Comparison and evolution of transcranial versus endoscopic endonasal approaches for suprasellar Meningiomas: A systematic review.

BACKGROUND: Meningiomas of the tuberculum sellae (TS) and planum sphenoidale (PS) are challenging to treat surgically. Transcranial approaches (TCAs) were the mainstay before endoscopic endonasal approaches (EEA) were developed, however the efficacy and safety of EEA approaches relative to TCA approaches remains unclear. METHODS: The authors conducted a PRISMA-compliant systematic review of existing literature detailing the outcomes of both approaches. PubMed, Embase, Cochrane Library, and Clinicaltrials.gov were searched. Studies were included if they analyzed TS and/or PS meningiomas, included ≥ 5 patients, and reported at least one outcome of interest. RESULTS: Overall, 44 retrospective studies met inclusion criteria, the majority being from single centers, between 2004 and 2020. In studies directly comparing postoperative outcomes among TCA and EEA approaches, EEA had significantly higher odds of visual improvement (OR = 3.24, p = 0.0053) and significantly higher odds of CSF leak (OR = 3.71, p = 0.0098) relative to TCA. Further, there were no significant differences between visual worsening (p = 0.17), complications (p = 0.51), and GTR rates (p = 0.30) for the two approaches. Meta-analysis demonstrated no significant association between nasoseptal flap (NSF) use and postoperative outcomes among EEA patients. There was also no significant association between study publication year and postoperative EEA outcomes. CONCLUSION: The present study demonstrates that EEA offers a viable alternative to TCA in the treatment of suprasellar meningiomas. In particular, EEA shows promise for superior visual outcomes, though postoperative CSF leaks are an important consideration among patients undergoing this approach.

Multiple aggressive squamous skin cancers in association with nonbullous congenital ichthyosiform erythroderma.

Nonbullous congenital ichthyosiform erythroderma (NBCIE) is one of the autosomal recessive inherited non-syndromic ichthyoses and is currently diagnosed on clinical grounds alone. Skin cancer is not a recognized complication of NBCIE. We report here two NBCIE patients who have developed multiple aggressive nonmelanoma skin cancers, predominantly cutaneous squamous cell carcinoma. NBCIE may be a risk factor for skin cancer development.

Rationale for the observed COX-2/COX-1 selectivity of celecoxib from Monte Carlo simulations.

Computational studies have yielded an analysis of the contributions to the free energy difference between the binding of celecoxib to COX-1 and to COX-2. The energetic and structural results point to the Ile to Val mutation at residue 523 as the key contributor to COX-2 selectivity; unfavorable steric contact between a sulfonamide oxygen and the delta methyl group of Ile523 destabilizes the complex with COX-1. The His to Arg change at residue 513 is less significant.

In-hospital mortality from abdominal aortic surgery in Great Britain and Ireland: Vascular Anaesthesia Society audit.

BACKGROUND: The mortality rate associated with elective aortic aneurysm repair is widely assumed to be in the region of 5 per cent. This figure does not take into consideration the effect of pre-existing risk factors. The Vascular Anaesthesia Society of Great Britain and Ireland conducted a large audit to estimate the in-hospital mortality rate associated with non-emergency infrarenal aortic surgery throughout the British Isles, and to determine the influence of risk factors on mortality rate. METHODS: This was a multicentre, prospective audit of 177 hospitals throughout the UK and Ireland. Data were collected by questionnaire to include all patients undergoing elective or urgent surgery for infrarenal abdominal aortic aneurysm or aortoiliac occlusive disease over 4 months. RESULTS: Nine hundred and thirty-three patients were recruited into the audit. The overall mortality rate was 7.3 per cent. Factors increasing the risk of death by up to fivefold included age over 74 years, urgent surgery, operation for occlusive disease, limited exercise capacity, a history of severe angina or cardiac failure, the presence of ventricular ectopics and abnormalities suggesting ischaemic heart disease on electrocardiography. CONCLUSION: Although the in-hospital mortality rate was similar to previously published figures, the rate increased considerably when commonly encountered risk factors were present.

Regulation of serotonin release in the lateral septum and striatum by corticotropin-releasing factor.

The serotonergic dorsal raphé nucleus (DRN) is innervated by corticotropin-releasing factor (CRF)-immunoreactive fibers and contains CRF receptor-binding sites, suggesting that endogenous CRF regulates this system. The present study examined the possibility that CRF in the DRN regulates the release of serotonin (5-HT) in forebrain terminal regions. Intracerebroventricular administration of CRF produced a bimodal effect on extracellular levels of 5-HT in the lateral septum. Doses of 0.3 and 1.0 microg decreased extracellular 5-HT levels, whereas both a higher (3.0 microg) and a lower (0.1 microg) dose had no effect. The reduction of extracellular 5-HT in the lateral septum by CRF (0.3 microg, i.c.v.) was blocked by pretreatment with the CRF receptor antagonist d-PheCRF(12-41) (3.0 microg, i.c.v.). Direct administration of CRF (30 ng) into the DRN reduced extracellular 5-HT levels in the lateral septum and the striatum. Furthermore, injection of d-PheCRF(12-41) (10 ng) into the DRN before ventricular administration of CRF (0.3 microg, i.c.v.) blocked the decrease in extracellular 5-HT in both the lateral septum and striatum. Taken together, these data support the hypothesis that CRF may modulate 5-HT release in terminal regions via its effects at the level of the DRN. This modulation supports a potential interaction between CRF and 5-HT in stress-related psychiatric disorders in which both systems have been implicated.

Lamotrigine monotherapy in children.

The effectiveness of lamotrigine as a monotherapeutic agent for a variety of pediatric epilepsies was reviewed retrospectively. Children were categorized as having focal vs generalized epilepsy and according to whether they were antiepileptic drug naive or drug exposed. Data collected included dosages, side effects, length of follow-up, number of prior drugs, and treatment response. Treatment was considered successful if the patient was seizure free for 6 months or more. Eighty-three children were identified (average age = 8.7 years); 43 had focal epilepsy, 32 had generalized epilepsy, and eight were not classified. Twenty-nine patients were classified as having specific syndromes. Fourteen patients were drug naive. The median follow-up period was 8 months (mean = 8.5). Overall, 45% were seizure free, 44% with focal epilepsy and 36% with generalized epilepsy. All children with juvenile myoclonic epilepsy and benign rolandic epilepsy of childhood were seizure free, although not all had been treated for at least 6 months. One third of drug-naive patients were seizure free. Rash was the most common side effect and was reported in five patients (6%); two patients discontinued the drug. None had Stevens-Johnson syndrome. One quarter of children experienced nonquantifiable improvements, namely increased alertness and improved behavior regardless of seizure control. Lamotrigine is effective as a monotherapeutic agent in children for both focal and generalized epilepsies. Side effects are relatively uncommon. Lamotrigine may be an effective firstline agent.

Multiple cutaneous immunocytoma with secondary anetoderma: a report of two cases.

We describe two men with multiple erythematous dermal nodules which were clinically and histologically consistent with a diagnosis of primary cutaneous immunocytoma. Both patients exhibited the very unusual feature of secondary anetoderma occurring in spontaneously resolving lesions. There is one previous report of anetoderma in association with a plasmacytoma. The pathogenesis remains unknown but release of cytokines such as interleukin-6 may be implicated.

The hyaluronan receptor RHAMM in noradrenergic fibers contributes to axon growth capacity of locus coeruleus neurons in an intraocular transplant model.

The hyaluronan receptor for hyaluronic acid-mediated motility (RHAMM) plays a role in cell migration and motility in many systems. Recent observations on the involvement of RHAMM in neurite motility in vitro suggest that it might also be important in axon outgrowth in situ. This was addressed directly by investigating both RHAMM expression in the rat CNS and the ability of anti-RHAMM reagents to interfere with tissue growth and axon outgrowth in intraocular brainstem transplants. By western blotting, anti-RHAMM antibody detected a RHAMM isoform of 75,000 mol. wt in both whole brain homogenate and synaptosome preparations, and a 65,000 mol. wt isoform in synaptosomes. Immunofluorescence of adult brain sections revealed RHAMM-like immunoreactivity in varicose fibers that were also positive for the noradrenergic marker dopamine-beta-hydroxylase. Not all noradrenergic fibers contained RHAMM, nor was RHAMM detected in other monoaminergic fiber types. Lesions of noradrenergic fiber systems with beta-halobenzylamine-N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4) eliminated RHAMM-positive fibers, but noradrenergic axons that sprouted extensively after this treatment were strongly RHAMM-positive. To assess RHAMM's role in fiber outgrowth, fetal brainstem tissue containing noradrenergic neurons was grafted into the anterior chamber of the eye. Treatment of grafts with anti-RHAMM antibody caused significant inhibition of tissue growth and axon outgrowth, as did a peptide corresponding to a hyaluronan binding domain of RHAMM. These agents had no such effects on transplants containing serotonergic and dopaminergic neurons. These results suggest that RHAMM, an extracellular matrix receptor previously shown to contribute to migratory and contact behavior of cells, may also be important in the growth and/or regenerative capacity of central noradrenergic fibers originating from the locus coeruleus.

Effects of corticotropin-releasing factor on brain serotonergic activity.

The serotonergic dorsal raphe nucleus is innervated by corticotropin-releasing factor (CRF) and expresses CRF receptors, suggesting that endogenous CRF impacts on this system. The present study characterized interactions between CRF and the dorsal raphe serotonin (5-HT) system. The effects of intracerebroventricularly (i.c.v.) administered CRF on microdialysate concentrations of 5-HT in the lateral striatum of freely moving rats were determined. CRF had biphasic effects, with 0.1 and 0.3 microgram decreasing, and 3.0 micrograms increasing 5-HT dialysate concentrations. i.c.v. administration of CRF inhibited neuronal activity of the majority of dorsal raphe neurons at both low (0.3 microgram) and high (3 micrograms) doses. Likewise, intraraphe administration of CRF (0.3 and 1.0 ng) had predominantly inhibitory effects on discharge rate. Together, these results suggest that CRF is positioned to regulate the function of the dorsal raphe serotonergic system via actions within the cell body region. This regulation may play a role in stress-related psychiatric disorders in which 5-HT has been implicated.

Induction of mutagenic DNA damage in human fibroblasts after exposure to artificial tanning lamps.

There is increasing concern about the adverse health effects associated with the use of sunbeds, particularly with respect to skin photocarcinogenesis. The induction of mutagenic DNA damage is a prerequisite for the development of skin tumours, and it is well established that direct types of damage such as cyclobutane pyrimidine dimers (CPDs) give rise to mutations in tumour suppressor genes and oncogenes. In addition, ultraviolet radiation may induce indirect types of DNA damage, including oxidative products, which are also potentially mutagenic. By using specific DNA repair enzymes (T4 endonuclease V and endonuclease III) and the comet assay we have been able to detect the induction of CPDs, oxidized or hydrated pyrimidine bases and single-strand breaks in cultured human fibroblasts (MRC-5) after exposure for between 15 s and 20 min on two different commercial sunbeds containing Philips 'Performance' 100W-R or Philips TL80W/10R lamps. The ratio of endonuclease III to T4 endonuclease V sensitive sites varied substantially between the two lamps and was 3.3% and 18%, respectively. The sunbed containing the 'Performance' 100W-R lamps was as potent at inducing CPDs as was natural sunlight in fine weather. These results establish that commercial tanning lamps produce the types of DNA damage associated with photocarcinogenesis in human cells, and complement epidemiological evidence indicating the potential risk of using sunbeds.

Effects of GDNF on fetal septal forebrain transplants in oculo.

Glial cell line-derived neurotrophic factor (GDNF) is a member of the TGF-beta superfamily of growth factors with marked neurotrophic activity on midbrain dopaminergic neurons. To investigate whether this trophic activity is shared by central cholinergic neurons, we investigated the effects of GDNF treatment during development of the medial septal area in rats. Adult Fischer 344 rats received intraocular transplants of fetal septal forebrain tissue (embryonic Day 17) which was preincubated for 20 min with either GDNF or vehicle. The two treatment groups subsequently received weekly intraocular injections of either GDNF (0.5 microgram in 5 microliters/injection) or vehicle for 6 weeks following transplantation. Transplants treated with GDNF grew twice as large as control grafts treated with vehicle. Immunohistochemical evaluations of the transplants revealed that there was no difference between the two groups in terms of acetylcholinesterase or low affinity neurotrophin receptor (p75) staining. In contrast, a significant increment in the number of GABA-ergic neurons was observed in transplants that received GDNF, as compared to vehicle-treated grafts. The overall number of neurons within the transplanted tissue was also elevated in the experimental group. There was no difference between the two groups in the distribution or density of astrocytes in the grafted tissue, as evidenced by immunohistochemistry with antibodies directed against glial fibrillary acidic protein. These results indicate that basal forebrain GABA-ergic neurons may be dependent on GDNF for their survival and/or for GABA synthesis, but that the cholinergic neurons in this area appear to be unaffected by GDNF administration during development.

Tyrosine hydroxylase in the cerebral ganglia of the American cockroach (Periplaneta americana L.): an immunohistochemical study.

We have investigated the distribution of tyrosine-hydroxylase-like immunoreactivity in the cerebral ganglia of the American cockroach, Periplaneta americana. Groups of tyrosine-hydroxylase-immunoreactive cell bodies occur in various parts of the three regions of the cerebral ganglia. In the protocerebrum, single large neurons or small groups of neurons are located in the lateral neuropil, adjacent to the calyces, and in the dorsal portion of the pars intercerebralis. Small scattered cell bodies are found in the outer layers of the optic lobe, and clusters of larger cell bodies can be found in the deutocerebrum, medial and lateral to the antennal glomeruli. Thick bundles of tyrosine-hydroxylase-positive nerve fibers traverse the neuropil in the proto- and deutocerebrum and innervate the glomerular and the non-glomerular neuropil with fine varicose terminals. Dense terminal patterns are present in the medulla and lobula of the optic lobe, the pars intercerebralis, the medial tritocerebrum, and the area surrounding the antennal glomeruli, the central body and the mushroom bodies. The pattern of tyrosine-hydroxylase-like immunoreactivity is similar to that previously described for catecholaminergic neurons, but it is distinctly different from the distribution of histaminergic and serotonergic neurons.

Successful surgical treatment of severe pretibial myxoedema.

We report a 46-year-old man with severe and long-standing pretibial myxoedema, who responded well to local surgical treatment. This improvement has been maintained over a 12-month period, perhaps because of concomitant treatment with octreotide.

Primary systemic amyloid with nail dystrophy.

We report a patient with the classical cutaneous findings of primary systemic amyloidosis, due to myeloma. He had developed a nail dystrophy, which is a recognized, but rare, feature in systemic amyloid.