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Biomedical subjects

S Puig

Publications and source records attributed to S Puig.

At least 91 records · Page 5Linked to original sources

Differential diagnosis of atypically located single or double hot spots in whole bone scanning.

UNLABELLED: Our study assessed the predictive value of atypically located hot spots in routine 99mTc-DPD (3,3 diphosphono-1, 2-propane dicarboxylic acid tetrasodium salt) bone scanning for osseous tumor spread in patients with a history of malignant tumor. METHODS: Of 1286 scans in consecutive patients with a history of malignant tumor, but with no current evidence of osseous tumor spread, 172 displayed one or two hot spots in the following locations: transverse process of a single vertebra, manubriosternal junction, unilateral process of L5/S1, unilateral shoulder, costal cartilage, single rib, and unilateral sternoclavicular joint. The final diagnosis could be established by a control bone scan after at least 6 mo, biopsy and/or postmortem, respectively, in 135 patients. RESULTS: Of the atypical hot spots, 11.1% were the first indication for osseous tumor spread. This diagnosis was most probable for single hot spots in the rib (25%) and shoulder (21%). Conversely, hot spots in the sternoclavicular joint never indicated malignancy. CONCLUSION: The likelihood of atypically located isolated hot spots indicating osseous tumor spread is higher than expected during routine investigations in patients with a history of malignant tumor but no current evidence for malignant disease. Only hot spots in the sternoclavicular joint did not indicate metastatic disease in our study.

Bone Neoplasms↗

Comparison and histopathological correlation of three parathyroid imaging methods in a population with a high prevalence of concomitant thyroid diseases.

The aim of this prospective study was to evaluate the diagnostic utility of a technetium-99m sestamibi dual-phase protocol enhanced by single-photon emission tomography (SPET) and semiquantitative analysis in comparison to established preoperative staging procedures in patients with primary hyperparathyroidism. Twenty-eight (50%) out of 56 patients had superimposed thyroid disease, and 12 patients had previously undergone neck surgery. Visual and semiquantitative analysis of planar 99mTc-sestamibi dual-phase imaging, SPET of the delayed phase, ultrasonography, and thallium-201 chloride-technetium-99m pertechnetate subtraction scintigraphy was further correlated with the histopathological examination of the surgical specimens. 99mTc-sestamibi dual-phase imaging achieved the highest sensitivity for side localization and precise localization compared with 201Tl-99mTc subtraction scintigraphy and ultrasonography, but the differences reached statistical significance only in comparison to ultrasonsography. Semiquantitative analysis did not enhance sensitivity. Adenoma detection by 99mTc-sestamibi dual-phase imaging was only correlated to serum calcium levels and osteocalcin, not to cell density or oxyphil cell count (SPET yielded additional information for the exact topographical localization of the parathyroid tumour in 22 (39%) patients with superimposed thyroid disease or previous neck surgery but did not enhance the overall detection rate.

Female↗

Inherited susceptibility to several cancers but absence of linkage between dysplastic nevus syndrome and CDKN2A in a melanoma family with a mutation in the CDKN2A (P16INK4A) gene.

Genetic predisposition plays an important role in the development of nearly 10% of cases of cutaneous malignant melanoma (CMM). The CDKN2A gene has been described as responsible for melanoma susceptibility in a proportion of families with CMM linked to 9p. CDKN2A encodes a cyclin-dependent kinase inhibitor also implicated in the carcinogenesis of several sporadic tumors. Even though the incidence of other cancers is higher in CMM families, pancreatic adenocarcinoma is the only other well demonstrated cancer associated with CDKN2A mutations in some CMM pedigrees. We describe a family with four cases of CMM, eight patients affected by other cancers, and nine patients affected by dysplastic nevus (DN) syndrome. A CDKN2A frameshift mutation (358delG) was present in all the CMM patients, in at least three of the patients with other cancers (CDKN2A status is unknown in four patients), and in only two of the DN patients (CDKN2A status is unknown in one patient). An absence of linkage between chromosome 9p markers and the 358delG CDKN2A mutation and DN was detected, indicating genetic heterogeneity for DN and CMM in this family. The study strongly suggests that CDKN2A mutations are involved not only in the predisposition to CMM but also to several other types of cancer.

Adult↗

Confirmation of a double-hit model for the NF1 gene in benign neurofibromas.

Neurofibroma is a benign tumor that arises from small or large nerves. This neoplastic lesion is a common feature of neurofibromatosis type 1 (NF1), one of the most common autosomal dominant disorders. The NF1 gene codes for a protein called "neurofibromin." It possesses a region that shares a high homology with the family of GTPase-activating proteins, which are negative regulators of RAS function and thereby control cell growth and differentiation. The evidence points to the NF1 gene being a tumor-suppressor gene. NF1 patients also have an increased incidence of certain malignant tumors that are believed to follow the "two hit" hypothesis, with one allele constitutionally inactivated and the other somatically mutated. Recently, somatic loss of heterozygosity (LOH) has been described for neurofibromas, and mutations in both copies of the NF1 gene have been reported for a dermal neurofibroma. The aim of our study was the analysis of the NF1 locus in benign neurofibromas in NF1 patients. We performed LOH analysis on 60 neurofibromas belonging to 17 patients, 9 of them with family history of the disease and 8 of them sporadic. We have analyzed five intragenic NF1 markers and six extragenic markers, and we have found LOH in 25% of the neurofibromas (corresponding to 53% of the patients). In addition, we found that in the neurofibromas of patients from familial cases the deletions occurred in the allele that is not transmitted with the disease, indicating that both copies of the NF1 gene were inactivated in these tumors. Therefore, the recent reports mentioned above, together with our findings, strongly support the double inactivation of the NF1 gene in benign neurofibromas.

Alleles↗

Formalin-evoked activity in identified primary afferent fibers: systemic lidocaine suppresses phase-2 activity.

Formalin injected subcutaneously into the paw is a frequently used pain assay; it evokes an initial period of licking and flinching followed by a period of quiescence and last by a second period of intense and protracted licking and flinching. The prominent second phase is believed to reflect the development of a central (spinal cord) facilitation. This conclusion is based on the assumption that formalin evokes an initial burst of activity in fine afferent fibers, followed by prolonged low levels of activity in C fibers. Detailed reports substantiating this essential assumption have not been published. Thus, we recorded in situ from single sural nerve fibers, identified by their conduction velocity and modality, in the barbiturate anesthetized rat. Following formalin (2.5%, 50 microliters) injection into their receptive fields, phase-1 activity was prominent in A beta and A delta fibers as well as in high-threshold C nociceptive afferent fibers. Phase-2 activity was observed in A delta fibers with receptive fields in hairy skin and in all mechanically sensitive C fibers. Mean phase-2 activity in these fibers was 1/2-2/3 of the magnitude achieved in phase 1. Mechanically insensitive fibers and A delta and C fibers with receptive field centers outside of the injection zone began firing 15 min or more post-injection and would contribute to phase-2, but not phase-1, behavioral activity. Intravenous infusion of low doses of lidocaine yielding plasma levels of 3.6-7.9 micrograms/ml administered during phase 2 blocked formalin-evoked activity in primary afferent fibers in a dose-related fashion without blocking either electrically or mechanically evoked activity. Effective plasma doses were comparable to those found to relieve neuropathic pain. These data indicate that phase 2 in the formalin test is more closely related to ongoing afferent input than had previously been thought.

Anesthetics, Local↗

Neuronal model of tactile allodynia produced by spinal strychnine: effects of excitatory amino acid receptor antagonists and a mu-opiate receptor agonist.

Touch evoked agitation (allodynia) can be induced by spinal delivery of strychnine and this effect is antagonized by intrathecal NMDA and non-NMDA receptor antagonists, but not by mu-opiate receptor agonists. In this study, we sought to characterize the effect of focal glycine-receptor inhibition on spontaneous and evoked activity in dorsal horn neurons of the chloralose-anesthetized cat. Strychnine (1 mM) applied near the neurons through a dialysis fiber caused an enhanced response to hair deflection, enlargement of the low threshold receptive fields and in some cells, an increase in afterdischarge. These changes were observed only in cells that were activated by both hair deflection and high intensity mechanical stimulation. Subsequent co-administration of an NMDA receptor antagonist (AP-7, 2.0 mM) preferentially blocked strychnine-associated effects without changing the original receptive field characteristics. Co-administration of a non-NMDA excitatory amino acid receptor antagonist (CNQX, 1 mM) with the strychnine served to block low (brush) and high intensity (pinch) afferent input. In contrast, addition of a mu-opiate receptor agonist (alfentanil 2.4 mM) to the strychnine perfusate selectively reduced responsiveness to high intensity stimulation, while having no effect on the exaggerated response to hair deflection. Given the functional and pharmacological similarity of the effects of spinal strychnine to post-nerve injury states in man, disinhibition due to a loss of glycinergic input may be associated with large myelinated fiber-mediated nociceptive states. Consistent with these data is the contention that under normal circumstances, afferent hair follicle input onto convergent neurons is regulated by a tonic glycinergic circuit. Removal of this regulatory influence leads to a magnification of low threshold tactile throughput in dorsal horn. This model may help to provide pharmacological insights into more efficacious treatments for such pain states that are relatively refractory to opioid therapies.

2-Amino-5-phosphonovalerate↗

Articular muscle of the knee: a muscle seldom recognized on MR imaging.

OBJECTIVE: We studied the MR imaging characteristics of the articular muscle of the knee, an important but seldom recognized structure of the distal thigh and knee. SUBJECTS AND METHODS: We used a 1.5-T system to prospectively evaluate the articular muscle of the knee in five healthy volunteers (10 knees); then we retrospectively studied the knee examinations of 24 patients (30 knees). One reader made duplicate readings to prospectively assess the sagittal proton density-weighted and axial T1-weighted images of the healthy volunteers. Three independent readers retrospectively evaluated the sagittal proton density-weighted images of the 24 patients. RESULTS: The articular muscle of the knee was identified in 100% of prospective studies (10/10) and in 83% of retrospective studies (25/30). For the prospective study group, measurements (mean +/- SEM) were as follows: number of bundles, 2.4 +/- 0.68 (range, 1-4); length of uppermost bundle, 47.2 +/- 4.06 mm; width of origin, 8.6 +/- 0.79 mm; angle of origin, 11.4 degree +/- 1.29 degree; and cross-sectional bundle width, 19.8 +/- 2.05 mm2. CONCLUSION: The articular muscle of the knee can usually be identified by MR imaging as an independent entity, separate from the great (vastus) muscle group.

Adolescent↗

Automated high-performance liquid chromatographic assay for lesopitron, a novel anxiolytic, in human plasma using on-line solid-phase extraction.

A totally automated liquid chromatographic assay method based on a Prospekt solid-phase extraction unit was developed for the analysis of lesopitron and its metabolite 5-hydroxylesopitron in human plasma. On-line solid-phase extraction of lesopitron, 5-hydroxylesopitron and its internal standard in human plasma was carried out using C2 cartridges. After washing, the test substances were eluted with mobile phase onto an ODS-2 Inertsil column and measured by fluorescence detection. The total time for one analysis was 25 min. The method developed was selective and linear in the concentration range from 1 to 40 ng/ml for both parent drug and metabolite. Recovery of lesopitron and 5-hydroxylesopitron were higher than 80% and the quantification limits were 1 ng/ml for both compounds. Coefficients of variation obtained for precision parameters were all below 14.5% and 13.9% for parent drug and metabolite, respectively. Good values of accuracy were also obtained.

Anti-Anxiety Agents↗

The radial sensory nerve entrapped between the two slips of a split brachioradialis tendon: a rare aspect of Wartenberg's syndrome.

A retrospective study was designed to verify how often an anatomic variation caused the radial sensory nerve entrapment at the forearm (Wartenberg's syndrome). This variation, in which the superficial branch of the radial nerve emerges from under the fascia between two slips of a split brachioradialis tendon, was mentioned once in a clinical textbook as a basis for nerve entrapment but was found to occur in 5 of 150 dissected arms in 4 of 75 cadavers (3.3% of the investigated arms) in a recent anatomic study. To evaluate the incidence of this variation, 143 operative reports from patients who had Wartenberg's syndrome were reviewed. The variation was observed in seven patients. We conclude that any operation for Wartenberg's syndrome should include a thorough investigation of the site where the radial sensory nerve emerges from under the fascia and, if the nerve emerges through a split brachioradialis tendon, the anomalous tendon slip should be divided.

Forearm↗

In vivo electrochemical monitoring of serotonin in spinal dorsal horn with Nafion-coated multi-carbon fiber electrodes.

Biosensors sensitive for in vivo monitoring of serotonin (5-HT) in the CNS by differential normal pulse voltammetry were constructed by coating treated multicarbon fiber electrodes (mCFEs) with Nafion (N-mCFE). In vitro sensitivities of mCFE and N-mCFE were compared in solutions ranging from 5 nM to 20 microM of uric acid (UA), 5-hydroxyindoleacetic acid (5-HIAA), and 5-HT. The mCFEs were three to seven times less sensitive for 5-HIAA or UA than for 5-HT. Nafion treatment dramatically decreased sensitivity for 5-HIAA and UA of N-mCFEs (approximately 10(3) times), whereas it remained in the nanomolar range for 5-HT. In vivo, in the dorsal horn of the lumbar spinal cord of anesthetized rats, the monoamine oxidase inhibitor clorgyline (10 mg/kg i.p.) produced a reduction (55 +/- 3% at 180 min) of peak 3 of oxidation current (characteristic of 5-hydroxyindoles) monitored with mCFEs, but with N-mCFEs (in this latter case the peak was termed 3N) peak 3N increased to 135 +/- 5% at 180 min. The 5-HT release-inducer p-chloroamphetamine (PCA; 6 mg/kg i.p.) induced a slight (12 +/- 3% at 150 min) decrease in peak 3 measured with mCFEs, whereas with N-mCFEs PCA induced a rapid increase of peak 3N (137 +/- 6% at 90 min). The xanthine oxidase inhibitor allopurinol (10 mg/kg i.p.) produced a decrease (30 +/- 3% at 180 min) in peak 3 (mCFEs), but peak 3N (N-mCFEs) was not affected (106% at 180 min). After pretreatment with allopurinol, PCA also produced an increase (135 +/- 6% at 90 min) in peak 3N.(ABSTRACT TRUNCATED AT 250 WORDS)

Allopurinol↗

Chromosome 9p deletions in cutaneous malignant melanoma tumors: the minimal deleted region involves markers outside the p16 (CDKN2) gene.

We have analyzed 12 microsatellite markers on chromosome 9p in 54 paired cutaneous malignant melanoma (CMM) tumors and normal tissues. Forty-six percent of the tumors, including two in situ CMMs, showed loss of heterozygosity (LOH) at 9p. Only one tumor was homozygously deleted for 9p markers. The smallest deleted region was defined by five tumors and included markers D9S126 to D9S259. Loss of eight or more markers correlated significantly with worse prognosis (P < .002). Among the primary tumors, 87.5% of those with large deletions have a high risk of metastasis, as compared with only 18% of those without deletions or with loss of fewer than 8 markers (P < .001). It was not possible to demonstrate homozygous deletions of p16 in any of the CMM tumors. In four tumors, the LOH for 9p markers did not involve p16. The reported data suggest the existence of several tumor suppressor genes at 9p that are involved in the predisposition to and/or progression of CMM and exclude p16 from involvement in the early development of some melanoma tumors.

Base Sequence↗

[Satisfaction of paid thrombocyte donors with instrumental thrombocytapheresis].

OBJECTIVE: The increasing need for single-donor platelet concentrates makes it necessary to motivate platelet donors to donate regularly. The authors examined the contentment of existing donors in order to create a basis for improvements and to raise the attractiveness of donation. DESIGN: Open empirical data acquisition. SETTING: Institute for Transfusion Medicine at the General Hospital Vienna. PARTICIPANTS: 211 platelet donors. INTERVENTIONS: Interview with a self-developed questionnaire. RESULTS: Whereas donors rate the work of the staff as being very good, they are less content with the surroundings in the pheresis unit. Younger and higher-educated donors as well as persons who have been donating for less than 5 years show more negative ratings than comparable groups. The financial compensation is important to ensure a high donation frequency. CONCLUSIONS: The attractiveness of donation could be raised by improving certain aspects of donation. In order to ensure a high donation frequency donors should be granted a financial compensation, as otherwise particularly younger donors, who are more likely to be seronegative for antibodies to CMV, would not donate any more or at least not that often.

Adult↗

Superficial branch of the radial nerve emerging between two slips of a split brachioradialis muscle tendon: a variation of possible clinical relevance.

One hundred and fifty upper extremities of 75 nonrandomized human cadavers were dissected to study the topographical relationship between the brachioradialis muscle tendon (BRMT) and the superficial branch of the radial nerve (SBRN). A split BRMT was found in nine arms, while in five of those nine arms the SBRN emerged from under the brachioradialis muscle between the two slips of a divided BRMT to become superficial. This topographical relationship is mentioned sparsely in very old literature, yet its frequency has not been studied before. Further clinical investigations should be undertaken to study the clinical relevance of the above-mentioned topographical relationship.

Female↗

Effect of RU 24969 on 5-HT metabolism in the medullary dorsal horn as studied by in vivo voltammetry.

The effect of i.p. administration of the preferential 5-HT1B agonist 5-methoxy-3(1,2,3,6-tetrahydro-4-pyridinyl)-1H-indole succinate (RU 24969) (10 mg/kg) has been investigated by in vivo 5-hydroxyindole electrochemical (peak 3) detection in the medullary dorsal horn (MDH) of acute anesthetized and unanesthetized freely moving rats. RU 24969 induced a significant decrease in peak 3 in the MDH of anesthetized rats. In freely moving animals, RU 24969 induced a biphasic effect. Thus, after the injection the curve remained above that of the saline group and returned to control levels up to 60 min. Subsequently the curve decayed to below the control values and rapidly plateaued for up to 180 min. The initial increase and the decrease thereafter were both statistically significant vs. saline. With reference to similar in vivo studies demonstrating the responsiveness of ascending serotonergic systems to RU 24969, it is concluded that the 5-HT metabolism in the serotonergic NMR-dorsal horn system is affected by this 5-HT1B agonist. However, the biphasic effect reported here in unanesthetized animals suggests that RU 24969 could act by two different ways on 5-HT metabolism and indicates that there could be a primary interaction of RU 24969 on the 5-HT uptake system (inhibition) which could, at first, prevail over the interaction with terminal autoreceptors.

Animals↗

Effects of tianeptine on 5-hydroxyindoles and on the morphine-induced increase in 5-HT metabolism at the medullary dorsal horn level as measured by in vivo voltammetry in freely moving rats.

The present study, by the use of in vivo electrochemical detection of 5-hydroxyindole (peak '3') in the bulbo spinal serotonergic system at the medullary dorsal horn (MDH) level, investigated the effects of the new tricyclic antidepressant (TCA) tianeptine, which has been shown to be a specific serotonin (5-HT) uptake enhancer. It was found that acutely administered tianeptine (10 mg/kg, i.p.) induced a marked significant increase in peak 3 within the dorsal horn, an in vivo observation which is in accordance with the biochemical properties of tianeptine as studied in forebrain structures. In addition, the effect of tianeptine on the morphine-induced increase in 5-HT metabolism was investigated, by comparison with the previous data obtained with the specific 5-HT uptake inhibitor femoxetine in the MDH. It was shown that tianeptine can display additive effect with morphine (10 mg/kg, i.p.) on 5-HT metabolism at the MDH level. These results are discussed in relation to the effects of classical TCAs and the particular properties of tianeptine.

Animals↗

Anticoagulants, antiaggregants or nothing following carotid endarterectomy?

Carotid endarterectomy (TEA) has proven to be beneficial for symptomatic patients. Anticoagulation (AC) and antiplatelet therapy (ASA) have been shown to prolong life following vascular surgery in patients with occlusive arterial disease (PAOD). To determine whether ASA or AC prolong life after TEA, retrospective analysis was undertaken, since cerebral haemorrhage is associated with the use of both drugs, especially AC. Between 1979-1986, 328 patients with stenotic lesions of the carotid bifurcation were operated upon electively. Patient survival and causes of death were the primary end points of the analysis. Recent data were obtained from the Austrian Central Bureau of Statistics. Cumulative survival rates were calculated by Kaplan-Meier estimation and differences determined by Breslow and Mantel tests. 36 patients were on AC, 157 on ASA and 135 remained without medication (0-group). Since the common risk factors in PAOD were unevenly distributed between groups, a stepwise Cox regression model was applied which revealed age (p < 0.01), cardiac pathology (p < 0.01) and diabetes (p < 0.05) as relevant for survival. Therefore, ASA patients and 0-group patients were selected and matched, employing the aforementioned prognostic criteria, and compared to the patients on long-term AC for various indications (vein bypass surgery, myocardial infarction, pulmonary embolism; i.e. data-matching). The median postoperative survival was 7.72 years for ASA and 8.48 years for AC, compared to 6.07 years for the 0-group (p = 0.0095 Breslow, p = 0.477 Mantel). There was no significant difference between AC and ASA treated patients. Irrespective of medication, the causes of death were well balanced, and no higher incidence of intracerebral haemorrhage was detected.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Effect of subcutaneous administration of the chemical algogen formalin, on 5-HT metabolism in the nucleus raphe magnus and the medullary dorsal horn: a voltammetric study in freely moving rats.

The effect of subcutaneous administration of the chemical algogen formalin, on serotonin (5-HT) metabolism in the nucleus raphe magnus (NRM) and the medullary dorsal horn (MDH) has been investigated using in vivo 5-hydroxyindole electrochemical (peak '3') detection with treated, multi-carbon fiber electrodes and differential pulse, or normal pulse, voltammetry in freely moving rats. The subcutaneous (s.c.) injection of 50 microliters of 10% formalin in the left forepaw was followed, at the NRM level, by a significant increase in the voltammograms as compared to controls (50 microliters of saline 0.9% s.c. in left forepaw) for about 70 min after the injection, before a return to control values. At the MDH level, the formalin injection induced no significant effect on peak 3, as compared to controls, during the first 70 min. After that, the voltammograms significantly increased and remained above controls for up to 180 min. Thus, the time-courses of NRM and MDH effects appear markedly different. These findings suggest that, depending on the anatomical level (NRM or MDH) and/or the period of observation, one can measure differences in the time-course of the increase in 5-HT metabolism in the NRM-dorsal horn serotonergic system by tonic noxious stimuli, such as the formalin test.

Animals↗