37% fear contracting AIDS in hospital.
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Biomedical subjects
Publications and source records attributed to H Anderson.
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The sensory projections from mechanosensory hairs on different body segments of the locust were filled with cobalt and their distribution within the central nervous system was described. A common feature of all projections was that in all ganglia axons were observed only in the median ventral tract and in the neuropil area known as the ventral association center. Within these restricted regions, axons from different segments or from different locations within a segment showed specific differences in the extent of their projection.
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Three hundred and two previously untreated patients with Stage IA-IVB Hodgkin's disease were reviewed to determine the prognostic significance of mediastinal involvement. Mediastinal bulk disease was defined as either a maximal mediastinal width of 7.5 cm or more, or a ratio of the maximum width of mediastinal disease to the maximum chest diameter of greater than or equal to 0.33, or a ratio of the maximum width of mediastinal disease to the chest diameter at T5-T6 greater than or equal to 0.33, or as an area of mediastinal disease greater than or equal to 100 cm2. Bulk disease outside the chest was defined as a mass of lymph nodes measuring 5 cm or more in any axis. The presence of mediastinal bulk disease was of adverse prognostic significance for remission duration and survival in patients with Stage IA-IIB Hodgkin's disease, but for patients with more advanced disease the effect of mediastinal bulk on remission duration and survival was not statistically significant. The mediastinal bulk variable which most significantly related to prognosis was the ratio of the maximum mediastinal disease to the chest diameter at T5-T6.
Three new resins have been developed that allow for the solid phase synthesis of C-terminal peptide N-alkylamides using Boc amino acids, usual side chain protecting groups and hydrogen fluoride cleavage and deprotection. These resins were prepared by reacting the appropriate alkylamine (NH2CH3, NH2CH2CH3, NH2CH2CF3) to Merrifield's 1% divinylbenzene cross-linked chloromethylated polystyrene resin. The application of these resins to the synthesis of C-terminal GnRH N-alkylamides illustrates the versatility of this approach. GnRH analogs were tested for their ability to release LH from cultured rat anterior pituitary cells. [DGlu6, Pro9-NHCH2CH3]-GnRH was synthesized for the first time using the solid phase approach and found to be three times more potent than [DGlu6]-GnRH. Other analogs including [DTrp6, Pro9-NHCH2CH3]-GnRH, [DAla6, Pro9-NHCH2CF3]-GnRH and related peptides were found to be equipotent and to have the same properties (HPLC retention times, amino acid analysis and specific rotation) as the corresponding peptides synthesized using less amenable strategies; yields were equivalent or better than those reported earlier.
In epidemiologic studies, total recordings of the amount of dental plaque and the degree of gingival inflammation tend to be too time-consuming. Various partial recording methods have accordingly been suggested. However, the validity of these methods when applied to different age groups has not been investigated sufficiently. The aim of the present study was to test whether different systems for partial recording of plaque and gingivitis can take the place of a full-mouth recording in children of different ages and in young adults. Ninety children, divided into three age groups (4-6, 7-9, 14-16 yr), and 30 adults (20-22 yr) were examined. The degree of gingival inflammation was recorded using the Gingival Index and the amount of dental plaque using the Plaque Index. Two partial recording methods were tested. One of these covered the teeth suggested by Ramfjord, modified for children with a primary dentition, and the other the front segment of the maxilla. The results were compared with those from an examination of all tooth surfaces. In all age groups excellent agreement was found between the partial recording method suggested by Ramfjord and a full-mouth recording of both the gingival state and the amount of dental plaque. Examination of the maxillary front segment was less accurate and resulted in a systematic underestimate.
The contribution of the renal nerves in maintaining blood pressure and modulating renal prostanoid synthesis was examined in established (less than 8 wk in duration) one-kidney, one-clip (1K,1C) hypertension in the rat. Systolic blood pressure was measured for 7 days after renal denervation, at which time the renal artery clip was removed. Twenty-four-hour urinary excretion of PGE2 and 6-keto-PGF1 alpha (stable degradation product of PGI2) was determined before and after denervation and unclipping. Compared with sham-denervated rats, denervation (n = 15) resulted in a small but significant fall in blood pressure (from 216 +/- 4 to 182 +/- 4 mmHg after 48 h) and an increase in urinary 6-keto-PGF1 alpha (from 31 +/- 4 to 43 +/- 5 ng/24 h after 24 h). There was no change in PGE2 excretion. Seven days after surgery, blood pressures were similar in denervated (202 +/- 4 mmHg) and sham-denervated (211 +/- 5 mmHg) rats and fell to a similar extent 24 h after unclipping (142 +/- 3 and 147 +/- 4 mmHg, respectively). Urinary 6-keto-PGF1 alpha increased from 25 +/- 5 to 74 +/- 11 in denervated and 21 +/- 2 to 72 +/- 9 ng/24 h in sham-denervated rats in the 24 h after unclipping. PGE2 excretion increased approximately twofold over this period. These findings indicate that the renal nerves have only a minor role in established hypertension in the 1K,1C rat and that the reversal of hypertension and stimulation of renal prostanoid synthesis following unclipping is not dependent on neural mechanisms.
Opportunistic viral infections were investigated in 156 adult patients admitted over one year to a medical oncology service: 35% of the total group and 65% of those with acute leukaemia experienced viral infections, 79% of which were with viruses of the herpes group. Surprisingly few enteric viruses were recovered. Reactivation of herpes simplex virus in the brains of these immunosuppressed patients was suggested by the demonstration by nucleic acid hybridization of herpes simplex virus DNA sequences in neurones and endothelial cells in patients with evidence of past infection with virus. Acyclovir was effective in therapy and prophylaxis. Twenty-three strains from 7 patients were tested for sensitivity to this antiviral: in 3 instances clinical resistance was observed but the strains were fully sensitive in vitro, as were all other strains tested.
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In a series of grafting operations on cockroach legs, epidermal cells from different positions or from the same position on the circumference of the femur were placed together. Where cells from different positions were confronted, new cuticular structures corresponding to the positions which would normally have lain between them were formed during the following moults. At the control junctions, where cells from the same positions were placed together, no new structures were formed. Grafted legs were examined histologically at various times after the operation. The events following grafting fell into four phases: wound healing--when epidermal cells migrated over the wound to re-establish epidermal continuity and cells adjacent to the wound divided to compensate for cell emigration; intercalation--when cell divisions took place at the host-graft borders where there was a positional discrepancy; proliferation--when the general growth of the epidermis occurred by widespread cell division; cuticle secretion--when apolysis occurred, cell division ceased, and cuticle secretion began. The results show that intercalary regeneration is associated with local cell division at the graft-host borders, and that these divisions are not confined to the normal proliferative phase of the moult cycle, but begin much earlier in the cycle, as soon as wound healing is complete. These results support epimorphic models (such as the Polar Coordinate Model) of pattern regulation, where change of positional value is tied to cell division, but they do not discount the possibility of a limited initial morphallactic phase.
The location of peanut agglutinin (PNA) binding was investigated in the segmental ganglia of the developing grasshopper embryo. Neuronal processes were stained but cell bodies were not. The first appearance of PNA binding in development was associated with the first neurons to initiate axon outgrowth, the progeny of the MP2 cells. In the early stages of development the location of PNA binding was congruent with that of antibodies against horseradish peroxidase (HRP), which bind to neurons. In more advanced ganglia only a subpopulation of those neuronal processes that bound auti-HRP also bound PNA. The results suggest that PNA-binding sites are present only on those neuronal processes which are still developing and raise the possibility that these molecules may play a rôle in neurite outgrowth and navigation.
Neurons innervating wind-sensitive hairs on the locust head form characteristic projections and connections within the CNS. These depend on intrinsic properties of the epidermis from which the hair and its neuron are formed (Anderson & Bacon, 1979; Bacon & Anderson, 1984). To investigate further these intrinsic properties and also extrinsic factors involved in guiding axon growth and determining synaptic connectivity, pieces of epidermis from the head were transplanted to the posterior head, prothorax, or mesothorax. Thus wind-sensitive neurons developing from the grafts were caused to grow into foreign parts of the CNS. The neuronal projections from the graft hairs were examined by filling the axons with cobalt, and their connectivity with an identified interneuron, the Tritocerebral Commissure Giant, was examined by recording electrophysiologically the activity of the interneuron during stimulation of the graft hairs. The results show that the neuronal projections are confined to one tract, the median ventral tract, and to one arborization area, the ventral association centre, in all ganglia; in all ganglia, neurons from different epidermal regions preserve their location-specific properties of forming ipsilateral or additional contralateral projections; the extent of their projection in the CNS is not interpretable in terms of intrinsic instructions only; in foreign ganglia, they fail to form connections with their normal target interneuron.
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Biologically active peptides synthesized by the solid phase methodology of Merrifield were purified by reversed-phase high-performance liquid chromatography using newly developed preparative radially compressed cartridges fitting Waters Assoc . Prep LC 500 liquid chromatograph. Cartridges were handpacked with Vydac C18, C4 or diphenyl derivatized silicas (pore size 300 A) of different particle sizes (10-20 micron). Large scale purification of gram amounts of gonadotropin releasing hormone analogs (agonist and antagonist) as well as amidated human pancreatic tumor growth hormone releasing factor (a 40-peptide) illustrate the resolutive power of this technique applied to the isolation of more than 300 synthetic peptides in our laboratory over the last two years. Difficult separations were achieved by changing supports (C18, C4, diphenyl) as well as mobile phase composition: (triethylammonium phosphate pH 2.25 or 6.5, 0.1% trifluoroacetic acid, ammonium acetate pH 6.5 and acetonitrile). Protected amino acids and peptides amenable to normal-phase chromatography on Vydac spherical underivatized silica were purified economically by the reversed-phase mode. It is understood that this general, convenient and versatile strategy may be applicable to the preparative scale isolation of any other class of compounds usually separated on reversed-phase high-performance liquid chromatography.
One hundred and eleven patients with advanced-stage, high-grade histology non-Hodgkin's lymphoma were studied over a 7-yr period and were treated with one form of chemotherapy and radiotherapy. Multivariate analyses were carried out to identify factors which could predict a favourable prognosis. A complete response, low serum LDH and absence of clinical evidence of liver involvement were associated with long-term survival. The presence of 'B' symptoms, bone marrow involvement, low serum albumin and male sex predicted a reduced chance of achieving a complete remission. For those patients who achieved a complete response, the subdivision of histologies, particularly according to the Kiel classification, was the only significant factor predictive of prolonged relapse-free and overall survival. This confirms the importance of identifying different histological subgroups of lymphoma when considering treatment planning.
One hundred and fourteen untreated patients with pathological stage (PS) IA-IIB supradiaphragmatic Hodgkin's Disease were randomised to mantle radiotherapy alone (55) or mantle radiotherapy followed by 6 courses of adjuvant chemotherapy with mustine, vinblastine, prednisolone and procarbazine- MVPP (59). Patients excluded were those outside the age range 16-65 years and those with massive mediastinal disease precluding laparotomy. Bulk disease was defined as a mass of lymph nodes measuring five centimetres or more in any axis. Mediastinal bulk was present if the ratio of the maximum width of mediastinal disease to the maximal chest diameter was more than one third. All patients achieved a complete remission. Median duration of follow-up was 62 months (range 16-97). The relapse free survival (RFS) was 81%; 69% for radiotherapy alone and 93% for adjuvant chemotherapy (P = 0.002). RFS was also shown to be adversely affected by B symptoms (P = 0.0003), bulk disease (P = 0.018), abnormal CXR (P = 0.037), and increasing stage (P = 0.039). Age, sex, histology, and number of sites involved had no significant effect upon RFS. A Cox multivariate analysis showed that only three variables had a significant adverse effect on RFS - radiotherapy alone, the presence of bulk disease, and B symptoms. The overall 5 year survival was 93% with no statistically significant difference between the two treatment groups (P = 0.54). Survival was adversely affected by three variables - B symptoms (P = 0.02), the presence of bulk disease (P = 0.002), and pathological stage (P = 0.05). High risk groups for relapse are those with bulk and B symptoms. This analysis has shown that RFS was significantly improved by adjuvant chemotherapy, but that overall survival was not.
Forty-one patients receiving remission induction chemotherapy with vincristine, adriamycin and prednisolone (VAP) for high grade lymphoma or acute lymphoblastic leukaemia were entered into a double blind, placebo controlled trial of oral acyclovir prophylaxis against herpes simplex virus (HSV) infection. The dose of acyclovir was 200 mg four times daily for the duration of chemotherapy (six weeks). Of the 40 evaluable patients, 20 were randomised to each arm. Prophylactic oral acyclovir significantly reduced the incidence of clinical HSV infection from 60% on placebo to 5% acyclovir (P less than 0.001), and the incidence of viral isolates from 70% on placebo to 5% on acyclovir (P less than 0.001).
This paper reports the five-year follow-up (range, 1-8 years) of 56 patients with pathologic stage IIIA Hodgkin's disease randomized for chemotherapy alone or chemotherapy followed by radiotherapy to previous areas of disease (26 treated with mustine, vinblastine, procarbazine, and prednisolone [MVPP] alone, 30 with MVPP and radiotherapy). Of the 56 patients 53 (95%) achieved a complete remission with chemotherapy and of these only five (9%) have relapsed; three died of Hodgkin's disease. There was no improvement in relapse-free survival associated with the uses of radiotherapy following chemotherapy but in view of the small numbers of relapses and the excellent results following chemotherapy alone, a significant improvement could not be expected. The use of MVPP alone can be recommended as an alternative therapy for patients with stage IIIA Hodgkin's disease. This avoids both the physical and psychologic morbidity associated with the high relapse rate following extensive primary radiotherapy and the necessity of combined modality treatment for about half these patients. The question of whether radiotherapy should be given to areas of previous bulk following chemotherapy has not yet been answered in this trial which is continuing.