 weeks [95% CI, 19.1 to 20.9 weeks] v 22.7 weeks [95% CI, 18.3 to 24.6 weeks]; P =.01). Both treatments were well tolerated. Diarrhea was the most common nonhematologic toxicity in both groups; treatment-related grade 3 or 4 diarrhea occurred in 19% of patients treated with EU/5-FU and 16% of patients receiving 5-FU/LV (P =.354). Grade 3 or 4 granulocytopenia occurred in 5% of EU/5-FU patients and 47% of 5-FU/LV patients. CONCLUSION: Safety profiles of both treatments were acceptable. Although antitumor activity was observed, EU/5-FU did not meet the protocol-specified statistical criteria for equivalence to 5-FU/LV in terms of OS.     

Complications following anterior approaches to the cervical spine

Summary The authors present a retrospective study of 535 consecutive anterior approaches to the cervical spine back to 5 years. The data were analyzed for post-operative complications. This surgical procedure has been commonly used for more than 40 years, but the post-operative complications due to the anterior approach itself were presented with few accompanying statistics, with various and contradictory results. Injury to nearly all of the structures has been reported in the literature, the more frequent problems are hoarseness and dysphagia; other complications include perforation of the oesophagus, hematomas, vascular injuryAnalysis of this data allows to understand better the specific problems related to this surgical approach, and to suggest precautions at each stage of the course of exposure of cervical vertebrae.     

Neonatal diabetes mellitus because of pancreatic agenesis with dysmorphic features and recurrent bacterial infections

Abstract:  Pancreatic agenesis is a rare cause of neonatal diabetes mellitus (NDM). It can be associated with malformations of the heart, the biliary tract, and the cerebellum. We report an infant with NDM because of pancreatic agenesis, intra-uterine growth retardation, dysmorphic features, and recurrent bacterial infections. He was born to healthy consanguineous parents. With adequate replacement of insulin and pancreatic enzymes, his blood glucose levels were controlled and his weight slowly increased. However, he continued to develop recurrent serious bacterial infections and died at the age of 11 months with sepsis and respiratory failure. Analysis of the PTF1A and PDX1 genes, which have been associated with congenital agenesis of the pancreas, did not reveal any mutation. Genetic abnormalities of chromosome 6 associated with transient neonatal diabetes as well as mutations in the KCNJ11 and ABCC8 genes encoding the pancreatic potassium channel were also excluded as a cause of the NDM in this patient. The association of permanent neonatal diabetes because of pancreatic agenesis, dysmorphism, and non-specific immunodeficiency is previously undescribed and may represent a new possibly autosomal recessive syndrome.     

Spontaneous and provoked growth hormone (GH) secretion and insulin-like growth factor I (IGF-I) concentration in patients with beta thalassaemia and delayed growth

Growth retardation in children with thalassaemia major is multifactorial. We studied the growth hormone (GH) response to provocation by clonidine and glucagon, measured the circulating concentrations of insulin, insulin-like growth factor-I (IGF-I), IGF-binding protein-3 (IGFBP3), and ferritin, and evaluated the spontaneous nocturnal (12 h) GH secretion in prepubertal patients with thalassaemia and age-matched children with constitutional short stature (CSS) (height SDS < -2, but normal GH response to provocation). The anatomy of the hypothalamic pituitary area was studied in patients with abnormal GH secretion using MRI scanning. Children with thalassaemia had significantly lower peak GH response to provocation by clonidine and glucagon (8.8 +/- 2.3 micrograms/l and 8.2 +/- 3.1 micrograms/l respectively) than did controls (17.6 +/- 2.7 micrograms/l and 15.7 +/- 3.7 micrograms/l respectively). They had significantly decreased circulating concentrations of IGF-I and IGFBP3 (68.5 +/- 19 ng/ml and 1.22 +/- 0.27 mg/l respectively) compared to controls (153 +/- 42 ng/ml and 2.16 +/- 0.37 mg/l respectively). Seven of the thalassaemic children had a GH peak response of < 7 micrograms/l after provocation. Those with a normal GH response after provocation also had significantly lower IGF-I and IGFBP3 concentrations than controls. Analysis of their spontaneous nocturnal GH secretion revealed lower mean (2.9 +/- 1.77 micrograms/l) and integrated (2.53 +/- 1.6 micrograms/l) concentrations compared to controls (4.9 +/- 0.29 micrograms/l and 5.6 +/- 0.52 micrograms/l respectively). Five of them had mean nocturnal GH concentration < 2 micrograms/l and four had maximum nocturnal peak below 10 micrograms/l. These data denoted defective spontaneous GH secretion in some of these patients. MRI studies revealed complete empty sella (n = 2), marked diminution of the pituitary size (n = 4), thinning of the pituitary stalk (n = 3) with its posterior displacement (n = 2), and evidence of iron deposition in the pituitary gland and midbrain (n = 7) in those patients with defective GH secretion (n = 9). Serum ferritin concentration was correlated significantly with the circulating IGF-I (r = -0.47, p < 0.01) and IGFBP3 (r = -0.43, p < 0.01) concentrations. These data prove a high prevalence of defective GH secretion in thalassaemic children associated with structural abnormality of their pituitary gland.