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Biomedical subjects

R D Welch

Publications and source records attributed to R D Welch.

At least 37 records · Page 2Linked to original sources
PubMed1992

Use of an implant for intraosseous infusion as supportive therapy for a Vietnamese pot-bellied pig with urethral obstruction caused by a polyp.

A Vietnamese pot-bellied pig with a urethral polyp was supported by total parenteral nutrition given through an intraosseous implant. Peripheral vascular access was difficult to establish and maintain in this anorectic pig, so a pediatric intraosseous implant was placed in the left tibia. Surgical repair of the urethra was not considered possible, and alternative techniques of a functional bypass were unacceptable to the owners, so euthanasia was elected. Histologic examination of the urethra revealed a polypoid structure believed to be similar to benign congenital polyps described in young boys.

Animals↗
PubMed1992

Pulsed spectral Doppler evaluation of a peripheral arteriovenous fistula in a horse.

Pulsed spectral Doppler ultrasonography was used to characterize the vascular involvement and anatomic boundaries of a peripheral arteriovenous fistula on the hemithorax of a horse. This information facilitated surgical removal of the fistula. Pulsed spectral Doppler evaluation of suspected peripheral vascular anomalies should be considered for the diagnosis of similar lesions, in which contrast angiography is not possible.

Animals↗
PubMed1992

DNA allosterically modulates the steroid binding domain of the estrogen receptor.

The ability of DNA to allosterically alter the conformation of the estrogen receptor's (ER) steroid binding domain was investigated. Using dissociation kinetics we observed that when DNA was bound to the DNA binding domain of the rat uterine ER the rate of estrogen dissociation from the steroid binding domain increased almost 2-fold. This change in the rate of estrogen dissociation depended on the concentration of DNA used and correlated with the thermodynamic binding affinities (Kd) of the ER for two different DNA sequences. We were unable to detect a DNA-induced change in the trypsin cleavage pattern of the amino terminal end of the ER. Using a whole cell dissociation kinetic assay with MCF-7 breast cancer cells we observed a 7-fold slower rate of estrogen dissociation from the ER within the cell than from the ER in vitro. This suggests that additional factors, other than DNA binding, may modify the steroid binding domain within the cell. We conclude that DNA can allosterically modulate the structure of the steroid binding domain of the ER, and we hypothesize that this conformational change may be necessary for the full transcriptional activity of the ER.

Allosteric Regulation↗
PubMed1992

Intraosseous infusion using the osteoport implant in the caprine tibia.

We evaluated the in vivo animal tolerance to intraosseous infusion via the Osteoport pediatric implant (model 2005PSO, Lifequest Medical, San Antonio, TX, U.S.A.) into the proximal tibia of immature goats and investigated the osseous effects of intermittent and sustained increases in intraosseous pressure (IOP). In group 1 (n = 3) autogenous whole blood was continuously infused (CI) for 5 days at flow rates producing an IOP of 30-45 mm Hg. Group 2 animals (n = 3) underwent a 5-s high-pressure infusion (HPI) of lactated Ringer solution (LRS) producing an IOP of 90-125 mm Hg twice daily for 10 days. In group 3, the Osteoports were left in place 5 (n = 2) or 10 days (n = 2) and evaluated for patency at 72-h intervals. An IOP > 35 mm Hg produced clinical evidence of bone pain. Bone mineral density was significantly increased (p < 0.05) in all implanted tibias (mean 1.04 g/cm2; range 0.87-1.21 g/cm2) compared with controls (mean 0.67 g/cm2; range 0.65-0.71 g/cm2). A nonsignificant increase (+9% to +31%) in periosteal new bone formation occurred in all implanted tibias. In the continuously infused group, there was a significant increase (p < 0.05) in cancellous new bone formation (+483%), percentage eroded bone surface (+143%), and osteoclast covered bone surface (+255%) compared with controls. HPI of LRS did not produce significant bone changes. Seemingly, the Osteoport provided a ready means of intraosseous infusion and may be associated with less complications than current methods of continual vascular access. Bone changes correlated more with the duration than the magnitude of increased intraosseous pressures.

Absorptiometry, Photon↗
PubMed1992

Prospective analysis of mental status progression in ethanol-intoxicated patients.

Distinguishing patients with uncomplicated ethanol intoxication from intoxicated patients with other causes of mental status depression is a common clinical dilemma. The authors serially tested mental status in a group of ethanol-intoxicated patients to determine the interval over which mental status changes could be attributed to uncomplicated intoxication. Study patients were identified by (1) admission breath ethanol greater than or equal to 100 mg/dL; (2) ethanol-related impairment necessitating further observation or treatment; and (3) not critically ill or exhibiting focal neurologic signs. Mental status scores (sums of specific indices of alertness, orientation, and agitation) were determined initially, 1 hour after arrival, then every 2 hours. Causes of mental status depression other than acute intoxication were diagnosed in 16 patients, while another 18 failed to completely normalize mental status by the time of emergency department discharge or hospital admission. The remaining 71 with uncomplicated ethanol intoxication required (mean +/- SD) 3.2 +/- 3.6 hours to normalize mental status scores. A large proportion, however, took considerably longer to normalize mental status: 15 (21%) took 7 or more hours, and three (4%) took as long as 11 hours. Although patients with ethanol-associated depression of mental status lasting 3 hours after emergency department admission should be carefully evaluated for other causes of mental status abnormalities, the authors' observations indicate considerable individual variation in the duration of mental status depression caused by uncomplicated ethanol intoxication.

Alcoholic Intoxication↗
PubMed1992

Controversial issues in clinical management of the simple wound.

The primary goals of the practitioner managing a simple wound are to encourage primary healing and avoid infection. We conclude from this analysis that the four basic aspects of wound management we have reviewed, the timing of wound repair, the preparation of the wound, local anesthetic management, and antimicrobial therapy, will continue to be fertile topics for investigation and debate.

Anesthesia, Local↗
PubMed1992

Idiopathic muscular hypertrophy of the equine small intestine: 11 cases (1980-1991).

The medical records of 11 horses with idiopathic muscular hypertrophy (MH) of the small intestine were reviewed to determine the clinical and pathological features of the disease. The median age of affected horses was 10.0 years (range 5-18 years). No breed or sex predisposition was apparent. Ten horses (91%) had chronic (23 days to 2.4 years) signs of mild, intermittent colic, and 1 horse had signs of severe colic of only 3 days' duration. Partial anorexia and chronic weight loss of variable duration (1-6 months) were prominent historical findings in 5 (45%) horses. Diagnostic tests, with the exception of exploratory caeliotomy, were ineffective for definitive diagnosis of intestinal MH as a cause of colic. In 2 horses, however, a thickened, rigid ileum was detected by palpation per rectum, and in 5 horses, multiple loops of distended small intestine were detected by palpation per rectum. Hypertrophy of both the circular and longitudinal layers of muscularis was determined as the cause of intestinal thickening in all horses. Muscular hypertrophy of the ileum was present in 9 (82%) horses. Two horses (18%) had MH of a section of jejunum only, and 4 (36%) horses had MH of the ileum in combination with MH of other sections of small intestine. Two (18%) horses had MH of the entire small intestine. In 9 (82%) horses, intestinal MH resulted in narrowing of the luminal diameter at the site of MH. Small diverticula were present on the mesenteric border of the hypertrophied ileum of 5 (45%) horses. Five linear (up to 150-cm) diverticula were present in the hypertrophied jejunum of 1 (9%) horse. Haemomelasma ilei was present on the antimesenteric serosal surface of affected intestine of 8 (73%) horses. Full-thickness rupture of the ileum with subsequent diffuse, septic peritonitis occurred in 3 (27%) horses.

Animals↗
PubMed1991

Incidence of cocaine-associated rhabdomyolysis.

STUDY HYPOTHESIS: Rhabdomyolysis is a common complication of cocaine use, and muscle symptoms fail to predict its development. STUDY POPULATION: A prospective, convenience sample of patients presenting to the emergency department of a large inner-city hospital with complaints related to cocaine use were eligible for inclusion. Patients were excluded if they had other potential causes of elevated creatine kinase (CK) levels or rhabdomyolysis. A control group comprised patients who were not cocaine users and satisfied the exclusion criteria. Sixty-eight patients were studied. METHODS: Initial evaluation included determination of the presence of muscle pain or swelling and total CK levels. Patients with a CK level of more than 800 U/L had additional tests, including a urine myoglobin, urine drug screen, and serum phosphorus. Rhabdomyolysis was defined by a serum CK level of more than 1,000 U/L (more than fivefold that of normal). CK levels were compared by two-tailed Student's t test. Muscle symptoms were compared with the development of rhabdomyolysis by Fisher's exact test. RESULTS: The CK level in the cocaine group was 931 +/- 1,785 U/L (mean +/- 1 SD). The CK level in the control group was 242 +/- 168 U/L (P = .028). Of the cocaine users, 24% (eight of 34) had rhabdomyolysis; one developed multiorgan failure and died. No patient in the control group had a CK level of more than 1,000 U/L. Only one cocaine user who developed rhabdomyolysis had muscle symptoms. Three cocaine users had muscle symptoms but did not develop rhabdomyolysis. No patient in the control group had muscle symptoms or developed rhabdomyolysis. Muscle symptoms did not predict the CK level (P = .55). CONCLUSION: This study revealed that 24% of the cocaine users had rhabdomyolysis. Many of the cases of rhabdomyolysis were not predictable from history or physical examination, making laboratory evaluation essential.

Adult↗
PubMed1991

Ethylmalonic/adipic aciduria: effects of oral medium-chain triglycerides, carnitine, and glycine on urinary excretion of organic acids, acylcarnitines, and acylglycines.

A 9-y-old girl with ethylmalonic/adipic aciduria was hospitalized to determine the possible therapeutic efficacy of oral carnitine and glycine supplementation. To provoke a mild metabolic stress, her diet was supplemented with 440 mg/kg/d of medium-chain triglycerides. She was treated successively with carnitine (100 mg/kg/d) for 5 d, neither carnitine nor glycine for 2 d, and then glycine (250 mg/kg/d) for 6 d. Consecutive 12-h urine collections were obtained throughout the entire period. The urinary excretion of eight organic acids, four acylglycines, and four acylcarnitines, which accumulate as a result of a metabolic block of five mitochondrial acyl-CoA dehydrogenases, were quantitatively determined by capillary gas chromatography, stable isotope dilution gas chromatography/mass spectrometry, and radioisotopic exchange HPLC, respectively. The excretion of each group of metabolites was calculated as the mean percentage of total output (mumol/24 h) during the four phases of the protocol (organic acids/acylglycines/acylcarnitines = 100.0%): 1) regular diet (3 d); 88.1/10.8/1.1; 2) medium-chain triglyceride supplementation (4); 82.5/15.6/1.9; 3) medium-chain triglycerides plus carnitine (5); 79.2/8.2/12.6; and 4) medium-chain triglycerides plus glycine (6); 81.0/18.7/0.3. Comparison between total and individual excretion of acylglycines and acylcarnitines indicates that oral glycine supplementation enhanced the conjugation and excretion of fatty acyl-CoA intermediates as efficiently as carnitine. We propose that oral glycine supplementation should be considered in the treatment of other inborn errors of metabolism associated with abnormal urinary excretion of acylglycines.

Acylation↗
PubMed1991

Effects of intra-articular administration of dimethylsulfoxide on chemically induced synovitis in immature horses.

The effects of intra-articular administration of dimethylsulfoxide (DMSO) on chemically induced synovitis in the middle carpal joint of 6 weanling horses were evaluated. Following aseptic collection of synovial fluid, the middle carpal joint of each forelimb was injected with 50 mg of Na-monoiodoacetate to induce synovitis. Eight days after injection, synovial fluid was obtained and the right middle carpal joints were injected with 2 ml of 40% DMSO in lactated Ringer solution. The corresponding joints of the left limb (control) were injected with 2 ml of lactated Ringer solution. Sampling and treatments were repeated on post-injection days 11 and 14, for a total of 3 treatments. Horses were visually evaluated daily for lameness and joint effusion. Synovial fluid was evaluated for color and clarity, differential and total WBC count, total protein content, and hyaluronic acid concentration. The Kaegi gait analysis system provided an objective assessment of lameness prior to inducing synovitis, again on day 7, and on day 17. At necropsy (day 17), synovial fluid, synovial membrane, and articular cartilage specimens were collected. Joint effusion was evident 12 hours after injection of Na-monoiodoacetate in all joints. Mild lameness was evident at 24 hours; however, the lameness resolved by 72 hours. Objective assessment of lameness did not reveal significant differences between treatment or control limbs. Hyaluronic acid concentrations increased significantly (P = 0.023) above baseline values in most joints over the study period. Synovial fluid WBC counts increased significantly (P = 0.002) following Na-monoiodoacetate injection and remained significantly (P = 0.002) above baseline values throughout the study.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Elective cesarean section in mares: eight cases (1980-1989).

From 1980 to 1989, 8 cesarean sections were performed on an elective basis in 5 mares. Four mares had partially obstructed pelvic canals; 2 of these mares had previously lost foals because of dystocia. Cervical adhesions that might obstruct passage of the fetus through the pelvic canal was suspected in the fifth mare. Cesarean section was performed prior to mares entering the first stage of labor. Readiness for birth was estimated by development of the mare's mammary gland and the presence of colostrum in the udder. A ventral midline celiotomy provided excellent exposure and healed without complications in all instances. Eight viable foals were produced. One foal developed bacterial pneumonia and septicemia after surgery and died. Follow-up evaluation of the 7 foals discharged from the hospital failed to reveal complications associated with elective cesarean section. All mares survived the procedure. Fetal membranes were retained for up to 72 hours following surgery; however, systemic complications secondary to retained placenta did not develop. Three mares were bred subsequent to elective cesarean sections, with each mare conceiving the year following surgery. Three foals were produced by 1 mare and 2 foals have been produced by another mare by elective cesarean sections.

Animals↗
PubMed1990

Surgical treatment of tarsal sheath effusion associated with an exostosis on the calcaneus of a horse.

A 2-year-old Thoroughbred colt was referred for evaluation of effusion within the tarsal sheath and associated lameness of the right hind limb. Conservative treatment consisting of needle aspiration and pressure bandaging had been unsuccessful. Radiography of the right tarsus revealed proliferative periosteal reaction along the distal caudal border of the sustentaculum tali and medial aspect of the calcaneus. The owners elected conservative treatment, using a local injection of corticosteroid and pressure bandaging the tarsus. Five months later, the severity of the effusion and lameness had increased. Radiography revealed increased reactive bone along the sustentaculum tali and mineralization of the plantar tarsal ligament and tarsal sheath. Surgical exploration revealed fibrous adhesions between the medial aspect of the calcaneus and the flexor tendon and associated soft tissue mineralization. The adhesions were broken down and the reactive bone along the calcaneus was removed. The mineralized soft tissue within the tarsal sheath was excised. Five months after surgery, the horse was sound at the trot, with only minimal tarsal sheath effusion. The response to treatment for tarsal sheath effusion and lameness caused by bony changes of the sustentaculum tali is often unsatisfactory. After responding poorly to conservative treatment, the horse in this report had a favorable outcome to the surgical intervention of this condition.

Animals↗
PubMed1990

Identification of 2-(2'-octenyl) succinic acid in urine.

2-(2'-octenyl)succinic acid has been identified in urine samples from children investigated for a possible inherited metabolic disease. Its structural identification has been achieved by gas chromatography/mass spectrometry using both electron ionization and chemical ionization and by tandem mass spectrometry (MS/MS) using fast-atom bombardment and high-resolution electron-ionization analyses of the molecular ion in a complex biological matrix. The localization of the double bond was obtained by interpretation of a unexpected rearrangement reaction occurring after dimethyl disulfide derivatization.

Gas Chromatography-Mass Spectrometry↗
PubMed1990

The enzymatic basis for the dehydrogenation of 3-phenylpropionic acid: in vitro reaction of 3-phenylpropionyl-CoA with various acyl-CoA dehydrogenases.

3-Phenylpropionic acid is an end-product of the bacterial degradation of unabsorbed phenylalanine in the intestinal lumen. As CoA ester, this metabolite has been considered to be a specific substrate for medium chain acyl-CoA dehydrogenase (MCAD). Its glycine-conjugate, 3-phenylpropionylglycine, has now been established as a pathognomonic marker in urine from patients affected with MCAD deficiency. However, no systematic studies to evaluate the reactivity of 3-phenylpropionyl-CoA with other known acyl-CoA dehydrogenases have so far been carried out to establish the specificity of this substrate for MCAD. We studied the in vitro reactivity of 3-phenylpropionyl-CoA with five rat and human liver acyl-CoA dehydrogenases using purified preparations. we demonstrated that MCAD effectively dehydrogenated 3-phenylpropionyl-CoA, and that no other acyl-CoA dehydrogenase exhibited any significant activity with this substrate. In the steady state condition, the Km of 3-phenylpropionyl-CoA for human MCAD was 50 microM. Gas chromatography/mass spectrometry analysis of the assay mixture identified trans-cinnamoyl-CoA as the product of the reaction. Furthermore, we showed by determination of the reaction products using gas chromatography/mass spectrometry selected ion monitoring that, in absence of the primary electron acceptor, 3-phenylpropionyl-CoA was slowly but significantly dehydrogenated by MCAD under aerobic conditions. These data suggest that MCAD may oxidize 3-phenylpropionyl-CoA in vivo using an alternative electron acceptor, to produce trans-cinnamoyl-CoA. This mechanism provides an explanation for the normal 3-phenylpropionylglycine excretion observed in urine from patients affected with glutaric aciduria type II and ethylmalonic/adipic aciduria.

Acyl-CoA Dehydrogenases↗
PubMed1990

Diagnosis of medium chain acyl-CoA dehydrogenase deficiency by stable isotope dilution analysis of urinary acylglycines: retrospective and prospective studies, and comparison of its accuracy to acylcarnitine identification by FAB/mass spectrometry.

In summary, we have demonstrated that the accurate quantitation of urinary HG and PPG by stable isotope dilution analysis is currently the most reliable method for the diagnosis of MCAD deficiency. This method is particularly useful for testing random samples from asymptomatic patients without any provocative test, and it is suitable to widely survey a fairly large population, such as patients with episodic manifestations and families with a history of SIDS.

Acyl-CoA Dehydrogenase↗
PubMed1989

Stable isotope dilution analysis of n-hexanoylglycine, 3-phenylpropionylglycine and suberylglycine in human urine using chemical ionization gas chromatography/mass spectrometry selected ion monitoring.

We describe a gas chromatographic/mass spectrometric method for the accurate determination of n-hexanoylglycine, 3-phenylpropionylglycine and suberylglycine in urine for the diagnosis of hereditary medium-chain acyl-CoA dehydrogenase (MCAD) deficiency. These acylglycines had previously been detected in urine from patients with MCAD deficiency, but their diagnostic values were unknown because of a lack of appropriate analytical methods. n-Hexanoyl(1,2-13C)glycine, 3-phenylpropionyl(2-13C,15N)glycine and suberyl(2-13C,15N)glycine were synthesized and used as internal standards. Ammonia chemical ionization was utilized to generate intense [M + H]+ ions for selected-ion monitoring quantification. The whole procedure is fast and can be performed by a low-resolution gas chromatographic/mass spectrometric system, giving accurate results over a range of three orders of magnitude (0.0167-16.7 micrograms/ml). The results from the analyses of 54 urine samples from 21 MCAD-deficient patients and various control samples using this method established that n-hexanoyglycine and 3-phenylpropionylglycine were highly diagnostic for this disease, while suberylglycine was found less specific.

Chemical Phenomena↗