Biomedical subjects
M Harris
Publications and source records attributed to M Harris.
Evidence of nerve sheath differentiation and high grade morphology in sclerosing epithelioid fibrosarcoma.
Sclerosing epithelioid fibrosarcoma is a recently described sarcoma in which ultrastructural evidence of fibroblastic differentiation forms part of the diagnostic criteria. This report describes a further case of this tumour, which showed evidence of both fibroblastic and perineurial differentiation by immunohistochemistry and electron microscopy, and which had areas of high grade morphology. The tumour metastasised and the patient died of disease 12 months after presentation. The relevance of these findings to diagnosis and differentiation in these tumours is discussed.
Transcriptional regulation of the thyrotropin-releasing hormone gene by leptin and melanocortin signaling.
Starvation causes a rapid reduction in thyroid hormone levels in rodents. This adaptive response is caused by a reduction in thyrotropin-releasing hormone (TRH) expression that can be reversed by the administration of leptin. Here we examined hypothalamic signaling pathways engaged by leptin to upregulate TRH gene expression. As assessed by leptin-induced expression of suppressor of cytokine signaling-3 (SOCS-3) in fasted rats, TRH neurons in the paraventricular nucleus are activated directly by leptin. To a greater degree, they also contain melanocortin-4 receptors (MC4Rs), implying that leptin can act directly or indirectly by increasing the production of the MC4R ligand, alpha-melanocyte stimulating hormone (alpha-MSH), to regulate TRH expression. We further demonstrate that both pathways converge on the TRH promoter. The melanocortin system activates the TRH promoter through the phosphorylation and DNA binding of the cAMP response element binding protein (CREB), and leptin signaling directly regulates the TRH promoter through the phosphorylation of signal transducer and activator of transcription 3 (Stat3). Indeed, a novel Stat-response element in the TRH promoter is necessary for leptin's effect. Thus, the TRH promoter is an ideal target for further characterizing the integration of transcriptional pathways through which leptin acts.
Outpatient management of low-velocity gunshot-induced fractures.
This prospective study evaluated the efficacy of an outpatient management protocol for patients with a gunshot-induced fracture with a stable, nonoperative configuration. Forty-one patients (44 fractures) with a grade I or II open, nonoperative fracture secondary to a low-velocity missile comprised the study population. Patients were treated by a standard protocol, which included 1 g of cefazolin administered in the emergency room and a 7-day course of oral cephalexin. Follow-up visits were performed until complete wound and fracture healing were achieved. Thirty-two (78%) of 41 patients underwent full follow-up. Average follow-up was 5.2 months. One (2.8%) fracture (distal fibula) developed a superficial infection, which responded to an additional week of oral antibiotics, and no patient developed a deep infection. There was 1 delayed union and 2 patients with painful retained shrapnel. These results demonstrate that patients with stable, low-velocity, gunshot-induced fractures can be managed effectively and safely on an outpatient basis using this protocol.
Promoting research in forensic psychiatry.
Explore the source record for details and available documents.
Factors associated with frequent admission to hospital for patients with chronic airflow limitation.
BACKGROUND: Chronic airflow limitation (CAL) is a common cause of admission and readmission to hospital. This study has explored associated factors with repeat hospital admission in patients with CAL. METHOD: A retrospective file review of patients admitted more than once to hospital during the 1999 calendar year, with a diagnosis of CAL. RESULTS: Two hundred and two patients admitted with CAL accounted for 284 admissions and 1815 bed days. Of these, 46 patients were admitted more than once accounting for 115 (40.5%) admissions and 730 (39.8%) bed days. The study found evidence of general practice involvement in 35 (30.5%) admissions immediately before presentation at the hospital emergency department (ED). The discharge summary following that admission revealed only 67 (54%) were referred back to their general practitioners for follow up. The number of admissions attending the ED between the hours of 9.00 am and 5.00 pm were 62 (53.9%) and 96 (83.5%) between the hours of 7.00 am and 10.00 pm. CONCLUSION: Treatments given in hospital were similar, in most cases, to what could be provided at home with appropriate community based support. General practitioners were involved in approximately one-third of those patients requiring admission or re-admission to hospital.
Aminophylline does not protect against radiocontrast nephropathy in patients undergoing percutaneous angiographic procedures.
BACKGROUND: Radiocontrast nephropathy (RCN) is one of the leading causes of hospital-acquired acute renal insufficiency. Adenosine, a renal vasoconstrictor, is thought to play a role in RCN. In this study, aminophylline, a non-selective adenosine-competitive inhibitor, was evaluated as a potential agent to protect against RCN. METHODS: Twenty-six patients treated with 200 mg intravenous aminophylline immediately prior to percutaneous coronary and peripheral procedures were individually matched to 26 controls for baseline creatinine (Cr), diabetes mellitus and amount of contrast used. The aminophylline-treated group was also similar to control with respect to baseline ejection fraction, amount of post-procedure hydration, age, blood pressure and the use of nephrotic drugs. RESULTS: There was no significant difference between the change from baseline Cr to peak measured Cr in either cases or controls. Also, when a change in Cr > or =25% from baseline was considered significant, Fisher's exact test did not show a difference between the 2 groups. CONCLUSION: Aminophylline does not appear to add a protective role in preventing against RCN in patients undergoing percutaneous angiographic procedures.
Enhanced primary care items. Their use in diabetes management.
BACKGROUND: The Enhanced Primary Care (EPC) items for care planning and case conferencing provide an opportunity for better quality care for people with chronic disease. OBJECTIVE: To explore the use of the EPC items in the structured care of diabetes based on evidenced based guidelines in general practice. DISCUSSION: Care planning and case conferencing are useful, especially in the structured care of patients who have poor control. The achievement of better health outcome for these patients depends upon a patient oriented and structured approach in collaboration with other health professionals. This needs to be supported by systems within the practice, Division and local community.
Leptin regulates prothyrotropin-releasing hormone biosynthesis. Evidence for direct and indirect pathways.
The hypothalamic-pituitary-thyroid axis is down-regulated during starvation, and falling levels of leptin are a critical signal for this adaptation, acting to suppress preprothyrotropin-releasing hormone (prepro-TRH) mRNA expression in the paraventricular nucleus of the hypothalamus. This study addresses the mechanism for this regulation, using primary cultures of fetal rat hypothalamic neurons as a model system. Leptin dose-dependently stimulated a 10-fold increase in pro-TRH biosynthesis, with a maximum response at 10 nm. TRH release was quantified using immunoprecipitation, followed by isoelectric focusing gel electrophoresis and specific TRH radioimmunoassay. Leptin stimulated TRH release by 7-fold. Immunocytochemistry revealed that a substantial population of cells expressed TRH or leptin receptors and that 8-13% of those expressing leptin receptors coexpressed TRH. Leptin produced a 5-fold induction of luciferase activity in CV-1 cells transfected with a TRH promoter and the long form of the leptin receptor cDNA. Although the above data are consistent with a direct ability of leptin to promote TRH biosynthesis through actions on TRH neurons, addition of alpha-melanocyte-stimulating hormone produced a 3.5-fold increase in TRH biosynthesis and release, whereas neuropeptide Y treatment suppressed pro-TRH biosynthesis approximately 3-fold. Furthermore, the melanocortin-4 receptor antagonist SHU9119 partially inhibited leptin-stimulated TRH release from the neuronal culture. Consequently, our data suggest that leptin regulates the TRH neurons through both direct and indirect pathways.
Multifidus spasms elicited by prolonged lumbar flexion.
STUDY DESIGN: The electromyogram of the L1-L7 multifidus muscles of the in vivo cat were recorded while applying a prolonged steady displacement to the lumbar spine through the L4-L5 supraspinous ligament, simulating a moderate anterior flexion. OBJECTIVE: To demonstrate that tension-relaxation and laxity of the viscoelastic structures (ligaments, discs, and capsules) induced by prolonged static flexion of the spine results in loss of reflexive muscular stabilizing activity and in muscular disorders that may lead to or are associated with low back pain. SUMMARY OF BACKGROUND: Epidemiologic data show that prolonged loading of the spine, such as in some occupational activities, can cause low back pain and muscle spasms. Direct experimental evidence linking prolonged loading to a decrease in spinal stability, low back pain, and muscle spasms was not found. It was hypothesized, however, that mechanoreceptors in the viscoelastic structures, when strained, reflexively activate the multifidus muscles to maintain intervertebral stability; that the reflexive muscular activity decreases with stress-relaxation and laxity in the viscoelastic structures; and that when severe strain and possible damage of the viscoelastic structures occurs with time, nociceptive receptors elicit spasms in the musculature and possible pain. METHODS: The lumbar spine of seven in vivo cat preparations was displaced through the L4-L5 supraspinous ligament into moderate flexion that was steadily maintained for 50 minutes while intramuscular electromyograms were recorded from each of the multifidus muscles of L1-L2 through L6-L7. Load and electromyogram were continuously monitored and recorded. Five additional preparations were used as controls, in which dissection and recordings were identical, but the lumbar flexion was excluded. RESULTS: Prolonged flexion of the lumbar spine resulted in initial reflexive electromyogram from the multifidus muscles that decreased to approximately 5% of its initial value as tension-relaxation began in the viscoelastic structures within the first 3 minutes, after which, random and unpredictable electromyogram discharges (i.e., spasms) of high amplitude were recorded from different levels. In some preparations the spasms were present in L1-L4, and in others in all the levels. In other preparations the spasms were recorded only at L5 and L6. The onset of the spasms was also unpredictable, because they were initiated in some cases within 2-3 minutes after the spine was loaded. In other cases, the spasms were observed anytime during the test period and up to 20 minutes after the load was removed. Spasms were also observed in the spinalis and longissimus muscles. CONCLUSIONS: Prolonged flexion of the lumbar spine results in tension-relaxation and laxity of its viscoelastic structures, loss of reflexive muscular activity within 3 minutes and electromyogram spasms in the multifidus and other posterior muscles.
Regulation of integrin alpha vbeta 3-mediated endothelial cell migration and angiogenesis by integrin alpha5beta1 and protein kinase A.
Recent studies indicate that angiogenesis depends, in part, on ligation of integrin alpha(5)beta(1) by fibronectin. Evidence is now provided that integrin alpha(5)beta(1) regulates the function of integrin alpha(v)beta(3) on endothelial cells during their migration in vitro or angiogenesis in vivo. Secretion of fibronectin by endothelial cells leads to the ligation of integrin alpha(5)beta(1), which potentiates alpha(v)beta(3)-mediated migration on vitronectin without influencing alpha(v)beta(3)-mediated cell adhesion. Endothelial cell attachment to vitronectin suppresses protein kinase A (PKA) activity, while addition of soluble anti-alpha(5)beta(1) restores this activity. Moreover, agents that activate intracellular PKA, such as forskolin, dibutyryl cAMP or alpha(5)beta(1) antagonists, suppress endothelial cell migration on vitronectin in vitro or angiogenesis in vivo. In contrast, inhibitors of PKA reverse the anti-migratory or anti-angiogenic effects mediated by alpha(5)beta(1) antagonists. Therefore, alpha(v)beta(3)-mediated endothelial cell migration and angiogenesis can be regulated by PKA activity, which depends on the ligation state of integrin alpha(5)beta(1).
European Task Force on Lymphoma project on lymphocyte predominance Hodgkin disease: histologic and immunohistologic analysis of submitted cases reveals 2 types of Hodgkin disease with a nodular growth pattern and abundant lymphocytes.
Paraffin blocks and clinical data from 521 patients with lymphocyte predominance Hodgkin disease (LPHD) diagnosed between 1970 and 1994 were collected from 16 European and United States oncological centers to establish the pathologic and clinical characteristics of a large patient cohort, to determine how frequent T-cell-rich large B-cell lymphoma (TCRLBCL) is among LPHD, and to find differential diagnostic criteria distinguishing between the 2 lymphoma categories. For this purpose, conventionally and immunohistologically stained sections were reviewed by a panel of hematopathologists. The diagnosis of LPHD was confirmed in only 219 of the 388 assessable cases (56.5%). This low confirmation rate was due mainly to the presence of a new variant of classical Hodgkin disease (CHD), which resembled, in terms of nodular growth and lymphocyte-richness, nodular LPHD and, in terms of the immunophenotype of the tumor cells, CHD and was designated nodular lymphocyte-rich CHD (NLRCHD). The nodules of LRCHD consisted-as in nodular LPHD-predominantly of B cells but differed from those present in LPHD in that they represented expanded mantle zones with atrophic germinal centers. Clinically, patients with LPHD and NLRCHD showed similar disease characteristics at presentation but differed in the frequency of multiple relapses and prognosis after relapse. Patients with LPHD and NLRCHD clearly differed from patients with CHD with nodular sclerosis or mixed cellularity, as they presented with an earlier disease stage and infrequent mediastinal involvement. As 97% of the LPHD cases showed a complete or partial nodular growth pattern, their differentiation from TCRLBCL was a rare problem in the present series. (Blood. 2000;96:1889-1899)
The Eastman Jubilee 1948-1998.
The postgraduate Eastman Dental Clinic and Institute of Dental Surgery were established in 1947. However their roots go back to Rochester in New York State where George Eastman was born in 1854. George Eastman literally changed the image of the world by creating popular photography. In 1914 he was driven by his painful neglected dentition to seek the help of Harvey Jacob Burkhart (pictured, right) who was considered to be the best dentist in the state. Burkhart provided him, for the first time in his adult life, with comfortable dentures, which not only restored function but also his appearance. George Eastman was overwhelmed with his new found comfort and social confidence.
The genome sequence of Drosophila melanogaster.
The fly Drosophila melanogaster is one of the most intensively studied organisms in biology and serves as a model system for the investigation of many developmental and cellular processes common to higher eukaryotes, including humans. We have determined the nucleotide sequence of nearly all of the approximately 120-megabase euchromatic portion of the Drosophila genome using a whole-genome shotgun sequencing strategy supported by extensive clone-based sequence and a high-quality bacterial artificial chromosome physical map. Efforts are under way to close the remaining gaps; however, the sequence is of sufficient accuracy and contiguity to be declared substantially complete and to support an initial analysis of genome structure and preliminary gene annotation and interpretation. The genome encodes approximately 13,600 genes, somewhat fewer than the smaller Caenorhabditis elegans genome, but with comparable functional diversity.
Aging affects the retrobulbar circulation differently in women and men.
BACKGROUND: While aging clearly has protean biological effects on every organ system, the differential effects of aging in women and men in the retrobulbar vasculature, to our knowledge, have never been investigated. Because glaucoma and age-related macular degeneration are closely linked to advanced age, we performed a cross-sectional study using color Doppler imaging of 4 retrobulbar vessels in both healthy women and men. OBJECTIVE: To define the influence of aging per se on ocular hemodynamics. METHODS: Women (n = 73) and men (n = 55), aged from 20 to 90 years, free of ocular and systemic disease, and with normal intraocular pressure, were recruited for this study. Postmenopausal women who were not receiving estrogen replacement therapy were also recruited. Studies involved color Doppler imaging analysis of the ophthalmic, central retinal, and nasal and temporal posterior ciliary arteries. Ophthalmic arterial peak systolic and end-diastolic velocities and a Pourcelot resistance index were determined for each vessel. RESULTS: In both sexes, ophthalmic arterial end-diastolic velocity decreased and the Pourcelot resistance index rose with advancing age (each P<. 001); peak systolic velocity in the ophthalmic vessel was age-independent. In contrast, central retinal arterial flow velocities were unaffected by age in both sexes. In the posterior ciliary arteries, in men, flow velocities and the Pourcelot resistance index were independent of age. However, in women, end-diastolic velocity decreased with age in both the nasal and temporal posterior ciliary vessel (each P<.05); peak systolic velocity was constant; the Pourcelot resistance index in each ciliary artery rose with advancing age (each P<.05). CONCLUSION: In healthy women and men, aging-induced changes in retrobulbar hemodynamics are comparable to alterations seen in patients with glaucoma or age-related macular degeneration, suggesting that vascular changes with senescence may contribute to increased risk for these diseases in older age. Arch Ophthalmol. 2000;118:1076-1080
A modified nasopharyngeal tube to relieve high upper airway obstruction.
Infants with high upper airway obstruction (UAO) are managed with a variety of techniques to relieve their UAO. Among these techniques, the least invasive and safest is the nasopharyngeal tube (NPT). However, the traditional NPT is not always satisfactory, and tracheostomies need to be done. We recently described a modified NPT technique that, in contrast to the traditional tube, does not add airway dead space and resistance, is easy to use, is well-tolerated, has proven highly successful, and allows the simultaneous use of oxygen nasal prongs. This modified NPT has many advantages over the traditional NPT as a temporary management of high UAO that resolves with growth of the infant. This report highlights the respiratory care of 10 infants with high UAO (Pierre Robin syndrome, Down syndrome, Goldenhar syndrome, isolated microngathia, and idiopathic hypotonia) who were managed with a modified NPT. The modified NPT described potentially reduces the need for surgical intervention to relieve high UAO in infants.
Biexponential recovery model of lumbar viscoelastic laxity and reflexive muscular activity after prolonged cyclic loading.
OBJECTIVES: To determine the rest duration required for full recovery of reflexive muscular activity and laxity/creep induced in the lumbar viscoelastic structures (e.g., ligaments, discs, etc.) after 50 min of cyclic loading, and to develop a model describing such recovery. BACKGROUND: It is well established that steady, cyclic or vibratory loading of the lumbar spine induces laxity/creep in its viscoelastic structures. It was also shown that such viscoelastic creep does not fully recover when subjected to rest equal in duration to the loading period. Rest periods of 24 h, however, were more than sufficient to allow full recovery. The exact period of time allowing full recovery of viscoelastic laxity/creep, and its pattern is not known. It is also not known what is the duration required for full recovery of reflexive muscular activity lost due to the laxity/creep induced in the spine during cyclic loading. METHODS: The lumbar spine of 'in vivo' feline preparations was subjected to 50 min of 0.25 Hz cyclic loading applied v ia the L4/5 supraspinal ligament. At the end of the loading period the spine was subjected to prolonged rest, interrupted by a single cycle loading applied hourly for measurement purposes until the laxity was fully recovered (>90%). Reflexive EMG activity was recorded with wire electrodes from the L-1-L-7 multifidus muscles. A biexponential model was fitted to the load and EMG recorded in the recovery period in order to represent viscous and elastic components of structures with different architecture (e.g., disc vs. ligament). RESULTS: Full recovery of the laxity induced by 50 min of cyclic loading at 0.25 Hz required 7 h and was successfully fitted with a biexponential model. Similarly, EMG activity was fully recovered in 4 hours, and often exceeded its initial value during the following 3 h. CONCLUSIONS: Full recovery of laxity induced in the lumbar viscoelastic structures by a given period of cyclic loading requires rest periods, which are several folds longer than the loading duration. Similarly, reflexive muscular activity requires 4 h of rest in order to be restored. Meanwhile, significant laxity can be present in the joints, exposing the spine to potential injury and low back pain. Increased EMG activity at the end of the recovery period may indicate that pain was possibly induced in the spinal structures, inducing hyperexcitability of the muscles during passive loading. RELEVANCE: Although the data was derived from a feline model, and its extrapolation to the human model is not straightforward, the general pattern of decreasing reflexive muscular activity with cyclic loading is expected in both species. Therefore, workers who subject their spine to periods of cyclic loading may be exposed to prolonged periods of laxity beyond the neutral zone limits, without protection from the muscles and therefore the risk of possible injury and low back pain. Pain and muscle hyperexcitability could also be a factor associated with cyclic loading, being expressed several hours after work was completed.