Morning versus evening administration of estradiol to girls with Turner syndrome receiving growth hormone: impact on growth hormone and metabolism. A randomized placebo-controlled crossover study

Timing of 17beta-estradiol (E2) administration in relation to that of GH could influence the "first pass effect" of E2 on hepatic IGF-I secretion. In order to test this hypothesis, a randomized double-blind placebo-controlled crossover study was conducted. Nine Turner girls (12.8-20.0y) were treated for 2 mo periods with GH 0.1 IU/kg/d sc at bedtime, and oral E2 6-11 microg/kg/d in the morning and placebo in the evening in one 2-mo period and vice versa in the other period. After each period, 24-h blood sampling was performed. IGF-I and mean 24-h integrated GH were comparable. However, the IGF-I/IGFBP-3 ratio was higher (p = 0.05) and insulin levels were lower after evening administration of E2 (24 h: p = 0.03). During an oral glucose tolerance test in the morning, glucagon and insulin were lower following evening E2 administration (ANOVA: glucagon, p = 0.03; insulin, p = 0.04), as well as insulin resistance tended to be lower (p = 0.09). CONCLUSION: The timing of oral E2 supplementation modulates the IGF-I/IGFBP-3 ratio, insulin and glucagon levels in Turner syndrome during GH treatment, Evening administration of oral estrogen together with evening injections of GH may be preferable.     

Evaluation of E-rosetting human lymphocytes with OKT11 and other monoclonal antibodies

Monoclonal antibody OKT11 was found to compete with sheep red blood cells for binding sites on human lymphocytes. Preincubation of lymphocytes with OKT11 eliminated E-rosette formation. In a study of 142 peripheral blood samples ranging from 1% to over 90% E-rosette- positive cells, comparison to the percent OKT11-positive cells yielded a correlation coefficient of 0.93. In normal donors, subsets of OKT11+ cells were identified using two-color immunofluorescent staining methods with OKT3, OKT4, and OKT8. On the average, approximately 13% of OKT11+ lymphocytes were OKT3- and 13% of OKT11+ lymphocytes were OKT4- and OKT8-. Based on our double antibody fluorescence intensity data, low antigen density OKT11+ lymphocytes were OKT3-. OKT4+ and OKT8+ lymphocytes in normal peripheral lymphocytes have similar OKT11 antigen density.     

Detection by polymerase chain reaction of residual cells with the bcl-2 translocation is associated with increased risk of relapse after autologous bone marrow transplantation for B-cell lymphoma

Although molecular biologic techniques can now detect minimal numbers of residual cancer cells in patients in complete clinical remission, the clinical significance of minimal residual disease has never been conclusively established. If the detection of minimal residual disease predicts which patients will relapse, then therapy could be altered based upon the detection of these cells. The t(14;18) can be detected by polymerase chain reaction (PCR) amplification in 50% of patients with B-cell non-Hodgkin's lymphoma and allows detection of one lymphoma cell in up to 1 million normal cells. To determine the clinical significance of the detection of minimal residual lymphoma cells in the bone marrow (BM) PCR amplification was used to detect the presence of residual lymphoma cells after autologous BM transplantation (ABMT) in serial BM samples from 134 patients with B-cell lymphoma in whom a bcl- 2 translocation could be detected. PCR analysis was performed on a total of 542 BM samples obtained while these patients were in complete remission. Disease-free survival was markedly increased in patients with no PCR-detectable lymphoma cells in the marrow compared with those in whom residual lymphoma cells were detected (P < .00001), and the presence of detectable lymphoma cells was associated with a 48-fold increase in the risk of relapse. Of the 77 patients (57%) with no PCR- detectable lymphoma cells in their most recent BM sample, none have relapsed. In contrast, all 33 patients (25%) who have relapsed had PCR- detectable lymphoma cells detected in their BM before clinical relapse occurred. In 19 patients (14%), residual lymphoma cells in the BM were detected early following transplantation and subsequently were no longer detectable, although these patients received no further therapy. In these patients, residual lymphoma cells may already have been irreversibly damaged by the high-dose therapy or an endogenous immune mechanism may be capable of eliminating residual lymphoma cells in some patients. Therefore, although the detection of minimal residual disease by PCR following ABMT in patients with lymphoma identifies those patients at high risk of relapse, the presence of residual minimal disease early after transplantation may not be associated with poor prognosis in a small subset of patients. Confirmatory studies will be required to determine more definitively the role of minimal disease detection to identify which patients require additional therapy.     

Primary biliary cystadenocarcinoma perforating the duodenum and left intrahepatic biliary tree -mimicking a hydatid cyst

Abstract: We report the case of a 76-year-old woman with biliary cystadenocarcinoma perforating the left biliary tree and exhibiting intra-tumoral gas bubbles resulting from invasion of the duodenum. The clinical history included subfebrile temperatures of 3 months duration, and pains associated with an abdominal mass in the right upper quadrant. Blood tests showed leucocytosis, and radiological studies revealed the features of a partially calcified septated tumor with nodular components combined with multiple gas-fluid levels, mimicking an infected hydatid cyst. Intraoperative ultrasonography, cholangiography and frozen section histology were necessary to prove the malignant nature of this cystic tumor. Provided that complete resection with strict adherence to oncological precepts is possible, the prognosis of cystadenocarcinoma is better than in hepatocellular or cholangiocellular carcinoma.     

Spontaneous regression of a monoclonal proliferation of large granular lymphocytes associated with reversal of anemia and neutropenia

A 43-year-old male with a phenotypically homogeneous, expanded subset of T cells presented in 1981 with anemia and neutropenia. The surface antigen phenotype of 99% of the peripheral blood lymphocytes was T3+, T8+, T4-, and they were morphologically large granular lymphocytes (LGL). The same cells comprised 37% of the marrow nucleated cells. Eight months after he presented, the peripheral blood T8+, LGL diminished spontaneously, and the anemia and neutropenia completely resolved. The patient remains hematologically normal as of October 1984. To determine if the T8+, LGL represented a clonal expansion, DNA from peripheral blood lymphocytes collected and cryopreserved when the patient was neutropenic and anemic, and when he was hematologically normal, was analyzed for clonal T-cell antigen receptor gene rearrangements. Using Southern blot analysis, a clonal DNA rearrangement was demonstrated, and this clone diminished but was still demonstrable in peripheral blood lymphocytes collected in 1984. The above observations implicate the expanded T8+, LGL in the pathogenesis of the neutropenia and anemia, yet the exact mechanism remains to be elucidated.     

Factors associated with variability in response of diabetic macular oedema after intravitreal triamcinolone

Purpose:  To identify factors associated with variability in anatomical and functional response of diabetic macular oedema (DMO) after 4 mg of intravitreal triamcinolone acetonide (ivTA), and for recurrence of macular oedema.
Design:  Pooled analysis of individual data from two randomized controlled trials.
Methods:  This was a multicentre study involving 107 eyes with DMO administered 4 mg ivTA. Predictive factors for response to treatment were evaluated with linear regression analysis. Factors associated with time to recurrence of oedema were studied with Cox proportional hazards modelling. Main outcome measures were maximum improvement in optical coherence tomography (OCT)-measured central foveal thickness (CFT) and best-corrected visual acuity (BCVA), final CFT and BCVA at 12 months and time to oedema recurrence.
Results:  Greater reduction of retinal thickening occurred in eyes with worse baseline thickening ( P  < 0.001). There was also greater improvement of visual acuity in eyes with poorer preoperative BCVA levels ( P  < 0.001). Age, duration of oedema and previous macular laser treatment had no significant effect on maximal BCVA or CFT improvement. Eyes given 4 mg triamcinolone alone were more likely to develop recurrence of oedema at 12 months than those given a combination of 4 mg triamcinolone plus sequential laser (hazard ratio 2.60 [95% confidence interval: 1.45–4.67]).
Conclusion:  Baseline OCT-measured retinal thickening and BCVA are important predictors of maximal anatomical and functional response of DMO to ivTA, respectively. Combination treatment strategy using sequential laser therapy may have a role in delaying recurrence of oedema after triamcinolone.     

LOGISTICS OF PERFORMING AN OPHTHALMIC ASSESSMENT IN ELDERLY INPATIENTS

SUMMARY To assess the feasibility of performing an ophthalmic assessment on elderly inpatients, we examined 48 patients over 75 years of age who were consecutively admitted to an acute elderly-care ward. Difficulties were encountered in 35 patients (73%). By employing simple methods to overcome these problems, useful information was obtained in all cases and the time taken to complete the examination ranged from six to 20 minutes (mean 7.5 minutes). Doctors looking after elderly patients should be encouraged to assess visual function and must not be deterred by anticipated logistical difficulties.     

Detection of residual lymphoma cells by polymerase chain reaction in peripheral blood is significantly less predictive for relapse than detection in bone marrow

Polymerase chain reaction (PCR) amplification of the t(14;18) has been shown to be a highly sensitive method to detect minimal residual disease in patients with non-Hodgkin's lymphoma (NHL) whose tumors bear this translocation. The ideal tissue source to detect residual lymphoma would be from a previously involved lymph node. However, lymphoid tissue is rarely available once patients achieve complete remission. Although PCR amplification has been used to detect residual lymphoma cells in both bone marrow (BM) and peripheral blood (PB) of patients in complete remission, it is presently unknown whether BM and PB are equivalent tissue sources to detect residual disease. In the present study, we compared the clinical utility of the detection of residual lymphoma in both the BM and the PB of patients with advanced-stage non- Hodgkin's lymphoma before, at the time of, and after high-dose therapy and autologous BM transplantation (ABMT). The detection of residual lymphoma in either the BM or PB was associated with decreased disease- free survival. However, in the present study, 44% of patients who relapsed had no evidence of circulating lymphoma cells in their PB. At the time of BM harvest, PCR-detectable residual lymphoma cells were detected in 211 of 212 patients; although, in a subset of these patients analyzed, lymphoma cells were detected in the peripheral blood of only 49% of patients. When residual lymphoma cells within the autologous BM are infused into the patient these cells are rapidly detectable circulating in the PB in the patient. These cells continue to circulate during the immediate posttransplant period and be detectable in the PB in the majority of patients who are infused with marrow containing residual lymphoma. We conclude that BM is a more informative tissue source than PB in detecting minimal residual disease at the time of and after ABMT, and that contamination of PB early after ABMT appears to be the consequence of reinfusion of lymphoma cells within autologous marrow.