Structural development of the lateral geniculate nucleus and visual cortex in monkey and man

This study concerns the development of the primary visual pathway of the primate. The lateral geniculate nucleus (LGN) is the principal thalamic relay to the visual cortex (area 17), and its neurons have similar morphological characteristics in both monkey and man, as identified by Golgi impregnation. The commonest neuron is the multipolar with a radiate or tufted dendritic tree; next is the bipolar neuron with two or three diametrically opposed dendritic trunks. Less frequent are neurons with beaded dendrites and others with fine, axon-like dendritic processes, possibly interneurons. The dendritic tree of all neurons remains generally within a lamina, but some dendrites cross interlaminar zones. LGN neurons are identifiable before birth and differ from their adult form by the presence of immature features, especially numerous dendritic and somatic spines, most frequent at birth in monkeys and at about 4 months postnatally in man. They disappear almost completely by 3 months in monkeys and 9 months in man. The human LGN has reached its ‘adult’ volume by this age.Two stages in the development of the human area 17 can be defined. The first is marked by a rapid growth to its ‘adult’ volume by about 4 months, and by intense synaptogenesis beginning in the foetus and reaching a maximum around 8 months. The second stage is one of stabilization in the volume of area 17 and loss of synapses to reach ‘adult’ synaptic density around 11 years, at about 60% of the maximum values.The formation of transitory morphological features in the first weeks or months of life coincides with a period of visual plasticity in infant monkeys and humans. Our observations can be correlated with experimental evidence for visual development in monkeys and with clinical evaluation of visual activity during the human preverbal stage, a period of great importance in the establishment of visual acuity, of stereopsis and of oculomotor function, all very sensitive to the numerous forms of visual deprivation.     

A review of single site minimally invasive surgery in infants and children

Videoscopic surgery has become the standard approach for most thoracic, abdominal, and pelvic procedures in adults and children. These procedures have widely recognized benefits including decreased postoperative pain, improved cosmesis, and decreased convalescence. In a recent attempt to further improve the cosmetic result of these operations, surgeons have begun to employ a single incision through which all the operating instruments are placed. This article seeks to review the current and future application of innovative minimally invasive surgery to pediatric surgery.     

A novel measure for pectus excavatum: the correction index

Objective

The Haller Index (HI), the standard metric for the severity of pectus excavatum, is dependent on width and does not assess the depth of the defect. Therefore, we performed a diagnostic analysis to assess the ability of HI to separate patients with pectus excavatum from healthy controls compared to a novel index.

Methods

After institutional review board approval, computed tomography scans were evaluated from patients who have undergone pectus excavatum repair and controls. The correction index (CI) used the minimum distance between posterior sternum and anterior spine and the maximum distance between anterior spine most anterior portion of the chest. The difference between the two is divided by the latter (×100) to give the percentage of chest depth the defect represents.

Results

There were 220 controls and 252 patients with pectus. Mean HI was 2.35, and the mean CI was 0.92 for the controls. The mean HI was 4.06, and the mean CI was 31.75 in the patients with pectus. In the patients with pectus, HI demonstrated a 47.8% overlap with the controls, while there was no overlap for CI.

Conclusions

The Haller index demonstrates 48% overlap between normal patients and those with pectus excavatum. However, the proposed correction index perfectly separates the normal and diseased populations.     

Distribution of GABA and neuropeptides in the human cerebral cortex

Summary Antibodies were used to identify neurons in human frontal and temporal cortex that were immunopositive to -aminobutyric acid (GABA) and the neuropeptides vasoactive intestinal polypeptide (VIP), substance P (SP) and somatostatin (SOM). Specimens were taken at surgical biopsy and fixed immediately after removal. The results described for both light and electron microscopy were obtained when relatively high concentrations of glutaraldehyde (2.5–3%) were present in the fixative. Specimens were examined from three adults and an infant aged 5 months. GABAergic neurons were present in all cortical layers, with fewest in layers I, deep III and V, and were mainly small, and round or oval. No labelled pyramidal neurons were detected. GABAergic puncta were common in the neuropil, probably representing axonal profiles. VIP-neurons were also found in all layers, including layer I, and were approximately twice as numerous as GABA-cells. SP-positive cells were found throughout the layers, but were sparse in layers I and VI. They were about three times commoner than GABAergic neurons. SOM-reactivity was demonstrated in about the same number of cells as that for SP. Again, this involved all layers, but layer I least. Peptidergic neurons were larger, on the average, than GABAergic cells, and were frequently pyramidal in character. In the infant, the distribution, size and frequency of immunoreactive neurons were similar to those in the adult. However, GABAergic puncta were commoner.This paper represents part of a study for the degree of Ph.D. in the National University of Singapore by WYO while at the Department of Anatomy, National University of Singapore.     

Innate Inflammatory Response and Immunopharmacologic Activity of Micafungin,Caspofungin, and Voriconazole against Wild-Type and FKS Mutant Candida glabrata Isolates

The direct or indirect interactions that antifungals have with the host immune response may play a significant role in defining their activity in vivo. However, the impact that acquired antifungal resistance has on the immunopharmacologic activity of antifungals is not well described. We assessed the immunopharmacologic activity of caspofungin, micafungin, and voriconazole among isolates of Candida glabrata with or without FKS-mediated echinocandin resistance. Clinical bloodstream isolates of C. glabrata from patients who did (n = 5) or did not (n = 3) develop persistent candidemia and who did (n = 2) or did not (n = 11) harbor FKS gene mutations were included. A cell-based assay was used to compare differences in macrophage activation among isolates when grown in the presence or absence of subinhibitory concentrations of caspofungin, micafungin, or voriconazole. In the absence of antifungals, macrophage activation was significantly lower for index C. glabrata isolates obtained from persistent candidemia patients than for those from nonpersistent patients (33% versus 79% increase over negative controls, respectively; P < 0.01). Growth of isolates possessing wild-type FKS genes in subinhibitory concentrations of micafungin or caspofungin, but not voriconazole, significantly increased macrophage inflammatory responses compared to untreated controls (1.25- to 2.75-fold increase, P < 0.01). For isolates harboring the FKS2 hot spot 1 (HS1) S663P mutation, however, a significant increase was observed only with micafungin treatment (1.75-fold increase versus negative control, P < 0.01). Macrophage activation correlated with the level of unmasking of β-glucan in the cell wall. The diminished macrophage inflammatory response to isolates that caused persistent candidemia and differential immunopharmacologic activity of echinocandins among FKS mutants suggest that certain strains of C. glabrata may have a higher propensity for immunoevasion and development of antifungal resistance during treatment.