Estimates of maternal risks of pregnancy for women with hereditary haemorrhagic telangiectasia (Osler-Weber-Rendu syndrome): suggested approach for obstetric services

Objectives  Hereditary haemorrhagic telangiectasia (HHT) affects 1 in 5–8000 individuals. Pregnancy outcomes are rarely reported. The major reason is that most women do not have their HHT diagnosed prior to pregnancy. Using a large well-characterised series, we studied all pregnancies known to have occurred in HHT-affected women, whether or not their diagnosis was known at the time of pregnancy. Our aim was to estimate rates and types of major complications of HHT in pregnancy, to guide management decisions.
Design  Cohort study, with prospective, retrospective and familial components.
Setting/Population  Tertiary referral centre population.
Methods  All 262 pregnancies in the 111 women with HHT and pulmonary arteriovenous malformations (PAVMs) reviewed between 1999 and 2005 were studied. Eighty-two women (74%) did not have a diagnosis of HHT/PAVM at the time of pregnancy. 222 pregnancies in their 86 HHT-affected relatives were also studied.
Main outcome measures  PAVM bleed, stroke and maternal death.
Results  Thirteen women experienced life-threatening events during pregnancy: 1.0% (95% CI 0.1–1.9) of pregnancies resulted in a major PAVM bleed; 1.2% (0.3–2.2%) in stroke (not all were HHT related); and 1.0% (0.13–1.9%) in maternal death. All deaths occurred in women previously considered well. In women experiencing a life-threatening event, prior awareness of HHT or PAVM diagnosis was associated with improved survival ( P  = 0.041, Fisher's exact test).
Conclusions  Most HHT pregnancies proceed normally. Rare major complications, and improved survival outcome following prior recognition, means that pregnancy in a woman with HHT should be considered high risk. Recommendations for pregnancy management are provided.     

Gastroparesis after combined heart and lung transplantation.

GOALS: To determine the prevalence, severity, and outcome of gastroparesis after heart and lung transplantation (HLT). STUDY: Ten patients (five women; age range, 27-57 years) underwent HLT at Temple University Hospital from 1996 to 1999. The charts of these patients were reviewed, including results from gastric emptying scans and upper endoscopies. Symptoms were assessed with a standardized questionnaire. RESULTS: The indications for HLT included pulmonary hypertension in six patients, Eisenmenger syndrome in two, and dilated cardiomyopathy and congenital heart disease in two. Four patients died before the start of this clinical analysis. The six surviving patients constituted our study population. The patients' posttransplantation follow-up period ranged from 1.4 to 4.4 years (average, 2.6 years). Five patients (83%) were symptomatic with nausea, vomiting, and postprandial abdominal distension. Solid phase gastric emptying was delayed in all five patients with mean gastric retention of 93% at 2 hours (normal <50%). Patients generally did not respond to prokinetic agents. Four patients required pyloroplasty with J tube placement for symptom control, nutrition, and delivery of immunosuppressive medication. CONCLUSIONS: There is a high prevalence of symptomatic gastroparesis in patients after HLT. The gastroparesis is severe and often resistant to prokinetic agents.     

Multi detector CT Imaging of Abdominal and Diaphragmatic Hernias: Pictorial Essay

Diagnosis of abdominal wall hernia is often a clinical problem, especially in occult or in obese patients. Multidetector CT is an accurate method of detecting various types of abdominal and diaphragmatic hernias. It clearly demonstrates the anatomical sites of hernial sac, its contents and possible complications.     

Role of kidney in the catabolic clearance of human platelet antiheparin proteins from rat circulation

Stimulated platelets release at least two antiheparin proteins: platelet factor 4 (PF4) and low affinity platelet factor 4 (LA-PF4) from which beta-thromboglobulin (beta TG) is derived. We have found previously marked elevation of LA-PF4/beta TG antigen in platelet poor plasma of patients with chronic renal failure, whereas levels of PF4 remained normal. Therefore, we examined the role of the kidneys in the metabolic clearance of LA-PF4/beta TG and PF4. The supernates of aggregates of thrombin-stimulated human platelets were injected into sham operated control rats, nephrectomized rats, and into rats with acute ureteral ligation. The disappearance of human LA-PF4/beta TG antigen and PF4 in rat plasma determined by specific radioimmunoassays followed biphasic exponential curves. The half-lives (t1/2) for the fast and slow components of LA-PF4 in control rats were 6.4 and 68.4 min. Nephrectomy significantly increased these times to 9.7 and 144 min, while ureteral ligation resulted in no significant change. Comparison of the level of LA-PF4/beta TG antigen and of creatinine in aorta and in renal vein showed 25%-30% extraction of these compounds by the kidney. Less than 0.1% of the total LA-PF4 antigen injected was recovered in the urine of control rats. In contrast to these results, the clearance of PF4 was not affected by nephrectomy. In conclusion: (1) functional renal tissue is necessary for normal clearance of LA- PF4/beta TG, but renal excretion does not play a major role in its elimination suggesting that the protein is catabolized by the kidney; and (2) catabolic clearance of PF4 does not depend on functioning kidney tissue.     

Iodinated curcumin bearing dermal cream augmented drug delivery,antimicrobial and antioxidant activities

Objectives: Curcumin (Cur) exhibits weak microbicidal activity owing to high lipophilicity and low cell permeability. Therefore, in the present investigation, Cur was iodinated using elemental iodine (I₂) to synthesise Cur–I₂ powder that was later formulated as Cur–I₂ dermal cream and characterised in vitro for antimicrobial and antioxidant activities.

Methods and results: Electrophilic addition of I₂ saturated the olefinic bonds of Cur, as confirmed by UV/visible spectroscopy, FT-IR, ¹H NMR and DSC techniques. In addition, in vitro skin permeation and retention analysis indicated that Cur–I₂ cream followed the first order and Higuchi model for drug release through the rat skin. The minimum inhibitory concentration (MIC) of Cur–I₂ powder was measured to be 60 and 90?µg/ml significantly (p?Staphylococcus aureus and Escherichia coli, respectively. Moreover, Cur–I₂ also exhibited strong antioxidant potential.

Conclusions: Cur–I₂ cream warrants further in vivo study to scale up the technology for clinical translation.