Sterol biochemistry in filamentous fungi: a coming of age.
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Biomedical subjects
Publications and source records attributed to D J Moore.
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Carotid plaque characteristics associated with the production of symptoms were identified with quantification of carotid plaque constituents in high-grade stenotic asymptomatic (n = 8) and symptomatic (n = 44) plaques. Asymptomatic plaques contained significantly more fibrous/collagen material (88%) than symptomatic plaques (66%) (p less than 0.05). Hemorrhage constituted 2% and 1% of asymptomatic and symptomatic plaques, respectively. The predominant nonfibrous material was a pink amorphous material mixed with cholesterol, which composed 7% of asymptomatic and 27% of symptomatic plaques (p less than 0.05). No relationship was found between plaque composition and the number of ipsilateral ischemic neurologic events, nor was there evidence of a healing process. B-mode ultrasound scanning had a sensitivity of 94% in identifying plaque with greater than 80% fibrous content. We believe that plaque composition may be a useful discriminating factor in selecting asymptomatic patients for carotid endarterectomy.
With the increase in the number of reported cases of child abuse it is important that medical practitioners should know the normal values for the size of the anus. Children aged 3 months to 15 years, attending a paediatric gastroenterology clinic for a routine examination, had a photographic record made of the anus 30 seconds after exposure of the anus as part of a standardised examination protocol. Anorectal disease, including Crohn's disease was present in eight children. Analysis of the 54 children without anorectal disease indicated that the anteroposterior diameter of the anus was less than 10.0 mm and the transverse diameter was less than or equal to 2.0 mm. Age, sex of the child, digital rectal examination, time since last defaecation and the capacity and contents of the rectum were unrelated to the size of the anus. In view of the difficulties which arise in suspected child abuse, medical practitioners should gain experience of the normal appearance and size of the anus. This can best be validated within a medicolegal framework if some form of standardised examination protocol is used. The key element of such an examination is not the position in which the child is examined but the time taken to observe the anus, to allow any dynamic changes to occur. An inspection time of 30 seconds in a cooperating conscious child is recommended.
Management of intractable venous ulceration remains an unrewarding task which is increasingly delegated to the realm of the vascular surgeon. The purpose of this pilot study was to assess the ulcer-healing effects of the newest form of biostimulation--the low power laser. Twelve patients with chronic venous ulcers unresponsive to conservative measures were treated with infrared laser irradiation for twelve weeks. Two ulcers healed completely and there was a 27% (p less than 0.01) reduction in size of the remaining ulcers. Treatment resulted in a 44% (p less than 0.01) increase in ulcer floor area occupied by healthy granulation tissue. The most dramatic effect of laser treatment was the reduction in ulcer pain, from 7.5 to 3.5 (linear analogue scale) (p less than 0.001). Laser irradiation had no effect on TcPO2, number of skin capillaries or pericapillary fibrin deposition in the lipodermatosclerotic area around the ulcer. The results of this pilot study are encouraging and a carefully controlled randomized study is indicated to compare low power laser irradiation to conventional treatment in the management of venous ulcers.
We report on the management of a patient with intractable venous claudication and ulceration due to bilateral iliac vein and inferior vena cava occlusion. An inverted V graft was constructed from two 8 mm diameter reinforced PTFE grafts. The upper end was anastomosed to the inferior infrarenal vena cava and the lower ends anastomosed to the common femoral veins. Bilateral arteriovenous fistulas were fashioned. Nine months later the graft is patent and the patient's only symptom is mild ankle edema. The theoretical advantage of this type of graft is that occlusion of one limb will not compromise the other, thus leaving a number of secondary options open if this should happen.
The presence of haemorrhage in carotid bifurcation atheromatous plaques is widely believed to be associated with the production of ischaemic neurological events. This study set out to characterise plaque composition in symptomatic (SYM) and asymptomatic (ASYM) patients and to identify, if possible, the origin of intra-plaque haemorrhage. Fifty-nine plaques (50 SYM and 9 ASYM) were serially sectioned and examined for haemorrhage, haemosiderin, fibrin, cholesterol and collagen. Immunoperoxidase and electron microscopy studies were carried out on sections from five plaques in order to identify blood breakdown products. Intra-plaque haemorrhage was identified in 40 (68%) plaques and was similar in SYM and ASYM plaques. In only one did it constitute more than 15% of plaque content, and in the remainder it consisted of small collections of erythrocytes constituting greater than 1% of plaque content in only 21 (35%) plaques. The predominant non-fibrous component was a pink amorphous material mixed with cholesterol. Apart from traces of platelet breakdown products there was no evidence of haemorrhage in this pink material. Plaque roof rupture or ulceration was seen in 39 (66%) and in almost all cases overlay the amorphous/cholesterol material. Blood vessels were identified in 51 87%) plaques but were in close proximity to haemorrhage in only nine (15%).
Despite advances in the design and care of in-dwelling catheters, sepsis remains a significant problem in patients on long-term parenteral nutrition. In recent years there have been a number of reports concerning the successful use of totally implanted subcutaneous venous access devices in the management of patients requiring long-term intermittent intravenous administration of cytotoxic therapy and frequent blood sampling. The use of such a system for the administration of supplementary home parenteral nutrition in a patient with short-bowel syndrome is reported.
Because alcohol has an adverse effect on zinc homeostasis, this study was designed to study if zinc content of the diet modifies the severity of fetal alcohol syndrome in a mouse model. The effect of varying zinc intake on the progeny of pregnant mice fed a liquid diet containing 15% of the calories as ethanol was studied. Prenatal mortality was higher when the mothers consumed alcohol with inadequate zinc intake. Because of the adverse effect of alcohol on zinc homeostasis and because zinc deficiency has been shown to potentiate alcohol embryopathy, one group was given zinc supplementation to four times the Recommended Dietary Allowance. Supplemental zinc above the Recommended Dietary Allowance was not protective and appeared to have an adverse effect on fetal weight and prenatal mortality. These results suggest that zinc intake should be optimized during pregnancy but that zinc supplementation above the Recommended Dietary Allowance does not reduce the incidence or severity of fetal alcohol syndrome.
The efficacy of a 10-day course of bovine colostrum with high antibody titre against the four known human rotavirus serotypes in protecting children against rotavirus infection was examined in patients admitted to hospital. Children aged 3 to 15 months were blocked in pairs according to ward accommodation (ie, isolation or open area). Each block contained 1 treated and 1 control child. The allocation to treatment or control (an artificial infant formula) was randomised. 9 of 65 control children but none of 55 treated children acquired rotavirus infection during the treatment period (p less than 0.001). The importance of protecting against rotavirus infection was highlighted by the fact that parents of symptomatic rotavirus-positive children sought medical attention seven times more often than did parents of symptomatic rotavirus-negative children (p less than 0.05).
The antitumor agent phyllanthoside is rapidly metabolized in vitro by mouse plasma. This metabolite has now been isolated from mouse plasma and its structural properties and cytotoxicity characterized. The isolated metabolite was estimated to be greater than 98% pure by HPLC analysis. Mass spectral analysis (fast atom bombardment and tandem mass spectrometry) indicated that the metabolite was the aglycone of phyllanthoside that resulted from the cleavage of the ester bond linking the aglycone and the disaccharide moieties of phyllanthoside. This identification was based on identical collision-induced dissociation spectra of both phyllanthoside and the metabolite. The aglycone was not formed by mouse plasma that had been boiled, filtered to remove proteins, or treated with 1.0 mM diisopropyl fluorophosphate. These results suggest that aglycone formation occurs as a result of plasma esterase activity. Michaelis-Menten constants, Vmax and Km, for conversion of phyllanthoside to the aglycone at 22 degrees C were estimated to be 1.1 mmol/ml plasma/min and 2.0 mM, respectively. Concentrations of phyllanthoside and metabolite required to inhibit cell-colony formation by human A204 rhabdomyosarcoma in vitro were 0.47 nM and 24 microM, respectively. The toxicity of phyllanthoside, and perhaps its efficacy as an antitumor agent in mice, may depend on its rate of conversion to the aglycone.
This investigation photoelastically compared the load-transfer characteristics of various bilateral distal-extension removable partial denture designs embodying intracoronal attachments and clasp assemblies. Six distal-extension designs that included the RPI clasp assembly, cast circumferential clasp, P.D. locking semiprecision, Thompson dowel nonlocking semiprecision, and McCollum and Stern G/L precision attachments were tested. Each prosthesis was subjected to various simulated occlusal loads. Evaluation of the load-transfer characteristics of the various designs was based on comparison of the recorded isochromatic fringe distributions. The RPI clasp assembly generated the most uniform stresses. In general, the four intracoronal retainer frameworks produced higher stresses than did the two clasp frameworks. The highest stresses were developed by the Stern G/L precision attachment.
Indicine N-oxide (INO) is a pyrrolizidine alkaloid (PA) with antitumor activity in animals and humans. Prior studies showed that despite the known hepatic toxicity of the PAs, INO did not produce hepatic toxicity in animals but caused unpredictable lethal hepatic toxicity in humans. In this study we have attempted to find a model system for predicting the hepatotoxic potential of antitumor PAs. Primary cultures of rat hepatocytes showed toxicity only with the most hepatotoxic PAs such as lasiocarpine, but did not detect toxicity with other PAs. Subchronic intraperitoneal administration of PAs to weanling rats and adult mice produced, in surviving animals, hepatic megalocytosis and centrilobular necrosis with heliotrine (H) and 9-O-(R(-)-2-(4'-chlorophenyl)-2-hydroxybutyryl)retronecine N-oxide (RC1NO) but only megalocytosis with INO. Thus, despite previous reports, weanling rats offered no advantage over adult mice for detecting significant hepatic toxicity with PAs. Phenobarbital pretreatment of the mice did not increase the hepatic toxicity of any of the PAs. Subchronic oral administration of PAs to adult mice produced hepatic megalocytosis and centrilobular necrosis in surviving animals with H and RC1NO and megalocytosis with INO. Animals that died acutely following oral administration of INO showed hepatic centrilobular necrosis. Administration of several courses of INO intravenously to dogs produced histological evidence of centrilobular hemorrhagic necrosis. It is concluded that there is no single animal model that will predict hepatic toxicity of the type seen in humans with the antitumor PAs. A combination of studies using adult mice and dogs and lethal doses of the PAs offers the best way of detecting potential hepatic toxicity.
A 19-year-old man was diagnosed with a rapidly enlarging arteriovenous malformation of the scalp and a mild degree of cardiomegaly. Operation to excise the large fistula took place under general anesthesia. Both external carotid arteries and their branches were controlled to prevent intraoperative hemorrhage, and dissection took place down to the periosteum. A split skin graft from the thigh was applied to the scalp defect. The patient recovered well with no further evidence of dyspnea or high output cardiac failure.
Twenty patients with ischemic rest pain were treated with intravenous pentoxifylline, 1,200 mg daily, for up to three weeks. Ten patients obtained sufficient relief to avoid surgical intervention. Seven of these had complete or near complete relief of rest pain, but the other three required continuing analgesia. Transcutaneous oxygen measurements showed a significant increase after the course of treatment. There were marked gastrointestinal side effects in six patients, necessitating early withdrawal from the study. Three of these six patients had shown a favorable response to medication prior to withdrawal. These preliminary results suggest that pentoxifylline may provide a sufficient increase in tissue oxygen availability to avoid, or at least postpone, surgical intervention. A double blind controlled study is required to further assess the efficacy of this drug as an intravenous treatment.
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This study compared the clinical efficacy of three mouthrinses containing either 0.12% chlorhexidine, phenolic compounds, or sanguinarine, which were used unsupervised, in a placebo-controlled, double-blind study of 6 months' duration. The study was conducted according to ADA clinical guidelines for evaluation of antigingivitis agents and was completed by 481 adults. Following baseline exams and a prophylaxis, subjects were randomly divided into treatment groups matched for age, gender, and gingivitis severity, and were instructed to use the rinses in accordance with manufacturer's directions. Followup examinations evaluated supragingival plaque, gingivitis, and gingival bleeding. Compared to placebo at 6 months, the group rinsing with 0.12% chlorhexidine had significantly less gingivitis (31% reduction), gingival bleeding (39% reduction), and plaque (49% reduction) and was significantly better than any of the other treatment groups (P less than 0.05). Both the phenolic and sanguinarine groups showed moderate, yet significant, reductions in plaque compared to placebo (24% and 12% respectively) yet were significantly less effective than the 0.12% chlorhexidine rinse (P less than 0.05). However, neither the phenolic nor sanguinarine rinses were significantly different than placebo in their effects on gingivitis or gingival bleeding. These results support previous published results on the superiority of 0.12% chlorhexidine when used in conjunction with professional care and as an adjunct to routine oral hygiene practices.
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