The Pediatric Cardiology Pharmacopeia: 2013 Update

The use of medications plays a pivotal role in the management of children with heart diseases. Most children with increased pulmonary blood flow require chronic use of anticongestive heart failure medications until more definitive interventional or surgical procedures are performed. The use of such medications, particularly inotropic agents and diuretics, is even more amplified during the postoperative period. Currently, children are undergoing surgical intervention at an ever younger age with excellent results aided by advanced anesthetic and postoperative care. The most significant of these advanced measures includes invasive and noninvasive monitoring as well as a wide array of pharmacologic agents. This review update provides a medication guide for medical practitioners involved in care of children with heart diseases.     

Prevalence of pelvic musculoskeletal disorders in a female chronic pelvic pain clinic

OBJECTIVE: To determine the prevalence of 2 musculoskeletal pain disorders among women presenting to a referral chronic pelvic pain clinic. STUDY DESIGN: This was a retrospective, cross-sectional study of 987 women (aged 14-79) presenting for evaluation from 1993 to 2000 at a university-based gynecologic chronic pelvic pain clinic. RESULTS: At the initial visit, all women completed standardized interviews and underwent a pelvic examination. Single-digit palpation of the levator ani and piriformis muscles was performed intravaginally. Among these women, 212 of 955 (22%) had tenderness of the levator ani muscles, while 128 of 943 (14%) had tenderness of the piriformis muscle (pain score > 3 of 10 on a visual analogue scale). Both levator ani tenderness and piriformis tenderness were associated with a higher total number of pain sites, previous surgery for pelvic pain, Beck Depression Inventory score, McGill Pain Inventory score and pain worsened with bowel movements (p < 0.05). CONCLUSION: Piriformis and levator ani pain are present in a significant proportion of female chronic pelvic pain patients. Further research into the natural course, diagnosis and treatment of pelvic musculoskeletal pain is needed to determine its true contribution to chronic pain.     

Severe Plasmodium vivax cerebral malaria complicated by hemophagocytic lymphohistiocytosis treated with artesunate and doxycycline

Malaria-related hemophagocytic lymphohistiocytosis is a rare, potentially fatal, hyperinflammatory disease entity which can be challenging to diagnose and treat. It is usually associated with Plasmodium falciparum infection. It is less frequently associated with Plasmodium vivax. Here we report an unusual case of a 23-year-old healthy Nigerian man who presented with fever, microangiopathic hemolytic anemia, acute renal failure, and confusion, and was diagnosed as having cerebral malaria-related hemophagocytic lymphohistiocytosis caused by P. vivax infection. He was successfully treated with intravenous artesunate and doxycycline with dramatic clinical improvement.     

The Use of Opportunistic Salpingectomy at the Time of Benign Hysterectomy

Study Objective

To delineate the use of opportunistic salpingectomy over the study period, to examine factors associated with its use, and to evaluate whether salpingectomy was associated with perioperative complications.

Novel causative variants in patients with achromatopsia

ABSTRACT

Purpose: To report five novel genetic variants in seven unrelated consanguineous families with achromatopsia (ACHM).

Methods: Patients were examined with multimodal retinal imaging and full-field electroretinography (ffERG). Genetic testing was conducted using next-generation sequencing (NGS).

Results: Three novel homozygous variants were detected in CNGA3: a missense c.967G > C (p.Ala323Pro) variant was detected in exon 8 (one patient), a splice site variant c.101 + 1G > A in intron 2 (three patients), and a splice site variant c.395 + 1G > T in intron 4(one patient). Another two novel variants were found in PDE6C: a homozygous missense variant c.1899C > A (p.His633Gln) in exon 15 (one patient) and a homozygous splice site variant c.1072-1G > C in intron 7 (one patient). Mutation segregation assessment was possible in 3 of the 7 families. All patients had nonrecordable ffERG 30-Hz flicker responses, reduced single-flash cone responses but preserved rod responses. Patients presented with variable degrees of foveal outer retinal layer loss and variable patterns of foveal hyperautofluorescence.

Conclusions: These novel variants expand the genotypes associated with ACHM and may help in future therapy development for ACHM.     

Coxiella burnetii,the causative agent of Q fever in Saudi Arabia:molecular detection from camel and other domestic livestock

Objective:To detect Coxiella burnetii(C.burnetii)DNA in clinical specimens from camel,goats,cattle and sheep in the Kingdom of Saudi Arabia.Methods:A total of 367 clinical samples including blood,milk,faeces and urine were collected from different livestock and subjected to PCR amplification using primers which amplify transposon-like region and transposase gene.Results:Positive amplification from both regions was obtained from camel,goats and cattle but not from sheep.A percentage of 10.8%samples yielded positive PCR amplification from both blood and milk,where 15 of 139 blood and 16 of 148 milk samples were positive.Faeces and urine showed higher percentages of positive samples reaching 40.8%and 23.8%respectively.Conclusions:The preferred route of shedding in camel appeared to be the faeces followed by urine,while that of goats appeared to be the faeces and that of the cattle appeared to be the milk.     

The mast cells of the multiple sclerosis brain

Traditional staining methods, plus indirect immunoperoxidase techniques for IgE and mast cell tryptase (MC_Tr) were used to study the mast cells (MCs) of multiple sclerosis (MS) and normal brains. The MCs varied in number in MS amongst perivascular inflammatory cells as well as free in the parenchyma, especially inside and around ‘chronic active’ plaques. Since MCs do not migrate, and rarely divide in maturity, they must have developed locally. Staining for IgE was moderately strong on and within MCs, and weak within some plasma cells. MC_Tr reacted strongly both within CNS and outside it. Being a strong neutral proteinase, MC_Tr, plus IgE, could conceivably have played some role in the pathogenesis of the MS plaques.     

Glomerular changes in microscopic haematuria, studied by quantitative immunoelectron microscopy and in situ zymography.

BACKGROUND:Haematuria of glomerular origin, even if mild, implies the development of defects in the glomerular basement membrane (GBM). In diseases where there is no infiltration of leukocytes into the glomerulus-such as thin basement membrane disease (TBMD) and histologically mild cases of IgA nephropathy (IgAN)-the mechanism by which such defects form is unclear. METHODS:Frozen renal tissue from 18 cases of TBMD, 18 of mild IgAN and 18 cases with no detectable abnormality were studied: (i) by quantitative in situ zymography, to estimate the activity of glomerular collagenases; and (ii) by quantitative immunoelectron microscopy to estimate the amount of major basement membrane proteins per unit length and per unit area of glomerular basement membrane. RESULTS:Cases of IgAN showed considerably more glomerular collagenase activity than normal (P=0.001). Thin basement membrane disease showed no difference in collagenase activity. A count of LCA-positive cells in glomeruli confirmed that the IgAN cases did not show glomerular leukocyte infiltration. Conversely, cases of IgAN showed no difference in GBM composition from normal, nor was any difference in GBM thickness detected in this group. However, cases of TBMD showed considerably less laminin (P=0.0008), fibronectin (P=0.002) and type VI collagen (P=0.0005) per unit length of basement membrane. Collagen IV showed a smaller reduction per unit length (P=0.01), but unlike the other protein studies it appeared to be present in higher concentration per unit area (P=0.03), suggesting that it is more 'compact' in TBMD disease. CONCLUSIONS:Two distinct mechanisms of haematuria seem to be involved in these two conditions. In IgAN there is increased activity of enzymes that can degrade GBM, probably reflecting mesangial cell activation. In TBMD an abnormal composition of the thinned GBM is confirmed. When considered with published reports of genetic abnormalities in TBMD, these results raise the possibility of an abnormal interaction between collagen IV and laminin.     

Extended Application of the Hybrid Procedure in Neonates with Left-Sided Obstructive Lesions in an Evolving Cardiac Program

The hybrid approach to management of hypoplastic left heart syndrome (HLHS) was developed as an alternative to neonatal Norwood surgery, providing a less invasive initial palliation for HLHS. We describe our experience in extending the concept of the hybrid procedure to palliate neonates with anatomically compromised systemic arterial blood flow in a variety of congenital cardiac anomalies and supporting its application as first-line palliation in centers developing their HLHS programs. Retrospective review of patients undergoing therapy for HLHS at a single institution from June 2008 to December 2014 was performed. Subject demographics, clinical and procedural data, along with follow-up, were collected. Thirteen patients had initial hybrid palliation for HLHS during the time frame indicated at a median age of 8 days (range 1–29 days) and median weight of 3.4 kg (range 2.4–4.6 kg). Diagnoses included typical HLHS (n = 6), right-dominant unbalanced atrioventricular septal defect with arch hypoplasia (n = 4), double outlet right ventricle [subpulmonic VSD (n = 1) and intact ventricular septum (n = 1)] with hypoplastic transverse aortic arch and borderline left ventricular dimensions. Standard approach with bilateral pulmonary artery banding and ductal stenting was carried out in all thirteen patients. Two patients required two ductal stents at the time of index procedure. There were no intraprocedural complications. Median intubation length post-procedure was 4 days (range 1–74 days). Median hospital stay post-procedure was 47 days (range 15–270 days). The overall mortality rate on follow-up through comprehensive stage 2 over the 6-year experience was 38 % (5 out of 13). Of note, the mortality rate was significantly lower in the latter 3 years of the study period when the procedure was adopted as a primary palliation for HLHS (14 % or 1 out of 7) compared to the initial 3-year period when it was reserved for higher risk cohorts (67 % or 4 out of 6). Median time to subsequent surgery was 3 months (range 1–4 months). One patient required further ductal stenting on follow-up and developed subsequently airway compression. On median follow-up of 24 months, two patients required pulmonary artery arterioplasty. The hybrid procedure may be used for palliation for a variety of cardiac lesions to avoid high-risk surgery in the neonatal period. This approach may be also an alternative in centers performing lower number of Norwood surgery, which has been associated with higher mortality.