Managing HIV. Part 7: Professional issues. 7.2 HIV and confidentiality.
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Biomedical subjects
Publications and source records attributed to M Scott.
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The major secreted pectin lyase (E.C. 4.2.2.10) from Aspergillus niger, strain 4M-147, has been purified and crystallized by the hanging-drop method using polyethylene glycol as precipitant. The crystals belong to the space group P2(1)2(1)2(1) with cell dimensions a = 45.2, b = 83.2, c = 93.1 A (1 A = 0.1 nm) and a single molecule in the asymmetric unit. The crystals diffract to at least 2.0 A resolution and are suitable for structure determination.
Apply the science, use a team approach, help patients to promote their own health, ensure access to support and accept a public health role. These are the practical lessons of our experience in HIV medicine.
To investigate IGF-I resistance in African Efe Pygmies, we examined clonal responsiveness to IGF-I in Epstein-Barr virus-transformed B-lymphocytes from three Efe Pygmies and three American control subjects. The Efe B-lymphoblasts did not increase clonal responsiveness when incubated with IGF-I (as high as 250 micrograms/liter) in contrast to the control B-lymphoblasts which showed a bimodal dose-response with a maximal stimulation of 50% above baseline. The proliferative response of Efe B-lymphoblasts was similar to that of control B-lymphoblasts when incubated with another growth factor, phorbol 12-myristate 13-acetate, which does not activate the IGF-I receptor. These findings indicate that Efe Pygmy B-lymphoblasts are resistant to IGF-I as measured by in vitro clonal proliferation assays. Coupled with our previous report of IGF-I unresponsiveness in Efe Pygmy HTLV-II-transformed T-lymphocytes, these data suggest that IGF-I resistance is generalized and may play a central role in the etiology of short stature in this population.
The mechanism by which estradiol, testosterone, 1,25(OH)2 vitamin D3, and triiodothyronine promote tissue growth is unknown, although, in some tissues, a role for local IGF-I has been suggested. We previously showed that HTLV-II-transformed T-cell lines from healthy adults augmented basal colony formation in response to peptide (growth hormone, parathormone, and adrenocorticotrophin) and glycoprotein (thyroid-stimulating hormone) hormones through stimulation of local IGF-I. T-cell lines from African Efe Pygmies, however, were resistant to the direct growth-promoting action of IGF-I, as well as to the growth-promoting action of growth hormone, parathormone, adrenocorticotrophin, and thyroid-stimulating hormone. We, therefore, used these cell lines to determine the mechanism of T-cell growth in response to steroid and thyroid hormones. We quantified colony formation of American control T-cell lines in the presence and absence of alpha IR-3 antibody against the type 1 IGF receptor and Pygmy T-cell lines in response to estradiol (36.7-1835 pmol/ liter), testosterone (34.7-17,350 pmol/liter), 1,25(OH)2 vitamin D3 (2.4-24,000 pmol/liter), and triiodothyronine (1536-192,000 pmol/liter). There were no statistically significant differences by ANOVA in overall response curves for any of the four hormones comparing control clonal responses in the presence or absence of alpha IR-3 and no statistically significant difference in overall responsiveness between control and Pygmy T-cell lines. From these data, we conclude that (i) normal T-cell lines grow in response to estradiol, testosterone, 1,25(OH)2 vitamin D3, and triiodothyronine; (ii) these responses are not mediated through local IGF-I since they are not blocked by pretreatment with antibody to the type 1 IGF receptor; and (iii) Pygmy T-cell lines, which are genetically resistant to IGF-I, grow equivalently to control T-cell lines in response to estradiol, testosterone, 1,25(OH)2 vitamin D3, and triiodothyronine, further underscoring the IGF-I independence of this stimulation in our system.
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Mirfentanil [N-(2-pyrazinyl)-N-(1-phenethyl-4-piperidinyl)-2-furamide] was studied for its antinociceptive and immunomodulatory effects in mice Mirfentanil (1.0-32.0 mg/kg) increased tail-flick latency to a thermal stimulus and this effect was antagonized (94 +/- 2%) by naltrexone (10.0 mg/kg). Unlike naltrexone, the delta opioid selective antagonist naltrindole (20.0 mg/kg) had no effect on mirfentanil-induced analgesia. In a dose-dependent fashion, the mu-selective antagonists beta-funaltrexamine (1.0-40.0 mg/kg) and naloxonazine (1.0-35.0 mg/kg) blocked mirfentanil (10.0 mg/kg)-induced analgesia up to 75% of the maximum analgesic effect. Norbinaltorphimine (10.0 mg/kg) partially blocked (35%) the maximum analgesic effect following mirfentanil (10.0 mg/kg) administration. Single doses of mirfentanil (0.1-32.0 mg/kg) had no effect on splenic NK activity. However, preadministration of mirfentanil (1.0-10.0 mg/kg) blocked morphine-induced suppression of splenic NK activity. Collectively, the results suggest that mirfentanil is a novel opioid that induces antinociception predominately through mu opioid receptors but, unlike morphine or fentanyl, does not suppress splenic NK activity.
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High-dose chemotherapy followed by autologous bone marrow transplantation (ABMT) enables dose escalation in the treatment of childhood malignancies. Here we report our experience of using peripheral blood progenitor cells (PBPC) to restore haematopoiesis in five children using a simple cell mobilising regime and non-cryopreservation of the harvests. Cells were mobilised using cyclophosphamide and granulocyte colony stimulating factor. Each patient underwent only two leukaphereses, the product being stored before use at 4 degrees C. Successful autologous PBPC transplantation was achieved with melphalan conditioning chemotherapy and re-infusion of the total progenitor cell product. No colony stimulating factors were administered after transplantation. The median numbers of mononuclear cells collected per patient was 10.0 x 10(8)/kg (range 8.13-19.44) and CFU-GM 57.6 x 10(4)/kg (range 10.4-178.85). All patients subsequently engrafted with the median number of days to a neutrophil count > 0.5 x 10(9)/l being 11 (range 10-16), and to a platelet count > 50 x 10(9)/l being 14 (range 12-31). The median number of in-patient days was only 20 (range 19-30). The median demand for blood was 2 units (range 1-2), and platelets 4 units (range 2-28). Usage of systemic antimicrobials and intravenous feeding was also low. Using this simple strategy, collection and transplantation of autologous progenitor cells can be a straightforward procedure in children. It is possible that this could enable dose escalation in some poor prognosis paediatric tumours.
BACKGROUND: Three antireflux operations-gastroplasty, fundoplication, and anterior gastropexy-were developed for performance at flexible endoscopy without laparotomy or laparoscopy. METHODS: An endoscopic sewing machine mounted on a standard gastroscope, endoscopic knotting devices, overtube, and nylon thread were used to perform these operations in adult beagle dogs. RESULTS: Gastroplasty (n = 10) was accomplished by suturing the anterior and posterior wall of the stomach to create a gastric tube (neoesophagus) along the lesser curve. An anatomic arrangement similar to fundoplication (n = 6) was achieved by invaginating the esophagus and fixing it to the stomach 2 cm distal to the cardioesophageal junction. Anterior gastropexy (n = 6) was performed using a technique similar to that used in creating percutaneous gastrostomies. There was no mortality. Ninety percent of sutures were seen at repeat endoscopy at 4 to 8 week intervals. The gastroplasty group was selected for more extensive evaluation. Manometry using a three-channel perfused catheter system before and after the procedures showed an increase in the lower esophageal sphincter pressure (preoperative median 4.6 mm Hg; post-operative median 13.33 mm Hg, p = 0.008) and cardiac yield pressures (preoperative median 10 mm Hg; postoperative median 19 mm Hg, p = 0.007). CONCLUSIONS: This study demonstrates the feasibility of performing antireflux operations at flexible endoscopy, without laparoscopy or laparotomy, by use of endoluminal suturing techniques.
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168 Rh specific monoclonal antibodies (Mabs) were evaluated in 43 laboratories. Red cells from 63 Rh variant phenotype donations were circulated in panels to evaluators. Circulation was organised to ensure adequate duplicate testing. Evaluators were asked to test each Mab at 3 dilutions in two specified techniques against normal phenotype cells, panel cells received and any other Rh variant cells they had available. Results were analysed by expressing the sum of reaction grades for each Mab with each variant cell as a percentage of the sum of reaction grades of that Mab with normal phenotype cells. Reactions with enzyme-treated cells were found to be highly variable between laboratories, and further analysis of these results was not attempted. Anti-D Mabs were sorted into groups which had the same pattern of reactions with different phenotype cells. 24 such patterns were identified, 17 corresponding to previously reported patterns and 7 new ones.
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Recently new criteria for diagnosing vascular dementia (VaD) have been suggested by (a) the State of California Alzheimer's Disease Diagnostic and Treatment Centres (ADDTC) and (b) the NINDS-AIREN group after an international workshop convened by the National Institute for Neurological Disorders and Stroke (NINDS), with support from the Association Internationale pour la Recherche et l'Enseignement en Neurosciences (AIREN). We have retrospectively applied the new criteria to two groups of patients who are thought by us to be suffering from VaD. The first group (20 patients) had a raised Hachinski Ischaemic Score, i.e. 7 or more (mean HIS = 9.5), and a second group (20 patients) with an HIS between 4 and 6 points (mean HIS = 4.9). In group 1, 19 patients fulfilled the ADDTC criteria for probable or possible VaD, compared with 16 patients who fulfilled the NINDS-AIREN criteria. In group 2, 11 patients fulfilled the ADDTC criteria for probable or possible VaD, compared with only five patients who fulfilled the NINDS-AIREN criteria. This suggests that the ADDTC criteria may be more sensitive than the NINDS-AIREN criteria and the HIS. However, post-mortem validation studies of the new criteria are needed to determine if the improved sensitivity of the ADDTC criteria is at the expense of their specificity.
The effect of leukoaraiosis or white matter low attenuation (WMLA) on cognitive function is not fully understood. We compared the neuropsychological performance of 37 Alzheimer's disease patients with WMLA on CT brain scans with a similar group of 31 Alzheimer's disease patients with no evidence of white matter lesions. Patients with WMLA performed significantly worse on tests of visuospatial function (Cube Analysis test, p = 0.004), and cognitive speed (Kenrick Digit Copying test, p = 0.05) compared to those with no visible white matter lesions. Patients with widespread WMLA performed generally worse in tests of cognitive function than those with frontal or a mixture of frontal and occipital WMLA. This was most significant in the areas of attention (forward digit span, p = 0.003), visual recognition (p = 0.004), and cognitive speed (p = 0.03). There is an association between impaired cognitive performance and the presence of WMLA in Alzheimer's disease patients, with WMLA probably contributing to the cognitive impairment. This is most evident in patients with widespread white matter lesions.
Epstein-Barr virus (EBV)-encoded latent membrane protein (LMP) has been detected in various reactive and neoplastic lymphoproliferations and in some epithelial malignancies. However, data are lacking on LMP immunoreactivity in normal and neoplastic hematopoietic cells. Therefore, the authors studied LMP staining in 29 paraffin-embedded tissues containing these cells and correlated the findings with polymerase chain reaction (PCR) analysis for a EBV-BAM HI W genome sequence in 15 of these cases. Latent membrane protein immunostains showed strong uniform marking of normal early myeloid and erythroid precursors, whereas neutrophils, bands and late normoblasts were negative. Leukemic myeloblasts and lymphoblasts were also strongly positive for LMP. Polymerase chain reaction analysis showed no evidence of EBV-BAM HI W genome in 13 cases with amplifiable DNA. This study indicates normal hematopoietic precursor cells and leukemic blasts mark strongly with monoclonal LMP antibody. Furthermore, the absence of EBV genome in these tissues suggests a lack of specificity of monoclonal LMP for EBV-infected cells in the marrow.
We describe a patient who had a left hilar mass initially diagnosed as probable bronchogenic carcinoma. When a paradoxic arterial embolus led to further investigation, the hilar mass was found to be a poststenotic dilatation due to a severe pulmonary valve stenosis. Percutaneous balloon valvuloplasty of the pulmonary valve was successfully done, and the patient is well 2 years after the procedure.