Corticosterone and corticotropin‐releasing factor acutely facilitate gamma oscillations in the hippocampus in vitro

Stressful experiences do not only cause peripheral changes in stress hormone levels, but also affect central structures such as the hippocampus, implicated in spatial orientation, stress evaluation, and learning and memory. It has been suggested that formation of memory traces is dependent on hippocampal gamma oscillations observed during alert behaviour and rapid eye movement sleep. Furthermore, during quiescent behaviour, sharp wave‐ripple (SW‐R) activity emerges. These events provide a temporal window during which reactivation of memory ensembles occur. We hypothesized that stress‐responsive modulators, such as corticosterone (CORT), corticotropin‐releasing factor (CRF) and the neurosteroid 3α, 21‐dihydroxy‐5α‐pregnan‐20‐one (THDOC) are able to modulate gamma oscillations and SW‐Rs. Using in vitro hippocampal slices, we studied acute and subacute (2 h) impact of these agents on gamma oscillations in area cornu ammonis 3 of the ventral hippocampus induced by acetylcholine (10 μm ) combined with physostigmine (2 μm ). CORT increased the gamma oscillations in a dose‐dependent fashion. This effect was mediated by glucocorticoid receptors. Likewise, CRF augmented gamma oscillations via CRF type 1 receptor. Lastly, THDOC was found to diminish cholinergic gamma oscillations in a dose‐dependent manner. Neither CORT, CRF nor THDOC modulated gamma power when pre‐applied for 1 h, 2 h before the induction of gamma oscillations. Interestingly, stress‐related neuromodulators had rather mild effects on spontaneous SW‐R compared with their effects on gamma oscillations. These data suggest that the alteration of hippocampal gamma oscillation strength in vitro by stress‐related agents is an acute process, permitting fast adaptation to new attention‐requiring situations in vivo.     

Anomalous origin of the right coronary artery from the pulmonary artery

Anomalous origin of the right coronary artery from the pulmonary artery was diagnosed by selective left coronary artery angiography in an asymptomatic five-year-old boy with a continuous murmur. The anomalous coronary artery, along with a cuff of the pulmonary artery, was re-implanted into the aorta. The patient is asymptomatic five years postoperatively.     

Ventriculosubgaleal shunt in the treatment of posthemorrhagic and postinfectious hydrocephalus of premature infants

Purpose

The aim of the study was to compare the characteristics of ventriculosubgaleal shunts during the clinical course of posthemorrhagic and postinfectious hydrocephalus in the neonatal period.

Patients and methods

The study comprised 102 premature babies in whom subgaleal shunt was consecutively inserted between 2006 and 2011. Seventy-two patients had posthemorrhagic hydrocephalus (mean gestational age 27.3?±?2.1 weeks, mean birth weight 1,036.9?±?327.7 g, mean age at insertion 51.4?±?56.2 days) and 30 patients were operated postinfectiously (27.5?±?2.2 weeks, 1,064.7 g?±?310.7 g, 115.9?±?47.8 days).

Results

The mean survival of subgaleal shunts was 87.9 days for the posthemorrhagic group and 75.6 days for the postinfectious group. Only six infants (8.3 %) did not need ventriculoperitoneal shunts later, all posthemorrhagic. There were meaningful differences between two groups with regard to ventriculosubgaleal shunt-related infections (8.3 % in posthemorrhagic versus 20.0 % in postinfectious) and shunt revision rate (6.9 % in posthemorrhagic versus 13.3 % in postinfectious), but these were not statistically significant. The need of ventriculoscopic procedures was notably more frequent in postinfectious group (1.4 versus 23.3 %).

Conclusion

In premature infants with ventriculomegaly, the subgaleal shunt is an effective temporary diversion tool. The complications were less with posthemorrhagic than with postinfectious hydrocephalus. With previous severe infections of prematures, the risk for complications regarding infection and obstruction will be 2.75 and 2.06 (odds ratios) times higher and more frequent need of ventriculoscopic procedures should be considered (odds ratio 21.6).     

Severity of Megakaryocyte-Driven Osteosclerosis in Mpig6b-Deficient Mice Is Sex-Linked

Patients with chronic myelofibrosis often suffer from osteosclerosis, which is associated with bone pain and may lead to bone marrow failure. The pathogenesis of myelofibrosis is linked to aberrant megakaryocyte development and function. Null and loss-of-function mutations in MPIG6B, which codes for the inhibitory heparan sulfate receptor G6b-B, result in severe macrothrombocytopenia, large megakaryocyte clusters, and focal primary myelofibrosis in mice and humans. We investigated the development of osteosclerosis in Mpig6b null (Mpig6b^−/−) mice. Although male and female Mpig6b^−/− mice presented with elevated bone marrow megakaryocyte number and macrothrombocytopenia, female Mpig6b^−/− mice developed progressive splenomegaly starting at 8 weeks of age. Micro–computed tomography (μCT) of femurs showed that female Mpig6b^−/− mice had increased cortical thickness and reduced bone marrow area starting at 8 weeks of age and developed occlusion of the medullary cavity by trabeculae by 16 weeks of age. In contrast, male Mpig6b^−/− mice developed only a small number of trabeculae in the medullary cavity at the proximal diaphysis and demonstrated a temporary decrease in bone volume fraction and trabecular thickness at 16 weeks. Ovariectomy of 10-week-old female Mpig6b^−/− mice prevented the development of medullary cavity osteosclerosis, whereas orchiectomy of male Mpig6b^−/− mice did not exacerbate their disease. Importantly, ovariectomized female Mpig6b^−/− mice also demonstrated improvement in spleen weight compared to sham-operated Mpig6b^−/− mice, establishing estrogen as a contributing factor to the severity of the megakaryocyte-driven osteosclerosis. © 2021 American Society for Bone and Mineral Research (ASBMR).     

Effect of 6-hydroxydopamine treatment on kynurenine aminotransferase-I (KAT-I) immunoreactivity of neurons and glial cells in the rat substantia nigra

Parkinson’s disease (PD), a progressive neurodegenerative disorder, is characterized by a preferential loss of dopaminergic neurons in the substantia nigra pars compacta (SNPC). Neurons in the SNPC are known to express tyrosine hydroxylase (TH); therefore, in a commonly used PD model, 6-hydroxydopamine (6-OHDA), a selective catecholamine neurotoxin, induces neuronal death in SNPC. We have shown with immunohistochemical techniques that kynurenine aminotransferase-I (KAT-I), the enzyme taking part in the formation of kynurenic acid (KYNA)—the only known endogenous selective NMDA receptor antagonist and a potent neuroprotective agent—is also expressed in the rat SNPC. We found that KAT-I and TH co-exist in the very same neurons of SNPC and that 6-OHDA injected into the lateral ventricle produced loss of the majority of nigral neurons. Densitometric analysis proved that, in consequence of 6-OHDA treatment, not only TH but also KAT-I immunoreactivity diminished considerably in the remaining SNPC neurons. Astrocytes in the substantia nigra were found to express KAT-I under normal conditions; the amount of this enzyme increased after administration of 6-OHDA, whereas microglial cells became KAT-I immunoreactive only after 6-OHDA treatment. Since intrinsic KYNA in SNPC neurons is perceptibly insufficient to protect them from the deleterious effect of 6-OHDA, it is hypothesized that biochemical approaches which increase KYNA content of the central nervous system might prevent the deleterious effect of 6-OHDA and, supposedly, also the neuronal degradation characterizing PD.     

Complications after bladder augmentation or substitution in children: a prospective study of 86 patients

Study Type – Therapy (case series) Level of Evidence 4 What’s known on the subject? and What does the study add? A lot of information has been gathered on the subject of complications following urinary bladder augmentation and/or substitution in the recent years. The present study, based on the analysis of 86 patients, gives a critical analysis of these complications (stone formation, bowel obstruction, hematuria‐dysuria syndrome, small bowel bacterial overgrowth, persistent vesico‐ureteral reflux, obstruction at the site of ureteral reimplantation, reservoir perforation, premalignant histological changes, decreased bladder capacity/compliance requiring reaugmentation, etc.). The study adds one more new complication (small bowel colonization following colocystoplasty performed with the cecum and ascending colon) and reports complications in a fairly big (by European standards) cohort of patients with a long follow‐up.

OBJECTIVE

• ? To evaluate complications after urinary bladder augmentation or substitution in a prospective study in children.

PATIENTS AND METHODS

• ? Data of 86 patients who underwent urinary bladder augmentation (80 patients) or substitution (6 patients) between 1988 and 2008 at the authors’ institute were analysed.
• ? Ileocystoplasty occurred in 32, colocystoplasty in 30 and gastrocystoplasty in 18. Urinary bladder substitution using the large bowel was performed in six patients.
• ? All patients empty their bladder by intermittent clean catheterization (ICC), 30 patients via their native urethra and 56 patients through continent abdominal stoma. Mean follow‐up was 8.6 years.
• ? Rate of complications and frequency of surgical interventions were statistically analysed (two samples t‐test for proportions) according to the type of gastrointestinal part used.

RESULTS

• ? In all, 30 patients had no complications. In 56 patients, there were a total of 105 complications (39 bladder stones, 16 stoma complications, 11 bowel obstructions, 5 reservoir perforations, 7 VUR recurrences, 1 ureteral obstruction, 4 vesico‐urethral fistulae, 4 orchido‐epididymitis, 4 haematuria‐dysuria syndrome, 3 decreased bladder capacity/compliance, 3 pre‐malignant histological changes, 1 small bowel bacterial overgrowth and 7 miscellaneous).
• ? In 25 patients, more than one complication occurred and required 91 subsequent surgical interventions. Patients with colocystoplasty had significantly more complications (P < 0.05), especially more stone formation rate (P < 0.001) and required more post‐ operative interventions (P < 0.05) than patients with gastrocystoplasty and ileocystoplasty.

CONCLUSIONS

• ? Urinary bladder augmentation or substitution is associated with a large number of complications, particularly after colocystoplasty.
• ? Careful patient selection, adequate preoperative information and life‐long follow‐up are essential for reduction, early detection and management of surgical and metabolic complications in patients with bladder augmentation or substitution.

     

Long-term,prolonged-release tacrolimus-based immunosuppression in de novo kidney transplant recipients: 5-year prospective follow-up of the ADHERE study patients

The objectives of this study were to assess long-term graft survival, patient survival, renal function, and acute rejections in de novo kidney transplant recipients, treated with once-daily prolonged-release tacrolimus-based therapy. The study was a 5-year non-interventional prospective follow-up of patients from the ADHERE study, a Phase IV 12-month open-label assessment of patients randomized to receive prolonged-release tacrolimus in combination with mycophenolate mofetil (MMF) (Arm 1) or sirolimus (Arm 2). From 838 patients in the randomized study, 587 were included in the long-term follow-up, of whom 510 completed the study at year 5. At 1 year post-transplant, graft and patient survival rates were 93.0% and 97.8%, respectively, and at 5 years were 84.0% and 90.8%, respectively. Cox proportional hazards analysis showed no association between graft loss, initial randomized treatment arm, donor age, donor type, or sex. The 5-year acute rejection-free survival rate was 77.4%, and biopsy-confirmed acute rejection-free survival rate was 86.0%. Renal function remained stable over the follow-up period: mean ± SD eGFR 4-variable modification diet in renal disease formula (MDRD4) was 52.3 ± 21.6 ml/min/1.73 m² at 6 months and 52.5 ± 23.0 ml/min/1.73 m² at 5 years post-transplant. These findings support the role of long-term once-daily prolonged-release tacrolimus-based immunosuppression, in combination with sirolimus or MMF, for renal transplant recipients in routine clinical practice.     

Severe neonatal respiratory distress with linear inspiratory pressure-volume curve

Twenty-four newborns with severe respiratory distress, treated by mechanical ventilation, are investigated by inspiratory pressure-volume curve. The curves are obtained by slow continuous inflation technique. Two shapes are described: concave curve, ten newborns (group I), linear curve, fourteen newborns (group II). The gestational age is over 36 weeks in both groups. Determination of respiratory mechanics is indicated when mean AaDO2 is higher than 500 torr in both groups, and when there is a hypercapnia (PaCO2 = 53 +/- 11 torr, with p less than 0.05) in group II. Mechanical ventilation is conducted with individually adjusted PEEP in group I, and without PEEP in group II. Twelve hours after; mean AaDO2 in group I (260 +/- 101 torr) and in group II (420 +/- 188 torr) are significantly different (p less than 0.05). The variance analysis in group II shows that PaCO2 and pH are normalized (p less than 0.001). All the newborns in group I recovered. Three newborns in group II died. Group I can be assimilated to hyaline membrane disease in full-term neonates. Practically, the cases of neonatal respiratory distress in which PEEP is not indicated can be identified by the functional characteristics of group II.     

Laser miniconization in mild and moderate dysplasia of the uterine cervix

Mass cytologic screening for cervical cancer often reveals only mild dysplasia not indicating conization but necessitating continual checkup. Such routine checkups are often insufficient, beside which the patients find them frustrating. Therefore a new method, called miniconization, for treatment of patients with vaginal smears showing mild or moderate dysplasia (cervical intraepithelial neoplasia/CIN/I-II), was developed. With the CO2 laser handpiece a 5-mm-thick disc of the cervix, including the whole transformation zone, was removed. This was followed by endocervical curettage. The advantage of the method over cryosurgery, electrocoagulation, and laser vaporization, for example, is that the tissue specimen as a whole disc including the transformation zone can be sectioned and examined histologically. Another advantage is the decreased risk of postoperative bleeding, which enables ambulant care. One hundred and fifty-one patients have hitherto been treated and carcinoma in situ has been found in 15.2% and microinvasive carcinoma in 1.3% of all these patients in whom vaginal smears showed mild or moderate dysplasia (CIN I-II).