Cable guys. Teaming up with CTEs (communication technology engineers) can untangle your communication infrastructure.
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Biomedical subjects
Publications and source records attributed to E Campbell.
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Teledermatology can be defined as the use of imaging and telecommunications technologies to provide skin care services at a distance. The potential value of teledermatology is especially great in rural and medically underserved areas that do not have, or cannot support, providers specializing in the diagnosis and management of skin diseases. Rural patients and primary care providers should be able to use teledermatology as a greatly simplified and potentially less expensive means of referral to an urban dermatologist. In an effort to gauge the impact of a simple teledermatology system on referral patterns and the management of rural patients with skin disorders, we studied baseline rates of referral to dermatologists from five primary care clinics in rural Oregon. Economical, easy-to-use teledermatology systems were subsequently installed, and the effects on patient referral and management were recorded over time. The interim results suggest that primary care providers (PCPs) are reluctant to refer patients with skin conditions, even when the primary care providers confidence in the correct diagnosis and treatment plan for that condition are relatively low. The installation of a teledermatology system increases the number of patients referred for specialist evaluation dramatically, even while the number of in-person visits to specialists fell. Although diagnostic agreement between dermatologists and primary care providers was mixed, a marked difference was found in their recommended treatment plans. A number of cases were found in which use of the telemedicine technology system resulted in reversing conditions that had been poorly controlled for a number of years prior to teleconsultation. This work is important as an indicator that referral rates to dermatologists may be inappropriately low in rural areas of the U.S., and that use of teledermatology may improve this trend.
Humanized anti-Tac (HAT) and Mik beta1 (HuMik beta 1) Abs directed at IL-2R alpha and IL-2R beta, respectively, inhibit IL-2 binding and biological activity and together act synergistically in vitro. The Abs have been used successfully in primate models of allograft rejection, graft-vs-host disease, and autoimmunity. We produced bifunctional humanized anti-IL-2R alpha beta Abs (BF-IgG) to combine the specificity of the two Abs into one entity by fusing HAT-producing NSO cells and HuMik beta 1-producing Sp2/0 cells. BF-IgG was purified using protein G-Sepharose affinity chromatography, followed by IL-2R alpha and IL-2R beta affinity chromatography and hydrophobic interaction chromatography. BF-IgG exhibited both anti-IL-2R alpha and anti-IL-2R beta specificities in binding assays. While the Ab binds the IL-2R with intermediate affinity (Kd = 2.82 nM), it does not inhibit IL-15 binding to its high affinity IL-15R. In Kit225/K6 (IL-2R alpha beta gamma+) cells, BF-IgG was 10-fold more potent than a HAT/HuMik beta 1 equimolar mixture in blocking IL-2-induced proliferation and, unexpectedly, was at least 65-fold more active than the mixture in blocking IL-15-induced proliferation. This dual inhibitory activity may be due to cross-linking of the IL-2R alpha and IL-2R beta, thus blocking IL-2 binding and possibly impeding the association of IL-2R beta with IL-15R. BF-IgG has potent immunosuppressant activities against both IL-2- and IL-15-mediated responses, and this antagonist could be more efficacious than HAT and/or HuMik beta 1 for the treatment of autoimmunity and the prevention of allograft rejection.
Familial Mediterranean fever (fMf) is an inherited condition characterized by polyserositis and is sometimes complicated by AA renal amyloidosis leading to nephrotic syndrome and renal failure. We present a case of a man with fMf who presented with rapidly progressive renal failure caused by light chain deposition disease. This disease association has not previously been described in the medical literature.
A proportion of human breast cancers result from an inherited predisposition to the disease. Mutations in the BRCA2 gene confer a high risk of breast cancer and are responsible for almost half of these cases. The recent cloning of the human BRCA2 gene has revealed that it encodes a large protein having little significant homology to known proteins. Here we describe the mouse Brca2 gene. The gene maps to mouse chromosome 5, consistent with its location on human chromosome 13q12. We have sequenced cDNA for the entire 3329 amino acid Brca2 protein and this has revealed that, like Brca1, Brca2 is relatively poorly conserved between humans and mice. Brca2 is transcribed in a diverse range of mouse tissues, and the pattern of expression is strikingly similar to that of Brca1. Taken together, our data highlight some intriguing similarities between two genes involved in inherited breast cancer susceptibility.
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Adozelesin, a synthetic analog of the antitumor antibiotic CC-1065, is a novel cytotoxic agent which inhibits DNA synthesis by binding to the minor groove of the DNA helix. Preclinical studies have shown a broad spectrum of activity against a variety of murine and human tumor xenograft models. We conducted a phase I study of adozelesin to (i) determine a recommended dose for phase II testing using a 10 min i.v. infusion, (ii) characterize the toxic effects of the drug using this schedule and (iii) document any antitumor activity observed. Adozelesin was administered as an i.v. infusion every 6 weeks. CBC and biological parameters were performed weekly. The starting dose of 10 microg/m2, corresponding to 1/30 the mouse equivalent lethal dose, was escalated, according to a modified Fibonacci scheme, until dose-limiting toxicity was encountered. Forty-seven adult patients with solid malignancies were entered in the study. Successive dose levels used were 10, 20, 33, 50, 70, 105, 120, 150 and 180 microg/m2. The main toxic effect was myelosuppression, which was dose limiting. The maximally tolerated dose was defined as 180 microg/m2. A minor response with a 4 month duration was reported in one previously treated patient with melanoma. We conclude that the recommended phase II dose of adozelesin given as a 10 min infusion is 150 microg/m2, repeated every 4 weeks.
A cross-sectional study using a structure interview was conducted with 304 women in the postnatal ward of a large NSW teaching hospital. Women were asked about any incontinence experienced in the last month of pregnancy, and about advice and interventions for bladder control or incontinence they had received during pregnancy. Sixty four per cent of women reported incontinence during pregnancy. Compared to women with no prior deliveries, those with a previous forceps delivery were 10 times more likely to experience incontinence, and with prior vaginal deliveries 4 times more likely to experience incontinence. Women who reported experiencing bouts of coughing on a regular basis during pregnancy were 4 times more likely to experience incontinence than those who did not. While 68% of the women reported being examined vaginally at least once during pregnancy, only 6% of the sample reported having their pelvic floor muscles tested during routine vaginal examination. Twenty three per cent of women reported having spoken with a healthcare professional regarding loss of bladder control. The results indicate that opportunities for continence promotion are not being utilized.
The therapeutic application of high-dose interleukin (IL) 2 in human malignancy is limited by severe multiorgan toxicities that are mediated, in part, by tumor necrosis factor (TNF) and IL-1. CT1501R (lisofylline; LSF) is one of several methyl xanthine congeners that inhibit the effects of TNF by the interruption of specific signal transduction pathways. This randomized, placebo-controlled trial was designed to assess the activity of LSF in reducing the toxicities of high-dose IL-2 therapy. Fifty-three patients with metastatic renal cancer or malignant melanoma were treated with i.v. bolus IL-2, 600, 000 IU/kg every 8 h for 5 days (14 doses), followed by 9 days of rest and another 5-day course of IL-2. Patients were randomly assigned to LSF, 1.5 mg/kg i.v. bolus, or placebo every 6 h during IL-2 therapy. All patients were to be treated to individual maximum tolerance of IL-2 at the intensive care unit level of support. The end points for statistical analysis were the number of IL-2 doses administered during the first cycle of treatment (maximum, 28) and the toxicities experienced by each group after the first 8 planned IL-2 doses. There was no difference between the LSF and placebo groups in the mean number of IL-2 doses tolerated in the entire first cycle of therapy (19.6 +/- 5.4 versus 19.5 +/- 5.8, P = 0.86) or in the first or second 5-day course of IL-2. The only significant difference in toxicities occurring through the eighth dose of IL-2 was in the maximum elevation of serum creatinine (mean, 1.7 +/- 0.8 for placebo versus 1.5 +/- 0.6 mg/dl for LSF, P = 0.013). A Monte Carlo analysis of major toxicities over the first 14-dose course of therapy showed a statistically significant difference favoring the LSF-treated group (P = 0.025). LSF was well tolerated, associated only with mildly increased nausea (P = 0.006 after eight IL-2 doses, but not significant for the entire first cycle). The antitumor activity was comparable in both groups (objective responses, 2 of 28 with LSF versus 4 of 24 with placebo). The mean peak plasma concentrations of LSF on days 1, 5, and 19 were 6.24, 3.83, and 5.04 micromol/liter, respectively. In conclusion, with this dose and schedule, LSF did not alter the toxicities of high-dose i.v. IL-2 sufficiently to impact the overall dose intensity of IL-2. Successful IL-2 toxicity modulation may require the use of higher doses of LSF, the development of agents with more potent anti-TNF activity, and/or combined modulating agents that function via distinct mechanisms to interrupt cytokine-mediated signaling.
BACKGROUND: Despite growing acceptance of relationships between academia and industry in the life sciences, systematic, up-to-date information about their extent and the consequences for the parties involved remains scarce. We attempted to collect information about the prevalence, magnitude, commercial benefits, and potential risks of such relationships by surveying a representative sample of life-science companies in the United States to determine their relationships with academic institutions. METHODS: We collected data by telephone from May through September 1994 from senior executives of 210 life-science companies (of 306 companies surveyed; response rate, 69 percent). The sample contained all Fortune 500 companies in the fields of agriculture, chemicals, and pharmaceuticals; all international pharmaceutical companies with sales volumes similar to those of the Fortune 500 companies; and a random sample of non-Fortune 500 companies in the life sciences drawn from multiple commercial and noncommercial directories. Both the survey instrument and the survey methods resembled those of our 1984 study of 106 biotechnology companies, allowing us to assess the evolution of relationships between academia and industry over the past decade. RESULTS: Ninety percent of companies conducting life-science research in the United States had relationships involving the life sciences with an academic institution in 1994. Fifty-nine percent supported research in such institutions, providing an estimated $1.5 billion, or approximately 11.7 percent of all research-and-development funding received that year. The agreements with universities tended to be short-term and to involve small amounts, implying that most such relationships supported applied research or development. Over 60 percent of companies providing support for life-science research in universities had received patents, products, and sales as a result of those relationships. At the same time, the companies reported that their relationships with universities often included agreements to keep the results of research secret beyond the time needed to file a patent. From 1984 to 1994, the involvement of industry with academic institutions has increased, but the characteristics of the relationships have remained remarkably stable. CONCLUSIONS: After more than a decade of sustained interaction, universities and industries seem to have formed durable partnerships in the life sciences, although the relationships may pose greater threats to the openness of scientific communication than universities generally acknowledge. However, industrial support for university research is much smaller in amount than federal support, and companies are unlikely to be able to compensate for sizable federal cutbacks.
A selection of biphenyl-analogues of 2-amino-7-phosphonoheptanoic acid (AP7), N-methyl-D-aspartate (NMDA) receptor antagonists with high affinity in vivo efficacy. The lead compound SDZ EAB 515 was found to inhibit L-phenylalanine uptake by the large neutral amino acid carrier in vitro and in vivo; active transport may thus confer a good bioavailability to this class of compounds. CNS effects were demonstrated by significant changes in 2-deoxyglucose-uptake in various brain regions at doses from 1 to 10 mg/kg i.p. With the most active agent, SDZ 220-581, full protection against maximal electroshock seizures (MES) was obtained at oral doses of 10 mg/kg in rats and in mice. The compound had a fast onset (< or = 1 hr) and a long duration (> or = 24 hr) of action. Motor-debilitating effects (impairment of rotarod performance) occurred at doses about 10 times higher than those required for protection against MES. Neuroprotective activity was demonstrated by the ability of the compounds to reduce the extent of quinolinic acid-induced striatal lesions in rats, in the dose range of 3-15 mg/kg (i.p.) or 10-50 mg/kg (p.o.). In the middle cerebral artery occlusion (MCAO) model of focal cerebral ischemia in rats, the test compounds reduced the infarct size by 40-50% when given i.v. before or by 20-30% when given i.v. 1 hr after MCAO. SDZ 220-581 provided 20-30% protection at > or = 2 x 10 mg/kg p.o. This compound also showed analgesic activity at low oral doses in a model of neuropathic pain, although higher doses were required in model of mechanical inflammatory hyperalgesia. Unexpectedly, SDZ 220-581 at low s.c. doses counteracted the antiparkinsonian effects of L-DOPA in MPTP-treated marmosets. (Sub)chronic administration of SDZ 220-581 did not reduce its ability to protect against quinolinic acid neurotoxicity, and no upregulation of NMDA receptors was detected using a [3H]CGP-39653 binding assay. In conclusion, from a series of biphenyl-AP7-derivatives, SDZ 220-581 is clearly the most active compound in vivo. Its pharmacological profile with a good, long-lasting oral activity might open up novel therapeutic applications for competitive NMDA receptor antagonists.
To study the potential of the fluorquinolone, PD 117596 to cause arthropathy in experimental animals, immature rabbits were orally administered the drug for five days at 0, 100, 350, 500 and 750 mg/kg. Characterization of changes induced in major synovial joints was based on: macroscopic and histopathologic observations, transmission electron microscopic examinations and magnetic resonance imaging. Preferentially targeting the knee, PD 117596 produced vesicles and erosions in articular cartilage which resembled, morphologically, those described in other laboratory species. Lesion incidence was not clearly dose-related. In the perivesicular region, degenerate chondrocytes were intermixed with hypertrophic cartilage cells and chondrocyte clusters. Ultrastructurally, hypertrophic chondrocytes were the consequence of karyomegaly and RER proliferation. Matrix density was reduced due to collagen and proteoglycan loss. Joint structures were readily visualized by magnetic resonance imaging which identified thickened articular cartilage, surface irregularities consistent with ruptured vesicles and separation of opposing articular surfaces secondary to synovival effusions. The immature rabbit, although less sensitive than the juvenile dog to the arthropathic effects of quinolones, was nonetheless a good model to study this experimental osteoarticular disease.
The study assessed the effectiveness of a programme aimed at increasing medical students' skills in counselling patients presenting for HIV testing/AIDS information. Senior medical students were randomly assigned to receive a short course in pre- and post-test counselling, or to a control group which received the usual curriculum. The students' performance in counselling simulated patients was videotaped at baseline and after 3 months. A subsample was also assessed at 12 months. Students receiving the programme showed significantly greater improvement in pre- and post-test counselling skills over 3 months than did the controls. For the sub-sample continuing to 12 months, a significant effect over time was found; however, there was no significant difference between the groups. This may have been influenced by the small sample sizes used for the 12-month assessment. General interactional skills improved for the over-all sample over 3 and 12 months, but again there were no significant differences between groups. Those exposed to the programme did not show significantly greater changes in either knowledge or attitude scores over either time frame, compared with controls. When taught in addition to the usual undergraduate curriculum at Newcastle University, this short interactional skills course significantly enhanced students' ability to provide pre- or post-test counselling for HIV/AIDS.
This study sought the views of midwives and obstetricians about what they considered to be important aspects of routine antenatal care. Midwives and obstetricians were randomly selected from the NSW membership lists of the Australian College of Midwives and the The Royal Australian College of Obstetricians and Gynaecologists, respectively. Seventy-eight percent of midwives (n = 196) and 52% of obstetricians (n = 114) completed a questionnaire which itemised components of routine care derived from the National Health and Medical Research Council's Guidelines for Antenatal Care. Participants were asked to rate each of the 77 components on a 4-point scale as either: very important; desirable but not essential; not necessary; or, don't know. Twenty-four (31%) of the components were rated as very important by at least 90% of midwives and 19 (22%) were rated as very important by at least 90% of obstetricians. 'Recording details of previous pregnancy complications' was the component most commonly rated as being very important by both groups. On 37 (48%) of the components there was a significant difference between midwives and obstetricians in terms of whether or not they rated the component as very important (p < 0.01). There were considerable differences between midwives' and obstetricians' views about the important components of routine antenatal care and a substantial proportion of both groups did not consider many of the components listed in the guidelines to be essential in routine care. The findings suggest that a revision of the current antenatal care guidelines is necessary.
Testicular hormones regulate the growth and development of the prostate. The presence of androgen receptors in prostatic tissue and their importance in the normal development of the prostate has been established. Age-related changes in the hormonal milieu, and perhaps steroid hormone receptor profile, could set in motion pathological changes leading to the onset of benign prostatic hyperplasia (BPH) or prostate cancer which primarily affect older men. The accumulation of dihydrotestosterone with age, the reawakening of the inductive potential of the prostatic stroma, the altered rate of apoptosis with age, and the age-related changes in the ratio of testosterone:estrogen have all been implicated in the etiology of BPH. In addition to androgen receptors, several studies have documented the presence of estrogen and progesterone receptors in BPH and prostate cancer. So far, most studies have focussed on the correlation between the presence/absence of steroid hormone receptors and response to hormonal therapy. The molecular mechanisms by which these steroid hormone receptors regulate the onset or progression of BPH and prostate cancer are not yet clear. The chronological changes in the levels and distribution of steroid hormone receptors in normal prostatic tissue and the effect of such changes on the synthesis of growth factors, growth factor receptors, and oncogenes should be investigated.
The POU-domain transcription factor Oct-2 is expressed in both B lymphocytes and sensory neurones, where its expression is regulated by nerve growth factor (NGF). In order to define a possible role for Oct-2 in neurotrophin signalling, we examined the expression of an NGF-regulated channel (capsaicin-evoked ion fluxes), neuropeptides (substance P, calcitonin gene-related peptide), structural proteins (neurofilaments and peripherin) and receptors (trks) in dorsal root ganglion neurones derived from perinatal transgenic mice containing a defective Oct-2 structural gene. Northern blots show that central nervous tissue contains a larger than normal (> 10 kb) mRNA transcript corresponding in size to an Oct-2 transcript encoding a defective protein. PCR analysis shows the absence of normal Oct-2 transcripts in dorsal root ganglia. In null mutants, capsaicin sensitivity, and neuropeptide and cytoskeletal protein expression were unaffected by the loss of Oct-2 expression. The number of sensory neurones and the gross morphology of CNS tissues that normally express high levels of Oct-2 were also examined and found to be normal in the null mutant. Heterozygous animals show normal thresholds of sensitivity to noxious heat and normal inflammatory responses. Oct-2 does not therefore play an essential role in the NGF responsiveness of sensory neurones in these animals.
Differences in psychological well-being between participants in wheelchair sport with congenital (n = 50) and acquired (n = 43) disabilities were examined. Psychological well-being was assessed by scores on mood, trait anxiety, self-esteem, and mastery. Analysis showed that the group with acquired disabilities had a more positive general mood, higher self-esteem and mastery, and lower trait anxiety than the group with congenital disabilities. This suggests that sports participants in wheelchairs who acquired their disabilities later in life have more positive scores on psychological well-being than those with congenital disabilities.
Because the kidney is the major excretory organ for drugs and toxins, it is especially susceptible to damage from such agents. While alternative medical therapies appear to be on an increase worldwide, there have been few case reports regarding their nephrotoxicity. However we have recently observed three patients who developed irreversible renal impairment, which we believe was due to such therapies.