Concerns expressed about the virological risks of xenotransplantation.
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Biomedical subjects
Publications and source records attributed to S Skinner.
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The aim of this study was to assess if albumin infusion in hypotensive, preterm infants improved blood pressure (BP), metabolic acidosis and core peripheral temperature difference, indicating that such infants had been hypovolemic. Thirty-seven infants, median gestational age 27 weeks (range 23-34) were studied. Their mean BP, core-peripheral temperature difference, pH and base deficit prior to and post albumin infusion were compared. Albumin infusion was associated with BP elevation (p < 0.01) and a small reduction in the base deficit (p < 0.01), but no significant changes overall in the pH or peripheral core temperature difference. Similar results were seen if only 34 infants less than or equal to 4 days of age treated for their first episode of hypotension were considered, although in that group there was also a modest rise in pH (p < 0.02). These data suggest clinically relevant hypovolemia is uncommon in hypotensive, preterm ventilated infants and hence volume expanders are inappropriate routine first therapy.
Combretastatin A4P (CA4P) is a prodrug that, in active form, binds to tubulin microtubules of capillary endothelial cells. Studies to date indicate it has significant activity as a specific tumor vascular targeting agent. The goals were to assess the effects of CA4P on tumor growth and microvasculature of colorectal liver metastases in the mouse model, using stereological and histological methods to measure tumor growth, and vascular corrosion casting and laser doppler flowmetry to assess effect on the microvasculature. Continuous s.c. infusion of CA4P produced a major reduction in tumor growth. The percentage of the liver occupied by metastases decreased from 20.55 +/- 13.3% in controls to 7.46 +/- 5.99% in treated animals (P = 0.03). Ultrastructural study of tumor microvasculature after a single dose of CA4P revealed marked effects 1 h after treatment. There was loss of patent microvessels at the normal liver-tumor interface. Central microvascular density was reduced, with constriction and tapering of vessels. CA4P appeared to cause no damage to normal liver tissue or vasculature. Tumor blood flow decreased from 37.6 +/- 13.9% in controls to 24.4 +/- 6.1% in tumors >5 mm in diameter, 1 h after treatment with CA4P (P < 0.03). Quantitative histology of tissue at 6 and 24 h after CA4P treatment showed a significant increase in tumor necrosis (48.7 +/- 21% and 55.5 +/- 19% compared with controls, 20.6 +/- 8%; P = 0.01). Continuous infusion with CA4P causes marked reduction in tumor volume. A single dose of CA4P causes major changes of the tumor microvasculature, reduction of tumor blood flow, and increase in tumor necrosis. CA4P has a potential role in the management of patients with liver metastases.
PURPOSE: Anal incontinence is a socially disabling problem affecting 1 to 2 percent of the population. Anal sphincter replacement is a treatment option if the problem is severe and not amenable to direct repair. The artificial bowel sphincter is an innovative approach. We report the technique for placement and the outcomes which have occurred in an initial series of 13 patients. METHODS: The Acticon Neosphincter artificial bowel sphincter consists of an inflatable cuff of silicone elastomer placed around the anal canal and connected to a pressure-regulating balloon in the iliac fossa via a control pump placed in the labium or scrotum. Thirteen patients with severe anal incontinence not amenable to other methods were treated. Causes of incontinence included obstetric damage in eight patients, surgical damage in two patients, imperforate anus in two patients, and spina bifida in one patient. RESULTS: Surgical placement of the device was straightforward, mean operating time was 65 minutes, and median length of stay was 3.6 days. One infection of the perineal wound occurred in the early postoperative period necessitating removal of the device. In two further patients the artificial bowel sphincter was removed because of late infection in one at seven months and because of erosion through the skin in another at three months. The artificial bowel sphincter has been activated in ten patients resulting in full continence to solids and liquids except in one patient with postvagotomy diarrhea who had some leakage of liquids during episodes of diarrhea. The mean (+/- standard deviation) continence score (Cleveland Clinic system; maximal incontinence = 20) changed from 18.7 +/- 1.6 preoperatively to 2.1 +/- 2.6 after activation (P < 0.0001). Quality of life measured using a continence-specific series of up to 39 questions changed from 77 +/- 16 percent of maximal reduction of quality preoperatively to 12 +/- 19 percent postoperatively (P < 0.001). CONCLUSIONS: The artificial bowel sphincter can be placed without technical difficulty and with low morbidity. Preliminary experience shows full restoration of continence in most patients and ease of use. Longer follow-up is needed to determine the extent of problems with infection, erosion, and mechanical failure.
BACKGROUND: Radioimmunoscintigraphy (RIS) is being used increasingly as a new investigation in the diagnosis of recurrent colorectal cancer. This study assessed the efficacy of 99mTc-radiolabelled PR1A3 scanning in a cohort of patients with possible recurrent colorectal cancer and the effects of scan interpretation on subsequent clinical management. METHODS: The scans and case notes of patients scanned over a 3-year period were reviewed. RESULTS: Forty-seven scans in 40 patients were available for analysis. In 39 instances in which scan interpretation could be verified accurately, sensitivity for recurrent colorectal cancer was 22 of 23 (96 per cent), specificity for recurrent colorectal cancer was eight of 16 (50 per cent), positive predictive value for recurrence was 22 of 30 (73 per cent) and negative predictive value for recurrence was eight of nine (89 per cent). In 16 of the 40 patients, scan interpretation strengthened a management decision or altered management. This was beneficial to ten patients and possibly detrimental to six. CONCLUSION: This study demonstrated that RIS is sensitive in the detection of recurrent colorectal cancer and benefited the patient in one-quarter of cases. For the majority of patients, accurate detection of recurrent disease cannot be followed by curative therapy, but there is an important subgroup of patients in whom RIS alters management beneficially. However, a randomized prospective study is needed to confirm this.
The purpose of this study was to determine the frequency and type of special education services provided to youths who had sustained one or more traumatic brain injuries (TBIs) according to parental report but who did not have verified TBIs according to school records. A parental questionnaire formulated for a related research project served as the basis for data collection. Results indicated the most common special education verification categories both for students with and without reported TBIs were speech-language impairment and specific learning disability. Approximately 29% of children with reported TBIs received special education services--a percentage not differing significantly from students without TBIs. However, students with TBIs whose parents reported long-term consequences were significantly more likely to receive special education services than students with TBIs whose parents did not report long-term consequence or students without TBIs. A chi-square analysis using the number of students whose reported TBIs occurred before versus after special education evaluations revealed no significant difference in the types of services received. However, those evaluated for special education services after sustaining TBIs were more than two times as likely to receive services for behavioural disorders than those evaluated prior to sustaining TBIs.
BACKGROUND: The incidence and severity of infections are increased when Intralipid or Diprivan are administered to patients. Intralipid promotes infection, presumably by inhibiting the reticuloendothelial system, thereby suppressing the host's constitutive immunity, whereas Diprivan supposedly promotes infection by supporting bacterial growth and increasing the inoculating dose. This study considers whether bacterial replication alone in Intralipid and Diprivan adequately explains the increased risk of infection associated with these agents or whether other factors might also be involved. METHODS: Staphylococcus aureus was cultured in 10% Intralipid or Diprivan at clinically relevant conditions or in Intralipid containing 0.005% (w/v) sodium EDTA, a current additive, to measure growth. To determine whether Intralipid affected infection, New Zealand white rabbits were injected intravenously with S. aureus with or without Intralipid. Twenty-four hours later, bacteria in lung, liver, spleen, and kidney tissues were enumerated. RESULTS: S. aureus failed to grow in Diprivan or Intralipid containing 0.005% EDTA. Whereas S. aureus did replicate in plain Intralipid, growth was delayed until the bacteria conditioned the media. Once initiated, growth was slow at clinically relevant temperatures. The administration of Intralipid to rabbits significantly increased the recovery of staphylococci from the kidneys, P < 0.001, relative to the other tissues 24 h after an intravenous inoculation with S. aureus, compared with rabbits receiving S. aureus with no Intralipid. CONCLUSIONS: These results suggest that Diprivan, and possibly Intralipid, represent poor media for the growth of S. aureus and may promote infection through mechanisms other than increased inoculum size.
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The sodium-calcium exchange activity is mediated by proteins encoded in a small gene family, of which the gene NCX1 is ubiquitously expressed in mammalian tissues. In this study, the multipartite promoter of this gene was analyzed in the human and rat genomes by means of DNA cloning, reverse transcriptase-polymerase chain reaction, and transient transfection of fusion constructs with the firefly luciferase gene into cultured rat aortic smooth muscle cells. The gene-proximal promoter, located 30 kilobase pairs (kb) away from the first coding exon 2, has features of a GC-rich housekeeping promoter and is apparently always active; in specific tissues, however, it is augmented by one or two additional promoters, located either within 1.5 kb upstream of it, or 35 kb upstream. The gene proximal promoter shows the highest activity in aortic smooth muscle cells. In mammalian species transcripts from all three promoters undergo splicing via an intermediate, containing two noncoding exons, of which the downstream one is normally not present in the terminal splicing product.
The intracellular free calcium concentration ([Ca2+]i) plays an important role in the regulation of vascular tone. In vascular smooth muscle cells (VSMCs) LDL causes changes in vascular tone by increasing [Ca2+]i. Pericytes are regarded as the microvascular counterpart of VSMCs and implicated in the regulation of microvascular cell biology under normal and pathological conditions (e.g., diabetes mellitus, arterial hypertension, arteriosclerosis). For this reason pericytes and VSMCs were compared in their ability to increase [Ca2+]i after stimulation with LDL. Single VSMCs and pericytes were loaded with 2 microM of the Ca2+-sensitive dye Indo-1/AM. Fluorescence was recorded at 405 nm (Ca2+-bound) and 485 nm (Ca2+-free). Cells in suspension were loaded with 2 microM of the calcium ionophore FURA-2 AM (excitation wavelengths: 340 and 380 nm, emission 505 nm). Basal [Ca2+]i levels were significantly higher in single pericytes (165 +/- 38 nmol/L, n = 41) than in VSMCs (150 +/- 39 nmol/L, n = 40, P = 0.0038). In cell suspensions the following values were obtained: Pericytes (113 +/- 27 nmol/L, n = 36) and VSMCs (109 +/- 26 nmol/L, n = 28), which are statistically not significant. For all concentrations of LDL used (except at 1 microg/ml n-LDL), the increase above basal values was significant and both cell types showed a clear dose-dependent reaction pattern. This study shows for the first time that pericytes and VSMCs increase their [Ca2+]i in a similar way after LDL stimulation. In analogy to aortic smooth muscle cells, our results indicate that LDL mediated [Ca2+]i changes in pericytes in the microvascular bed may cause vasoconstriction leading to impairment of blood flow in the microvasculature.
Completed questionnaires from parents of youths attending a public middle school or high school and parents of youths admitted to an institution for juvenile delinquents provided information about incidents of traumatic brain injury (TBI) in their children. Results revealed that approximately 40% of the non-delinquent youth and 50% of the delinquent youth had sustained one or more TBIs during their childhood or youth. The majority of injuries appeared to be mild and had no permanent consequences. However, the parents of more than one-third of the delinquent youth with TBI histories reported long-term effects on academic performance, behavior and emotional control, activity level, and/or interactions with friends and family members; parental reports of long-term effects occurred significantly less frequently among the non-delinquent youth. The most common causes of TBI differed between the two adolescent populations. Non-delinquent youth sustained TBIs most frequently from blows to the head during sporting events, and delinquent youth sustained TBIs with approximately equal frequency from sporting events, fall, motor vehicle accidents and fights.
BACKGROUND: Pericytes are regarded as the microvascular counterpart of smooth muscle cells and implicated in the regulation of blood pressure at the microvascular level. Ca2+ plays an important role in biochemical processes involved in blood pressure regulation and can be activated by low-density lipoprotein (LDL) cholesterol. OBJECTIVE: To determine whether stimulation either of single cells or of cells in suspension by LDL would produce any difference in the increase in cytosolic free calcium levels ([Ca2+]i). DESIGN AND METHODS: Single pericytes were loaded with 2 micromol/l of the Ca2+-sensitive dye Indo-1/AM. The Indo-1 fluorescence was recorded at 405 nm (Ca2+-bound) and 485 nm (Ca2+-free) after stimulation with LDL. Pericytes in suspension were loaded with 2 micromol/l of the Ca2+-sensitive dye FURA-2/AM. The FURA-2 fluorescence kinetics were recorded at 340-380 nm. Ratios of fluorescence at the two wavelengths were transformed to [Ca2+]i. RESULTS: Basal [Ca2+] levels appeared to be higher in single cells (148+/-13 nmol/l, n = 20) than they were in cells in suspension (128+/-8 nmol/l, n = 25; P= 0.0078). After stimulation with LDL the increase in [Ca2+]i in both systems was about 220% above baseline. A clear dose dependency was seen for both systems. CONCLUSIONS: Single pericytes and pericytes in suspension increase their [Ca2+]i after stimulation with LDL dose-dependently. Even though single-cell measurements revealed some technical limitations, their responses were comparable to those obtained in a cell suspension. In analogy to aortic smooth muscle cells, our results indicate that LDL might also play a blood-pressure-regulatory role in the microvasculature.
Apnea in the neonatal period frequently is associated with prematurity. Full-term infants who develop apnea usually have associated clinical conditions such as infection, shock, metabolic disorders, neonatal abstinence syndrome, intracranial pathology, and gastroesophageal reflux. Gastric ulcer also is a rare phenomenon in the neonatal period. We describe a full-term infant presenting with apnea. Upon investigation, a 6-channel pneumocardiogram revealed central apnea and multiple episodes of low esophageal pH (< 4), which is suggestive of gastroesophageal reflux. This was confirmed by an upper gastrointestinal series. A small antral ulcer crater also was demonstrated. When assessing the etiology of apnea in a full-term infant, gastroesophageal reflux and gastric ulcer should be considered.
The author, a family nurse practitioner, describes how homeopathic medicines and the homeopathic conceptual framework distinguish her practice from a conventional one. An introduction to homeopathic health care includes a brief history of the discovery of homeopathy, the homeopathic view of the healing process, and the origins of disease. Factors that would influence a person's candidacy for homeopathy are discussed. Case studies are included.
Plasma renin-angiotensin parameters were measured before and 24h after binephrectomy (BNx) in male Swiss (Ren-1, Ren-2) and BALB/c (Ren-1) female mice (representing the extremes of differences in tissue renin expression), together with in vivo inhibition of residual renin. Plasma Ang II increased from 18.9 +/- 7.3 to 48.1 +/- 16.9 pg/ml after BNx in conscious Swiss mice (+/- sd, p < 0.001, n = 11&12), renin activity (PRA) increased 2.76 times, angiotensinogen (aogen) increased 4.57 times and renin concentration (PRC) fell by 65%. In BALB/c, Ang II+Ang III decreased slightly (56.6 +/- 11 to 37.7 +/- 14.7, p < 0.05, n = 5&6), PRA was unchanged, aogen increased 12 times and PRC fell by 93%. Plasma ACE decreased by 26% and 28% respectively. Aogen did not increase further when post BNx plasma renin was inhibited with antirenin in vivo during 20h. Thus plasma angiotensin is maintained or considerably increased following BNx in mice and the change is consistent with first-order kinetics with respect to renin and aogen in the circulation. Whether the strain carries one or two renin genes, high renal and extrarenal renin production combined with a low plasma aogen phenotype yields resting angiotensin levels similar to other mammals. A kinetic regulation of aogen levels is proposed in mice wherein Ang II production is limited by low substrate concentration thereby ensuring normotension in the face of abundant extrarenal renin secretion.