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Biomedical subjects

D Kelly

Publications and source records attributed to D Kelly.

At least 91 records · Page 5Linked to original sources

Early neuromuscular recovery characteristics following administration of mivacurium plus vecuronium.

PURPOSE: This study was designed to describe the early recovery characteristics, as well as the speed of onset of neuromuscular block, after a combination of mivacurium and vecuronium. METHODS: In this controlled, randomized study, 30 consenting ASA I-III patients were assigned to three treatment groups. The "2M2V" group received twice the dose necessary to cause 95% depression of the evoked twitch response (2 x ED95) of mivacurium (0.15 mg.kg-1) plus 2 x ED95 of vecuronium (0.1 mg.kg-1); the "2V" group received 2 x ED95 of vecuronium; and the "4V" group received 4 x ED95 of vecuronium. Evoked neuromuscular responses of the adductor pollicis were assessed with an adductor pollicis force transducer. The time until maximum block and times to 10% and 25% recovery (T10 and T25) in each group were expressed as mean +/- standard deviation and compared using ANOVA. RESULTS: Onset of block in the 2M2V group was 27% faster than in the 2V group (2.0 +/- 0.6 vs. 2.7 +/- 0.8 min respectively, P < 0.05) and was similar to the 4V group (1.95 +/- 0.3 min, P = NS). The times until 10% recovery were similar in the 2M2V and 4V groups (59.9 +/- 12 vs 68.2 +/- 25 min, P = NS) and were slower than in the 2V groups (37.2 +/- 9 min, P < 0.05). Between T10 and T25 recovery after 2M2V resembled that after 2V (6.7 +/- 3 vs 5.7 +/- 1 min, P = NS) and was faster than after 4V (10.9 +/- 7 min, P < 0.05). CONCLUSIONS: When 2 x ED95 of mivacurium is added to 2 x ED95 of an intermediate or long-acting relaxant, recovery after T10 will proceed as if one had administered the longer-acting agent alone.

Humans↗

Anaesthetic management of a patient with familial normokalaemic periodic paralysis.

PURPOSE: We describe the anaesthetic management of a patient with the autosomal dominant inherited disease, normokalaemic periodic paralysis. The disease results in intermittent bouts of limb and respiratory muscular weakness in association with hypothermia, stress, prolonged fasting or exercise. Unlike hypokalaemic and hyperkalaemic periodic paralysis, the more common variants of the disease, normokalaemic periodic paralysis is not accompanied by alterations in the plasma potassium concentration. CLINICAL FEATURES: A five-year-old boy presented for emergency scrotal exploration. He had a family history of periodic paralysis and had experienced previous episodes of weakness, two of which had required hospitalization for respiratory distress. On admission there was no evidence of weakness and serum potassium concentration was 4.2 mMol.L-1. A spinal anaesthetic was performed and the procedure was uncomplicated by muscle paralysis above the level of the spinal block. CONCLUSION: Avoidance of known precipitating factors and judicious use of neuromuscular blocking drugs has been advocated in patients with this disorder presenting for surgery. In appropriate circumstances, spinal anaesthesia represents a useful option in patients with normokalaemic periodic paralysis.

Anesthesia↗

Partial intestinal obstruction induces substantial mucosal proliferation in the pig.

Parenteral nutrition and improving supportive treatment have resulted in prolonged survival for patients with short bowel syndrome. However, definitive therapy for patients with short bowel syndrome must focus on increasing small intestinal mucosal mass. Intestinal lengthening procedures rely on intestinal dilation to accomplish this. The authors hypothesized that partial intestinal obstruction would result in consistent dilation of the intestine and would provide increased intestinal mass for use in intestinal lengthening. The authors developed a partially obstructing prosthetic valve to dilate the intestine before intestinal lengthening. This report describes the changes elicited by the valve. Twelve weanling pigs were divided randomly into two groups of six. One group had valve placement 240 cm distal to the ligament of Treitz; the other had sham surgery. The survival rate was 100% for both groups, and the mean weight gain was similar. Both groups were fed pig chow mush and were killed 5 weeks after surgery. Intestinal diameter was measured, and the small intestine was harvested, preserved, and sectioned for microscopic examination. The mean bowel diameter 15 cm proximal to the valve was 4.7 cm in the valved group and 3.3 cm in the sham group (42% increase). Total mucosal thickness, villus height, crypt depth, and villus density were significantly greater for the valved pigs in all sections (proximal and distal to the valve). Surface index and intestinal circumference were significantly greater in the valved pigs in all sections proximal to the valve, but there was no significant difference in these values for sections distal to the valve. There was no significant difference in villus cell density between the two groups at any location. Chronic partial obstruction of the small intestine results in consistent dilation of the intestine, with growth of all layers of the bowel, including the mucosa. This dilation and mucosal growth results in a true increase in surface area and is an ideal first step toward sequential lengthening.

Animals↗

Subcutaneous cysts: another cause of "failed" spinal anesthesia?

Spinal anesthesia continues to be one of the major techniques in the arsenal of the modern anesthesiologist. Inadequate anesthesia may follow a spinal anesthetic for a variety of reasons. We report a case in which entry of a spinal needle into a subcutaneous cyst mimicked the free flow of cerebrospinal fluid seen with dural puncture. This was confirmed by microscopic examination of the fluid, which was consistent with the contents of a subcutaneous cyst. This represents an unusual cause for failure of spinal anesthesia. Such a possibility should be borne in mind, especially when "clear fluid" return occurs through a spinal needle placed at a relatively superficial depth.

Adult↗

Double-blind, placebo-controlled, crossover trial of glycine adjuvant therapy for treatment-resistant schizophrenia.

BACKGROUND: It has been proposed that schizophrenia is associated with underactivity of brain glutamatergic neurotransmission, especially at the level of the N-methyl-D-aspartate (NMDA) subtype of glutamate receptor. Glycine potentiates NMDA receptor-mediated neurotransmission, indicating that it may serve as an effective therapeutic agent in the treatment of schizophrenia. METHOD: Eleven treatment-resistant patients with chronic schizophrenia completed a double-blind, placebo-controlled, six-week, randomly assigned, crossover treatment trial of 0.8 g/kg body weight/day of glycine, added to their prior antipsychotic treatment. RESULTS: Glycine was well tolerated, resulted in significantly increased serum glycine levels and induced a mean 36 (7%) reduction in negative symptoms (P < 0.0001). Significant improvements were also induced in depressive and cognitive symptoms. The greatest reduction in negative symptoms was registered in the patients who had the lowest baseline serum glycine levels. CONCLUSIONS: These results extend previous findings and suggest an additional approach to the pharmacotherapy of negative symptoms and cognitive deficits in schizophrenia.

Adult↗

The localisation and characterisation of insulin-like growth factor-I receptors and the investigation of melatonin receptors on the hair follicles of seasonal and non-seasonal fibre-producing goats.

To define the hormonal influences that are directly involved in the hair follicle cycles of animals with differing patterns of fibre growth and moulting, we have investigated the possible presence of IGF-I and melatonin receptors on the dermis and hair follicles of cashmere and Angora goats, sampled in February. March and June, using quantitative in vitro autoradiography. The presence of IGF-I receptors in the dermis of both breeds of goat was determined using cryostat sections incubated with 50 pM 125I-labelled IGF-I in the presence or absence of 50 nM IGF-I. Sections of the growing tip of deep antlers concerning the cartilaginous zone, a tissue known to contain high concentrations of specific IGF-I receptors, were used as a positive control. As the production of antler velvet uniquely involves the generation of hair follicles de novo, the presence of IGF-I receptors in the velvet-producing region was also investigated. In both breeds of goat, specific 125I-IGF-I binding was localised over the inner and outer root sheath, the matrix, the germinal matrix, the dermal papilla and the sebaceous glands and satisfied the basic kinetic criteria considered to be representative of a specific IGF-I receptor. Analysis of saturation isotherms using a one-site binding model revealed dissociation constants (Kd) in the range 0.1-0.9 nM and theoretical maximal numbers of binding sites (Bmax) between 21.4 and 45.6 fmol/mg tissue. Kd and Bmax values derived from cashmere and Angora goats sampled at different times of the year did not differ significantly between breeds or sampling times. Specific 125I-IGF-I binding was also localised to the developing follicles on the deer antler dermis. The presence of melatonin receptors within the goat dermis was also investigated. Sections were incubated with 100 pM 2-[125I]iodomelatonin with or without 0.1 microM melatonin, along with sections of sheep pars tuberalis which are known to contain high levels of high-affinity melatonin receptors. No displaceable 2-[125I]iodomelatonin binding was found on any sections of the cashmere or Angora skin analysed. It is therefore concluded that melatonin receptors are not present on the hair follicles or associated structures. IGF-I receptors are present on the hair follicle and sebaceous gland and may be involved in the growth of both seasonally and non-seasonally produced fibre and in the development of antler velvet.

Animals↗

Resection of benign hepatic lesions with selective use of total vascular isolation.

BACKGROUND: The main morbidity associated with hepatic resection is related to excessive blood loss. Total vascular isolation (TVI) may be used to minimize blood loss in difficult hepatic resection cases. STUDY DESIGN: We reviewed our criteria for use of TVI and our experience in 43 patients who underwent hepatic resection for benign lesions between January 1990 and January 1995. Total vascular isolation was used in 23 patients; 20 resections were performed without TVI. RESULTS: We found TVI particularly useful for resection of highly vascular lesions, and lesions located centrally or adjacent to major vessels. The use of TVI reduced blood loss in difficult hepatic resections; transfusion requirements for these patients were similar to requirements for the resection of peripheral lesions. Fewer complications directly related to hepatic resection were encountered in the TVI group. CONCLUSIONS: Appropriate use of TVI will improve results after difficult hepatic resections and allow maximal sparing of normal hepatic tissue when operating on benign lesions.

Adolescent↗

Temephos distribution and persistence in a southwest Florida salt marsh community.

The distribution and persistence of the mosquito larvicide temephos was monitored throughout an intertidal salt marsh community in southwest Florida following routine aerial applications of Abate 4-E (43% temephos) from 1988 through 1993. Temephos was found to be more highly concentrated in the surface water microlayer than in mid-depth water, exhibiting a mean of 330 micrograms/liter at the surface and 12 micrograms/liter at mid-depth from 1 fl. oz./acre applications and 120 micrograms/liter in the surface and 4.5 micrograms/liter in mid-depth water for 0.5 fl. oz./acre applications. Concentrations at both surface and mid-depth diminished rapidly within the first 24 hours. Mangrove leaves provided the most persistent reservoir for temephos, remaining more than 7 days. Temephos residues also were observed in select salt marsh organisms, including the sheepshead minnow (Cyprinodon variegatus), adult fiddler crabs (Uca rapax) and the ribbed mussel (Geukensia sp.).

Florida↗

Regulation of the transforming growth factor-beta 2 gene promoter in embryonal carcinoma cells and their differentiated cells: differential utilization of transcription factors.

Previous studies demonstrated that differentiation of embryonal carcinoma (EC) cells increases the expression of the TGF-beta 2 gene and identified a CRE/ATF-like motif in the TGF-beta 2 promoter that is necessary for its activity. This suggested that differentiation may increase the transcription of this gene by differential binding of transcription factors to the CRE/ATF-like motif. To test this possibility, we performed gel mobility shift analysis using double-stranded oligodeoxynucleotides containing the TGF-beta 2 CRE/ATF-like motif and nuclear extracts prepared from F9 EC cells and F9-differentiated cells. We determined that the DNA/protein complexes formed by the EC nuclear extracts, but not the complexes formed by differentiated cell nuclear extracts, are recognized and supershifted by an ATF-1 specific antibody. This observation is consistent with our Western immunoblot analysis that detects AFT-1 in the EC cells, but not in their differentiated counterparts. In addition, we provide evidence that protein phosphorylation influences the formation of complexes between F9 nuclear proteins and the CRE/ATF-like motif. Together, our studies identify a likely role for the CRE/ATF-like motif in the regulation of TGF-beta 2 and suggest that this site binds one set of nuclear proteins in EC cells, where the gene is not expressed, and a different set of nuclear proteins in the differentiated cells, where the gene is expressed.

Activating Transcription Factor 1↗

Cis-regulatory elements and transcription factors involved in the regulation of the transforming growth factor-beta 2 gene.

Embryonal carcinoma (EC) cells and embryonic stem (ES) cells provide useful model systems for studying differentiation during early mammalian development. Previous studies have demonstrated that differentiation of two restricted mouse EC cell lines is accompanied by activation of the TGF-beta 2 gene. Moreover, one negative and two positive regulatory regions upstream of the transcription start site were identified, which appear to play key roles in the transcriptional regulation of the human TGF-beta 2 gene. In this report, we demonstrate that the same three regulatory regions strongly influence the activity of the TGF-beta 2 promoter in differentiated cells derived from the multipotent human EC cell line, NT2/D1, and from the murine totipotent ES cell line, CCE. We also determined that the same three regions are active in the regulation of the TGF-beta 2 gene in the murine parietal endoderm-like cell line, PYS-2. However, an additional negative regulatory region appears to contribute to the regulation of the TGF-beta 2 gene in PYS-2 cells. Last, mutation of a CRE/ATF element located just upstream of the transcription start site of the TGF-beta 2 gene reduces significantly the activity of the TGF-beta 2 promoter in the differentiated cells. However, in contrast to our previous findings, our gel mobility shift analyses demonstrate that this CRE/ATF element is bound by similar proteins in nuclear extracts prepared from undifferentiated and differentiated mouse EC cells as well as from undifferentiated human EC cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Biliary complications after paediatric liver transplantation: Birmingham's experience.

Between 1983 and 1992, 112 children underwent liver transplantation. Of 138 grafts, 60 (43.4%) were whole livers, 77 (55.6%) were reduced livers, and 1 (0.7%) was a split liver. Biliary complications (BC) were defined as any abnormality, even minor, related to the biliary tract. Results were analysed with a minimum follow-up of 9 months. Some 36 grafts (26.1%) in 34 patients (30.4%) presented with BC: bile leaks (17 grafts), biliary obstructions or dilatations (16 grafts), and other complications (3 grafts). Management was mainly surgical with biliary reconstruction via a Roux-en-Y loop. Interventional radiology had an increasing role in recent years. BC were associated with a mortality of 1.8% (2/112), a graft loss rate of 4.3% (6/138), and significant morbidity. Among the various factors whose association with BC was studied, the date of transplantation, the use of reduced grafts and the use of gallbladder conduits appeared to be the main determining factors for BC. From multivariate analysis the use of reduced grafts emerged as the most important factor in reducing BC. We therefore conclude that BC are associated with significant morbidity, but general improvements in both surgical and medical management seem to account for better results in recent years.

Adolescent↗

The Biosure Study: influence of composition of diet and food consumption on longevity, degenerative diseases and neoplasia in Wistar rats studied for up to 30 months post weaning.

The 1200-rat Biosure Study had six interrelated aims: (1) To see whether dietary restriction (80% ad lib.) reduces the age-standardized incidence of fatal or potentially fatal neoplasia before the age of 30 months. (2) To see whether the beneficial effects of diet restriction can be achieved by (a) limiting the daily period of access to food to 6 hr, or by (b) limiting the energy value of the diet. (3) To see whether reduced calorie intake between weaning and age 4 months influences survival and/or incidence of non-neoplastic and neoplastic diseases. (4) To compare effects of food consumption, energy intake and protein intake on survival and disease. (5) To study the relationships between body weight at different ages with eventual survival and disease incidence. (6) To provide a database for studying relationships between various in-life measurements and eventual survival and disease incidence in individual animals. Twelve groups of SKF Wistar rats consisting of 50 animals of each sex were fed according to different dietary regimens from when they were weaned at the age of 3 wk until they died, or had to be killed because they were sick, or until the experiment was terminated at 30 months. For five of the 12 dietary regimens, satellite groups consisting of 30 animals per sex were maintained in parallel and used to supply information on the effect of diet on circulating hormone levels during the course of the study. During the 13 wk post weaning a Standard Breeder diet (SB) was provided either ad lib. (four groups), 80% ad lib. (three groups), or with access to food limited to 6 hr per day (one group). During this same period two other groups were fed a Low Nutrient Breeder diet (LB) ad lib. A further group was fed a Low Nutrient Maintenance (high fibre) diet (LM) ad lib. Finally, one group was fed the high protein Porton Rat diet (PR) ad lib.(ABSTRACT TRUNCATED AT 400 WORDS)

Age Factors↗

The cost of modern technology.

Continuous infusion of intravenous (i.v.) drugs is increasing in popularity, as technological advances in equipment (such as "smart" pumps) and pharmacologic improvements of drugs (such as ultra-short acting drugs) are introduced into clinical anesthesia practice. Such new technology, however, also introduces potential new complications. We report one such complication associated with the improper manufacturing of a proprietary i.v. tubing and cassette system.

Anesthesia, Intravenous↗

Laparoscopic pelvic lymphadenectomy during epidural anesthesia.

This report describes the perioperative management of a 70-year-old man undergoing bilateral pelvic lymphadenectomy. Because of concerns regarding this patient's high risk for myocardial ischemia, the four-hour surgical procedure, which included the formation of pneumoperitoneum, was performed during epidural anesthesia with minimal sedation. The anesthetic implications of pneumoperitoneum during regional anesthesia are discussed.

Aged↗

Posttraumatic cerebral arterial spasm.

Posttraumatic cerebral arterial spasm (vasospasm) has been demonstrated in the past by angiography, and recently by transcranial Doppler ultrasonography. Posttraumatic vasospasm is a delayed complication that involves the large basal intracranial arteries (e.g., internal carotid, middle cerebral, basilar) and occurs in 25-40% of head trauma patient. The time course of posttraumatic vasospasm resembles that of vasospasm associated with aneurysmal subarachnoid hemorrhage with onset occurring 2 or more days after injury. A study of the relationship of admission CT scan findings to the incidence of vasospasm suggests that intradural bleeding, which extends into the CSF (subarachnoid, intraventricular, and subdural hemorrhage), plays a role in the pathogenesis of posttraumatic arterial spasm. The preliminary results of a large prospective study of head trauma patients suggest that vasospasm may be an important determinant of outcome from severe head injury.

Brain Injuries↗

The neurochemical and metabolic cascade following brain injury: moving from animal models to man.

Experimental traumatic brain injury produces a series of cellular events contributing to a neurochemical and neurometabolic cascade. This cascade is defined by the release of neurotransmitters resulting in a massive ionic flux, which, consequently, produces an increase in glycolysis. This increase in glycolysis is followed by a metabolic diaschisis, which is related to the degree and extent of behavioral deficits. Clinical efforts have now determined that a similar cascade occurs in human head injury, validating the animal model as well as providing new assessment strategies for the management and treatment of brain injury.

Animals↗

Sialylation of intestinal microvillar membranes in newborn, sucking and weaned pigs.

Affinity cytochemistry and biochemistry revealed distinctive temporal changes in the expression of sialylated and compositionally related membrane glycoconjugates in the pig small intestine between birth and weaning. The expression of membrane NeuAc alpha 2,6 moieties, recognized by Sambucus nigra agglutinin-1, was high in newborn pigs, declined slightly during sucking and was very low in weaned animals. Conversely, the expression of membrane NeuAc alpha 2.3 moieties, recognized by Maackia amurensis agglutinin-2, was low at birth but higher in sucking and weaned animals. Histoblood group O- and A-antigen expression was first detected in a minority of sucking pigs, but was evident in all weaned pigs examined. Lactase glycoforms were isolated from solubilized microvillar membranes of newborn and weaned pigs. The newborn (predominantly alpha 2,6-sialylated) and weaned (predominantly alpha 1,2-fucosylated) glycoforms exhibited similar specific activity, indicating that postnatal lactase decline in the pig intestine is unrelated to temporal changes in membrane sialylation and fucosylation.

Agglutinins↗