Comparison of neuronal and glial numerical density in primary and secondary visual cortex of man

Summary The numerical density of neurons and glial cells was estimated in visual area 18 of the adult human cerebral cortex and compared with that of area 17. Blocks of areas 17 and 18 came from the same brains and this allowed the comparison of 1) neuronal and glial numerical densities through the whole cortical depth with calculation of the neuron/glia ratio, 2) neuronal and glial numbers under one square millimeter of cortical surface, and 3) neuronal numerical densities in three groups of identified layers. The mean neuronal density is approximately 40000 neurons/mm³ in area 17 and 31500/m³ in area 18. The mean glial density is around 27000/mm³ in area 17 and 32000/mm³ in area 18. This gives a neuron/glia ratio of approximately 1.5 in area 17 and of 1.0 in area 18, but the total cellular density is similar in both areas. There are about 90000 neurons and 64000 glial cells under one square millimeter of cortical surface in area 17, and some 73000 neurons and 74000 glial cells in area 18. The higher neuronal density in area 17 is found through the whole depth of cortex and does not seem to be more pronounced in layer IVc of area 17 compared to layer IV in area 18 than in the groups of layers II–III and V–VI.     

Laminar distribution of cytochrome oxidase staining in cetacean isocortex.

The distribution of cytochrome oxidase activity was studied in the cerebral cortex of two species of cetaceans, the harbour porpoise Phocoena phocoena, and the bottlenose dolphin Tursiops truncatus. Two main patterns of distribution of cytochrome oxidase were detected. The first, characteristic of the visual and auditory cortices of the lateral and suprasylvian gyri, is typified by a peak density in layer III, contrasting with low levels in layers II, V and VI. The second is found in wide areas of the limbic lobe, the insular cortex, the temporal operculum and the occipital cortex. In these regions, distribution of cytochrome oxidase is more uniform, with little difference between layers III, V and VI. A transitional pattern is found in the most dorsal parts of the limbic lobe, the parietal operculum, the ectosylvian gyrus and in orbitofrontal cortex. As areas of high cytochrome oxidase activity have been described in various land mammals to correspond to zones of major excitatory input and, in particular, to characterise the cortical layers that receive thalamocortical afferents, we propose that the thalamocortical input to cetacean sensory cortex, in which a typical layer IV is absent, may be mainly to layer III. This view is supported by the high density of neurons positive for the inhibitory transmitter gamma-aminobutyric acid that is also found in layer III of cetacean cortex, another typical feature of thalamocortical recipient zones.     

Plastic Surgery After Ablative Cancer Surgery

Plastic and reconstructive surgery often is conceptualized either as “cosmetic” or as involving complex operations with massive flaps or time-consuming and difficult microsurgery. A number of personal cases are used to illustrate that reconstruction after cancer surgery, even reconstruction of some large tumors, can be performed with modern modifications of classic local flaps, but that sound knowledge and skill in basic surgical and plastic techniques are inescapable prerequisites.     

Managing dermatologic toxicities of epidermal growth factor receptor inhibitors

There is considerable evidence that epidermal growth factor receptor (EGFR) plays an important role in non-small-cell lung cancer tumor growth and proliferation. Clinical experience with EGFR inhibitors, such as erlotinib, gefitinib, and cetuximab, has suggested that there are subgroups of patients with non-small-cell lung cancer that demonstrate dramatic responses to these agents. Researchers have sought to determine whether molecular or clinical characteristics correlate with therapeutic outcomes. Rash, the most commonly reported adverse effect of anti-EGFR therapy, has also been examined as a potential marker of response. Several trials evaluating anti-EGFR therapies have reported a positive correlation between rash and response and even rash and survival. If rash is truly a predictor of outcome, it becomes imperative that clinicians identify effective methods for managing this toxicity to avoid unwanted dose reduction, therapy interruption, delay, or discontinuation in patients experiencing a therapeutic benefit. Unfortunately, because of a lack of well-defined rash etiology, variability of use, and interpretation of rash grading scales, as well as a lack of clinical trials evaluating approaches to rash management, we are left without systematic, evidence-based guidelines for treatment. Preliminary results of a prospective study evaluating a rash treatment algorithm developed at the University of Texas M. D. Anderson Cancer Center have been positive, and there is universal agreement that initiation of more prospective trials to evaluate EGFR-inhibitor rash management is needed.     

Prenatal development of GABA-immunoreactive neurons in the human striate cortex.

The prenatal development of neurons immunoreactive to gamma-aminobutyric acid (GABA) in the striate cortex (area 17) of human foetuses aged from 14 weeks to term was studied immunocytochemically. In the 14 week foetus GABA-immunoreactive cells occurred in all layers of area 17 with the highest density in the marginal zone (MZ), subplate (SP), deep intermediate zone (IZ) and ventricular zone (VZ). The cortical plate (CP), which gives rise to most of the definitive adult cortical layers, had relatively low concentrations of GABAergic cells. By 17 weeks the density in the proliferative VZ had declined. At 20 weeks some of the adult layers were recognisable; the density of GABA-positive neurons was now highest in the definitive cortex, especially the deep layers (layers VI and V), was lower in the superficial cortical plate, and was lowest in IZ, where the white matter would form. The peak of GABA-immunoreactive neuronal density continued to move superficially during development, and was in layer IVc by 30 weeks. The laminar distribution stabilised from 30 weeks with three dense bands: in layer IVc and superficial V, layer IVa, and layers II and superficial III. The tangential distribution of GABAergic neurons was determined in two older brains (32 and 39 weeks) and no unequivocal spatial periodicity was observed in this plane. The mean cross-sectional area of GABAergic neurons in area 17 increased with foetal age, and also increased from superficial to deep layers at each age. Most GABA-immunoreactive neurons in younger brains contained immunonegative or weakly positive nuclei and had few visible processes, while in the older brains most neurons contained positive nuclei and had more visible processes. The proportion of GABA-immunoreactive bipolar cells declined during development while that of multipolar cells increased. GABAergic neurons thus differentiate early in human foetal striate cortex. They are initially most numerous in the proliferative layers deep to the developing definitive cortex; from 20 weeks of gestation, their peak moves superficially into the maturing deep layers (VI and V) and a stable laminar distribution is attained by 30 weeks, with peaks in layers II/IIIm, IVa and IVc/V. There is no obvious horizontal periodic distribution before term.     

Ganciclovir pharmacokinetics and cytokine dynamics in renal transplant recipients with cytomegalovirus infection

Ganciclovir is considered to be the first-line treatment for cytomegalovirus (CMV) in renal transplant recipients. This infection is also associated with elevations of specific plasma cytokines post-transplantation. To investigate daily cytokine response to therapy and ganciclovir pharmacokinetics, 4 transplant recipients (3 males, 1 female) with stable renal allograft function diagnosed with CMV infection were enrolled less than 4 months post-transplant. A creatinine clearance (ClCr) was generated by the Cockroft-Gault (C-G) equation (range: 42.3-68.5 mL/min) to determine ganciclovir dosing. Blood samples were collected for ganciclovir and cytokine [including interleukin (IL)-1beta, IL-2, IL-3, IL-4, IL-6, IL-8, IL-10, TNF-alpha, GM-CSF, and interferon (IFN)-gamma analyses after 7 d of intravenous (i.v.) ganciclovir (dosage range: 165-400 mg daily) therapy and again after 7 d of oral (p.o.) ganciclovir (dosage range: 1000 mg, 2-3 times daily) therapy. Pharmacokinetic ganciclovir was described with a two-compartment model. Total clearance of ganciclovir was consistently greater than ClCr, suggesting tubular secretion. Peak concentrations for i.v. ganciclovir averaged 8.39+/-1.87 microg/mL with minimum concentrations of 0.48+/-0.35 microg/mL. Plasma concentrations were lower but more sustained during a p.o. dosing interval (max=2.12+/-0.58 microg/mL, min=1.15+/-0.34 microg/mL). IL-6, IL-8, IL-10, and TNF-alpha were detectable at multiple times during the study periods while the remainder of the cytokines were only intermittently detectable. Average concentrations (i.v. versus p.o. study period) for TNF-alpha were 40.1+/-17.5 versus 22.1+/-11.2 pg/mL, for IL-8 were 17.1+/-15.6 versus 4.12+/-2.59 pg/mL, and for IL-10 were 7.39+/-5.54 versus 2.64+/-1.06 pg/mL. Concentrations were similar for IL-6 during both studies (9.39+/-5.42 versus 14.7+/-14.8 pg/mL). TNF-alpha, IL-8, and IFN-gamma appeared to correlate with CMV antigenemia. Further investigation of ganciclovir disposition and changes in plasma cytokines in renal transplant recipients during CMV infection may provide insight into variable antiviral responses in renal transplant recipients.     

Sources of thalamic afferent neurons, projecting into the suprasylvian gyrus of the dolphin cerebral cortex

The sources of a thalamic input to different loci of the suprasylvian gyrus (SSG) of the porpoise (Phocaena phocaena) cortex were studied by means of the retrograde HRP and fluorescent tracing methods. After injections of HRP into the anterior part of the SSG most cells were labelled in the lateral part of the ventrobasal complex. Some cells were also labelled in the ventroposteroinferior nucleus, posterior nucleus and caudally in the ventral parvocellular medial geniculate (MG). After injections of bisbenzimide in the middle part of the SSG many labelled cells were found in the ventral parvocellular MG and in the inferior pulvinar. Less cells were labelled in the magnocellular MG, lateral pulvinar and posterior nucleus. After bisbenzimide injection into the posterior part of the SSG the similar distribution of labelled cells was found but a sheet of labelled cells was shifted more laterally.     

Reduced dendritic spine density on cerebral cortical pyramidal neurons in schizophrenia

OBJECTIVE—A pilot study of the density ofdendritic spines on pyramidal neurons in layer III of human temporaland frontal cerebral neocortex in schizophrenia.
METHODS—Postmortem material from a groupof eight prospectively diagnosed schizophrenic patients,five archive schizophrenic patients, 11 non-schizophrenic controls,and one patient with schizophrenia-like psychosis, thought to be due tosubstance misuse, was impregnated with a rapid Golgi method. Spineswere counted on the dendrites of pyramidal neurons in temporaland frontal association areas, of which the soma was in layer III(which take part in corticocortical connectivity) and which met strictcriteria for impregnation quality. Altogether 25 blocks were studied inthe schizophrenic group and 21 in the controls. If more than one blockwas examined from a single area, the counts for that area wereaveraged. All measurements were made blind: diagnoses were onlydisclosed by a third party after measurements were completed. Possibleconfounding affects of coexisiting Alzheimer's disease were taken intoaccount, as were the effects of age at death and postmortem interval.
RESULTS—There was a significant (p<0.001)reduction in the numerical density of spines in schizophrenia (276/mmin control temporal cortex and 112/mm in schizophrenic patients, and299 and 101 respectively in the frontal cortex). An analysis ofvariance, taking out effects of age at death and postmortem interval,which might have explained the low spine density for some of theschizophrenic patients, did not affect the significance of the results.
CONCLUSION—The results support theconcept of there being a defect in the fine structure of dendritesof pyramidal neurons, involving loss of spines, in schizophreniaand may help to explain the loss of cortical volume without loss ofneurons in this condition, although the effect of neuroleptic drugscannot be ruled out.