Structure-activity relationship of macrocyclic and linear gadolinium chelates: Investigation of transmetallation effect on the zinc-dependent metallopeptidase angiotensin-converting enzyme

Transmetallation between commercially available solutions of gadolinium (Gd) chelates and the zinc (Zn)-dependent angiotensin-converting enzyme (ACE) was investigated. In vitro, the strongest inhibitions were observed for the linear Gd complexes, Gd diethylene-triamine pentaacetic acid (DTPA) bis-methylamide (BMA) (IC₅₀ = .016 ± .006 mmol/1) and Gd-DTPA (IC₅₀ = .350 ± .034 mmol/1). The two macrocycles Gd tetraazacyclododecane tetraacetic acid (DOTA) and Gd-HP-DO3A were similar and 400 times less active than Gd-DTPA-BMA. These effects were mainly due to the presence of free ligand for DTPA and calcium (Ca) chelate in the case of DTPA-BMA because the addition of Zn²⁺ in the same quantities suppresses their inhibitory effects. In vivo, these two solutions of linear Gd chelates significantly inhibited ACE activity (Gd-DTPA: 67 ± 9% versus baseline; and Gd-DTPA-BMA: 73 ± 2% versus baseline at the clinical dose of .1 mmol/kg), whereas no significant effect was observed for the two macrocyclic chelates Gd-DOTA and Gd-HP-DO3A. Formulating the Gd chelate solution with either an excess of free ligand or Ca chelate (to decrease Gd³⁺ release) in the case of linear Gd chelate may have deleterious biologic consequences.     

Hyperreactio luteinalis in a normal pregnancy: Sonographic and MRI findings

A case of hyperreactio luteinalis in an otherwise normal pregnancy is reported. Ascites was present, but no peritoneal implants or adenopathy were seen. Findings that would have suggested the correct diagnosis are the symmetrical and bilateral pattern of the mass, as well as the rather uniform size of the loculi, which were 1 to 3 cm in diameter.     

Définition et évolution du statut nutritionnel au cours d'une greffe osseuse allogénique (15 malades): Rôle de la nutrition parentérale et de l'apport azoté

Our work concerned 15 patients (9 males, 6 females) with a mean age of 29.5 years, having a hematologic malignant disease and undergoing allogenic bone marrow transplantation.We studied :

1. The metabolic disorders induced by the conditioning regimen (chemotherapy and total body irradiation) pregraft accompanying cytolysis (day −7, −5, −2).

2. The corrective effect of a total parenteral nutrition introduced 2 days before the transplantation and pursued during 30 days post-graft (day −2 to day 30).

3. The interest of a high calorie intake (BEE × 2) and, after randomisation, of a variable nitrogen intake (24% of the total calorie intake for group A [8 patients] and 14% for group B [7 patients]). The patient characteristics of these two groups were closely comparable. Urinary parameters were studied daily (3-methylhistidine, cratinine, nitrogen) and blood parameters weekly (transferrin, pre-albumin, albumin, retinol binding protein).

We observed globally :

-- An excellent result of the nutritional support without significant weight loss;

-- protein catabolism stopped with a recovery of synthesis of RBP after day 7 and pre-albumin from day 7;

-- a decrease in muscle catabolism.

The randomized study showed :

-- a significant difference in nitrogen excretion between group A and group B;

-- earlier and better protein synthesis recovery in group A, particularly with regard to RBP and pre-albumin.

In conclusion, we recommend for the patients undergoing bone marrow transplantation :

-- nutritional support should be introduced before the conditioning regimen;

-- a high calorie intake (BEE × 2) with a nitrogen intake between 14% and 24% of the total calorie intake;

-- cyclic parenteral nutrition should be pursued during the second and third month post-graft.

Family management of schizophrenia: A comparison of behavioral and supportive family treatment

This paper reports a comparison of behavioral and supportive family treatment for family management of schizophrenia. The family project applied two psychoeducational approaches to a highly treatment resistant population of young adults afflicted with chronic mental illness. The study compares and contrasts the effects of behavioral and supportive family management programs on clinical outcomes. Clinical improvements were associated with both family interventions. Discussion is provided on the relevance of this work to the growing body of evidence concerning the efficacy of psychoeducational family intervention for the management of schizophrenia.     

An armoured endotracheal tube obstruction in a child

The case of a child whose tracheal tube became obstructed intraoperatively 30 minutes after intubation is reported. It appears that this obstruction was related to the development of bubbles within the walls which expanded upon exposure to nitrous oxide and diffusion of that gas into the bubbles. The authors want to point out the risk of gas diffusion into the walls of the tube and the possibility that repeated sterilization may enhance the development of bubbles. Les auteurs rapportent l’observation d’un enfant de sept mois dont la sonde tracheale s’est obstruée 30 minutes après l’intubation. Cette obstruction était due à l’expansion de bulles incluses dans la paroi du tube après exposition au N₂O et diffusion de celui-ci à l’interieur des bulles. Ils accusent également la stérilisation répétée de la sonde armée (contre l’avis du constructeur) d’avoir favorisé le développement de ces inclusions bulleuses.     

Evidence for monoaminergic involvement in triadimefon-induced hyperactivity

Triadimefon is a triazole fungicide that produces hyperactivity in both mice and rats similar to that seen following administration of compounds with catecholaminergic activity (e.g., d-amphetamine). To determine whether the triadimefon-induced hyperactivity is due to an action on CNS catecholaminergic systems, we evaluated the effects of combined treatment of triadimefon with either the tyrosine hydroxlase inhibitor d,l--methyl-p-tyrosine methyl ester HCl (MPT) or the amine depletor reserpine. Adult male Long-Evans hooded rats, approximately 70 days of age were used. Dosage-effect functions were determined for MPT (0–200 mg/kg IP), reserpine (0–2.5 mg/kg IP), d-amphetamine (0–3 mg/kg IP), and methylphenidate (0–40 mg/kg IP). Motor activity was measured as photocell interruptions in figure-eight mazes. The interaction between triadimefon and MPT was determined with the following groups: 1) vehicle control; 2) 200 mg/kg triadimefon PO; 3) 100 mg/kg MPT; and 4) both MPT and triadimefon. A similar design was used to determine the interaction between triadimefon and reserpine (0.62 mg/kg), MPT and d-amphetamine (1.5 mg/kg), and reserpine and methylphenidate (5.0 mg/kg). In the first experiment MPT did not block the increased motor activity produced by triadimefon (i.e., both triadimefon alone and MPT in combination with triadimefon produced significant increases in motor activity). MPT did, however, block d-amphetamine-induced hyperactivity. Since MPT did not antagonize the effect of triadimefon, these data suggest that increased motor activity produced by triadimefon is not mediated through release of newly synthesized catecholamines. In contrast, pretreatment with reserpine blocked the hyperactivity induced by both triadimefon and methylphenidate, which suggests that triadimefon-induced hyperactivity may be due to an interaction with CNS catecholamines stored in reserpine-sensitive pools.The research described in this article has been reviewed by the Health Effects Research Laboratory, US Environmental Protection Agency, and approved for publication. Approval does not signify that the contents necessarily reflect the views and policies of the Agency nor does mention of trade names or commercial products constitute endorsement or recommendation for use. Presented in part at the Annual Meeting of the Society for Neuroscience, New Orleans, LA, November, 1987     

Validating signals of ovulation: Do women who think they know,really know?

This study was carried out to test whether women who think they know when they ovulate, really know. Fifty-three women of age 18.7 to 46.1 (mean age 28.4 years) participated in initial interviews about ovulation. Criteria for recruitment included perceived ovulation, regular menstrual cycles, and not using hormonal contraception. Women collected and refrigerated urine samples from day 5 until they thought they ovulated. Samples collected within 48 h of the perceived signal were then tested for a pre-ovulatory LH surge. Of the 53 original participants, 36 women provided urine samples for 1-6 cycles, so that 87 cycles were tested. Subjective signals of ovulation varied between women and between cycles but included abdominal pain and changes in cervical discharge, libido, and mood. Of the 87 cycles tested, during which women identified one or multiple signals of ovulation, 37 of the 87 urine specimens tested positive for an LH surge for a concordance rate of 42.5%. Using the first tested cycle from the 36 women who provided urine specimens, 13 of those specimens demonstrated an LH surge, for a concordance rate of 36.1%. That rate dropped to 28% (7/25) when women who used basal body temperature as an ovulatory signal were excluded. Finally, the mean level of accuracy among the 15 women who contributed 3-6 urine specimens for testing was 48.9%. The results of this study demonstrate a low degree of concordance between LH surge and perceived ovulation among women who think they know when they ovulate. The most motivated study participants were right about half of the time. Although there is variation among women in their ability to know when they ovulate, this study suggests that, for most women, ovulation is concealed.     

Collaboration--a new IT-service in the next generation of regional health care networks

During the past 10–15 years, Regional Health Care Networks (RHCN) have been established in many regions throughout the world. RHCN build on well-known techniques, methodologies and appropriate standards. Most of the European Countries today have set up IT strategic plans that focus on the establishment of RHCN. The benefits of having access to all relevant information are tremendous and contribute to cost-effective and coherent health services. By the rapid spread and use of Internet, technology has made it possible to interconnect all kinds of applications. In 2000, the most experienced regions in Europe joined PICNIC, a European project to develop the Next Generation Regional Health Care Networks and to support their new ways of providing health and social care. The previous generation of Regional Health Care Networks supported the interconnection of applications by transfer of messages. Messaging is an effective means of integration for isolated high-specialised systems that only need to exchange data. This service will continue to be one of the most important services in the future health care networks. However, tighter coupling may be desirable in some instances to avoid replicating the same functionality in several applications. In other words, certain services can be common and used by a number of applications instead of building that service inside each application. These common services are called middleware services. In PICNIC (http://www.medcom.dk/picnic), a new middleware Collaboration IT service has been identified and developed. This service allows the end users to perform real-time clinical collaboration, with exchange of text, structured data, voice and images across the limits of a single region. A clinical collaboration is associated with the shared clinical context to provide a record of relevant clinical information and facilitates synchronous as well as asynchronous collaboration. This new IT service builds on the increasing popularity of instance messaging and presence systems that facilitate smooth transition between synchronous and asynchronous interaction. The new Collaboration IT service is expected to have a strong impact on the practice of health care in the next generation of Regional Health Care Networks.     

Band-pass response properties of rat SI neurons

Rats typically employ 4- to 12-Hz "whisking" movements of their vibrissae during tactile exploration. The intentional sampling of signals in this frequency range suggests that neural processing of tactile information may be differentially engaged in this bandwidth. We examined action potential responses in rat primary somatosensory cortex (SI) to a range of frequencies of vibrissa motion. Single vibrissae were mechanically deflected with 5-s pulse trains at rates /=3 Hz. In contrast with this low-pass feature of the response, several other characteristics of the response revealed bandpass response properties. While average evoked response amplitudes measured 0-35 ms after stimulus onset typically decreased with increasing frequency, the later components of the response (>15 ms post stimulus) were augmented at frequencies between 3 and 10 Hz. Further, during the steady state, both rate and temporal measures of neural activity, measured as total spike rate or vector strength (a measure of temporal fidelity of spike timing across cycles), showed peak signal values at 5-10 Hz. A minimal biophysical network model of SI layer IV, consisting of an excitatory and inhibitory neuron and thalamocortical input, captured the spike rate and vector strength band-pass characteristics. Further analyses in which specific elements were selectively removed from the model suggest that slow inhibitory influences give rise to the band-pass peak in temporal precision, while thalamocortical adaptation can account for the band-pass peak in spike rate. The presence of these band-pass characteristics may be a general property of thalamocortical circuits that lead rodents to target this frequency range with their whisking behavior.     

High frequency of precancerous lesions of gastric cancer associated with Helicobacter pylori and response to treatment,in Chiapas,Mexico

Stomach cancer is the second cause of death in Mexico in patients with malignant tumors. This disease represents a public health problem. A strong association has been described between chronic infection with Helicobacter pylori and gastric cancer. This malignancy is preceded by a series of preneoplastic conditions, including chronic atrophic gastritis (CAG), intestinal metaplasia (IM), and dysplasia. The objective of this study was to establish the prevalence of preneoplastic conditions associated with infection of Helicobacter pylori in the state of Chiapas and its eradication with antibiotics. Persons infected with Helicobacter pylori and with CAG were identified by serology against CagA protein and serologic levels of gastrin. An endoscopy with biopsy was performed at the beginning of the study, and at 6 weeks and 1 year thereafter. A total of 281 people were enrolled and randomly assigned to treatment or placebo group. CAG was found in 59%, IM in 51%, and dysplasia in 13%. In intent-to-treat and per-protocol analysis, Helicobacter pylori was eliminated in 70 and 76%, respectively. These results indicate high frequency of preneoplastic conditions associated with Helicobacter pylori and an excellent eradication rate. They also offer a possible alternative for preventing gastric cancer.