Early Decay of Pain-related Cerebral Activation in Functional Magnetic Resonance Imaging: Comparison with Visual and Motor Tasks

Background: Although pain-related activation was localized in multiple brain areas by functional imaging, the temporal profile of its signal has been poorly understood. The authors characterized the temporal evolution of such activation in comparison to that by conventional visual and motor tasks using functional magnetic resonance imaging.

Methods: Five right-handed volunteers underwent whole brain echo-planar imaging on a 3 T magnetic resonance imaging scanner while they received pain stimulus on the right and left forearm and performed visually guided saccade and finger tapping tasks. Pain stimulus on the right and left forearm consisted of four cycles of 15-s stimulus at 47.2-49.0[degrees]C, interleaved with 30-s control at 32[degrees]C, delivered by a Peltier-type thermode, and visually guided saccade and finger tapping of three cycles of 30-s active and 30-s rest conditions. Voxel-wise t statistical maps were standardized and averaged across subjects. Blood oxygenation level-dependent signal time courses were analyzed at local maxima of representative activation clusters (t > 3.5).

Results: Pain stimulus on the right forearm activated the secondary somatosensory (S2), superior temporal, anterior cingulate, insular, prefrontal cortices, premotor area, and lenticular nucleus. Pain stimulus on the left forearm activated similar but fewer areas at less signal intensity. The S2 activation was dominant on the contralateral hemisphere. Pain-related activation was statistically weaker and showed less consistent signal time courses than visually guided saccade- and finger tapping-related activation. Pain-related signals decayed earlier before the end of stimulus, in contrast to well-sustained signal plateaus induced by visually guided saccade and finger tapping.     

Interleukin-1 alpha enhances hepatotoxicity of tumor necrosis factor-alpha in galactosamine-sensitized mice.

The possible involvement of interleukin-1 alpha (IL-1 alpha) in the pathogenesis of murine hepatitis model induced with galactosamine and lipopolysaccharide (LPS) was investigated. The injection of 10 ng/mouse of LPS in combination with 10 mg/mouse of galactosamine into mice induced hepatic damage at 24 hours. Treatment with anti-mouse IL-1 alpha antiserum 30 min before galactosamine/LPS injection showed a tendency to reduce the liver injury, while pretreatment with anti-mouse tumor necrosis factor-alpha (TNF) antiserum significantly protected mice from liver injury. The use of recombinant murine TNF, instead of LPS, in combination with galactosamine could elicit hepatic damage, whereas recombinant murine IL-1 alpha could not substitute for LPS. However, recombinant murine IL-1 alpha enhanced the hepatotoxic effect of recombinant murine TNF in galactosamine-sensitized mice. These results suggest that TNF plays a major role in the pathogenesis of galactosamine/LPS hepatitis in mice and that IL-1 alpha acts synergistically with TNF in this hepatitis model.     

Defective control of Epstein-Barr virus-infected B cell growth in patients with X-linked lymphoproliferative disease.

We studied the cellular function and lymphokine production of T cells from patients with X-linked lymphoproliferative disease (XLP) when activated by the challenge with Epstein-Barr virus (EBV) infection. We used an assay system in which T cells were stimulated with membrane antigens of autologous EBV-infected B lymphoblastoid cell lines (B-LCL) and we examined cellular and humoral factors derived from the stimulated T cells which control the growth of EBV-infected B-LCL. Immunoglobulin secretion from the autologous B-LCL was suppressed with radiosensitive suppressor cells in the patients with XLP. The degree of suppression was correlated with the immunoglobulin levels in the serum of the patients with acquired hypogammaglobulinaemia (P less than 0.05). In addition, T cells from the patients with XLP failed to produce interferon-gamma (IFN-gamma) (P less than 0.001). Moreover, the T cell supernatants from the patients with XLP were less potent to inhibit the B-LCL growth. This diminished inhibition of the B-LCL growth was correlated well with the decreased concentration of IFN-gamma in the T cell supernatants. These findings suggest that suppressor cells may be activated in the patients with the hypogammaglobulinaemia phenotype of XLP, but the frequent development of B cell lymphoma in hypogammaglobulinaemia indicate that immunoglobulin suppression may not exert enough pressure on the in vivo growth of EBV-infected B cells. The defective secretion of IFN-gamma may be, at least partially, responsible for the abnormal cytotoxic T cell and natural killer activities found in the patients with XLP, and may indicate the clinical evaluation about the preventive injection of IFN-gamma against the development of malignant lymphoma.     

Localization of somatostatin (SRIF) SSTR-1, SSTR-2 and SSTR-3 receptor mRNA in rat brain by in situ hybridization

In situ hybridization histochemistry was performed to analyse the distribution of the messenger RNA (mRNA) of three putative somatostatin (SRIF) receptors in rat brain, using oligonucleotide probes derived from the cDNA coding for SSTR-1, SSTR-2, and SSTR-3 receptors.SSTR-1 signals were found in layers VVI of the cerebral cortex, in primary olfactory cortex, taenia tecta, subiculum, entorhinal cortex, granular layer of the dentate gyrus, amygdala and cerebellar nuclei. Signals for SSTR-2 were found in the frontal cerebral cortex (layers IV, V and VI), taenia tecta, claustrum, endopiriform nucleus, locus coeruleus, medial habenula, subiculum, granular cell layer of the dentate gyrus and amygdala. High levels of SSTR-3 hybridization were found in the olfactory bulb, primary olfactory cortex, islands of Calleja, medial habenula, amygdala, granular layer of the dentate gyrus, various thalamic and pontine nuclei and in the granular and Purkinje cell layers of the cerebellum.The distribution of the hybridization signals of the oligoprobes is consistent with the labelling of specific SRIF binding sites in rat brain. Especially, SSTR-2 and SSTR-1 oligos seem to label regions in which SS-1 and SS-2 receptors, respectively, have been previously characterized in autoradiographical studies. The situation is less clear with SSTR-3 mRNA, since SRIF binding in adult rats is usually low or absent in cerebellum, although some cerebellar nuclei appear to be labelled in the adult. The localization of SSTR-1, SSTR-2 and SSTR-3 mRNAs suggests that SRIF receptor subtypes in rat brain show profound differences in their distribution and are involved in a variety of central, in addition to neuroendocrine, functions.Monique Rigo, who contributed very significantly to this work, died tragically on January 21, 1993 Correspondence to: D. Hoyer at the above address     

Clearance of Mucus from Endotracheal Tubes during Intratracheal Pulmonary Ventilation

Background: Intratracheal pulmonary ventilation (ITPV) is a form of tracheal gas insufflation in which all gas emerges in a cephalad direction from the tip of a reverse-thrust catheter positioned within an endotracheal tube. In vitro experiments have shown that this rapid gas flow, with 5 ml/h of normal saline added to the gas flow, continuously removes tracheal secretions from within the endotracheal tube. The authors evaluated its effectiveness to remove mucus in long-term studies in sheep.

Methods: Fourteen healthy sheep were tracheally intubated and ventilated for 3 days with ITPV or with volume-controlled ventilation. Measurements were made of the total amount of secretions within the endotracheal tubes (weight gain), the protein content within the endotracheal tubes, and the increase in resistance to constant air flow. The structure of the airways was examined grossly and histologically. Three additional sheep were ventilated for 24 h with ITPV, and Evans Blue dye was added to the saline to assess the distribution of the infused saline.

Results: There was significantly less mucus in endotracheal tubes of sheep ventilated with ITPV than with conventional ventilation, as shown by minimal weight gain (0.70 +/- 0.14 g vs. 2.44 +/- 0.81 g; P < 0.001), lower protein content (14.09 +/- 10.79 mg vs. 294.99 +/- 153.06 mg; P <0.001), and lower resistance to constant air flow (6.15 +/- 0.54 cm H2 O [center dot] l sup -1 [center dot] s sup -1 vs. 15.34 +/- 5.28 cm H2 O [center dot] l sup -1 [center dot] s sup -1; P < 0.001). Results of gross and histological examinations of the tracheas of animals in both groups were similar, and the tracheas were well preserved. More than 95% of the instilled saline was recovered during ITPV. Only traces of Evans Blue dye were found near the tip of the endotracheal tubes.     

Relation of Family History of Cancer and Environmental Factors to the Risk of Colorectal Cancer: A Case-control Study

The relation of a family history of cancer and environmentalfactors to colorectal cancer was investigated in a case-controlstudy conducted from 1992 to 1994 at 10 medical institutionsin Japan using a self-administered questionnaire, and 363 casesof colorectal cancer were compared with 363 controls matchedfor sex and age. A family history of colorectal cancer was positivelyassociated with colon cancer (odds ratio (OR)=2.0, 95% confidenceinterval(Cl)1.03–3.87) and rectal cancer (OR=2.1 Cl 0.94–4.48),but a family history of other cancers did not increase the risk.The proportion of patients with a family history of colorectalcancer within first-degree relatives was 12.4% — appreciablyhigher than figures previously reported in Japan. On the otherhand, the incidence of hereditary non-polyposis colorectal cancerwas 1.4%, and lower than previous estimates. Among dietary factors,a western-style diet significantly increased the risk of bothcolon and rectal cancer (OR = 2.3 Cl 1.30–3.88 and OR=2.1Cl 1.26–3.63, respectively). Consumption of rice was protectiveagainst both colon and rectal cancer(OR=0.5 Cl 0.31–0.82and OR = 0.3 Cl 0.18–0.65, respectively). Animal meat,oily food, fish, vegetables and fruit were shown to affect therisk, but no statistically significant correlation was found.Among other factors, constipation increased the risk of coloncancer (OR= 2.0 Cl 1.02–3.76) and consumption of coffeeraised the risk of rectal cancer (OR =1.7 Cl 1.07–2.82).Our findings suggest that a family history of colorectal canceris an important risk factor for this disease, and does not contradictthe hypothesis that the risk of colorectal cancer in Japan maybe influenced by westernization of lifestyle. However, we wereunable to find conclusive evidence that familial clusteringof this disease is strongly affected by environmental factorsor genetic diseases such as hereditary non-polyposis colorectalcancer.     

Effect of aortic valve replacement on left ventricular function in adult patients with aortic stenosis]

Echocardiographic and hemodynamic studies were obtained in 16 consecutive adult patients who underwent aortic valve replacement (AVR) with St. Jude Medical valve for aortic stenosis (AS). Three cases of congenital AS was included and two of them had undergone aortic valvotomy in childhood. One of 16 patients died due to late cardiac tamponade six weeks after AVR. Postoperative studies showed improved left ventricular (LV) functions. LV end diastolic and end systolic diameter (LVDs and LVDs) fell from 50.3 and 38.2 to 44.6 and 31.6 mm respectively (p less than 0.05). Fractional shortening (%FS) rose from 26.5 to 32.2% (p less than 0.05). End systolic wall stress (ESWS) fell from 126.2 to 69.6 k dynes/cm2 (p less than 0.01). Cardiac index and pulmonary arterial wedge pressure improved from 3.4 and 14.4 to 3.6 l/min/m2 and 10.5 mmHg respectively (ns). Preoperatively, six were functional class II, eight were class III and one was class IV (New York Heart Association classification). Postoperative improvement was as follows, eight: class I, seven: class II. In four cases, preoperative echocardiography revealed most depressed LV function in %FS (smaller than 21%) and ESWS (greater than 140). Postoperatively they improved from 18.3 and 164 to 26.0% and 72.8 k dynes/cm2 respectively. These results suggested that depressed LV function in the patients with longstanding AS was largely related to limited preload reserve due to LV enlargement and mechanical unloading of LV (correction of afterload mismatch) resulted in improvement of LV function. In conclusion, LV dysfunction owing to AS alone is reversible and AVR results in great clinical improvement.