Background. The efficacy and toxicity of total body irradiation (TBI) in patients with chronic lymphocytic leukemia (CLL) and low grade non‐Hodgkin's lymphomas (NHL) were evaluated.
Methods. Between ...January 1984 and September 1992, 81 consecutive patients, 40 affected with CLL and 41 with low grade NHL, with symptomatic Stage III and IV disease, were treated with TBI followed by prednimustine.
TBI was given with a 6 MV linear accelerator, applying two opposite alternating fields, including total body, with two fractions of 15 cGy given per week (3‐day interval). A total dose of 150 cGy was given over 5 weeks. Six to nine courses of prednimustine (100 mg/m2 orally for 5 consecutive days every 4 weeks) was administered 2 months after TBI treatment as consolidation therapy.
Results. Of 40 patients with CLL, 18 (Group I; median age 58.5 years) were younger than 65 years and 22 (Group II; median age 73 years) were older. The overall response rates were 78% in Group I and 91% in Group II, with a median response time of 16.5 and 16 months, respectively. Hematologic toxicity was 72% in Group I and 73% in Group II. It was reversible in all but one heavily pretreated patient who died of progressive anemia and thrombocytopenia after TBI alone. In the 40 patients with CLL, the response rate was 85%; there were 5 complete responses (CRs) (12.5%) and 29 partial responses (PRs) (72.5%).
Of the 41 patients with NHL, 29 (Group I; median age 55 years) were younger than 65 years and 12 (Group II; median age 71.5) were older. The overall response rate in both groups was 83%, with median response times of 18.5+ and 14.5+ months for Groups I and II, respectively. Hematologic toxicity was 59% in Group I, whereas it was 50% in Group II. It was reversible in all patients. Overall, in the 41 patients with symptomatic Stage III and IV low grade NHL, the response rate was 82.8%; there were 10 CRs (24.3%) and 24 PRs (58.5%).
The prednimustine regimen was generally well tolerated.
Conclusions. In our experience, TBI given in a dose of 150 cGy in 10 fractions twice a week, followed by prednimustine, is an effective treatment for patients with CLL and patients with low grade NHL. This treatment also is effective in patients older than 65 years. The toxicity is acceptable, particularly when TBI and prednimustine are given as initial treatment. Pretreated patients should be monitored strictly.
•Post-trauma ketamine injection induced long-lasting social interaction impairments.•Post-trauma dexmedetomidine injection did not affect long-term behavioral responses.•Post-trauma propofol ...injection induced long-term cognitive and social alterations.
Intensive Care Unit (ICU) or emergency care patients, exposed to traumatic events, are at increased risk for Post-Traumatic Stress Disorder (PTSD) development. Commonly used sedative/anesthetic agents can interfere with the mechanisms of memory formation, exacerbating or attenuating the memory for the traumatic event, and subsequently promote or reduce the risk of PTSD development. Here, we evaluated the effects of ketamine, dexmedetomidine and propofol on fear memory consolidation and subsequent cognitive and emotional alterations related to traumatic stress exposure. Immediately following an inhibitory avoidance training, rats were intraperitoneally injected with ketamine (100–125mg/kg), dexmedetomidine (0.3-0.4mg/kg) or their vehicle and tested for 48h memory retention. Furthermore, the effects of ketamine (125mg/kg), dexmedetomidine (0.4mg/kg), propofol (300mg/kg) or their vehicle on long-term memory and social interaction were evaluated two weeks after drug injection in a rat PTSD model. Ketamine anesthesia increased memory retention without altering the traumatic memory strength in the PTSD model. However, ketamine induced a long-term reduction of social behavior. Conversely, dexmedetomidine markedly impaired memory retention, without affecting long-lasting cognitive or emotional behaviors in the PTSD model. We have previously shown that propofol anesthesia enhanced 48h memory retention. Here, we found that propofol induced an enduring traumatic memory enhancement and anxiogenic effects in the PTSD model. These findings provide new evidence for clinical studies showing that the use of ketamine or propofol anesthesia in emergency care and ICU might be more likely to promote the development of PTSD, while dexmedetomidine might have prophylactic effects.
Background
Gonadotropin-releasing hormone analogs (GnRHas) are effective in increasing the final height of children with idiopathic central precocious puberty (ICPP). However, in previous years, some ...transient metabolic complications have been described during this treatment, for which there are no long-term outcome data. Our study aimed to evaluate the efficacy of GnRHas and clarify if body mass index (BMI) at diagnosis of ICPP could influence long-term outcomes.
Methods
This was an observational, retrospective study that recruited a cohort of girls with ICPP. Data for anthropometric measures, fasting lipid profile, and glucose metabolism were collected at baseline when GnRHas treatment started (T1), at the end of the treatment (T2), and near-final height (nFH) or final height (FH) (T3). Predicted adult height (PAH) was calculated at T1 following Bayley and Pinneau’s method. Analysis was carried out using BMI standard deviation score (SDS) categories at T1 (group A, normal weight, vs. group B, overweight/obese).
Results
Fifty-seven girls with ICPP who were treated with GnRHas were enrolled in the study (group A vs. group B: 33 vs. 24 patients, aged 7.86 ± 0.81 vs. 7.06 ± 1.61 years, respectively;
p
< 0.05). In the study population, nFH/FH was in line with the target height (TH) (
p
= 0.54), with a mean absolute height gain of 11.82 ± 5.35 cm compared with PAH. Even if the length of therapy was shorter (group A vs. group B: 1.84 ± 2.15 vs. 2.10 ± 0.81 years, respectively;
p
< 0.05) and the age at menarche was younger (group A vs. group B: 10.56 ± 1.01 vs. 11.44 ± 0.85 years, respectively;
p
< 0.05) in group B than in group A, the nFH/FH gain was still comparable between the two groups (
p
= 0.95). At nFH/FH, BMI SDS was still greater in group B than in group A (
p
= 0.012), despite the fact that BMI SDS significantly increased in group A only (
p
< 0.05). Glucose metabolism got worst during GnRHa with a complete restoring after it, independently from pre-treatment BMI. The ratio of low-density to high-density lipoprotein cholesterol transiently deteriorated during treatment with GnRHas in group A only (
p
= 0.030).
Conclusions
Our results confirm the effectiveness of treatment with GnRHas on growth and do not support the concern that being overweight and obese can impair the long-term outcomes of GnRHas therapy. However, the observed transient impairment of metabolic parameters during treatment suggests that clinicians should encourage ICPP girls treated with GnRHas to have a healthy lifestyle, regardless of their pretreatment BMI.
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