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M D Cunningham

Publications and source records attributed to M D Cunningham.

At least 37 records · Page 2Linked to original sources
PubMed1993

Hemorrhagic adrenal cyst.

Adrenal cysts are uncommon. They may be fatal if they hemorrhage and are not rapidly diagnosed. Most adrenal cysts are small and asymptomatic. When they are symptomatic, it is usually because the cyst has enlarged, causing flank discomfort, gastrointestinal complaints, and hemorrhage. Occasionally, a palpable mass may be found. It is thought that hemorrhage occurs secondary to trauma or some toxic or infectious process. The author describes a case in which a previously healthy man had a sudden hemorrhage within a benign adrenal cyst with infarction of the kidney. A discussion of adrenal cysts follows.

Adrenal Gland Diseases↗
PubMed1992

Peptides related to the carboxyl terminus of human platelet factor IV with antibacterial activity.

A peptide (C13) corresponding to the last 13 amino acids of the carboxyl terminus of human platelet factor IV was found to be antibacterial. Amino acid substitutions predicted to disrupt either the amphipathic or alpha-helical nature of C13 rendered the peptide inactive. Antibacterial activity was demonstrated in normal human serum on bacteria which had been previously exposed to low levels of cefepime, a beta-lactam antibiotic. Peptide analogues were examined for more potent antibacterial activity in an antibacterial assay that employed normal human serum and low levels of cefepime. A peptide analogue (C18G) with 80-fold more antibacterial activity than C13 was identified. Studies in C8-deficient sera confirmed an essential role of human serum complement for optimal antibacterial activity. Additional studies showed low levels of cefepime, although not essential, enhanced the antibacterial activity of C18G. Animal protection experiments demonstrated that either peptide C18G or an analogue with all D amino acids (C18X) significantly increased the survival of neutropenic mice when coadministered with a low level of cefepime. This work has resulted in the identification of a new group of antibacterial peptides.

Amino Acid Sequence↗
PubMed1991

Beta-lactam antibiotics potentiate magainin 2 antimicrobial activity in vitro and in vivo.

The ability of magainin 2 to augment antibiotic therapy was examined. Susceptibility to magainin 2 was determined on Escherichia coli incubated in the presence and absence of sublethal concentrations of antibiotics both in vitro and in vivo. Experiments in buffer and normal human serum revealed that E. coli exposed to sublethal amounts of cefepime, a beta-lactam antibiotic, was significantly more susceptible to the antimicrobial activity of magainin 2. Bacteria incubated with subinhibitory concentrations of other beta-lactam type antibiotics, but not amikacin (an aminoglycoside) or ciprofloxacin (a quinolone), were also more susceptible to magainin 2 in normal human serum. Bacteria were less susceptible to magainin 2 when they were examined in heat-inactivated serum. Complement was shown to be required for magainin 2 activity in serum by using C8-deficient sera. The combination of magainin 2 and cefepime was shown to be more antimicrobial in normal human serum for a variety of bacterial strains. Magainin 2 was completely inactive as a therapeutic agent when it was administered alone (2 mg per mouse) but significantly increased the survival of mice when it was administered with a low level of cefepime.

Animals↗
PubMed1990

Solubilization and partial purification of 3-((+-)-2-carboxypiperazine-4-yl)-[1,2-3H]propyl-1-phosphonic acid recognition proteins from rat brain synaptic membranes.

The receptors on neuronal membranes for N-methyl-D-aspartate (NMDA), an analog of L-glutamic acid, are the focus of intensive study because of their importance in many neurophysiological and neuropathological states. Since there is very little knowledge of the molecular characteristics of the NMDA receptors, we undertook the development of methods for the solubilization and purification of proteins that form the receptor complex. Optimal conditions for solubilization of NMDA receptors from isolated synaptic plasma membranes involved the use of the zwitterionic detergent 3-[(3-cholamidopropyl)dimethylammonio]-1-propane-sulfonate (CHAPS) together with NH4SCN, 10% glycerol, and the nonionic detergent polyoxyethylene 10 tridecyl ether. The presence of NMDA receptors was monitored as the binding activity for the specific NMDA receptor ligand 3-((+-)-2-carboxypiperazine-4-yl)-[1,2-3H]propyl-1-phosphonic acid ([3H]CPP). Approximately 50% of membrane proteins were solubilized, and an equal quantitative recovery of [3H]CPP-binding proteins was achieved. The selectivity of [3H] CPP-binding proteins for excitatory amino acid agonists and aminophosphonocarboxylic acid antagonists remained essentially unchanged following solubilization. The effect of the NMDA receptor modulator, glycine, and of the ion channel-blocking cation Mg2+ on [3H]CPP-binding proteins was drastically altered by solubilization. Both became activators of [3H]CPP-binding sites. The NMDA receptor agonist ibotenic acid was used to develop an affinity matrix for the isolation of the NMDA receptor complex. The [3H]CPP-binding proteins were selectively eluted by the introduction of 2 mM Mg2+ in the elution buffers. This fraction was highly enriched in CPP-binding entities and in a protein of 58-60-kDa molecular size. The CPP binding activity of the proteins in this fraction was enriched by a factor of approximately 20,000 over that of brain homogenate. There was no L-[3H]glutamate binding activity associated with this fraction. Proteins interacting with glutamate, NMDA, and ibotenate were recovered in the 1 M KCl-eluted fraction. We propose that the 58-60-kDa protein is the aminophosphonocarboxylic acid antagonist-binding subunit of the NMDA receptor complex.

Animals↗
PubMed1990

Reintroduction of continuous negative pressure ventilation in neonates: two-year experience.

Continuous negative pressure ventilation utilizes subatmospheric pressure around the thorax to improve oxygenation. It has not been routinely used since the mid-1970s. We treated 37 infants with the combination of continuous negative pressure (CNP) and intermittent mandatory ventilation (IMV), after failing to attain a PaO2 of greater than or equal to 50 torr on IMV alone. Lung diseases included pulmonary interstitial emphysema (PIE), respiratory distress syndrome (RDS), and pulmonary artery hypertension (PAH) due either to meconium aspiration syndrome (MAS) or other causes (non-MAS). All infants had evidence of severe parenchymal pulmonary disease, or pulmonary artery hypertension resulting in persistent hypoxemia and hypotension. In the PIE group, CNP was started later in the course of the disease, and both positive pressure and oxygen were maintained for a longer period. The group of infants with non-MAS PAH required CNP and positive pressure ventilation for the shortest period of time. The infants with PIE also had a greater incidence of bronchopulmonary dysplasia (BPD) and intraventricular hemorrhage (IVH). In addition, three patients with PIE died. In the non-MAS patients with PAH, no complications and no deaths occurred. The response to CNP was a rapid improvement in oxygenation in all groups with the greatest increase of PaO2 in the non-MAS PAH infants: from 30 torr prior to the initiation of CNP to 140 torr within 30 minutes. No significant changes in pH or PaCO2 occurred in any group. Significant decreases in ventilator rate, mean airway pressure (Paw) and FIO2 in peak inspiratory pressure were possible by 12 hours of CNP.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Pressure↗
PubMed1990

Influence of subinhibitory concentrations of cephalosporins on the serum sensitivity of Pseudomonas aeruginosa.

The effect of sublethal concentrations of antibiotics on the serum sensitivity of Pseudomonas aeruginosa was examined. Cefepime, ceftazidime, and imipenem but not amikacin nor ciprofloxacin increased the serum bactericidal activity of pooled normal human serum. Killing was both serum- and antibiotic dose-dependent. Increased sensitivity to the bactericidal action of serum in the presence of cefepime was observed for several different clinical isolates. With the use of C8-deficient sera, the late components of the complement pathway were shown to be essential for bacterial killing. A significant increase in the amount of [125I]C9 based on bacterial mass was observed with bacteria incubated with cefepime compared with non-antibiotic- or amikacin-treated controls. No major change in the amount of type of lipopolysaccharide was observed when cefepime-treated and control bacteria were compared. The data show that cefepime and other cephalosporins at sublethal concentrations increase the complement-mediated bactericidal activity of serum against P. aeruginosa.

Amikacin↗
PubMed1989

Clinical evaluation of a direct fluorescent monoclonal antibody test for detection of Pseudomonas aeruginosa in blood cultures.

A direct fluorescent monoclonal antibody test (DFA; Genetic Systems Corp., Seattle, Wash.) was evaluated for the detection of Pseudomonas aeruginosa in 178 blood culture broths obtained from 128 patients. The DFA identified 44 (98%) of 45 blood cultures positive for P. aeruginosa and was negative in 131 (98%) of 133 blood cultures which grew gram-negative rods other than P. aeruginosa. Upon further investigation, saline suspensions of the organism from the false-negative blood culture were strongly (4+) DFA positive. The false-positive reactions were not due to cross-reactivity, as shown by lack of DFA staining of the non-P. aeruginosa isolates following subculture to agar media. The specificity of the reagent was further demonstrated by directly staining culture isolates including 10 serotypes of P. aeruginosa (all positive) and 57 selected gram-negative bacilli including eight species of Pseudomonas that were not P. aeruginosa (all negative). DFA staining of blood culture broths was easy to perform and read with minimal background fluorescence. The DFA method can be performed in 50 min and appears promising as a rapid method for the identification of P. aeruginosa bacteremia.

Antibodies, Monoclonal↗
PubMed1989

Intensive care monitoring of pulmonary mechanics for preterm infants undergoing mechanical ventilation.

Changing lung dynamics and ventilator settings were studied prospectively from onset of respiratory distress syndrome in 32 very low birthweight infants (790-1,460 g, mean 1,173 g). Infants were studied in the first and second week of life using pneumotachography for dynamic compliance and lung resistance calculated from spontaneous breaths. Infants were ventilated to maintain pH at or above 7.30, PCO2 40-50 torr, and PO2 50-70 torr. Eleven infants developed chronic lung disease (CLD). In the first week, CLD infants had lower compliance (0.87 vs. 1.01 mL/cm H2O) and higher resistance (94.23 vs. 76.29 cm H2O/L/sec) than non-CLD infants. CLD infants required greater mean airway pressure (9.56 vs. 7.02 cm H2O; P = .05) and higher peak inspiratory pressures (21.85 vs. 15.71 cm H2O; P = .01). Oxygen requirements were greater for CLD infants (FIO2 0.59 vs. 0.45, P = .05). During the second week compliance for CLD infants improved (1.00) and resistance decreased slightly (92.23), but peak inspiratory pressure settings remained higher for CLD infants (19.60 vs. 14.95 cm H2O; P = .02). Although pulmonary mechanics remained stable for both groups, infants exposed to continuously greater peak inspiratory pressure and oxygen concentration proved susceptible to CLD. Developing a match of ventilator settings to improve pulmonary mechanics may lessen CLD of infancy.

Humans↗
PubMed1988

Immune labeling and purification of a 71-kDa glutamate-binding protein from brain synaptic membranes. Possible relationship of this protein to physiologic glutamate receptors.

Immunoblot studies of synaptic membranes isolated from rat brain using antibodies raised against a previously purified glutamate-binding protein (GBP) indicated labeling of an approximately 70-kDa protein band. Since the antibodies used were raised against a 14-kDa GBP, the present studies were undertaken to explore the possibility that the 14-kDa protein may have been a proteolytic fragment of a larger Mr protein in synaptic membranes. Protease activity during protein purification was prevented by introducing five protease inhibitors, and a three-step purification procedure was developed that yielded a high degree of purification of glutamate-binding proteins. The major protein enriched in the most highly purified fractions was a 71-kDa glycoprotein, but a 63-kDa protein was co-purified during most steps of the isolation procedure. The glutamate-binding characteristics of these isolated protein fractions were very similar to those previously described for the 14-kDa GBP, including estimated dissociation constants for L-glutamate binding of 0.25 and 1 microM, inhibition of glutamate binding by azide and cyanide, and a selectivity of the ligand binding site for L-glutamate and L-aspartate. The neuroexcitatory analogs of L-glutamate and L-aspartate, ibotenate, quisqualate, and D-glutamate, inhibited L-[3H]glutamate binding to the isolated proteins, as did the antagonist of L-glutamate-induced neuronal excitation, L-glutamate diethylester. On the basis of the lack of any detectable glutamate-related enzyme activity associated with the isolated proteins and the presence of distinguishing sensitivities to analogs that inhibit glutamate transport carriers in synaptic membranes, it is proposed that the 71-kDa protein may be a component of a physiologic glutamate receptor complex in neuronal membranes.

Animals↗
PubMed1988

A validation of a scoring system to evaluate the condition of transported very-low-birthweight neonates.

A scoring system was developed to objectively evaluate the condition of transported preterm infants. The "transport score" used five variables: blood glucose, blood pressure, pH, pO2, and temperature. Each variable was scored 0, 1, or 2, with a total achievable score from 0 to 10. Twenty-one matched pairs of infants included one infant who lived and one who died. The transport scores upon admission of infants who lived was significantly greater than the scores of those who died (P less than 0.01). Scores less than eight were predictive of death (sensitivity 62%, specificity 81%). The system was then applied prospectively to 106 different infants after stabilization by the hospital-of-origin (pre-transport) and upon admission to the neonatal intensive care unit (post-transport). Although 75 (76%) of the 99 surviving infants had both stabilization and admissions scores of eight or more, only 2 (29%) of the 7 infants who died had both scores of eight or more. Of 85 infants with a stabilization score of eight or greater, only 3 (3.5%) died, while of 21 infants with stabilization scores less than eight, 4 (19%) died. Similarly, of 90 infants with an admission score of eight or more, only 4 (4.4%) died, while of 16 with an admission score of less than eight, 3 (19%) died. We conclude that transport scores provide a valid indication of the condition of preterm infants and may be used to provide quality assurance for stabilization and transport efforts.

Academic Medical Centers↗
PubMed1988

Evaluation of an immunofluorescent-antibody test for rapid identification of Pseudomonas aeruginosa in blood cultures.

An immunofluorescent-antibody test was developed for rapid detection of Pseudomonas aeruginosa in blood cultures. The test uses a murine monoclonal antibody specific for all strains of P. aeruginosa. In initial tests, bright uniform immunofluorescence signals were seen when each of the 17 international serotypes, as well as 14 additional isolates of P. aeruginosa, were examined. No immunofluorescent staining was observed when 37 other gram-negative and 15 gram-positive species were studied. In a clinical study, the assay was applied to broth smears of 86 gram-negative bacilli isolated from 74 bacteremic patients and 28 additional clinical isolates of Pseudomonas sp. and other oxidase-positive gram-negative bacilli recovered from various body sites. Smears were made directly from blood cultures which were positive for gram-negative bacilli by Gram staining. Eleven (15%) of 74 patients with gram-negative bacteremia had a positive test for P. aeruginosa. Including the results of these 11 isolates recovered in a prospective study and an additional 10 isolates from a retrospective study, we obtained a sensitivity and specificity of 100% (21 positive specimens and 103 negative specimens, respectively). These preliminary results suggest that this is a useful reagent for rapid presumptive identification of P. aeruginosa in blood cultures. With the immunofluorescent-antibody test, P. aeruginosa could be identified within 1 h of Gram stain evidence of gram-negative bacteremia.

Antibodies, Monoclonal↗
PubMed1988

Effect of dietary energy source and concentration on performance of dairy cows during early lactation.

Eighteen Holstein heifers were placed into groups of 3 according to projected calving date, prepartum BW, and prepartum condition score. Following parturition, animals within each group were assigned randomly to one of three diets and remained on the experiment for 45 d. Diets consisted of forage:concentrate ratios of 72:28, 53:47, or 73:27 (isocaloric to the 53:47 ratio by addition of 8% soybean oil). Diets were fed twice daily as total mixed rations. Blood, rumen fluid, and adipose tissue were sampled at -7, 5, 20, and 45 d of lactation. Performance means were, respectively: DM intake (kg/d) 13.9, 14.9, and 12.4; milk (kg/d) 24.5, 25.8, and 18.6; milk fat (%) 3.77, 3.59, and 3.62; milk protein (%) 3.03, 2.99, and 3.11; body condition score (0 = thin, 5 = fat) 1.53, 1.87, and 1.99; and BW (kg) 514, 523, and 505. Cows fed soybean oil had higher ruminal isoacids than those fed the other diets and higher acetate than cows on the 53:47 diet. Diets had no effect on blood metabolites or activity of adipose glycerol-P dehydrogenase (EC 1.1.1.8). The soybean oil diet reduced short-chain fatty acids and increased long-chain fatty acids in milk. Feed intake and milk production were highest for cows receiving the 53:47 diet. As expected, animals on the 72:28 diet did not consume adequate energy to maintain high production which concurrently resulted in lower body condition scores.

Animal Nutritional Physiological Phenomena↗
PubMed1986

Perinatal risk assessment for patent ductus arteriosus in premature infants.

Data from 2107 inborn premature infants monitored for hemodynamically significant patent ductus arteriosus were used to develop means for clinically assessing at birth the risk of developing patent ductus arteriosus during the first 30 days of life. The overall 30-day incidence rates in birth weight categories 500 to 999, 1000 to 1499 g, and 1500 to 1750 g were 41, 17, and 7%, respectively. At-birth risk estimates obtainable from the derived multivariate functions ranged from 0 to 78% for the 500 to 999 and 1000- to 1499-g categories, and from 0 to 20% for the 1500- to 1750-g category. The derived risk functions provide for enhanced selectivity in the application of measures for the prevention of patent ductus arteriosus.

Adolescent↗
PubMed1986

Classroom performance and social factors of children with birth weights of 1,250 grams or less: follow-up at 5 to 8 years of age.

Of 43 long-term survivors with birth weights of 1,250 g or less, 33 were compared with peers and school-aged siblings for educational levels and needs. Of the 33 children in school, three (9.1%) were in classes for children with major handicaps, whereas 30 (90.9%) were found to be comparable to their classmates by teachers and/or test scores, but 14 (47%) were receiving remedial instruction to perform at grade level. Of 13 children with school-aged siblings, three required more hours of assistance by specialized teaching staff than their siblings. The group without the need for specialized teaching staff had older mothers and tended to reside in higher socioeconomic households. Overall, our children with birth weights of 1,250 g or less (51.5%) required more special education efforts than the general school population (24.1%), thereby enabling most to compare favorably with their peers.

Child↗
PubMed1985

Association of elective repeat cesarean delivery and persistent pulmonary hypertension of the newborn.

Seventy-one cases of persistent pulmonary hypertension of the newborn have been reviewed in an attempt to identify possibly preventable causes. Three groups of infants were identified. The first group consisted of 36 infants with evidence of perinatal asphyxia. The second group was made up of 23 infants who exhibited a variety of associated factors including pneumonia, septic shock, and congenital diaphragmatic hernia. A third group included 12 infants delivered by elective repeat cesarean section. Infants in the third group did not have evidence of perinatal asphyxia, meconium aspiration, or infection. Chest roentgenograms revealed amniotic fluid aspiration in seven cases, retained lung fluid in three cases, and normal findings in two cases. All 12 infants in the third group developed respiratory distress which eventually progressed to respiratory failure and persistent pulmonary hypertension of the newborn. These data suggest that infants of elective repeat cesarean deliveries are at risk for developing persistent pulmonary hypertension of the newborn and constitute a group of patients with a potentially preventable course of events.

Asphyxia Neonatorum↗