Change to abacavir-lamivudine-tenofovir combination treatment in patients with HIV-1 who had complete virological suppression

Patients who have not received previous antiretroviral treatment (ART) have a high failure rate on the combination treatment of abacavir, lamivudine, and tenovir. We assessed the virological failure rate in eight patients with HIV-1 who switched to this combination after having complete virological suppression from their previous long-term ART (median 8.0 months, range 7.5-18.0). Five of the eight patients showed virological failure. Four of these five patients had either the K65R mutation, the M184V/I mutation, or both. This combination of drugs cannot therefore be recommended as alternative treatment in patients with HIV-1 who are fully virologically suppressed.     

Deep brain stimulation of the centre median-parafascicular complex in patients with movement disorders

The centre median-parafascicular (CM-Pf) complex of the thalamus is considered to be a possible target for deep brain stimulation (DBS) in patients with movement disorders. In a prospective study on the effect of CM-Pf DBS versus somatosensory thalamic DBS on chronic neuropathic pain, three of 12 patients had additional movement disorders. Bifocal quadripolar electrodes were implanted by computed tomography guided stereotactic surgery under local anaesthesia contralaterally to the side of the pain for test stimulation. Two of the three patients with movement disorders had permanent implantation of CM-Pf electrodes. During test stimulation of the left CM-Pf complex for several days, a 67 year old woman received no benefit with respect to the neuropathic pain, but the choreoathetotic movements of her right foot ceased. As the pain syndrome was not improved, she decided not to have permanent implantation. A 74 year old man with postzoster neuralgia and allodynia enjoyed excellent relief from his pain with chronic CM-Pf DBS. In addition, improvement in the tremor at rest was noted. A 72 year old man had sustained reduction in his stump dyskinesias. Further evaluation of the possible role of the "forgotten" central and medial thalamic nuclei in the treatment of movement disorders may be warranted.     

Vector-averaged gravity-induced changes in cell signaling and vitamin D receptor activity in MG-63 cells are reversed by a 1,25-(OH)2D3 analog,EB1089

Skeletal unloading in an animal hindlimb suspension model and microgravity experienced by astronauts or as a result of prolonged bed rest causes site-specific losses in bone mineral density of 1%-2% per month. This is accompanied by reductions in circulating levels of 1,25-(OH)(2)D(3), the active metabolite of vitamin D. 1,25-(OH)(2)D(3), the ligand for the vitamin D receptor (VDR), is important for calcium absorption and plays a role in differentiation of osteoblasts and osteoclasts. To examine the responses of cells to activators of the VDR in a simulated microgravity environment, we used slow-turning lateral vessels (STLVs) in a rotating cell culture system. We found that, similar to cells grown in microgravity, MG-63 cells grown in the STLVs produce less osteocalcin, alkaline phosphatase, and collagen Ialpha1 mRNA and are less responsive to 1,25-(OH)(2)D(3). In addition, expression of VDR was reduced. Moreover, growth in the STLV caused activation of the stress-activated protein kinase pathway (SAPK), a kinase that inhibits VDR activity. In contrast, the 1,25-(OH)(2)D(3) analog, EB1089, was able to compensate for some of the STLV-associated responses by reducing SAPK activity, elevating VDR levels, and increasing expression of osteocalcin and alkaline phosphatase. These studies suggest that, not only does simulated microgravity reduce differentiation of MG-63 cells, but the activity of the VDR, an important regulator of bone metabolism, is reduced. Use of potent, less calcemic analogs of 1,25-(OH)(2)D(3) may aid in overcoming this defect.     

Contributions of the home literacy environment to preschool-aged children's emerging literacy and language skills

This paper reports on a study that examined both the concurrent and logitudinal connections between multiple components of the home environment and indicators of preschool-aged children's literacy and language development. Data were collected from 85 parents and their children at two different times. Results of structural path models indicated that (a) parental literacy habits were positively associated with parental reading beliefs, (b) parental reading beliefs were positively associated with parent-child literacy and language activities in the home, and (c) parent-child literacy and language activities were positively associated with children's print knowledge and reading interest. Parental demographic characteristics were associated with children's expressive and receptive language skills. The results highlight how different components of the home literacy environment are associated with different components of preschool-aged children's literacy and language abilities, findings that become more important as educators and policy-makers look for ways to enhance children's literacy and language development.     

Recombinant human thyrotropin (rhTSH) in the management of differentiated thyroid cancer

Recombinant human thyrotropin (rhTSH) has been evaluated in 38 patients with differentiated thyroid cancer. The patients had all been treated previously by operation and 31 had received radioiodine 131I. The patients continued to take thyroid hormone and changed to a low iodine diet for 14 days before and throughout the week of testing. The rhTSH was injected intramuscularly on two consecutive days, 74 MBq 131I was administered on the next day and scintigraphy completed 48 h after that. TSH was measured before administration of 131I, and thyroglobulin after the scan. All patients preferred this method to withdrawal of thyroid hormone, but 45% had mild symptoms including headache and nausea. The average TSH was 127 mU x l(-1), and was inversely related to the weight of the patients. Thirty-four had negative scans with a mean uptake of 0.06%. Thyroglobulin values above 10 ng x ml(-1) were found in seven patients, of whom four had similar findings when scanned after withdrawal of thyroid hormone. Of four with positive scans, two had undetectable thyroglobulin. The rate of clearance of 131I was compared in patients studied at 72 h who were hypothyroid and at 48 h in euthyroid patients given rhTSH and was found to be longer in the latter. We conclude that rhTSH can be used to stimulate thyroid tissue to trap 131I and secrete thyroglobulin. Both scan and thyroglobulin should be obtained. The method is well tolerated.     

Minimally invasive surgical staging for esophageal cancer

Background: The incidence of esophageal adenocarcinoma is increasing in the United States, and the 5-year survival rate is dismal. Preliminary data suggest that conventional imaging is inaccurate in staging esophageal cancer and could limit accurate assessment of new treatments. The objective of this study was to compare minimally invasive surgical staging (MIS) with conventional imaging for staging esophageal cancer. Methods: Patients with potentially resectable esophageal cancer were eligible. Staging by conventional methods used computed tomography (CT) scan of the chest and abdomen, and endoscopic ultrasound (EUS), whereas MIS used laparoscopy and videothoracoscopy. Conventional staging results were compared to those from MIS. Results: In 53 patients, the following stages were assigned by CT scan and EUS: carcinoma in situ (CIS; n= 1), I (n= 1), II (n= 23), III (n= 20), IV (n= 8). In 17 patients (32.1%), MIS demonstrated inaccuracies in the conventional imaging, reassigning a lower stage in 10 patients and a more advanced stage in 7 patients. Conclusions: In 32.1% of patients with esophageal cancer, MIS changed the stage originally assigned by CT scan and EUS. Therefore, MIS should be applied to evaluate the accuracy of new noninvasive imaging methods and to assess new therapies for esophageal cancer. Received: 5 April 1999/Accepted: 15 March 2000/Online publication: 12 July 2000     

Antibiotic sequential therapy for febrile neutropenia in pediatric patients with malignancy

Children suffering malignant diseases can experience phases of bone marrow depression during intensive chemotherapy. The influence of antibiotic sequence therapy on the course of diseases was examined in 41 pediatric patients with malignant diseases. Inclusion criteria were neutropenia (ANC < 500/microL), rectal body temperature over 38.5 degrees C, and increased C-reactive protein (CRP, cutoff > 5.0 mg/L). The first stage of therapy comprised the following antibiotics: piperacillin, teicoplanin, and gentamicin. In stage 2 imipenem, teicoplanin, and tobramycin were administered. Fluconazole was the antifungal drug of choice in stages 1 and 2. In the first level of antibiotic therapy 68% of the patients showed a positive reaction. The C-reactive protein was a sensitive parameter, which significantly decreased with 3 days of therapy. A total of 72% of the bacteriological smears were sterile. All patients survived the septic phase.     

Ectopic cervical thymus in a 12-year-old boy: a case report

Thecase of a 12-year-old boywith ectopic cervical thymus is reported. This is a rare differential diagnosis in cervical tumors in childhood. The clinical symptoms might present as complications; in rare cases malignant transformations have been reported. The diagnosis ectopic cervical thymus can be achieved only histologically. Due to possible malignant transformation, it is mandatory to excise this thymus tumor totally.     

Induction of chromosome-specific aneuploidy and micronuclei in human lymphocytes by metabolites of 1,3-butadiene

1,3-Butadiene is a carcinogen in rodents, but its potential carcinogenicity to humans remains controversial. Numerous studies have shown that butadiene and its metabolites cause sister chromatid exchanges in vitro and in vivo. To test for other types of genotoxicity, the micronucleus assay and fluorescence in situ hybridization (FISH) have been used to detect chromosome damage in human lymphocytes caused by two reactive metabolites of butadiene, diepoxybutane (DEB) and monoepoxybutene (MEB). DEB (0.5-5.0 microM) significantly increased micronucleus formation 4- to 6-fold (P <0.01) and MEB (1-500 microM) by 2- to 4-fold (P <0.01) over control levels. The ability of DEB and MEB to induce aneuploidy of chromosomes 7, 8, 12, and X was examined using dual-color FISH in both interphase and metaphase cells. These chromosomes were chosen because of their involvement in leukemogenesis. Both DEB and MEB caused dose-dependent increases in hyperdiploidy of chromosomes 12 and X, but had no discernible effect on chromosomes 7 and 8. These results suggest that DEB and MEB cause chromosome-specific aneuploidy in human cells. If formed in sufficient amounts, DEB and MEB may produce chromosome damage of the type found in leukemia following exposure to butadiene.      

Growth hormone (GH) profiles in response to continuous subcutaneous infusion of GH-releasing hormone(1— 29)-NH2 in children with GH deficiency

Six children presenting with partial growth hormone (GH) deficiency (mean GH peak in two different tests, 8.0 k1.3 μ g/l ) aged 8–10.3 years (mean, 2.7 ± 0.9 years) were treated for 6 months by continuous subcutaneous infusion of GH-releasing hormone(1–29)-NH, (GHRH(1–29)-NH₂); 24-hour GH profiles and height velocity were measured. A biphasic effect of GHRH(1–29)-NH₂ infusion was observed. After an early substantial increase in the 24-hour integrated concentration of GH, from 1.6 ± 0.1 to 3.5 ± 0.7 μg/l/minute, a subsequent consistent decrease occurred by 3 months, which was more pronounced after 6 months (mean 24-hour integrated concentration of GH, 1.9± 0.9 μg/l/minute). This effect reflects modification of both pulse amplitude and frequency of GH secretion. At the end of the study, one child had complete suppression of GH secretion and two others showed only one peak above 5 μg/1 during a 24-hour period. No correlation was found between these changes and height velocity. Three children did not grow significantly; the other three children who had a growth response to GHRH(1–29)-NH₂ were those with the lowest 24-hour integrated GH concentration at the end of the study. The possible mechanisms involved in this biphasic effect, including GHRH antibodies, changes in somatostatin levels and/or desensitization of pituitary GHRH receptors, have been investigated.