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Biomedical subjects

J Schmidt

Publications and source records attributed to J Schmidt.

At least 433 records · Page 24Linked to original sources

Intravenous contrast medium accentuates the severity of acute necrotizing pancreatitis in the rat.

BACKGROUND/AIMS: Contrast-enhanced computed tomography (CECT) is used to show areas of decreased pancreatic perfusion in severe acute pancreatitis (AP). To evaluate possible adverse effects of the contrast medium (CM) on the course of AP, the impact of intravenous CM in AP of graded severity in the rat was studied. METHODS: Pancreatitis of three levels of severity was induced in Sprague-Dawley rats with intravenous cerulein hyperstimulation plus time- and pressure-controlled intraductal infusion of saline or glycodeoxycholic acid. At 7 hours, control and pancreatitis animals received intravenous ionic CM, nonionic CM, or saline. The principal outcome measures were 24-hour survival, trypsinogen activation peptides (TAP) in ascites, and histological acinar necrosis score. RESULTS: There was no measurable effect of CM on the index features in control animals or animals with mild or moderate AP. In severe AP, CM caused a significant increase in mortality, ascites TAP, and necrosis score. CONCLUSIONS: Intravenous CM increases pancreatic injury when administered early in the course of severe experimental AP. Because CM may convert borderline ischemia to irreversible necrosis, CECT performed early in pancreatitis to show poor perfusion and predict areas of necrosis may depict a self-fulfilling prophecy. Early CECT should be reconsidered and perhaps avoided.

Acute Disease↗

Buprenorphine reduces cerebral glucose metabolism in polydrug abusers.

Buprenorphine is a mixed opioid agonist-antagonist, which acts as a partial mu agonist and a kappa antagonist. The present study evaluated the acute effects of buprenorphine on cerebral glucose metabolism (CMRglc) in six human substance abusers using a double-blind, placebo-controlled, counterbalanced, crossover design. Each subject participated in two positron emission tomographic (PET) studies, 1 week apart, following the injection of buprenorphine (1 mg, intramuscularly) and placebo. Buprenorphine significantly reduced CMRglc and the regional cerebral metabolic rate for glucose (rCMRglc) by up to 32% in all but three of 22 bilateral and in 4 midline regions (p < .05). No region showed an increase in rCMRglc. Buprenorphine also produced miosis, respiratory depression, and subjective ratings of euphoria and sedation in comparison to placebo (p < .05). These observations extend previous findings of reduced CMRglc following acute treatment with morphine and other nonopioid euphorigenic drugs.

Adult↗

Adipose differentiation of cartilage in vitro.

Xiphoids of newborn mice consist of young chondrogenic cells of primary cartilage. During in vitro cultivation, xiphoids showed, morphologically, characteristics of adipose differentiation. This process progressed with time and by day 21 of the culture most of the cells in the xiphoids represented morphological mature adipocytes. During this period, the level of mRNA of lipoprotein lipase, and adipocyte-characteristic gene, increased steadily, while the level of collagen type II mRNA decreased. Continuous DNA synthesis during the cultivation period, even in mature adipocytes confirmed the viability of the cells. Mandibular condyles of newborn mice obtain chondroprogenitor cells as well as young and mature chondroblasts and represent secondary cartilage. Under identical culture conditions mandibular condyles obtained from the same mice undergo osteogenic differentiation and form mature bone within 7 to 10 days. Common to both xiphoids and mandibular condyles is the capacity to transdifferentiate, but they show distinct, divergent differentiation pathways. These findings indicate that cartilagenous tissue of xiphoids undergoes transdifferentiation into adipose tissue in vitro.

Adipose Tissue↗

Nutritional and metabolic variables correlate with amino acid forearm flux in patients with severe head injury.

OBJECTIVE: To measure the arterial-venous amino acid flux across the forearm muscle in patients with severe head injury. DESIGN: Prospective, interventional study. SETTING: Level I trauma hospital in the neurosurgery intensive care unit (ICU) at a university medical center. PATIENTS: Eight nonsteroid-treated patients with severe head injury. INTERVENTIONS: Patients were prospectively randomized to receive either standard or supplemental intravenous zinc therapy. MEASUREMENTS AND MAIN RESULTS: Net forearm alanine, glutamine, tyrosine, phenylalanine, and branch-chain amino acid forearm flux were measured and compared with metabolic markers of energy expenditure and nitrogen excretion. There was a significant inverse relationship between the measured energy expenditure/predicted energy expenditure ratio and glutamine flux (r2 = .62; p < .05). The patients with the highest measured energy expenditure/predicted energy expenditure ratio had the greatest release of glutamine from forearm muscle. Nitrogen balance was significantly correlated with leucine flux (r2 = .53; p < .05) and with isoleucine flux (r2 = .67; p < .05). The patients with the most positive nitrogen balance had the least release of branch-chain amino acids from skeletal muscle. Tyrosine flux was highly correlated with net amino acid flux (r2 = .76; p < .01). Tyrosine flux was therefore indicative of overall muscle catabolism. Four patients had an overall negative flux of amino acids from skeletal muscle. Three patients had an overall negative flux of branch-chain amino acids. CONCLUSIONS: This preliminary descriptive report suggests that increased skeletal muscle efflux of amino acids correlates significantly with metabolic variables of hypermetabolism and hypercatabolism in nonsteroid-treated, head-injured patients.

Adult↗

Modulation of high-threshold transmission between heart interneurons of the medicinal leech by FMRF-NH2.

1. We examined high-threshold synaptic transmission between oscillatory pairs of leech heart interneurons. Inhibitory postsynaptic currents (IPSCs) could be reliably evoked by depolarizing the presynaptic neuron in voltage clamp from a holding potential of -35 mV. At this presynaptic potential, the Ca2+ currents underlying graded transmission are completely inactivated, and we conclude that a high-threshold Ca2+ current is extant in heart interneurons. Further evidence for this was that inhibitory postsynaptic currents were blocked when Co2+ replaced Ca2+ in the saline and thus high-threshold transmission was dependent on the presence of external Ca2+. 2. When IPSCs were evoked by a 200-ms duration voltage step from a holding potential of -35 mV in the presynaptic neuron, the time course of turn-on of the IPSC consisted of a fast (time-to-peak = 17.5 +/- 1.93 (SE) ms [n = 7]) and a slow (time-to-peak = 250 +/- 28.5 ms [n = 8]) component. FMRF-NH2 reduced the amplitude of the fast component but did not affect the slow component. When the presynaptic voltage step was ended the IPSC turned off with a single exponential time course. FMRF-NH2 slowed the time course of turn-off of the IPSC. 3. When IPSCs were evoked by a 1500-ms duration voltage step from a holding potential of -35 mV in the presynaptic neuron, these IPSCs peaked around 300 ms. Following the peak, the IPSC decayed with a single exponential time course. FMRF-NH2 accelerated the time course of this decay. At potentials of 0 mV and +5 mV, FMRF-NH2 produced a significant decrease in the peak current and at potentials of -5 mV and 0 mV, produced a significant decrease in the current integral. 4. High-threshold IPSCs could also be evoked by a spike in the presynaptic neuron. Bath application of 1 microM FMRF-NH2 decreased the amplitude of the spike-evoked IPSC and slowed the time course of its falling phase. 5. We examined the effect of FMRF-NH2 on the quantal synaptic transmission. Bath-application of FMRF-NH2 increased binomial p, the probability of release, and decreased binomial n, the number of units available for release. FMRF-NH2 had no effect on q, the unit size, when calculated from the distributions of PSPs, and increased the coefficient of variation (CV). 6. The lack of a change in q and the increase in CV suggested that FMRF-NH2 acted at a presynaptic location.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Ocular drug safety and HMG-CoA-reductase inhibitors.

150 patients suffering from primary hypercholesterolemia were divided into three different groups receiving (1) lovastatin, (2) simvastatin, or (3) fenofibrate as controls. The aim of the study was to detect possible drug-induced ocular side effects, especially in the lens. The study period was 2 years. Ophthalmological examination and Scheimpflug photography were performed at the beginning and every 6 months. Increases or decreases in the visual acuity were distributed very similarly in the three groups. Definite evidence of side effects was not found, nor was there evidence of deleterious effects on refraction. The intraocular pressure revealed intraindividual fluctuations without clinical significance. Many changes were observed in the lens, all were minimal, including those of the extreme lens periphery which had no effect on visual acuity. The present study shows the great value of Scheimpflug photography with densitometric image analyses because of its objectivity when compared with other methods. Our observations provide good evidence that lovastatin and simvastatin have no undesirable toxic effects on the lens and other ocular tissues, compared with fenofibrate.

Color Perception↗

Switching in the activity state of an interneuron that controls coordination of the hearts in the medicinal leech (Hirudo medicinalis).

The rhythmically active heart interneuron HN(5) in the medicinal leech exhibits two distinct activity states, which have been associated with different coordination states of the two hearts. During the active state, it discharges high-frequency bursts of action potentials interrupted by rhythmic inhibitory input from other interneurons. In the inactive state, the same cell receives rhythmic inhibition but the membrane potential remains subthreshold between these volleys, producing few or no action potentials. We investigated differences in the membrane properties of the cell during the active and inactive states. The membrane potential in the active state oscillates on average between about -56 +/- 6 mV (S.D.) and -45 +/- 7 mV; the mean oscillation amplitude is 11 +/- 4 mV. In the inactive state, the membrane potential oscillates on average between -58 +/- 6 mV and -55 +/- 6 mV with a mean amplitude of 3 +/- 1 mV. The overall conductance of an HN(5) interneuron during the active state is approximately 10 nS lower than that during the inactive state, indicating that an outward current is turned off during the active state or turned on during the inactive state. This outward current is not voltage-dependent in the range -80 mV to -10 mV, as shown in voltage-clamp experiments by a linear current-voltage relationship. The reversal potential of this current is approximately -60 mV, indicating that chloride or potassium ions underlie the current. Using dynamic-clamp, we show that by adding an artificial current with a linear voltage-dependence (leak conductance) to an HN(5) interneuron (conductance 15 nS, reversal potential -60 mV), the cell can be transferred from its active to its inactive state.

Animals↗

[Murine leukemia virus Akv promotes bone tumor development in fos-transgenic mice].

Newborn hMT-fos-LTR transgenic C3H mice and their non-transgenic siblings were infected with Akv, derived from the ecotropic provirus of the AKR mouse. Bone sarcomas in non-infected transgenics were observed in 20% (3/15) of females at 448 +/- 25 days and in 8% (1/12) of males at 523 days. Akv-infected transgenics developed bone tumors with higher frequency and at younger age: Females in 69% (20/28) at 268 +/- 122 days, males in 83% (24/29) at 279 +/- 109 days. In the majority of the bone tumors of Akv-infected transgenics (70% in females, 59% in males) cellular atypia was lacking and the histological pattern resembled human parosteal osteosarcoma. Only 50% (12/24) of bone tumors in Akv-infected transgenics revealed newly integrated virus sequences by Southern analysis. PCR analysis detected Akv sequences in DNAs of all tumors. Obviously, the insertion of Akv in a few cells induced the considerably accelerated bone tumor growth.

Animals↗

[Computer-assisted experimental implantation technique for comparative quality assessment of various cementation techniques in cemented hip prosthesis implantation].

For the anchorage of femoral prosthesis stems in total hip arthroplasty, various cement application techniques are used. Experimental comparison of these techniques requires a set-up in which only the cementing technique itself is tested. We used a computer-controlled implantation device based on a milling machine and standardized artificial femur models. The stems are reproducibly positioned by the machine and any influence of manual positioning during the implantation is excluded. The results can be evaluated macroscopically and radiologically with no interference by disturbing bone--with sufficient sensitivity to objectify differences in cement quality. The increase in pressure in the peripheral medullary cavity, which is responsible for the embolisation, can be determined experimentally for the individual cementing technique. The experimental implantation device described enables a standardized comparison of various cementing techniques.

Bone Cements↗

[Treatment of salivary incontinence. A proposal of a new surgical technic and the preliminary results].

Drooling is not induced by an excess of salivary but by incontinence, in case of patients with cerebral palsy and neurologically damaged. Than radical techniques of excision, duct ligations of salivary glands, the authors propose an original association of deviation of submandibular and parotid ducts behind the anterior pillar of soft palate. They discuss it with other therapeutics already proposed in the literature.

Adult↗

Interstitial protease activation is the central event in progression to necrotizing pancreatitis.

BACKGROUND: Although intracellular protease activation is thought to be an early event in acute pancreatitis, factors determining progression from edematous to necrotizing pancreatitis are largely unknown. With enterokinase as a probe and an immunoassay quantifying free trypsinogen activation peptides (TAP), we sought evidence for the presence of interstitial trypsinogen in edematous pancreatitis and documented the effects of its ectopic activation. METHODS: Edematous pancreatitis in the rat was induced by supramaximal stimulation with cerulein (5 micrograms/kg/hr) and coupled with enterokinase infused into the pancreatic duct at 30 mm Hg. Blue dextran infusion at this pressure corroborated interstitial delivery. Rats with no stimulation, maximal physiologic stimulation (0.25 microgram/kg/hr of cerulein), or intraductal saline infusion served as controls. TAP levels measured by enzyme-linked immunosorbent assay, 6-hour survival, and histopathology were used as end points. RESULTS: Intraductal enterokinase infusion alone or in combination with maximal physiologic stimulation generated only slight increases in TAP level and no or minimal pancreatic injury. In contrast, enterokinase superimposed on edematous pancreatitis (supramaximal cerulein stimulation) produced fulminant pancreatitis and rapid death of all animals within 6 hours. Pancreatic histopathology showed severe intrapancreatic hemorrhage, acinar inflammation, and necrosis. TAP levels were significantly higher in plasma (p = 0.02), urine (p = 0.05), and ascites (p < 0.001) when compared with all other groups. CONCLUSIONS: In edematous pancreatitis a large pool of trypsinogen accumulates in the interstitial space. Activation of these proenzymes leads to catastrophic consequences and may underlie progression from mild to necrotizing pancreatitis.

Animals↗

A rural emergency department.

The appropriate use of emergency departments is of growing concern. By knowing which patients are more likely to make inappropriate visits to these departments, efforts can be directed to encourage more suitable care. Our study was done in a rural county hospital in eastern New Mexico. Data were collected from all emergency department visits over a 4-week period. Patient and physician questionnaires were administered to assess aspects of emergency department use, including appropriateness based on published criteria, physicians' opinion of appropriateness, groups who made inappropriate visits, and the perception of the need for and the urgency of a visit. We found that 32% of visits were inappropriate based on published criteria and 24% were considered inappropriate by physician opinion. Two groups with a high rate of inappropriate visits were Hispanics and Medicaid recipients. Patients and physicians have differing opinions of the urgency of a visit and of how soon medical treatment is required. To decrease the frequency of inappropriate use of emergency departments, educational efforts should be focused on the subgroups with high rates of such use.

Adolescent↗

A novel operon organization involving the genes for chorismate synthase (aromatic biosynthesis pathway) and ribosomal GTPase center proteins (L11, L1, L10, L12: rplKAJL) in cyanobacterium Synechocystis PCC 6803.

Many of the ribosomal protein (RP) genes in both bacterial and chloroplast genomes occur, for reasons not yet understood, in operons that include nonribosomal genes. Here we report such an operon organization in a cyanobacterium (Synechocystis PCC6803) involving the genes for four RPs that are important in the GTPase function of the ribosome and the aroC gene encoding chorismate synthase, a key enzyme in the shikimate pathway for biosynthesis of aromatic amino acids and cell wall components. The Synechocystis aroC encodes a 362-amino-acid residue protein which is 52, 60, and 68% identical to two eubacterial (both 52%), yeast, and a higher plant (Corydalis) chorismate synthase, respectively. The gene was overexpressed in Escherichia coli, and the gene product was shown to cross-react with antibodies to Corydalis chorismate synthase; it also complemented an aroC-lacking E. coli strain. The Synechocystis rpl1 and rpl11 genes encode polypeptides of 237 and 141 amino acid residues, respectively, also with high sequence identities to the corresponding RP sequences from other eubacteria and higher plant chloroplasts. The gene order is shown to be: rpl11-86bp spacer-rpl1-460bp spacer-rpl10-87-bp spacer-rpl12-206bp spacer-aroC. Southern and Northern blot analyses of Synechocystis DNA and RNA, respectively, revealed a single cluster of these genes per genome which is transcribed from a common promoter to an unusually long, approximately 9500-nucleotide transcript. Several constructs of the cyanobacterial aroC and rpl12 genes were made and expressed in E. coli to examine the mechanisms for their very differential expression from a polycistronic mRNA (e.g. four copies L12/ribosome; chorismate synthase, a non-abundant protein). These results present the first biochemical/molecular genetic evidence of shikimate pathway in the cyanobacterial group.

Amino Acid Sequence↗