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Biomedical subjects

D Kelly

Publications and source records attributed to D Kelly.

At least 73 records · Page 4Linked to original sources

The effect of solubility and hyperlipidemia on perioperative arterial blood gas tensions.

A case is presented to illustrate the need for technical care when handling blood gas samples. The physics of solubility are used to show hour samples changed their oxygen tension (pO2) during handling, while investigating a clinical case to show the effect of hyperlipidemia on blood gases. It appeared that inadvertent access to air allowed atmospheric oxygen to equilibrate with the sample. The physical laws predicting the effect of partial pressure and temperature on gas solubility in a liquid are illustrated by the pO2 levels measured in this case. Effects due to hyperlipidemia were not observed. The calculations are described in detail. Brief suggestions for sample handling to avoid misleading results from such cases are discussed.

Blood Gas Analysis↗

Nitrate-reducing bacteria on rat tongues.

Nitrite-producing bacteria (NPB) were isolated from tongues of laboratory rats. The most commonly found nitrite-producing organism was Staphylococcus sciuri, followed by Staphylococcus intermedius, Pasteurella spp., and finally Streptococcus spp. Both morphometric quantification of bacteria on tongue sections and enumeration of culturable bacteria (CFU) showed an increase in the density of bacteria towards the posterior tongue. Up to 65% of bacteria were located in the deep clefts on the posterior tongue. The proportion of culturable NPB in the total culturable microbial population increased from 6% (10(5) CFU cm-2) on the anterior tongue to 65% (10(7) CFU cm-2) on the posterior tongue. Different species compositions of NPB were found on different tongue sections with S. intermedius populations decreasing and S. sciuri and Pasteurella populations increasing towards the posterior tongue. Nitrite production was sensitive to oxygen, and significant nitrite production was only detected on the posterior tongue where the majority of bacteria are situated in deep clefts in the tongue surface. This study suggests the importance of bacteria in nitrite production, from nitrate, on the tongue. Nitrite produced on the tongue may subsequently form nitric oxide in the acidic environment of the stomach. Because of the antimicrobial properties of nitric oxide, a key role for nitrate-reducing tongue bacteria in host animal defense against food-borne pathogens in proposed.

Animals↗

Evaluation of PAPNET testing as an ancillary tool to clarify the status of the "atypical" cervical smear.

To assess the utility of the PAPNET system (Neuromedical Systems Inc., Suffern, NY) in clarifying the status of cervical smears showing borderline abnormalities, we analyzed the results of five cytotechnologists who reclassified 200 "atypical" smears by evaluating PAPNET images only. The interobserver agreement (reliability) of the PAPNET reviewers was computed, and their readings were compared with three standards: the consensus diagnosis of five pathologists who used light microscopy, the detection of cancer-associated human papillomavirus DNA by Southern analysis, and the correlation with diagnoses of biopsy specimens obtained during passive follow-up. The PAPNET reviewers classified 18 to 65% of cases as normal, 25 to 42% as equivocal, and 10 to 55% as abnormal. Unanimous interobserver agreement was achieved in only 24 (13%) cases. Four of the five PAPNET reviewers agreed moderately well with the results of the pathology reference panel. In four of the five PAPNET reviews, classification of cases as abnormal was strongly correlated with the detection of cancer-associated types of human papillomavirus. Consensus PAPNET results of abnormal were predictive of abnormal histologic findings at follow-up. Theoretically, if colposcopy had been performed on all of the women with equivocal or abnormal PAPNET results (based on the consensus of the panel), as much as 95% of biopsy-confirmed lesions could have been detected, but 79% of women would have been referred. Restriction of colposcopy referral to women with definitely abnormal PAPNET readings would have reduced referrals to 31%, but the sensitivity of the triage would have dropped to 51% of biopsy-confirmed lesions.

Biopsy↗

Targeted CNS expression of interferon-gamma in transgenic mice leads to hypomyelination, reactive gliosis, and abnormal cerebellar development.

Circumstantial and experimental evidence has implicated the immune cytokine interferon-gamma (IFN-gamma) as a key mediator in the pathological changes that are observed in many demyelinating disorders, including the most common human demyelinating disease, multiple sclerosis. To produce an animal model with which to study the effects of IFN-gamma on the CNS, we have generated transgenic mice in which the expression of IFN-gamma has been placed under the transcriptional control of the myelin basic protein (MBP) gene. Transgenic mice generated with this construct have a shaking/shivering phenotype that is similar to that observed in naturally occurring mouse models of hypomyelination (e.g., shiverer, jimpy, quaking), and these transgenic animals have dramatically less CNS myelin than control animals. Reactive gliosis and increased macrophage/microglial F4/80 immunostaining were also observed. Additionally, major histocompatibility complex (MHC) class I and class II mRNA levels were increased in the CNS of MBP/IFN-gamma transgenic mice, and the increase in MHC class I mRNA expression was detected in both white and gray matter regions. Furthermore, cerebellar granule cell migration was abnormal in these animals. These results strongly support the hypothesis that IFN-gamma is a key effector molecule in immune-mediated demyelinating disorders and indicate that the presence of this cytokine in the CNS may also disrupt the developing nervous system.

Animals↗

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↗