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PubMed1996

In vitro progenitor analysis in a Diamond Blackfan anaemia patient who responded once but not twice to interleukin-3 therapy, using short-term and long-term cultures and c-kit analysis.

Interleukin-3 (IL-3) therapy as a treatment for Diamond Blackfan anaemia (DBA) patients has been largely disappointing despite early hope it would be suitable for stimulating arrested erythropoiesis. Initial hope came from in vitro discoveries that IL-3 (+EPO) generated well-haemoglobinized BFU-E colonies in some patients, but was soon tempered by the realization that in vitro and in vivo IL-3 response did not, in the majority of cases, correlate. Nevertheless in vitro testing has been the main focus in analysing the abnormality in the stem and progenitor cell compartment in DBA. Here we report in vitro analysis of a DBA patient who responded once to IL-3 therapy, but not a second time following relapse, using short-term culture, long-term culture and c-kit analysis. Progenitor numbers before and after the first therapy were in the high normal range, but after relapse were much reduced below normal levels. Long-term cultures suggested some arrested progenitors had been reactivated into normal cycle by the first therapy, but may not have been replaced by more immature progenitors. c-kit analysis revealed increased expression in all tested cell populations. These results imply that the first IL-3 therapy reactivated some erythroid progenitors but left the progenitor pool depleted when more immature cells remained arrested.

Cell Count↗

PubMed1985

Pharmacokinetics of trihexyphenidyl after short-term and long-term administration to dystonic patients.

Although trihexyphenidyl has been used effectively for many years in the treatment of Parkinson's disease, little is known about its pharmacokinetics. Using a sensitive radioreceptor assay for anticholinergic drugs, we assayed trihexyphenidyl in human serum and studied its pharmacokinetics following short-term and long-term administration to patients with dystonia. Previously untreated patients had a biphasic semilogarithmic plot of serum concentration-time consisting of an initial rapid distribution phase and a later slower elimination phase. Patients on long-term treatment showed only the slower elimination phase. Elimination followed first-order kinetics and was rapid, with a half-life of 3.7 +/- 0.4 (SEM) hours. There was no relationship between half-life and peak serum level, age, duration of therapy, or etiology or severity of dystonia. Although acute anticholinergic side effects paralleled the rise and fall of serum anticholinergic levels, the response of dystonia did not.

Adolescent↗

PubMed1984

The effects of clonidine, prazosin, and propranolol on short-term and long-term habituation of the acoustic startle response in rats.

The unique effect of clonidine in facilitating habituation of the acoustic startle response [10] was replicated. However, clonidine had no effect on between-session habituation, showing a pharmacological dissociation between short- and long-term habituation. Systematic manipulation of ISI showed clonidine's habituation-facilitating effect to be most striking with longer within-session ISIs where habituation was relatively weak in controls. Comparing clonidine's effect to that of two other hypotensive agents, prazosin and propranolol, showed that the habituation-facilitating effect was not due to blood pressure effects. Prazosin, an alpha 1-adrenergic blocker, facilitated short-term habituation, but significantly less so than did clonidine, an alpha 2-agonist. Propranolol, a beta-adrenergic blocker, had no effect on short-term habituation. Both prazosin and propranolol impaired long-term habituation, but propranolol did so without suppressing initial response levels. The data suggest that a synapse with both alpha-1- and alpha 2-adrenoceptors may be critically involved in habituation of the acoustic startle response. A beta-adrenergic involvement in long-term habituation is tentatively suggested.

Acoustic Stimulation↗

PubMed1989

Short-term and long-term soft tissue profile changes after mandibular advancements using rigid fixation techniques.

This study was designed to describe short- and long-term soft tissue profile changes that follow surgical advancement of the mandible, to provide a database for prediction of facial changes following surgery. A number of hard and soft tissue landmarks were identified on serial cephalometric tracings of 31 patients. The long-term data (x = 14.0 months postsurgery) showed that changes in soft tissue landmarks overlying the skeletal structures followed their hard tissue counterpart in a 1:1 ratio in the horizontal direction. Horizontal hard to soft tissue landmark changes between mandibular incisor and lower lip, however, were found to be different; the average ratio was 0.43:1.00. Short-term data (x = 2.7 months postsurgery) showed soft tissue changes to be stable when compared to long-term changes.

Adolescent↗

PubMed1988

Low birthweight breech infant: short-term and long-term outcome by method of delivery.

The effect of the delivery method on the short-term and long-term morbidity and mortality of the very low birthweight breech-presenting infants was evaluated. Although some previous studies question the benefit of cesarean section for the premature breech infants, the mortality rate and the incidence of birth injuries were significantly lower in the abdominally delivered group than in those delivered vaginally. The long-term follow-up clearly demonstrates that the vaginally delivered infants had a substantially higher incidence of cerebral palsy, visual damage, deafness, and severe developmental delay. It is concluded that cesarean section may be the preferred delivery method for the breech-presenting infants weighing 1000 to 1999 gm, offering a better quality of life.

Birth Injuries↗

PubMed1995

Evidence for a mechanism that can provide both short-term and long-term haemopoietic repopulation by a seemingly uniform population of primitive human haemopoietic precursor cells.

One of the controversies surrounding the repopulating capacities of haemopoietic stem cells is whether or not the same or different populations are responsible for short-term and long-term repopulation after transplantation. To address this question, we analysed results obtained from an in vitro model for the clonal production of granulocyte-macrophage colony-forming cells (CFU-GM) by individual primitive multilineage precursors in adult human bone marrow. The primitive precursors adhere to plastic and produce CFU-GM in a 1-week long 'delta' type culture. The clones that form are classified as having short maturation pathways (clones containing predominantly day 7 CFU-GM) or long maturation pathways (clones containing predominantly day 21 CFU-GM). The results indicate that individual primitive (P delta) cells produce clones that reach full maturity after different periods of time so that cells corresponding to a range of maturational stages can become available simultaneously. Consequently, transplanted stem cells may be able to provide both rapid and long-term mature cell recovery whilst at the same time reconstituting the stem cell pool. These results suggest that it might be possible to use highly purified stem cell populations, devoid of committed progenitors, for clinical transplantation.

Bone Marrow Cells↗

PubMed1989

Short-term and long-term effects of brown and black masheri (pyrolysed tobacco product) on vitamin A and vitamin C levels in mice and hamsters.

The short-term and long-term effects of two most commonly used brown and black masheri were studied in Swiss mice and Syrian golden hamsters. In short-term studies, both the types of masheri extracts (ME) at 3/4 LD50 dose given ip did not have any effect on either liver or plasma vitamin C levels (both species). However, a decrease in liver vitamin A was observed only in hamsters injected with black ME. Similar effect was not observed in mice injected with both the types of masheri extracts. In long-term studies, when both the types of masheri were fed through diet at 10% level for 20 months, no effect was observed on hepatic or plasma vitamin C levels in mice (both sexes), while an increase in vitamin C levels was observed in black masheri diet fed hamsters. A depletion in liver vitamin A was observed in hamsters fed both the types of masheri. Such an effect was observed only in black masheri diet fed Swiss mice (both sexes) and brown masheri diet fed Swiss females.

Animals↗

PubMed1999

Cyclosporine therapy in inflammatory bowel disease: short-term and long-term results.

Intravenous cyclosporine therapy followed by oral cyclosporine therapy reduce the need for urgent surgery in steroid-refractory inflammatory bowel disease (IBD). Our objective is to report short- and long-term results of cyclosporine therapy in IBD patients. Thirteen patients with steroid-refractory IBD, seven patients with ulcerative colitis (UC), and six patients with Crohn's disease (CD) were treated with intravenous cyclosporine (4 mg/kg/day) for a mean period of 11.4+/-2.8 days (range, 4-15 days). Subsequently the patients were started on oral cyclosporine (8 mg/kg/day) and followed for a mean of 10.3+/-10 months (range, 1-30 months). Twelve patients responded to intravenous cyclosporine therapy. One patient with UC developed sepsis on the fourth day of intravenous cyclosporine therapy and needed urgent colectomy. Nine of 12 initial responders (6 patients with UC and 3 patients with CD) relapsed during follow-up despite oral cyclosporine and underwent elective surgery. One patient with CD relapsed 3 months after discontinuation of oral cyclosporine. Only two patients with CD are in long-term remission. There were no long-term side effects in any of the 13 treated patients. In conclusion, intravenous cyclosporine was effective in inducing remission or significant improvement in 12 of 13 patients with steroid-refractory IBD. However, with subsequent oral cyclosporine the remission could be maintained only for a short while. Each of the six patients with UC needed colectomy and three of the five patients with CD had intestinal resection within 12 months despite oral cyclosporine therapy.

Administration, Oral↗

PubMed2003

Short-term and long-term physical effects of exposure to CS spray.

CS gas (2-chlorobenzylidene malonitrile) is widely used in an incapacitant spray that causes intense lacrimation, blepharospasm and burning sensations in the throat and nose. Questions have been raised about its safety. We obtained information on short-term and long-term symptoms, and performed ear, nose and throat examinations and respirometry at 8-10 months, in 34 young adults who had been exposed to CS spray in a confined space during a confrontation with police. The group was subdivided into those who had been sprayed directly on the face (n=10) and those exposed indirectly. At one hour, all but 2 individuals still had symptoms; respiratory and oral symptoms were significantly more prevalent in the directly exposed group. At one month, only oral symptoms were significantly more prevalent. At 8-10 months, symptoms were still reported but there were no differences between the groups and clinical examinations revealed no specific abnormalities. There was no convincing evidence of long-term physical sequelae from exposure to CS spray.

Adult↗

PubMed2001

Aortopexy in severe tracheal instability: short-term and long-term outcome in 29 infants and children.

BACKGROUND: Tracheal instability is a hazardous situation after operation for esophageal atresia. In cases with life-threatening apneas, aortopexy is a therapeutic option. To assess efficacy, short-term and long-term outcome was analyzed retrospectively. METHODS: Between 1985 and 2000, 29 patients (age, 1.5 months to 5.2 years) were operated on. A flaccid trachea after operation for esophageal atresia was the cause for life-threatening apneas in 27, and there was external vascular compression in 2 patients. The operative procedure consisted of ventropexy of the aortic arch to the sternum and ventral thoracic wall. RESULTS: There was neither early nor late mortality. A reversible lesion of the phrenic nerve was observed in 2 patients, a pneumothorax in 3, and secondary wound healing in 1. In all but 1 patient symptoms improved markedly or disappeared within days or within the first 3 months postoperatively. An increased susceptibility to respiratory infections was observed in long-term follow-up. CONCLUSIONS: Aortopexy can be performed with no mortality and low morbidity. Aortopexy is effective to prevent further life-threatening apneas, but does not prevent an increased susceptibility to respiratory infections.

Aorta, Thoracic↗

PubMed2006

Short-term and long-term effects of guar on postprandial plasma glucose, insulin and glucagon-like peptide 1 concentration in healthy rats.

Ingestion of guar gum decreases postprandial glycemia and insulinemia and improves sensitivity to insulin in diabetic patients and several animal models of diabetes. The aim of the present study was to compare the short-term and long-term effects of guar on plasma insulin and glucagon-like peptide 1 concentration in healthy rats. In the short-term experiments, the concomitant intragastric administration of glucose and guar reduced the early increment in plasma glucose, insulin and glucagon-like peptide 1 concentration otherwise induced by glucose alone. Comparable findings were made after twelve days of meal training exposing the rats to either a control or guar-enriched diet for fifteen minutes. Mean plasma glucose concentrations were lower while mean insulin concentrations were higher in the guar group than in the controls according to intragastric glucose tolerance tests conducted in overnight fasted rats maintained for 19 to 36 days on either the control or guar-enriched diet. The intestinal content of glucagon-like peptide 1 at the end of the experiments was also lower in the guar group. Changes in body weight over 62 days of observation were comparable in the control and guar rats. Thus, long-term intake of guar improves glucose tolerance and insulin response to glucose absorption, without improving insulin sensitivity, in healthy rats.

Animals↗

PubMed2004

Comparison of multivisceral resection and standard operation for locally advanced colorectal cancer: analysis of prognostic factors for short-term and long-term outcome.

PURPOSE: The aim of the present study is to clarify the characteristics of multivisceral resection and to discuss strategies for improving the overall outcome of multivisceral resection for locally advanced colorectal cancer. METHODS: The study included 323 patients who electively underwent curative surgery for pT3-pT4 colorectal carcinoma without distant metastasis. We evaluated the short-term and long-term outcome of multivisceral resection relative to that of the standard operation by means of multivariate analysis of the prognostic factors. RESULTS: Of 323 patients, 53 (16.4 percent) received multivisceral resection because of adhesion to other organs. Multivisceral resection was significantly associated with tumor size, depth of invasion, operative blood loss, operation time, and blood transfusion (all: P < 0.0001). Overall morbidity rates were 49.1 percent after multivisceral resection vs. 17.8 percent after the standard operation (P < 0.0001), and postoperative mortality rate was 0 percent in both groups (not significant). Only multivisceral resection (odds ratio, 2.725; 95 percent confidence interval, 1.125-6.623; P = 0.0264) was an independent factor for overall postoperative complications. The survival rate of patients after multivisceral resection was similar to that after the standard operation (5-year rate, 76.6 percent vs. 79.5 percent, P = 0.9347). Lymph node metastasis (hazard ratio, 2.510; 95 percent confidence interval, 1.460-4.315; P = 0.0009) and blood transfusion (hazard ratio, 2.353; 95 percent confidence interval, 1.185-4.651; P = 0.0145) were independently associated with patient survival. CONCLUSIONS: For locally advanced colorectal cancer, the long-term outcome after multivisceral resection is comparable to that after the standard operation. However, it should be recognized that multivisceral resection is associated with higher postoperative morbidity. In addition, a reduction in the incidence of blood transfusion may contribute to improving patient survival.

Aged↗

PubMed2005

[Role of hepatitis C virus superinfection in hepatic pathologic changes of patients with chronic hepatitis B: a retrospective short-term and long-term comparative study].

OBJECTIVE: To observe the effect of hepatitis C virus (HCV) superinfection on the short-term and long-term hepatic pathological changes in patients with chronic hepatitis B (CHB). METHODS: HCV-RNA of twice corresponding period serum samples was detected via reverse transcription polymerase chain reaction assay from 230 patients with CHB for whom liver biopsy was performed at an interval of 0.5-15 years, respectively. The hepatic pathological changes of the patients with CHB who were serum HCV-RNA positive at the beginning of observation and persistently positive between the starting and ending of observation were respectively compared with those of serum HCV-RNA negative and persistently negative patients. RESULTS: 41 patients (17.83%) were positive for serum HCV-RNA at the beginning of observation. There were significant differences in the severity of hepatic inflammatory activity grade and fibrosis stage between serum HCV-RNA positive and negative patients with CHB (P < 0.05). Twenty-nine patients were persistently positive for serum HCV-RNA in the beginning and end of observation. Compared with persistently negative patients who were 116 patients selected from the above-mentioned 230 patients and they were comparable with HCV-RNA persistently positive patients in mean follow-up time, age and sex, the long-term progression of hepatic inflammatory activity grade and fibrosis stage in persistently positive patients were more speedy (P < 0.01). CONCLUSION: HCV superinfection worsens the hepatic pathological changes of patients with CHB and speeds up its progression.

Adult↗

PubMed1989

Oral toxicity of 1,2-dichloropropane: acute, short-term, and long-term studies in rats.

The objective of this investigation was to characterize the acute and short- and long-term toxic potency of orally administered 1,2-dichloropropane (DCP). In the acute and short-term studies, male rats of 250-300 g were gavaged with 0, 100, 250, 500, or 1000 mg DCP/kg in corn oil once daily for up to 10 consecutive days. Although ingestion of DCP caused body weight loss and CNS depression, few other toxic effects were manifest 24 hr after a single dose of the chemical. Morphological changes were limited to liver centrilobular cells in 500 and 1000 mg/kg rats. Similarly, elevated activity of some serum enzymes occurred only at these two highest dose levels. Hepatic nonprotein sulfhydryl (NPS) levels were decreased and renal NPS levels increased at 24 hr. In the short-term study resistance developed to DCP hepatotoxicity over the 10 consecutive days of exposure, as reflected by progressively lower serum enzyme levels and by decreases in the severity and incidence of toxic hepatitis and periportal vacuolization. Nucleolar enlargement in hepatocytes, however, was observed at all dosage levels at 5 and 10 days. There were a number of manifestations of hemolytic anemia, including erythrophagocytosis in the liver, splenic hemosiderosis and hyperplasia of erythropoietic elements of the red pulp, renal tubular cell hemosiderosis, and hyperbilirubinemia. Urinalyses and histopathology revealed no evidence of nephrotoxicity. In the long-term study, male rats initially weighing 180-200 g were gavaged five times weekly for up to 13 weeks with 0, 100, 250, 500, or 750 mg DCP/kg. As over one-half the 750 mg/kg group died within 10 days, the survivors were sacrificed. Histopathological changes in the 750 mg/kg animals included mild hepatitis and splenic hemosiderosis, as well as adrenal medullary vacuolization and cortical lipidosis, testicular degeneration and a reduction in sperm, and increased number of degenerate spermatogonia in the epididymis in some members of the group. Similar testicular and epididymal degenerative change also were observed in some 500 mg/kg animals after 13 weeks of dosing. There was a progressive increase in the number of deaths in the 500 mg/kg group, such that more than 50% were dead by 13 weeks. No deaths occurred in the 100 or 250 mg/kg groups. The DCP dosage regimen also produced a dose-dependent decrease in body weight gain. DCP exhibited very limited hepatotoxic potential and no apparent nephrotoxic potential in the long-term study. Slight elevations in serum ornithine-carbamyltransferase activity, periportal vacuolization, and active fibroplasia in the liver were seen in the 500 mg/kg animals.

Administration, Oral↗

PubMed1997

Effect of short-term and long-term treatments with sigma ligands on the N-methyl-D-aspartate response in the CA3 region of the rat dorsal hippocampus.

1. Long-term treatments with the sigma ligand haloperidol decrease the density of sigma receptors in mammalian CNS. We have shown that sigma ligands, such as di(2-tolyl)guanidin (DTG), potentiate dose-dependently, with bell-shaped dose-response curves, the neuronal response of pyramidal neurones to N-methyl-D-aspartate (NMDA) in the CA3 region of the rat dorsal hippocampus. sigma Ligands producing such a potentiation were denoted 'agonists'. This potentiation was suppressed by low doses of other sigma ligands denoted 'antagonists'. High doses of DTG and JO-1784 did not modify the NMDA response but acted as 'antagonists' by suppressing the potentiation induced by sigma 'agonists'. 2. Following a 21-day treatment with haloperidol as well as with high doses of DTG or JO-1784, after a 48 h washout, the acute administration of sigma 'agonists' failed to induce any potentiation of the NMDA response. Following a 21 day treatment with a low dose of DTG or JO-1784, after a 48 h washout, the neuronal response to microiontophoretic applications of NMDA was markedly increased. A 21 day treatment with low or high doses of (+)-pentazocine, after a 48 h washout, did not produce any change. 3. Following a two day treatment with a high dose of haloperidol, DTG, JO-1784 and (+)-pentazocine, after a 24 h washout, the potentiation of the NMDA response induced by the acute administration of the sigma 'agonists' was unchanged. 4. With the minipumps on board, with DTG and JO-1784, a dose-dependent enhancement of the NMDA response was seen but no effect was observed in the groups of rats treated at the same doses with haloperidol or (+)-pentazocine. 5. The present data suggest that long-term treatments with sigma 'antagonists' induce a desensitization of the th receptors, whereas long-term treatments with th 'agonists' induce a supersensitivity of the th receptors.

Animals↗

PubMed2000

Long-term oxygen therapy vs long-term ventilatory assistance.

The use of positive-pressure nasal ventilation in combination with LTOT in stable COPD patients with hypercapnic respiratory failure controls hypoventilation and improves daytime ABGs, sleep, and quality of life. Nasal ventilation in COPD is unlikely to produce benefit unless used with supplemental oxygen therapy at night. The patients who show the greatest reduction in overnight PaCO2 with ventilation are the patients most likely to benefit from long-term ventilatory support. Although there is now evidence for short-term benefit from NPPV in hypercapnic COPD, large multicenter studies with survival, exacerbations, and hospital admissions as the primary end points are required to evaluate longer-term effects of this potentially important intervention.

Bronchiectasis↗

PubMed2005

Short-term and long-term results of resectoscopic myomectomy with and without pretreatment with GnRH analogs in premenopausal women.

OBJECTIVE: The aim of this study was to analyze the safety and efficacy of resectoscopic myomectomy and to evaluate the influence of GnRH analog pretreatment on short- and long-term surgery outcome. METHODS: Data were collected from 80 consecutive resectoscopic myomectomies performed on premenopausal women. Forty-two patients (52.5%) had not received any preoperative medical treatment and in their case surgery was performed during the early proliferative phase (group A), whereas 38 patients (47.5%) had been treated with 2 months of intramuscular GnRH analog (triptorelin, Decapeptyl 3.75 mg) (group B). Myomas were classified according to the Wamsteker classification. The surgical time, recovery time, and complications were considered as short-term results. A 24-month follow-up was performed in order to assess long-term results, such as abnormal uterine bleeding recurrence, myomas recurrence, and need of repeat surgery. RESULTS: Patients' mean age was 38.8 +/- 5.39 years (range: 24-47) in group A and 38.97 +/- 7.46 years (range: 20-49) in group B. Forty-eight myomas were excised in group A (1.1 +/- 0.53 myoma per patient; mean diameter: 28.72 +/- 11.57 mm) and 42 in group B (1.09 +/- 0.29; mean diameter: 29.73 +/- 14.47 mm). Myoma type distribution was similar in both groups. Surgical time of the pretreated patients (group B) was significantly longer than that of untreated patients (group A 40 +/- 18.06 versus group B 57.65 +/- 29.61 min; P = 0.002). No significant difference was found between the two groups in the length of postoperative stay (group A 1.05 +/- 0.22 days versus group B 1.15 +/- 0.44). Only one complication occurred, represented by a uterine perforation. Histopathology revealed the presence of cellular myomas, without atypia, in three patients of each group. At follow-up, abnormal uterine bleeding occurred in 36.3% of group A patients and in 26.6% of group B patients, but the difference showed no statistical significance (P = 0.57). Five patients of myoma recurrence were observed, three in group A and two in group B. Only two patients, one from each group, required repeat hysteroscopic surgery. CONCLUSIONS: GnRH analog pretreatment, even if extremely beneficial in anemic patients, does not seem to improve short- and long-term outcome following resectoscopic myomectomy. Surgical time of pretreated patients is significantly longer, maybe because of difficulty in cervical dilatation, although further study is needed in order to confirm this hypothesis.

Adult↗

PubMed1999

Short-term and long-term hemodynamic and clinical effects of metoprolol alone and combined with amlodipine in patients with chronic heart failure.

BACKGROUND: Initiation of beta-blocker therapy is often limited by worsening congestive heart failure, which may manifest as worsening hemodynamics. Deleterious hemodynamic effects might be mitigated with the vasodilation of combined calcium channel/beta-blocker therapy. METHODS AND RESULTS: This prospective, randomized study assessed the safety and efficacy of metoprolol alone or combined with amlodipine on hemodynamic parameters at baseline, 2 hours after the first dose of study medication, and after 12 weeks of therapy in patients receiving background triple therapy for mild to severe heart failure. Functional, exercise, and hormonal status were assessed at baseline and end of study. Twenty-nine patients (mean age 50 +/- 12.1 years) were enrolled; 21 completed 12 weeks of treatment. Mean ejection fraction at baseline was 13.4% +/- 5.7%; 79% of patients had heart failure classified as New York Heart Association class III, and 66% had heart failure of idiopathic origin. Heart rate and blood pressure did not change with short-term therapy in either group. The first dose of both regimens produced significant increases in systemic vascular resistance and significant decreases in cardiac output and index and stroke volume and stroke work indexes; combination therapy acutely yielded small but statistically significant increases in pulmonary artery, pulmonary capillary wedge, and right atrial pressures. Long-term therapy with both regimens produced significant decreases in heart rate, systemic vascular resistance, and pulmonary capillary wedge pressure and significant increases in cardiac output and index and stroke volume and stroke work indexes. Combination therapy produced significant long-term decreases in blood pressure. CONCLUSIONS: There was no further measurable benefit with the addition of amlodipine to metoprolol compared with the effects of metoprolol alone. Therapy with metoprolol alone and the combination of metoprolol and amlodipine was well tolerated in patients with mild to severe heart failure, as evidenced by a lack of adverse effects on hemodynamic parameters over the short term and clinical and hemodynamic improvement with long-term treatment.

Adrenergic beta-Antagonists↗