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Pressor effect of NG-nitro-L-arginine in pentobarbital-anesthetized rats.

The pressor effect of NG-nitro-L-arginine (L-NNA), a potent inhibitor of nitric oxide (NO) synthesis, was studied in pentobarbital anesthetized rats. Iv injections of L-NNA from 0.25 to 8 mg/kg caused bradycardia and a dose-dependent increase in mean arterial pressure (MAP) with a maximal response of 43 +/- 5 mmHg and ED50 value of 1.3 +/- 0.2 mg/kg. The time course of the response to the injection of a single dose of L-NNA was also determined. Peak response was reached 60 min after the injection of a single dose (4 mg/kg, iv) and the effect lasted greater than 5 h. The rising phase of the pressor response was accompanied by slight bradycardia while the recovery phase was associated with significant tachycardia. Iv injections of L-arginine (12.5-200 mg/kg) caused transient dose-dependent reductions in MAP. The pressor effect of L-NNA (4 mg/kg, iv bolus) was dose-dependently attenuated by L-arginine. The results show that L-NNA is an efficacious and long-acting pressor agent and are consistent with the hypothesis that endogenous NO plays an important role in the regulation of blood pressure.

Anesthesia↗

Independent time courses of supraspinal nociceptive activity and spinally mediated behavior during tonic pain.

The behavioral response to acute tissue injury is usually characterized by different phases, but the brain mechanisms underlying changes in pain-related behavior over time are still poorly understood. We aimed to analyze time-dependent changes in metabolic activity levels of 49 forebrain structures in the formalin pain model, using the autoradiographic 2-deoxyglucose method in unanesthetized, freely moving rats. We examined rats during the first phase of pain-related reactions ('early' groups), or during the third recovery phase, 60 min later, when the supraspinally mediated behavioral responses were reduced ('late' group). In the early groups, metabolic rates were bilaterally increased over control values in the periaqueductal gray, zona incerta and in several thalamic nuclei (anteroventral, centrolateral, lateral dorsal, parafascicular, posteromedial, submedius, ventromedial, and ventrobasal complex), as well as in the habenulae and in the parietal, cingulate, antero-dorsal insular, and anterior piriform cortex. A contralateral, somatotopically specific activation was found in the putative hindlimb representation area of the somatosensory cortex. In the late group, noxious-induced activation declined in most structures. However, metabolic rates were higher than controls in the periaqueductal gray and zona incerta and in two other structures not previously active: the prerubral area/field of Forel and the arcuate hypothalamic nucleus. These findings provide a time-dependent functional map of nociceptive and anti-nociceptive forebrain circuits during tonic pain. The parallel decrease in licking behavior and forebrain activity, at times when spinally mediated limb flexion responses were still present, suggests that endogenous antinociceptive systems may differently modulate spinal and supraspinal nociceptive networks following acute tissue injury.

Animals↗

Coma with abnormal movements and prolonged cognitive disturbances: a new subset of acute encephalopathy.

We describe two children who presented with an acute encephalopathy preceded by a prodromal illness. The disease was marked by an active phase of coma or confusion with abnormal motor movements, followed by a recovery phase with a rapid return of motor function and a gradual improvement in speech and social behavior. No cause was found. These may be additional representative cases of a new syndrome of encephalopathy which is characterized by a distinctive course and a relatively good prognosis.

Acute Disease↗

The evolution of a brain abscess the complementary roles of radionuclide (RN) and computed tomography (CT) scans.

Serial Tc-99m glucoheptonate brain scans demonstrated a brain abscess in a patient from the earliest phase of acute focal encephalitis (cerebritis) through the capsule formation and the recovery phase. The role of the RN and CT scans in the diagnosis of the early stage of cerebritis and the complementary nature of RN and CT scans in intracranial infections, particularly abscesses, are discussed. Guidelines for the use of RN and CT scans are suggested.

Brain Abscess↗

In vivo intestinal uptake of immunoreactive bovine albumin in piglet enteritis.

We examined the uptake of bovine serum albumin (BSA) from the intestine into the circulation of 3-week-old piglets infected with transmissible gastroenteritis virus. Transfer of immunoreactive bovine serum albumin (iBSA) from the intestinal lumen into the circulation was enhanced during both the early invasive phase of this viral enteritis (12-h postinoculation) and the diarrheal phase (84-h postinoculation). In some animals, enhanced uptake persisted into the recovery phase, 324 h after inoculation. Gel filtration studies suggested that iBSA had the molecular size characteristic of native BSA; no immunoreactive fragments of BSA were detected. Based on studies of two animals, the half-life of iBSA approximated that of porcine albumin. Further study is required to determine the immunological consequences of the enhanced uptake of protein occurring during viral infection of the intestine.

Animals↗

The use of the H*1 in predicting marrow recovery following ablative chemotherapy in leukaemia and lymphoma.

Twenty-three cytopenic episodes in 18 patients undergoing ablative chemotherapy for the treatment of leukaemia or lymphoma were monitored from commencement of treatment until recovery, by automated differential counts using the Technicon H*1 Autoanalyser, with particular reference to abnormal white cell flags and large unstained cell (LUC) percentage. The blast flag was indicated in this recovery phase in 100% of patients and in 85% this preceded bone marrow recovery (defined as neutrophil count greater than 0.5 X 10(9)/l) by a mean of 10 days. On average the blast flag was indicated for 8 days in total. Bone marrow function continued to improve in all patients with no evidence of relapse. An increase in the LUC percentage on the differential count reached a maximum at 18 days, 6 days prior to marrow recovery. The ability to detect impending marrow recovery by means of the positive blast flag, may be of great value when patients have been cytopenic for many days.

Autoanalysis↗

Metabolic, ionic, and electrical responses of gerbil brain to ischemia.

The effects of short- or long-term complete cerebral ischemia were studied in the gerbil brain using a multi-parameter monitoring system. Metabolic (NADH redox state) and hemodynamic responses were monitored by surface fluorometry-reflectometry. Ionic activities (K+ and pH) were measured by surface macroelectrodes. Electrical activity was evaluated by monitoring the general electrocorticogram (ECoG) as well as local DC steady potential (two sites). Two groups of gerbils were studied to compare the effects of 4-5 min occlusions with those of 30 min complete ischemia. During bilateral carotid artery occlusion the cortex is exposed to complete ischemia resulting in the complete depletion of O2 with attendant maximal reduction of NADH. Extracellular K+ began to increase as soon as energy reserves were decreased with a time course suggesting two different kinetic areas. Surface pH decreased very shortly after the occlusion. During the recovery phase, NADH was reoxidized soon after recirculation, whereas the pH and K+ recovery showed a short delay. ECoG did not recover even when all other parameters reached base-line levels. The recovery of all the measured parameters was correlated to the duration of the ischemic insult; i.e., the recovery from 30 min of ischemia took significantly longer than after 5 min of ischemia. We conclude that pH recovery depends on recirculation and adequate O2 supply to the tissue, whereas K+ recovery required not only an adequate O2 supply but also the integrity of the adenosine triphosphatase system.

Animals↗

Recovery from psychotic illness: a 15- and 25-year international follow-up study.

BACKGROUND: Poorly defined cohorts and weak study designs have hampered cross-cultural comparisons of course and outcome in schizophrenia. AIMS: To describe long-term outcome in 18 diverse treated incidence and prevalence cohorts. To compare mortality, 15- and 25-year illness trajectory and the predictive strength of selected baseline and short-term course variables. METHODS: Historic prospective study. Standardised assessments of course and outcome. RESULTS: About 75% traced. About 50% of surviving cases had favourable outcomes, but there was marked heterogeneity across geographic centres. In regression models, early (2-year) course patterns were the strongest predictor of 15-year outcome, but recovery varied by location; 16% of early unremitting cases achieved late-phase recovery. CONCLUSIONS: A significant proportion of treated incident cases of schizophrenia achieve favourable long-term outcome. Sociocultural conditions appear to modify long-term course. Early intervention programmes focused on social as well as pharmacological treatments may realise longer-term gains.

Adult↗

Management of a gunshot wound to the face resulting in a mandibular body fracture with burying of a bicuspid crown into the tongue.

Gunshot wounds to the maxillofacial region are unpredictable and run the gamut from minor injuries to severe mutilating and life threatening injuries. This patient although unfortunate to have been the victim of mistaken identify resulting in the gunshot wound, was fortunate that the bullet hit his bicuspid, which probably served to deflect its path away from vital structures, thus saving his life. This accounts for the buried bicuspid crown found in the midline of the body of the tongue. Rigid internal fixation of maxillofacial fractures minimizes risks to the airway that may occur if patients are in post-operative maxillo-mandibular fixation during the post-anesthetic recovery phase. In addition, the use of rigid internal fixation speeds up the recovery and the patient's ability to return to function after surgery. Above, we presented an interesting case of a mandibular anterior body fracture resulting from a gunshot wound in the face and resulting in the burying of a bicuspid crown in the substance of the tongue, treated under general nasoendotracheal anesthesia and the use of rigid internal fixation (EDCP).

Adult↗

Enhanced glomerular procoagulant activity and fibrin deposition in rats with mercuric chloride-induced autoimmune nephritis.

The mechanism involved in glomerular fibrin deposition was investigated during mercuric chloride (HgCl2)-induced autoimmune glomerulonephritis in the Brown Norway rat. To ascertain whether the local hemostatic system was activated secondarily to the immunological conflict, the ability of glomerular lysates to induce coagulation in vitro was assessed in treated and control rats. Glomerular procoagulant activity (PCA) of HgCl2-injected rats was measured on day 12 (latent phase of the disease), day 20 (acme), and days 32 and 42 (recovery phase) after the first mercury injection. PCA rose 3-fold (p less than 0.02) at day 20 and then almost returned to control values. Proteinuria, PCA, and the incidence of glomerular fibrin deposits peaked concomitantly at day 20. Glomerular PCA was characterized as thromboplastin. The number of Ia positive cells detected by monoclonal OX-6 antibody was not different from the control number at any phase of the disease; the number of macrophages per glomerular section detected by electron microscopy at day 20 in HgCl2-injected rats was 1.80 +/- 0.60, versus 0.30 +/- 0.11 in the controls. No correlation was found between glomerular PCA and either the number of monocytes/macrophages or of Ia-positive cells present in the glomeruli. Since glomerular PCA was maximal at the onset of fibrin formation in the glomeruli and then decreased toward its basal level, and since the fibrin disappeared, it is concluded that increased production of thromboplastin by glomeruli, with activation of the extrinsic coagulation pathway, may contribute to intraglomerular fibrin deposition in HgCl2-induced glomerulonephritis.

Animals↗

Regulation of thrombopoiesis: effects of the degree of thrombocytopenia on megakaryocyte ploidy and platelet volume.

We have established a murine model and techniques with which to serially study thrombocytopoiesis after induction of experimental immune thrombocytopenia of variable severity and duration. Bone marrow megakaryocyte ploidy distribution was determined by using unfractionated bone marrow, a polyclonal megakaryocyte-specific probe, and two-color, fluorescence-activated flow cytometry. With these techniques, the modal megakaryocyte ploidy class in normal murine bone marrow was 16N. Serial studies of bone marrow megakaryocyte ploidy after the induction of acute, severe thrombocytopenia (platelet count, less than 0.05 X 10(6) microL) demonstrated no detectable change in the ploidy distribution at 12, 24, and 36 hours after the onset of thrombocytopenia. At 48 hours, the modal ploidy class shifted from 16N to 32N, and the 64N class increased significantly (P less than .001). The ploidy distribution returned to normal 120 hours after the onset of thrombocytopenia. A lesser degree of thrombocytopenia (platelet count reduction to 0.100 to 0.200 X 10(6)/microL) delayed the modal ploidy class shift from 16N to 32N until 72 hours after the onset of thrombocytopenia. Chronic, severe thrombocytopenia (platelet count, less than 0.05 X 10(6)/microL for seven days) resulted in a modal ploidy class shift from 16N to 32N during the thrombocytopenic phase and an enhanced increase in the 64N megakaryocyte class during the recovery phase. Mean platelet volume (MPV) was simultaneously measured on isolated total platelet populations after induction of thrombocytopenia. MPV was significantly increased (P less than .001) as early as eight hours after the onset of acute, severe thrombocytopenia, 40 hours before a shift in the ploidy distribution. Mild thrombocytopenia (platelet count reduction to 0.400 X 10(6)/microL) was not associated with a ploidy shift but did result in a significantly increased MPV (P less than .001). These studies demonstrate that the temporal relationship and magnitude of the effects of thrombocytopenia upon megakaryocyte ploidy distribution are dependent upon the degree and the duration of the thrombocytopenic stimulus and that the effects of experimental thrombocytopenia on platelet volume and megakaryocyte ploidy are dissociated.

Acute Disease↗

[Recovery after ketamine-diazepam and thiopental-fentanyl-infusion anesthesia with jet-ventilation for laryngomicroscopy].

Using two infusion anaesthesiamethods for laryngomicroscopy in 187 non-selected patients we studied the recovery phase with the aid of a special questionnaire filled in by the recovery room nurse. Premedication was with Thalamonal and atropine. Muscle relaxation was achieved by a succinylcholine drip. Induction doses: fentanyl 0.05-0.1 mg and thiopental 3-5 mg/kg bodyweight (Th-group) or diazepam 10-20 mg and ketamine 1 mg/kg bodyweight (K-group). Infusion doses: Thiopental 11.7 mg/min. (Th-group) or diazepam 0.2 mg/min. and ketamine 2 mg/min (K-group). Anaesthesia lasted for 20-30 min. We observed and noted during recovery: Breathing, cough-frequency and -quality, alertness, reaction to speech and stimulation, orientation, motor behaviour and well-being. Anaesthesia was sufficient in both groups. The patients of the K-group woke up earlier and their laryngeal reflexes seemed to stabilize quicker than in the Th-group. Because of the elevation of blood pressure caused by the stimulation of the laryngoscopy both methods are not recommended for patients at risk from high blood pressure.

Adult↗

Blood pressure response to exercise in young subjects with and without parental history of hypertension.

We examined 150 young male adults in the Italian Air Force to evaluate the correlation between blood pressure (BP) response to bicycle exercise and early structural changes of the left ventricle and the carotid arteries. The subjects were divided into three subgroups: (1) borderline hypertensives; (2) normotensives having one or both parents with hypertension; (3) normotensives without family history of hypertension. All subjects underwent a submaximal exercise test, echocardiography and carotid ultrasonographic study. The echocardiographic examination showed no significant difference between the three subgroups, while the vascular ultrasonographic examination showed a significant difference in carotid thickness between borderline hypertensives and the two other groups. The exercise test induced an abnormal hypertensive response only in the borderline group. We also considered the variation of systolic BP between maximum stress and the 1st, 3rd, 5th and 8th minute of recovery phase. From our data it seems that more than the exercise test, recovery BP values may be suggestive of an exaggerated cardiovascular response.

Adult↗

Fractal analysis of lung alveoli during the acute phase vs. repair phase of an adenoviral infection in canines.

Acute viral respiratory infections are commonly associated with alterations in lung growth. Recently, fractal techniques have been demonstrated to show changes in alveolar perimeter after canine adenovirus type 2 (CAV2) infection in a beagle puppy model. In the present study, we investigated whether the fractal dimension (Df) of the alveolar perimeter was changed in the acute phase (2-3 weeks after inoculation, 131d CAV2 group) or during the recovery phase (approximately 22 weeks after inoculation, 235d CAV2 group) after a single bout of CAV2. There were sham CAV2 groups, 130d and 238d controls, corresponding to the CAV2 groups. The Df of alveolar perimeter length was significantly increased in the 235d CAV2 puppies compared to all of the other beagle puppy groups. On the other hand, the fractal dimensions for alveolar perimeter length for the other beagle puppy groups were very similar. In a related human study of patients (age range of 25 h to 19 y, N = 11), who died of non-respiratory causes, showed no consistent change in Df of alveolar perimeter length with normal lung growth and development. We conclude that fractal analysis of alveolar perimeter length can be used as an index of permanent lung injury after insult to the growing lungs.

Acute Disease↗

Serum potassium levels, red-blood-cell potassium and alterations of the repolarization phase of electrocardiography in old subjects.

Seventeen elderly patients are described, who showed minor changes in the e.c.g. recovery phase. Serum potassium levels appeared to be normal, but red-blood-cell potassium was found to be more or less markedly reduced. Restoration of the latter to normal values, which followed treatment with potassium salts was also associated with normalization of the e.c.g. pattern. These observations demonstrate that electrolyte disorders, and particularly hypokalaemia, may determine 'minor' alterations of repolarization much more frequently than is usually thought, and that determination of serum potassium levels is not a reliable tool for detecting potassium depletion, which is more accurately reflected by red-blood-cell potassium concentration.

Aged↗

Minimally invasive surgery for gastric cancer--toward a confluence of two major streams: a review.

The minimalization of therapeutic invasiveness in order to preserve quality of life (QOL) is a major topic in the management of early gastric cancer. After laparoscopic surgery for gastric cancer was introduced by Kitano et al. in 1991, an enthusiasm to develop laparoscopic procedures has grown steadily. In the initial phase, early gastric cancer limited to the mucosal layer with no risk of lymph node metastasis was treated by laparoscopic wedge resection or intragastric mucosal resection. Since technical and instrumental advances in endoscopic treatment were achieved by gastroenterologists, these cases can be managed by intraluminal endoscopic approaches. The attention of surgeons then shifted to more radical procedures such as laparoscopic gastrectomy with lymph node dissection, which is comparable to open surgery and can be indicated even in advanced cancer. Although this paradigm shift has already been realized in the field of colorectal surgery, we must pay attention to the particular biological nature of gastric cancer in terms of the potential of peritoneal dissemination. While early-phase recovery after surgery has been improved by laparoscopic surgery, preservation of late-phase QOL by function-preserving surgery is also essential in this regard; therefore, the sentinel node (SN) concept has been a much-discussed topic in gastric cancer surgery to approach this aspect. Recently, the validity of the SN concept has been demonstrated by a number of single institutional studies, and prospective multicenter trials are currently ongoing. Theoretically, various types of function-preserving surgery could be applied in cases of early gastric cancer with negative SNs as less invasive surgery to improve long-term QOL. Although we still have to solve several remaining issues in the treatment of gastric cancers, a confluence of these two major streams, laparoscopic surgery and sentinel node navigation surgery, would enable us to apply a novel individualized minimally invasive approach, both in terms of degree of incisional access and extent of function preservation.

Gastrectomy↗

Comparison of linear versus inverse exponential methadone reduction curves in the detoxification of opiate addicts.

A linear methadone detoxification procedure is compared with an inverse exponential reduction curve in a double-blind study. The inverse exponential curve resulted in withdrawal symptomatology which was significantly greater during the acute phase of the opiate withdrawal curve and was not significantly different during the recovery phase. There was no difference between groups in the time course of the withdrawal syndrome, in peak symptom severity, nor in patient compliance. Separate analyses for high-dose and for low-dose addicts show variation in the suitability of the two curves according to dose. The implications for future research and treatment of the opiate withdrawal syndrome are discussed.

Adult↗

The cost of residential addiction treatment in public housing.

The cost of providing addiction treatment services in a variety of settings is useful information for program administrators, policy makers, and researchers. This study estimates the economic costs of providing substance abuse treatment services at Safeport, a three-phase residential treatment program focusing on addicted women living in public housing. Economic (opportunity) costs are estimated for each phase separately and for the complete program. Results indicate that the total cost of providing treatment services at Safeport in 2001 was $1,325,235. This total cost comprises $549,737 for stabilization or early abstinence (Phase I), $400,098 for relapse prevention and self-sufficiency (Phase II), and $375,400 for independent living preparation and long-term recovery (Phase III). Average daily census (number of clients/families on a typical day) was just over 11 clients/families in each phase or 34 clients/families for the entire program. The average length of stay in the three phases of the program was 12 weeks for Phase I, 20 weeks for Phase II, 18 weeks for Phase III, and 50 weeks overall. The average weekly cost per client amounted to $930 for Phase I, $677 for Phase II, $635 for Phase III, and $748 over the full program. The average cost per treatment episode amounted to $11,163 for Phase I, $13,541 for Phase II, $11,435 for Phase III, and $36,136 for the complete program. Future research should compare these cost estimates with corresponding outcome data from Safeport to perform a comprehensive economic evaluation.

Adult↗