Biomedical subjects
J Valentine
Publications and source records attributed to J Valentine.
Acute respiratory failure and ECMO.
In recent years, we have experienced advances in treatments for severe ARDS. One that holds promise for these critically ill adult patients is ECMO, which can provide gas exchange and lung rest for the patient in severe reversible respiratory failure. Advances in ECMO techniques, appropriate patient selection and the development of heparinized tubing will all improve the potential for survival in patients who are placed on ECMO therapy in the future.
Construction and expression of alpha 1-proteinase inhibitor mutants and the effects of these mutations on secretion of the variant inhibitors.
Human alpha 1-proteinase inhibitor (A1Pi) deficiency, associated with the Z variant A1Pi gene, results from defective secretion of the inhibitor from the liver and appears to be a direct consequence of replacement of Glu342 with Lys. To investigate the effect of the amino acid occupying position 342 on secretion of A1Pi, we have used oligonucleotide-directed mutagenesis of A1Pi cDNA to randomly change the codon specifying this amino acid. Since replacement of Glu342 by Lys leads to a change in the predicted secondary structure for this protein, we also tested the possibility that defective secretion of A1PiZ is the result of this type of alteration. For this purpose, site-directed mutagenesis was used to produce sequences encoding A1Pi retaining Glu342 but predicted to have A1PiZ type secondary structure. The effects of 10 different amino acids occupying position 342 on the secretion of A1Pi were determined by pulse-chase experiments and by enzyme-linked immunosorbent assay of medium from transiently transfected COS cells. Results of these studies show that secretion of A1Pi is most efficient when position 342 is occupied by a negatively charged amino acid, efficient but somewhat less so when occupied by a neutral amino acid, and least efficient when a positively charged residue is present. The mutation designed to alter secondary structure had no effect on the secretion of A1Pi. As indicated by immunofluorescence microscopy and mobility of intracellular A1Pi on sodium dodecyl sulfate-polyacrylamide gel electrophoresis, lowered secretion is accompanied by accumulation of A1Pi in the endoplasmic reticulum of the transfected cells. These results are compatible with the ideas that secretion of A1Pi is directly influenced by the amino acid occupying position 342, that a positively charged amino acid in this position is especially detrimental to secretion of this protein, and that the rate-limiting step in the secretion of the altered forms is transport from endoplasmic reticulum to Golgi.
Traumatic hemipelvectomy.
Traumatic hemipelvectomy is an uncommon and devastating injury with few patients alive when they reach the hospital. There are only 19 reported survivors of this injury. This group includes 17 males and 2 females. All had severe, associated injuries. The mechanism of injury involved motorcycle, automobile, pedestrian/motor vehicle, or heavy machinery accidents. All surviving patients are young (10-34 years of age). Most suffered from a variety of postoperative complications. Two interesting patients with traumatic hemipelvectomy are reported. One involves a new mechanism of injury, the propellor of a motorboat. The management of these 2 patients is explained, the experience of others with similar injuries is reviewed, and the benefit of reconstruction with the gluteus myocutaneous flap is discussed.
Nebulisers in acute childhood asthma.
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Topical imipenem therapy of aminoglycoside-resistant Pseudomonas keratitis in rabbits.
We used a rabbit model of bacterial keratitis to assess in vivo efficacy of topical imipenem, a highly potent beta-lactam antibiotic with an unusually broad spectrum of activity, including aminoglycoside-resistant Pseudomonas aeruginosa. Albino rabbits received intrastromal injections of 5 x 10(2) organisms of an aminoglycoside-resistant strain of P. aeruginosa. At five hours postinoculation, imipenem (5 mg/ml) therapy was initiated using one drop per 30 minutes for 12 hours. Corneal tissue was then excised for colony forming unit counts. Imipenem was highly effective in reducing colony forming unit counts to zero in comparison to 4.1 x 10(5) organisms for untreated controls. A second regimen beginning 24 hours postinoculation of one drop per hour for 24 hours was also successful in significantly reducing colony forming units vs controls (P less than .05). These data suggest that topical imipenem may have clinical applicability in the treatment of P. aeruginosa keratitis.
Electromagnetic field focusing (EFF) probe for intravascular endarterectomy. Preliminary feasibility study.
Vaporization of atheromas in 10 human aorta segments immersed under flowing blood in vitro were done using the EFF probe. No increase in packed cells of the flowing blood following atheroma vaporization were noted suggesting absence of post vaporization debris. No damage to the aorta underlying the vaporized atheroma was noted on light microscopy suggesting well localized vaporization process. This study suggests that EFF probe might be a safe tool for intravascular endarterectomy.
Seeding with endothelial cells derived from the microvessels of the omentum and from the jugular vein: a comparative study.
Segments of an experimental polytetrafluoroethylene graft (9 cm long, 6 mm I.D.) of high porosity were implanted in 25 dogs as aortic interposition grafts. Nine grafts were seeded with a mean of 7 x 10(5) viable endothelial cells (ECs) derived from the jugular vein (group A) and eight were seeded with a mean of 7 x 10(5) viable ECs derived from the microvessels of the omentum (group B). Eight grafts were not seeded and they served as controls (group C). Animals were put to death 5 weeks after graft implantation. The thrombus-free area was measured at 81% +/- 10% in group A, 65% +/- 22% in group B, and 25% +/- 13% in group C (p less than 0.05, group A vs group B; p less than 0.05, group B vs group C). The thickness of the subendothelial layer was 151 +/- 60 microns in group A, 280 +/- 60 microns in group B, and 100 +/- 75 microns in group C (p less than 0.001, group B vs groups A and C). The production of 6-keto-PGF1 alpha in the presence of sodium arachidonate was higher in seeded grafts (p less than 0.05). Omentally derived microvessel ECs can be seeded in vascular grafts; refinements in the technique of EC procurement are required to minimize contamination and to obtain ECs with more effective biologic activity.
Bacterial and host factors affecting Pseudomonas aeruginosa colonization versus bacteremia in granulocytopenic patients.
In order to evaluate bacterial factors which might predispose to P. aeruginosa colonization or bacteremia in the granulocytopenic patient, 132 isolates recovered from 44 oncology patients were evaluated for antigenic serotype, iron correctable sensitivity to pooled human serum, antibiotic susceptibility, production of lecithinase, elastase, protease, gelatinase, pyocyanin and pyoverdin. Similarly, potential host factors, primarily total iron binding capacity, were evaluated in a subpopulation of acute leukemia patients composed of 13 control patients without P. aeruginosa cultured during their hospital course, 11 colonization only patients and 15 P. aeruginosa bacteremia patients. No significant differences were observed between strains recovered from bacteremia vs. colonization patients for extracellular enzyme activity, pigment production, serum sensitivity and antigenic serotype. Significant differences were observed between bacteremia and colonizing strains for antibiotic susceptibility to ticarcillin, 40% vs. 76% (P less than 0.002); piperacillin, 44% vs. 86% (P less than 0.006); and cefsulodin, 60% vs. 90% (P less than 0.02). Of the host factors evaluated in the acute leukemia patients, significant differences were observed between the TIBC nadir of control patients and both colonization patients (P less than 0.0002) and bacteremia patients (P less than 0.0004). P. aeruginosa bacteremia was associated with the temporal occurrence of TIBC nadir and the detection of the organism. These data suggest a possible role for beta-lactam antibiotic resistance and host iron binding capacity as determinants and possible predictors of P. aeruginosa sepsis in the granulocytopenic patient.
The study of the effect of human chorionic gonadotrophic (HCG) hormone on the survival of adrenal medulla transplant in brain. Preliminary study.
Autologous adrenal cortex was completely dissected off the medulla using microdissection. The adrenal medulla tissue was transplanted to the lateral ventricle in twenty-one adult rats. Group A consisting of ten animals received 200 units of HCG per 100 gram body weight daily for one week and then on every alternate day for seven weeks. The remaining rats (group B) served as control. After eight weeks the brains were removed and a volumetric study was done using histological sections. High pressure liquid chromatography (HPLC) with electrochemical detection for catecholamine assay of the graft was also undertaken. The graft survival in group A was significantly higher (p less than 0.005) than group B. The level of norepinephrine was significantly higher in group A while dopamine was higher in group B. The higher volume of graft tissue in group A suggests that HCG may help in increased survival and growth of the transplanted tissue. Higher levels of norepinephrine in group A would suggest a tendency for such grafts to be active to a greater extent with the treatment of HCG.
Green Mountain Oncology Group--CCOP: an evolving regional cancer program.
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Electromagnetic field focusing (EFF) probe in aneurysm thrombosis. Preliminary report.
Due to its capability of producing a well localized intense heat field of predictable dimensions, the electromagnetic field focusing probe was evaluated experimentally as a surgical tool in aneurysm thrombosis. Aneurysm models were created by anastomosing a segment of vein to the abdominal aorta. Seventy-five such aneurysms were created in seventy-five animals. The aneurysms were then placed under the solenoidal radiofrequency coil and the tip of the field focusing probe was inserted into them. Intense heat was delivered with well defined, effective and quick thrombosis and shrinkage of the aneurysm. Nineteen of the aneurysms were followed for up to one week. Histological studies were conducted showing complete thrombosis of the aneurysm with good preservation of the aorta. With further refinement of this technique, it is hoped that stereotaxic aneurysm thrombosis might be possible.
Maternal and childhood nutrition among Aborigines of the Kimberley region.
A cross-sectional anthropometric survey of 128 Aboriginal children under five years of age and of 388 Aboriginal girls and women of child-bearing age was undertaken in seven communities in the Kimberley Region of Western Australia. More than 20% of the children were undernourished, three individuals severely so. All but one of those who were undernourished were over 12 months of age. Less than 60% of the female subjects of child-bearing age had a satisfactory nutritional status; one-sixth were undernourished and one-quarter, mostly older women, were overweight. The findings indicate that poor nutrition is widespread among Aboriginal female subjects of child-bearing age. Maternal malnutrition may contribute significantly to unsatisfactory nutrition and health in Aboriginal infants and young children.
Gunshot injuries in children.
Ninety consecutive patients between 2 and 15 years of age sustaining gunshot wounds were analyzed and a management algorithm evolved. Key management steps included fluid resuscitation in the field by trained paramedical personnel and recognition of the severity of the wound when large-caliber or shotgun injuries were encountered. Arteriograms were most helpful in locating vascular injuries; venograms were inaccurate. Morbidity was directly related to missile size and impact area, and to the number of organs injured. Any hospitalization beyond 2 weeks' duration should have social service, home-bound school service, psychiatry, and physical therapy in consultation. During a 5-year period only two of the 90 patients died secondary to hemorrhagic shock.
Impaired hearing in X-linked hypophosphataemic (vitamin-D-resistant) osteomalacia.
We assessed the hearing of 25 patients with X-linked hypophosphataemic osteomalacia. Twelve patients had subjective hearing loss and 2 had had episodic tinnitus, deafness, and vertigo similar to that in Ménière's disease. On pure-tone audiometry, 19 patients were shown to have sensorineural hearing loss, 3 of whom had evidence of an added conductive element. Tests were done to delineate sensory (cochlear) from neural deafness. Analysis of the stapedius reflex threshold, percentage speech discrimination score, tone decay, and loudness recruitment showed a disturbance of cochlear function. The possible mechanisms responsible for this dysfunction are discussed in the light of pathologic characteristics of familial hypophosphataemia and its extraosseous manifestations. Sensorineural hearing loss, a previously unrecognised complication of familial hypophosphataemic osteomalacia, occurs frequently.
Focused hyperthermia with a magnetic resonance imaging (MRI) unit and an interstitial grounded probe.
The feasibility of using a commercial magnetic resonance imaging (MRI) scanner to do either imaging or hyperthermic treatment was demonstrated. Radiofrequency (RF) induced focal heating of phantoms and animal tissues was performed using a MRI scanner as the RF power source and a grounded interstitial probe as a device to produce hyperthermia via eddy current convergence. In the therapeutic mode, a pulse width of 900 microseconds and interval of 50 ms were used to give 2% duty cycle (closest simulation to continuous wave (CW) mode without bypassing imaging filters). Temperature in the vicinity of the grounded probe was measured with a field nonperturbing fluoroptic probe. Temperatures increased 4.5 degrees C in 5 minutes in a dielectrically uniform phantom, 3.1 degrees C in 6.7 minutes in rats' leg muscles, and 5.0 degrees C in 6.0 minutes in rats' peritoneum. The MRI of the phantom with the grounded probe and the fluoroptic probe was obtained using spin echo sequences. The potential advantage of this approach is visualization of deep-seated tumors and hyperthermic treatment with minimal modification of the MRI scanner.
Follow-up of attempted suicide in Christchurch.
Ninety-eight subjects who had attempted suicide and 102 general practice controls previously interviewed were followed-up at 18-24 months. The former continued to show greater social and psychiatric disability than controls and more than one-third made repeat suicide attempts. Nevertheless, as a group, the attempted suicides showed significant improvement in mental state, and familial and interpersonal relationships, whereas controls reported little change in most measures. Persistence of suicidal ideation and repeat attempts were correlated with the diagnosis of psychosis and personality disorder and predictions about the likelihood of further suicidal activity were accurate. Although 92% of patients were referred for further treatment, 38% of these were judged to have dropped out prematurely. Completion of treatment and being in ongoing treatment were positively correlated with patients' self reports of improvement. The findings are compared to experience elsewhere and to a previous Christchurch follow-up study.
A cytochrome c methyltransferase from Crithidia oncopelti.
The mitochondrial cytochrome c-557 of Crithidia oncopelti contains two lysine residues and an N-terminal proline residue that are methylated in vivo by the methyl group of methionine. The purified cytochrome can act as a methyl acceptor for a methyltransferase activity in the cell extract that uses S-adenosylmethionine as methyl donor. Crithidia cytochrome c-557 is by far the best substrate for this methyltransferase of those tested, in spite of the fact that methylation sites are already almost fully occupied. The radioactive uptake of [14C]methyl groups from S-adenosylmethionine occurred only at a lysine residue (-8) and the N-terminal proline residue. This methyltransferase appears to differ from that of Neurospora and yeast [Durban, Nochumson, Kim, Paik & Chan (1978) J. Biol. Chem. 253, 1427-1435; DiMaria, Polastro, DeLange, Kim & Paik (1979) J. Biol. Chem. 254, 4645-4652] in that lysine-72 of horse cytochrome c is a poor acceptor. Also, the Crithidia methyltransferase appears to be stable to carry lysine methylation much further to completion than do the enzymes from yeast and Neurospora, which produce very low degrees of methylation in native cytochromes c.