Effect of thymosin alpha 1 on hypothalamic hormone release.

Thymosin alpha 1 (T alpha 1) is a well-characterized immunopotentiating polypeptide originally isolated from calf thymus. We have recently shown in vivo, probable hypothalamic effects of T alpha 1 to decrease the release of the pituitary hormones, TSH, PRL and ACTH from the pituitary gland. Therefore, in the present study we evaluated the effect of the peptide on the release of hypothalamic regulatory hormones: thyrotropin-releasing hormone (TRH) and corticotropin-releasing hormone (CRH), as well as somatostatin (SRIH), from medial basal hypothalamic (MBH) fragments incubated in vitro. After a preliminary time-course study indicated that a 30-min incubation period was optimal, it was used for all the other experiments. At the end of the incubation the tissue was still able to respond to a depolarizing K+ concentration for 15 min by a 4-fold increase of TRH concentration compared to control basal release during the preceding 30 min. T alpha 1 was shown to inhibit the release of TRH and CRH from MBH fragments incubated in vitro with a minimal effective dose (MED) of 10(-11) M. SRIH and CRH release was also inhibited but the MED for these peptides was 10(-9) M. The relative responsiveness to the action of T alpha 1 was TRH greater than CRH, which was greater than SRIH. This correlated with our previous in vivo results for pituitary hormone release, except in the case of SRIH since we previously did not detect any significant effect of the peptide on growth hormone release. Finally, we evaluated the possible involvement of other neurotransmitters in the effect of T alpha 1 on TRH release.(ABSTRACT TRUNCATED AT 250 WORDS)     

The hooked element in the pes of turtles (Testudines): a global approach to exploring primary and secondary homology

The hooked element in the pes of turtles was historically identified by most palaeontologists and embryologists as a modified fifth metatarsal, and often used as evidence to unite turtles with other reptiles with a hooked element. Some recent embryological studies, however, revealed that this element might represent an enlarged fifth distal tarsal. We herein provide extensive new myological and developmental observations on the hooked element of turtles, and re‐evaluate its primary and secondary homology using all available lines of evidence. Digital count and timing of development are uninformative. However, extensive myological, embryological and topological data are consistent with the hypothesis that the hooked element of turtles represents a fusion of the fifth distal tarsal with the fifth metatarsal, but that the fifth distal tarsal dominates the hooked element in pleurodiran turtles, whereas the fifth metatarsal dominates the hooked element of cryptodiran turtles. The term ‘ansulate bone’ is proposed to refer to hooked elements that result from the fusion of these two bones. The available phylogenetic and fossil data are currently insufficient to clarify the secondary homology of hooked elements within Reptilia.     

Endoscopic transconjunctival optic nerve sheath fenestration for progressive idiopathic visual field deficit: a case report

Intra-orbital optic nerve sheath fenestration (ONSF) is an effective option in patients with progressive vision loss due to idiopathic intracranial hypertension. Most proposed techniques involve surgical trauma and require disinsertion of the medial rectus muscle; thus, less invasive surgical procedures are needed. Here, a feasible and effective technique of endoscopic intra-orbital ONSF through a conjunctival incision is presented, in a patient with a progressively compromised visual field, papilloedema, and distended subarachnoid space around the optic nerves. The retrobulbar segment of the optic nerve was exposed for incision, avoiding manipulation of the lateral orbital rim bones and irritation of the ciliary microvessels and nerves. The patient regained the entire visual field. ONSF was safely and effectively performed endoscopically through a narrow corridor gained by brushing away the orbital fat with minimal traction on the medial rectus muscle. The small postoperative wound was associated with faster and easier convalescence, and less tissue trauma versus conventional open approaches.     

No Specific Brain Protection Against Thermal Stress in Fever

Summary  Knowledge about human brain temperature is still very limited, despite evidence demonstrating the critical influence of mild increases in temperature on the ischaemic brain. It has been suggested that in passive and exercise hyperthermia the brain may be protected against thermal damage by a mechanism of selective brain cooling (SBC). It is said to bring about suppression of the temperature of the brain, rendering it significantly lower than trunk and arterial blood temperature. Yet very little is known about the possible role of this mechanism in fever, a condition fundamentally different from “physiological” hyperthermia, especially when it occurs in brain – damaged patients.  In our investigation we retrospectively analysed the results of direct recordings of cerebral temperature within the subdural space (T_sd) and within the brain parenchyma (T_br−16 cases) in 63 unanaesthetized patients following neurosurgical procedures, including 23 with fever >38 °C. The differences between trunk temperature, measured in the rectum (T_re) or in the oesophagus (T_es), and the intracranial temperature, were calculated in all subjects. A statistically significant reduction of these differences, in step with increasing fever, would be compatible with demonstrating a process of selective brain cooling.  The offsets T_re−T_sd, T_re−T_br, and T_es−T_sd were plotted against T_re over a wide range of body temperature and near zero correlation was found. This finding suggests that brain temperature in fever was not selectively suppressed by any specific thermolytic mechanism and that dissipation of the main bulk of cerebral metabolic heat both in normothermia and in fever depends on heat uptake by arterial blood.  The results suggest that the brain in fever can be seriously jeopardized by heat stress and no specific cooling mechanism exists, to reduce it below body temperature in feverish neurosurgical patients. T_br and/or T_sd remained the highest body temperature in 14 out of the 23 patients during fever.     

Expression of extra class I major histocompatibility antigens on T-cell acute lymphoblastic leukemia (ALL) lymphoblasts

The presence of extra HLA antigens has been demonstrated, serologically and biochemically, on the surface of lymphoblasts from a patient with acute lymphoblastic leukemia of the T-cell subtype (T-ALL). Family analysis of this patient revealed the presence of the expected antigens, plus an additional HLA antigen (A24) which could be demonstrated by cytotoxicity on the lymphoblasts. Absorption studies revealed that the lymphoblasts had the ability to remove cytotoxic antibodies from alloantisera; similarly, absorption of these alloantisera with normal cells removed the reaction against the extra antigen from the lymphoblasts. The extra HLA molecules were also demonstrated by one-dimensional IEF. Two heavy chain-like molecules, together with the beta 2m subunit, were obtained after removal of appropriate antigens from externally labeled leukemia cells by the use of monoclonal antibody W6/32, which detects a class I specific determinant. The pI of the one heavy chain was shown to be very similar to that of the serologically detected A24. Our data thus suggest that the extra antigens detected by serological reagents may have been due to activation of silent class I MHC gene(s) at the protein level.     

Effects of calcium channel modulators on the proliferation of mouse spleen lymphocytesin vitro

The effects of nimodipine (voltage-dependent calcium channel blocker), CGP 28392 and BAY K 8644 (novel dihydropyridine derivatives that are considered as calcium entry stimulators) on the spontaneous proliferation of mouse spleen lymphocytes were studiedin vitro. [³H]-thymidine incorporation into DNA of lymphocytes was used as an sensitive index of the cell proliferation. It has been found that nimodipine (10^–4 M–10^–6 M) significantly inhibited the [³H]-thymidine uptake in a dose dependent fashion with ED₅₀ value of 2.4×10^–5 M. Unexpectedly, CGP 28392 (10^–4 M–10^–7 M) acts as a calcium entry blocker and produces a strong inhibitory effect on lymphocyte proliferation (ED₅₀–2×10^–5 M). BAY K 8644 at a high concentration (10^–4 M) also has an inhibitory effect but at a lower concentration (10^–6 M–10^–10 M) significantly increased [³H]-thymidine uptake and abolished the inhibitory effect of nimodipine. This effect of nimodipine was also reversed by 5×10^–3 M calcium chloride. These findings indicate that calcium channel modulators can regulate the proliferation of mouse spleen lymphocytesin vitro.     

Analysis of intracranial pressure signals using artificial neural networks

Intracranial pressure (ICP) is influenced by an array of predictable and unpredictable factors. Statistical modelling of this signal has only limited applicability because of the significant load of stochastic components. We tested the efficiency of an alternative approach, based on the methodology of artificial neural networks (ANNs) in the on-line prediction of future values of ICP and in the classification of signal properties. Satisfactory accuracy of forecasting was achieved with the ANNs for a 3-minute prediction horizon, while the prediction quality with autoregressive models of statistical origin was proved unsatisfactory. The results obtained with the ANNs were further improved when signal pre-processing with wavelet transform was employed. Nevertheless, even with the ANN methodology, no sudden breakdowns in the ICP signal (which in this respect might be compared to a "catastrophe") can be forecast with any practical applicability. We therefore applied two ANN algorithms, oriented at classification and discrimination of the global properties of the ICP signal. The neural network was expected to discriminate those sets of signal properties, which were assumed to correspond to certain clinical conditions of the patient. In a "dynamic pattern classification" the network was presented with several sections of ICP records. This was combined with information about the assignment of a given record to one of four arbitrary classes of danger. In this mode no data pre-processing was carried out, in contrast to our second approach, in which the signal was pre-processed with statistical analyses and only these intermediate coefficients were fed to the ANN classifier. The results obtained with both classification methods at their present stage of training were similar and approximated to a 70% rate of judgements consistent with expert scoring. Nevertheless, the method based on the assessment of global parameters of the ICP record seems more promising, because it leaves the possibility of extending the set of training data by information from other diagnostic modalities. The study aims towards the development of a pseudo-intelligent computer expert system, which has would be taught salient links between data extracted from the ICP signal and higher- order data, which contributed to the expert score. Hence the system would be able to make decisions on the basis of a reduced set of input information, available from a standard monitoring modality.     

Intracranial Pressure Processing with Artificial Neural Networks: Classification of Signal Properties

Intracranial pressure (ICP) is commonly used by neurosurgeons as a source of valuable information about the current condition of the neurosurgical patient. Nevertheless, despite years of effort, extracting clinically valuable information from the ICP signal is still problematical. Approaches, using current values of ICP, may fail to disclose imminent risk, because unpredictable factors can rapidly change the properties of the signal. An alternative approach is to determine some global characteristics of the signal within a longer time interval and such statistical analyses have been proposed by several authors. A further, rarely considered, problem is assessment of the results obtained from the point of view of their practical utility and/or such classification of the obtained properties of the signal that they correspond to certain clinical states of the patient. While this might be a typical task for discriminant analysis, we approached the analysis using an alternative methodology, that of computational intelligence, implemented in artificial neural networks (ANN). We tested two variants of the ANN algorithms for classification and discrimination of global properties of the ICP signal. In a "dynamic pattern classification" the network was presented with several sections of ICP records together with information from the expert-neurosurgeon, classifying 4 risk groups. In this mode no data pre-processing was carried out, in contrast to our second approach, in which the signal had been pre-processed using published statistical analyses and only these intermediate coefficients were fed into the ANN classifier. The results obtained with both classification methods at their current stage of training were similar and approximated to a 70% rate of judgements consistent with the expert scoring. Nevertheless, the method based on the assessment of global parameters from the ICP record looks more promising, because it leaves the possibility for modification of the set of parameters analysed. The new parameters may include information extracted not only from the ICP signal, but also from other diagnostic modalities, like colour coded Doppler ultrasonography. The ultimate goal of this work is to build up a pseudo-intelligent computer expert system, which would be able to reason from a reduced set of input information, available from a standard monitoring modality, because it had been taught salient links between these data and higher-order data, upon which expert scoring was based.     

Human Brain Temperature In Vivo: Lack of Heating During Color Transcranial Doppler Ultrasonography

This study was undertaken to assess the effect of ultrasound on human brain temperature in vivo. The investigation consisted of direct recording of intracranial temperature during color transcranial Doppler (TCD) sonography in a neurosurgical patient. The temperature was recorded from 3 thermocouples. One was implanted together with an intracranial pressure sensor into a surgically reduced intraparenchymal hematoma, the second was placed within the subdural space close to the temporal acoustic window, and the third was located extracranially at the outer surface of the temporal bone. Tympanic temperatures were also measured to give an approximation of global brain temperature. A 2.5-MHz transducer was used, and the system settings were as follows: spatial peak temporal average intensity = 234 mW/cm2 in B-mode at a maximum power of 32.3 mW and 2132 mW/cm2 in Doppler mode at a maximum power of 149.3 mW. Neither increase in the intraparenchymal brain temperature nor increase in the temperature at the bone/soft tissue interface was observed during 30 minutes of insonation. The ipsilateral tympanic temperature increased by only 0.06 degree C, and this value may be regarded as a measure of the overall increase in brain temperature. Passive cooling effect produced by the transducer, which was at ambient temperature, was found to reach the brain surface and to surpass any possible heating caused by the ultrasound. The results indicate that no noticeable increases in human brain temperature occur in response to ultrasound emitted by a color TCD device at high transmitter power settings within the diagnostic range.