Placental pathology and neurological morbidity in preterm infants during the first two weeks after birth

Background

The placenta plays a crucial role during pregnancy and dysfunction causes long-term neurological problems. Identifying placenta-related risks for neurological problems shortly after birth may provide clues for early interventions aiming to improve neurological outcome.

Objective

To determine the association between placental pathology and neurological morbidity in preterm infants during the first two weeks after birth.

Study design

Placentas of 52 singleton, preterm infants (GA: 25–31 weeks, BW: 560–2250 grammes) were examined for histopathology. The infants' neurological condition shortly after birth was determined by assessing the quality of their general movements (GMs): normal, abnormal, or hypokinetic, on days 5, 8, and 15. A motor optimality score (MOS) was also assigned.

Results

Examination of the placentas revealed maternal vascular underperfusion (n = 29), ascending intrauterine infection (AIUI) (n = 19), villitis of unknown aetiology (n = 6), chronic deciduitis (n = 11), foetal thrombotic vasculopathy (FTV) (n = 9), and elevated nucleated red blood cells (NRBCs) as a marker for foetal hypoxia (n = 7). None of the placental lesions were significantly associated with the quality of GMs or MOS.

Conclusions

This study indicated that placental lesions were not associated with infants' neurological condition as measured by the quality of their general movements during the first two weeks after birth.     

Guidelines for Best Practice in the Audiological Management of Adults with Severe and Profound Hearing Loss

Individuals with severe to profound hearing loss are likely to present with complex listening needs that require evidence-based solutions. This document is intended to inform the practice of hearing care professionals who are involved in the audiological management of adults with a severe to profound degree of hearing loss and will highlight the special considerations and practices required to optimize outcomes for these individuals.     

Dietary fish oil suppresses experimental immunoglobulin a nephropathy in mice

Dietary fish oil (FO) supplementation reportedly retards the progression of renal disease in patients with immunoglobulin (Ig)A nephropathy (IgAN), the most common glomerulonephritis worldwide. Using an experimental mouse model in which early immunopathological hallmarks of IgAN are induced by the mycotoxin vomitoxin (VT), the ameliorative effects of FO ingestion on this disease were evaluated in two studies. In Study 1, the capacity of VT to induce IgAN was evaluated in mice fed for 12 wk AIN-76A diets containing 50 g/kg corn oil (CO), 50 g/kg CO plus 9 mg/kg tert butylhydroquinone (TBHQ), or 5 g/kg CO plus 45 g/kg menhaden FO that contained 200 mg/kg TBHQ. Serum IgA, serum IgA immune complexes and kidney mesangial IgA deposition were greater in mice fed VT + CO compared with the CO control group, whereas all three variables were significantly attenuated in mice fed VT + FO. Although TBHQ also had attenuating effects, these were significantly less than those for the VT + FO group. In Study 2, the effects of feeding modified AIN 93G diets containing either 70 g/kg CO or 10 g/kg CO plus 60 g/kg FO for 20 wk on VT-induced IgAN were compared. Again, consumption of FO attenuated all three immunopathological variables. In addition, spleen cell cultures from the VT + FO group produced markedly less IgA than those cultures from mice fed VT + CO. Taken together, the results suggested that diets containing FO may impair early immunopathogenesis in VT-induced IgAN and that this was not totally dependent on the presence of the antioxidant TBHQ.     

Occurrence of esophageal granular cell tumors in The Netherlands between 1988 and 1994

Granular cell tumors (GCT) of the esophagus are rare. The tumor is generally beleived to be of neurogenic origin and shows a malignant course in 2–4% of cases. No unanimity has been reached regarding the management of this tumor. A national survey was conducted on the incidence of GCT of the esophagus, related symptoms, management, and follow-up. A national survey was performed on all newly registered esophageal GCTs in the PALGA system (Dutch register of all pathology diagnoses) for seven consecutive years (1988–1994). Fifty-two new cases (17 men, 35 women; median age 46 years, range 22–77 years) were registered. In 44 cases clinical data could be obtained (survey response 85%). The majority of the GCTs were solitary (42/44) and localized in the distal esophagus (33/44). At endoscopy the size of the tumor was estimated at <5 mm in 50%, 5–10 mm in 25%, and 10–30 mm in 18%. Most patients (40/44) presented with nonspecific gastrointestinal symptoms, only four had dysphagia (tumor size >1 cm). No malignancies were reported. Management of the tumor included excisional biopsy (1/44), endoscopic polypectomy (3/44), and surgical excision (1/44). Endoscopic follow up (1–60 months) in 16 out of 17 patients left untreated showed either a stable tumor size or regression of the tumor. In one case with multiple GCT's a slight tumor growth was seen after a follow-up period of 48 months. Esophageal GCTs in the Netherlands are rare, and mostly diagnosed incidentally. Most patients suffer from nonspecific symptoms; dysphagia occurs only with tumors >1 cm. The usual clinical course of esophageal GCTs is benign. Patients without dysphagia probably do not require routine endoscopic follow-up, provided they are instructed to contact their physician, once dysphagia develops.     

What is to be done with vancomycin-resistant enterococcal infections?

Recently, three epidemics in Dutch hospitals were caused by vancomycin-resistant enterococci (VRE). Although the number of infections was small, spread of colonization was extensive and many infection control measures were necessary to prevent further spread. VRE are relatively avirulent bacteria. However, few, if any, antibiotics are available for treatment of infections caused by VRE and the genetic code for resistance may be transferable to other, more virulent, bacteria, such as methicillin-resistant Staphylococcus aureus (MRSA). Although colonization and infection with MRSA have become endemic in many surrounding countries, such a situation has been prevented in the Netherlands by employing an aggressive 'search and destroy' policy. Although many questions regarding the optimal approach of VRE remain unanswered, a similar policy as employed for MRSA will not be possible. In contrast to MRSA, colonization with VRE occurs in the open population, no populations with increased risk for colonization appear to be definable and colonization cannot be eradicated. Based on common sense, a differentiated approach seems indicated in which extensive infection control measures should only be implemented when spread of a single genotype has been demonstrated. A reference laboratory should be created for uniform genotyping.     

Pharmacokinetic and pharmacodynamic characteristics of ganirelix (Antagon/Orgalutran). Part I. Absolute bioavailability of 0.25 mg of ganirelix after a single subcutaneous injection in healthy female volunteers

Objective: To assess the absolute bioavailability of ganirelix (Antagon/Orgalutran; NV Organon, Oss, the Netherlands) after a single SC injection.

Design: Randomized, crossover, pharmacokinetic study.

Setting: Phase I clinical research unit.

Patient(s): Nineteen healthy female volunteers of reproductive age.

Intervention(s): Two separate injections of 0.25 mg of ganirelix were given, one subcutaneously and one intravenously, with a washout period of 1 week between injections. Blood samples were taken for assessment of serum ganirelix concentrations, and blood pressure, heart rate, and adverse events were monitored.

Main Outcome Measure(s): Pharmacokinetic parameters.

Result(s): Fifteen subjects were evaluated. The mean concentration-time profile after SC administration was comparable to that after IV administration. The mean (±SD) peak concentration and time of occurrence after SC administration were 14.8 ± 3.2 ng/mL and 1.1 ± 0.3 hours, respectively. The mean (±SD) half-lives after IV administration and SC administration were highly similar (12.7 ± 3.7 hours and 12.8 ± 4.3 hours, respectively). Mean (±SD) AUC_0–∞ (area under the concentration-time curve) values of 105 ± 11 ng/mL × hours and 96 ± 12 ng/mL × hours were calculated for IV administration and SC administration, respectively, resulting in an absolute mean (±SD) bioavailability of 91.3% ± 6.7%. Both treatments were well tolerated.

Conclusion(s): Ganirelix is absorbed rapidly and extensively after SC administration, resulting in a high absolute bioavailability of >90%.