Biomedical subjects

D L Mollitt

Publications and source records attributed to D L Mollitt.

At least 19 recordsLinked to original sources

PubMed1996

Death from pelvic fracture: children are different.

This study compares outcome from pelvic fractures in children with that of adults. Data for 23,700 children registered in the National Pediatric Trauma Registry (NPTR) were compared with those of 10,720 adults recorded over 5 years in the registry of our level I trauma center. Patients were categorized by open versus closed fracture and by fracture type as defined by a modification of the Key and Conwell system. Outcome was evaluated by mortality rate and incidence of fracture-induced fatal exsanguination. The 722 pelvic fractures recorded in the NPTR represent 3% of the population and is half the frequency represented by the 532 adults evaluated (P < .001). The overall mortality rate was 5% for children and 17% for adults. Two children died of fracture-related exsanguination; there were 18 such deaths among the adults. Pelvic ring disruption was encountered more commonly among adults, and was associated with a significantly higher mortality rate. Patients with initial hemodynamic instability were more likely to die, although children less so than adults. The authors conclude that children do not die of pelvic fracture-associated hemorrhage as often as adults. Massive blood loss in the child occurs most commonly from solid visceral injury rather than from pelvic vascular disruption.

Adult↗

PubMed1995

Effect of sepsis on erythrocyte intracellular calcium homeostasis.

OBJECTIVES: To examine erythrocyte intracellular calcium dynamics in clinical sepsis and experimental endotoxemia. DESIGN: Prospective, multiexperimental study utilizing in vitro manipulation and evaluation of human erythrocytes. SETTING: University research laboratory. PATIENTS: Healthy, elective surgical patients, "septic" surgical patients, and normal volunteers. INTERVENTIONS: For all experimental studies, whole blood specimens were incubated with 2 micrograms/mL of Escherichia coli endotoxin (experimental) or an equivalent volume of phosphate buffered saline (control). Incubations were performed in specimens pretreated with 0.4 mM of verapamil and/or 50 mM of dantrolene. Incubations were performed in the presence and absence of extracellular calcium. Incubations were also performed utilizing pre- and posttreatment with 1 mM of adenosine 5'-triphosphate (ATP) and/or 30 mM of adenosine. MEASUREMENTS AND MAIN RESULTS: Free cytosolic calcium concentration was determined by fluorescent spectroscopy, utilizing the calcium chelator, FURA-2AM. Sepsis was associated with a significant increase in erythrocyte intracellular calcium concentration as compared with nonseptic controls (96.26 vs. 45.38 nM; p < .001). Similar changes could be induced by endotoxin incubation of whole blood (84.52 vs. 40.45 nM; p < .001). This endotoxin-induced increase was independent of extracellular calcium concentration and was only partially ameliorated by calcium-channel blockade. Inhibition of intracellular calcium release was ineffective in altering the endotoxin-induced increase in the erythrocyte intracellular calcium value. In contrast, pretreatment with either adenosine or ATP minimized these increases. Posttreatment with ATP, but not adenosine, allowed partial reversal of this endotoxin-induced increase in intracellular calcium. CONCLUSIONS: Sepsis induces alterations of erythrocyte intracellular calcium homeostasis. A significant increase in free cytosolic concentrations of intracellular calcium is characteristic of this altered homeostasis. These changes are reproducible by the incubation of whole blood with endotoxin. This increase in cytosolic calcium concentration appears to be independent of extracellular calcium concentration, transmembrane calcium channels, and/or intracellular calcium stores. It can, however, be modulated through provision of high-energy phosphates and/or their precursors to the cell itself.

Adenosine↗

PubMed1995

Leukocyte modulation inhibits endotoxin-induced disruption of intracellular calcium homeostasis.

OBJECTIVE: Sepsis is associated with disruption of intracellular calcium homeostasis. The specific mechanisms responsible for these changes remain unclear. This study attempts to modify endotoxin-induced alterations in erythrocyte intracellular calcium dynamics through modulation of the activated leukocyte and its products. METHODS: Paired anticoagulated whole-blood specimens were obtained from healthy adult volunteers (n = 30). Specimens were incubated with 2 micrograms/mL endotoxin [lipopolysaccharide (LPS)] or saline control in the presence and absence of the white blood cell. Studies were repeated in specimens pretreated with allopurinol, superoxide dismutase, and pentoxifylline (PTX). After incubation, erythrocytes were separated, washed, and loaded with the fluorescent calcium chelator, FURA-2. Free cytosolic calcium concentration was determined on 10(6) cells using fluorescent spectroscopy. Values were computer-calculated every 1.8 seconds for 1 minute, and mean results were used for analysis. Differences were evaluated by analysis of variance. RESULTS: The LPS resulted in a significant increase in intracellular calcium concentration (LPS 70.95 nM vs. control 44.04 nM). This increase was dependent on the presence of the white blood cell and could not be induced in its absence (control 30.15 --> LPS 32.78). Pretreatment inhibited these endotoxin-induced alterations: allopurinol, 50.49 nM; superoxide dismutase, 49.12 nM; and PTX, 40.23 nM (p < 0.01). CONCLUSIONS: Endotoxin induces a significant increase in intracellular calcium concentration. This alteration seems to be mediated by activated neutrophils and can be ameliorated by both leukocyte modulation (PTX) and free radical scavengers.

Allopurinol↗

PubMed1995

Selective management of pediatric esophageal foreign bodies.

Esophageal foreign body is a relatively common consultation from the Pediatric Emergency Room. This study evaluates optimal selective management of esophageal foreign bodies in the pediatric patient. Eighty-six children have been referred for esophageal foreign body. Fifteen had been symptomatic for 48 or more hours before being seen. In eight, there was a known history of previous repair for esophageal atresia. In 88%, the foreign body was opaque, most frequently a coin. The most common nonopaque foreign body was retained food. Upon diagnosis, 72 children were taken to radiology, where balloon extraction under fluoroscopic control was attempted. Fourteen children went directly to the operating room for endoscopy and foreign body removal. Balloon extraction was successful in 62 cases (86%), and the children were discharged directly from the Emergency Department. The foreign body was successfully removed at esophagoscopy in the 10 cases that failed attempts at balloon extraction. Since 1990, successful extraction has been accomplished in 100% of cases (29/29). Neither balloon extraction nor endoscopy was associated with morbidity or mortality. Endoscopy was, however, associated with total hospital charges approximately 400% higher than balloon extraction. Fluoroscopically guided balloon extraction of appropriate esophageal foreign bodies is a safe and cost-effective alternative to endoscopy. Failure of nonoperative management does not complicate subsequent endoscopic removal. Patients with symptoms > 48 hours, a history of prior esophageal atresia, and/or nonopaque esophageal foreign bodies do not preclude attempt at balloon extraction.

Catheterization↗

PubMed1994

The effect of endotoxin on neonatal erythrocyte intracellular calcium concentration.

Erythrocyte membrane deformability is dependent on the maintenance of "normal" intracellular calcium (Ca) levels. Red cell flexibility is known to be altered in the septic neonate. In turn, this adversely affects viscosity and compromises flow in the microcirculation. It has been suggested that this may play a role in the mesenteric hypoperfusion associated with necrotizing enterocolitis. This study was designed to determine the effect of endotoxin on erythrocyte Ca homeostasis in the neonate. Paired specimens were obtained from the umbilical cord of 10 healthy neonates. The samples were incubated with either buffered saline (control) or 2 micrograms/mL of Escherichia coli endotoxin (LPS). Erythrocytes were then isolated, washed, and loaded with the fluorescent Ca chelator, FURA-2. The free cytosolic Ca concentration was determined by spectroscopic analysis of the ratio of fluorescent intensities at 340 nm and 380 nm. Results were obtained every 1.8 seconds for 1 minute, and the mean value was used for analysis. In 10 additional neonates, the white blood cells were removed before incubation in saline and LPS, and the erythrocytes were evaluated as described above. Differences were analyzed statistically by the paired t test. In the presence of white blood cells, endotoxin resulted in a significant increase in free cytosolic Ca concentration (LPS, 42.602 +/- 5.166 nmol; control, 31.661 +/- 4.002 nmol; P < .02). However, no significant difference were detected when cells were incubated in the absence of white blood cells (LPS, 32.374 +/- 2.479 nmol; control, 34.021 +/- 2.549 nmol). Endotoxin induces a significant increase in neonatal free cytosolic Ca concentration.(ABSTRACT TRUNCATED AT 250 WORDS)

Calcium↗

PubMed1994

Sepsis-induced alterations in the erythrocyte membrane.

Sepsis is known to alter red blood cell (RBC) deformability, and this change in flexibility may play a role in the pathophysiology of the hemodynamic alterations characteristic of the septic syndrome. The etiology of this red cell change is unclear. This study evaluates erythrocyte size and cell membrane fluidity during clinical (septic surgical patients) and experimental (endotoxin incubation) sepsis. Membrane lipid viscosity was assessed by fluorescent spectroscopy. Mean corpuscular volume and hemoglobin concentration was determined by automated counter. There was a significant increase in erythrocyte membrane lipid viscosity (P < 0.001) in both the clinical and experimental septic models. No difference was detected, however, in RBC mean corpuscular volume or hemoglobin concentration. These findings suggest that sepsis-induced alterations in erythrocyte deformability are due primarily to an increase in the membrane lipid viscosity and are unrelated to alterations in the cell surface area to volume ratio.

Erythrocyte Membrane↗

PubMed1993

The effect of endotoxin on the neonatal erythrocyte.

Intestinal ischemia is considered a major factor in the development of necrotizing enterocolitis (NEC). Despite this, the majority of affected infants lack documentation of clinical events associated with obvious gut hypoperfusion. Recent evidence in adults suggests that endotoxin may impair flow in the microcirculation through alterations in erythrocyte deformability. As the gut serves as a semipermeable reservoir of endotoxin in the stressed neonate, such localized activity may result in intestinal ischemia at the microcirculatory level through alterations in the red cell membrane. This study evaluates the role of endotoxin on neonatal erythrocyte membrane viscosity. Paired anticoagulated whole blood specimens were obtained from the umbilical cord of 10 neonates at delivery. Samples were incubated with either 2 micrograms/mL of E coli endotoxin (LPS) or an equal volume of saline (control). Following incubation, erythrocytes were isolated, washed, and incorporated with the fluorescent membrane probe TMA-DPH. Membrane viscosity was assessed by spectroscopic analysis of the fluorescent emissions induced by excitation of the probe at 365 nm. Results were calculated as anisotropy and analyzed for differences by ANOVA. Endotoxin resulted in a significant increase in red cell membrane viscosity as compared to control (LPS 291.2 +/- 5.1 v Control 271.7 +/- 3.3, P < .01). As the effects of endotoxin are known to be primarily the result of white blood cell (WBC) activation, this study was repeated in an additional 10 neonates in whom WBCs were removed prior to endotoxin/saline incubation.(ABSTRACT TRUNCATED AT 250 WORDS)

Endotoxins↗

PubMed1993

Role of the leukocyte in endotoxin-induced alterations of the red cell membrane. Second place winner of the Conrad Jobst Award in the Gold Medal paper competition.

Sepsis and endotoxemia are known to be associated with alterations in the red cell membrane that result in diminished flexibility. This decreased flexibility may be responsible, in part, for the microcirculatory abnormalities accompanying sepsis. The etiology of these sepsis-associated changes remains unclear. This study evaluates the role of the white blood cell in these abnormalities. Specimens were obtained from 44 volunteers and divided into two treatment groups. Group I specimens were incubated with Escherichia coli endotoxin (2 micrograms/ml) followed by removal of the white blood cells. The white blood cells were removed from group II specimens before endotoxin incubation. Paired, saline-incubated samples served as controls. After incubation, washed erythrocytes were evaluated for deformability and membrane viscosity. Deformability was assessed by filtration through 4.7-microns membranes. Red cell deformability was expressed as filtration rate (volume of cells per second per square centimeter). Membrane viscosity was assessed by fluorescent spectroscopy of cells into which the membrane probe 1(4-(trimethylamino)-phenyl)-6-phenyl-1,3,5-hexatriene had been incorporated. Results were expressed as anisotropy. Endotoxin resulted in a significant increase in erythrocyte membrane viscosity (experimental, 0.296 +/- 0.002 vs. control, 0.284 +/- 0.002, P < 0.001). This was reflected by a significant decrease in cellular deformability (experimental, 142.55 +/- 6.55 vs. control, 157.86 +/- 8.63, P < 0.01). However, these alterations are not a direct effect of endotoxin, but require the presence and participation of the white blood cell and/or its mediators (experimental, 0.301 +/- 0.002 vs. control, 0.300 +/- 0.001, P = NS).

Awards and Prizes↗

PubMed1991

The role of pentoxifylline in endotoxin-induced alterations of red cell deformability and whole blood viscosity in the neonate.

Endotoxin induces alterations in the neonatal red cell membrane that result in decreased deformability and an increase in whole blood viscosity. These rheologic alterations are detrimental to flow in the microcirculation. Pentoxifylline (PTX), a methyl xanthine derivation, increases red cell deformability presumably through its effect on intracellular adenosine 5-triphosphate. The purpose of this study was to evaluate the effect of PTX on endotoxin-induced alterations in the neonatal red blood cell. Anticoagulated whole blood specimens obtained from the cord of 12 neonates at birth were used to study the effects of Escherichia coli endotoxin (LPS) with and without PTX (50 micrograms/mL) on red cell deformability and whole blood viscosity. LPS resulted in a significant (P less than .001) decrease in deformability compared with controls. PTX reversed these endotoxin-induced alterations (P less than .01), normalizing deformability to control values (P = NS). LPS resulted in a significant increase (P less than .005) in blood viscosity that was reversed by PTX (P = NS). Pentoxifylline reverses the detrimental rheologic effect of endotoxin in the neonate. This activity may be helpful in sustaining normal microcirculation in neonatal sepsis.

Blood Viscosity↗

PubMed1991

Error in fluid and calorie calculation in the surgical neonate.

Nutritional management has become an integral part of the care of the surgical neonate. In most teaching institutions, this is the responsibility of the resident staff with varying degrees of supervision. The purpose of this study was to assess the accuracy of this management. Eleven parameters of fluid and nutritional status were determined daily on all surgical newborns in the neonatal intensive care unit (NICU). The values were calculated by the housestaff in traditional fashion, based on available bedside data, and entered into the charts. Similar values were calculated, based on the same data, by a trained clinical nurse specialist using a preprogrammed, hand-held computer. Values were then compared for significant difference. Approximately 2,500 calculations were analyzed. Overall, there was a statistically significant error detected in the housestaff evaluation of both fluid and nutritional status. This discrepancy was greatest in infants weighing less than 2 kg. Similarly, there was an inverse correlation between the degree of error and houseofficer level. These data indicate a potential risk in the management of the surgical neonate. This risk is greatest in the small infant, indicating the need for close supervision of critical physiological computations within the teaching NICU.

Computers↗

PubMed1991

The nature and reversibility of hypothermia-induced alterations of blood viscosity.

This study evaluates the nature and reversibility of the increase in whole blood viscosity known to be induced by hypothermia. Anticoagulated samples were obtained from normal volunteers and were assayed for cellular deformability by 4.7 microns membrane filtration of whole blood (n = 12) and washed RBCs (n = 10). Results were expressed as filtration rate. Specimens were evaluated for plasma (n = 10) and whole blood (n = 12) viscosity by cone plate viscometer. All assays were sequentially performed at 30 degrees, 34 degrees, and 37 degrees C and difference analyzed by paired t test. Hypothermia resulted in significant impairment of cellular deformability, which was reversed by rewarming: [table: see text] Hypothermia also resulted in a significant increase in plasma viscosity (mean difference = 0.5426 centipoise, p less than 0.02), which was likewise reduced on rewarming. The increase in whole blood viscosity associated with hypothermia is secondary to both diminished cellular deformability and increased plasma viscosity. Both of these alterations are reversible with appropriate rewarming.

Blood Viscosity↗

PubMed1991

Does patient age or intestinal pathology influence the bacteria found in cases of necrotizing enterocolitis?

To evaluate the relationship between bacterial colonization in neonatal peritonitis and patient age or intestinal pathology, we retrospectively reviewed peritoneal culture results from 96 infants having surgery for necrotizing enterocolitis. Microorganisms recovered mirrored those usually found as fecal flora within the neonatal intensive care unit. These reflect, in turn, the abnormal colonization intrinsic to care in the intensive care nursery. Analysis revealed no significant correlation between the disease and either age of the infant or intestinal site of disease.

Age Factors↗

PubMed1991

A randomized clinical trial of ampicillin, gentamicin and clindamycin versus cefotaxime and clindamycin in children with ruptured appendicitis.

This prospective, randomized, double-blind study compares the efficacy, safety and cost-effectiveness of ampicillin, gentamicin and clindamycin (AGC) or cefotaxime and clindamycin (CC) for the treatment of children with complicated appendicitis. Ninety-seven children were randomized. Forty-seven were assigned to the AGC regimen and 50 received CC. Forty-two patients in the AGC group had an appropriate therapeutic outcome, whereas 48 of 50 children who received CC completed the trial successfully (p = NS). There were no differences between the groups with reference to the duration of antibiotic administration, fever, leukocytosis or length of hospitalization. Complications of therapy were uncommon and neither regimen demonstrated a significant advantage from an economic standpoint. We concluded that, in childhood, complicated appendicitis can be treated with either CC or AGC with equal efficacy.

Adolescent↗

PubMed1989

The effect of initial operative repair on the recovery of intestinal function in gastroschisis.

Recent reports concerning the treatment of gastroschisis suggest that primary closure results in more rapid return of gastrointestinal function, a shortened hospitalization, diminished perinatal complications, and improved long-term survival. A 4-year retrospective review of infants treated for gastroschisis at the University of Florida yielded 30 infants requiring repair of this abdominal wall defect. The series included 19 males and 11 females, and the average abdominal wall defect measured 4 cm in its greatest dimension. Nine infants (mean weight, 2,275 gm) were repaired using a staged closure using a silastic (six) or cutaneous (three) silo. Complete fascial closure was accomplished in an average of 8 days in the silastic group and 15 days in the infants with skin flaps. Mean age at start of enteral feeds was 23 days, with complete oral feedings at 43 days. Twenty-one infants (mean weight, 2,127 gm) underwent primary fascial closure. Three deaths occurred in the perioperative period: one from acute renal failure and two from sepsis secondary to a segment of necrotic intestine. An additional infant developed postoperative necrotizing entercolitis but recovered. Two infants in this group also had jejuno-ileal atresia requiring extensive small bowel resection. In the remaining 15 infants, oral alimentation was initiated for an average of 23 days, with full oral alimentation at 46 days. The data suggest that the recovery of the gastrointestinal system, adequate enough to support total oral alimentation, is unrelated to the initial surgical procedure chosen to obtain fascial closure in the newborn with gastroschisis. In addition, vigorous attempts at primary fascial closure may jeopardize intestinal viability, diminish ventilatory function, and result in unnecessary morbidity and mortality.

Abdominal Muscles↗

PubMed1989

Perinatal nonimmune hydrops: diagnostic ultrasonography and related aspects of management.

Nonimmune hydrops fetalis may become the commonest form of hydrops seen in Western countries during the perinatal period, and it has at least a 50% mortality. This report describes five infants with nonimmune hydrops associated with maternal hydramnios and with congenital fetal lesions or disorders, ie, mediastinal teratoma, pulmonary leiomyosarcoma, Beckwith-Weidemann syndrome with omphalocele, fetal tachycardia, and Down's syndrome. Three of the infants survived the neonatal period and two of these underwent surgery for resection of their tumors early in the neonatal period. The third had an omphalocele repaired at 6 hours of age. The literature is reviewed with respect to the pathophysiology of nonimmune hydrops. Its diagnosis and treatment are discussed, with special emphasis on the role of ultrasound in its early diagnosis and optimal prenatal and postnatal management, and on the morbidity seen in survivors.

Female↗

PubMed1988

The microbiology of neonatal peritonitis.

To review the bacteriology of neonatal intra-abdominal sepsis, we reviewed peritoneal cultures from 86 newborns undergoing operation for necrotizing enterocolitis (NEC) for the type and incidence of microorganism recovered. As a control, we conducted a similar review in 59 children with perforated appendicitis during the same period. Necrotizing enterocolitis was characterized by a lower incidence of polymicrobial contamination (1.7 organisms per patient vs 2.4 organisms per patient, NEC vs appendicitis) and an uncharacteristic pattern of isolates. Although enteric gram-negative bacilli were recovered in 80% of newborns, the incidence of Escherichia coli was only 21% in the NEC group vs 69% in the appendicitis group, while Klebsiella and Enterobacter species represented the most common gram-negative isolates recovered (63% vs 17%). More than 50% of neonatal cultures yielded gram-positive cocci, most frequently coagulase-negative staphylococci (30% vs 0%) and enterococci (17% vs 5%), as compared with more frequent streptococcal isolates in the appendicitis group (50% vs 10%). Anaerobes were seldom recovered in NEC cases (6%), but they were present in 50% of appendicitis cases. Additionally, Candida isolates were recovered in 10% of NEC cases (0% of appendicitis group). These results indicate the unique bacteriology of peritonitis in the critically ill newborn and probably reflect abnormal colonization in the neonatal intensive care unit.

Appendicitis↗

PubMed1988

The role of coagulase-negative Staphylococcus in neonatal necrotizing enterocolitis.

Coagulase-negative Staphylococcus has emerged as a prominent pathogen in the neonatal intensive care unit and a recent report has implicated this organism in necrotizing enterocolitis (NEC). This same study suggests that Staphylococcus epidermidis is most commonly associated with a "mild form of enterocolitis." This prompted a review of the role of coagulase-negative Staphylococcus in the surgical complications of NEC. Between 1982 and 1986, 86 newborns underwent operation for perforation or intestinal necrosis secondary to NEC. Blood cultures, obtained within 72 hours of surgery, were positive in nine of 71 infants (13%). One third of these grew coagulase-negative Staphylococcus. Peritoneal cultures obtained at the time of operation were positive in 71 neonates. The incidence of Staphylococcus epidermidis was 30%. In a third of these cases, coagulase-negative Staphylococcus was the only organism covered. Overall mortality within the group was 33%. Coagulase-negative Staphylococcus was the single most frequent organism recovered from those infants who expired (35%). This data clearly indicates that Staphylococcus epidermidis must be considered as a significant pathogen in NEC. It is associated with both morbidity and mortality and, therefore, warrants appropriate aggressive therapy when recovered from the neonate with enterocolitis.

Enterocolitis, Pseudomembranous↗

PubMed1988

The Pediatric Trauma Score as a predictor of injury severity: an objective assessment.

The ability of the Pediatric Trauma Score (P.T.S.) to predict injury severity and mortality was evaluated by analysis of its relationship with the Injury Severity Score (I.S.S.) of 615 children entered into the National Pediatric Trauma Registry (N.P.T.R.). Mean age was 8.2 years and mortality was 3.5%. Mean I.S.S. of survivors was 8.1 in comparison to 59.7 for nonsurvivors. Linear regression coefficient determined from analysis of these variables produced a slope of -3.7 with a statistically significant correlation of P.T.S. to I.S.S. (p less than 0.001; r2 = 0.89). Analysis of the mortality for each cohort of patients with the same P.T.S. identified three categories of mortality potential. Children whose P.T.S. was greater than 8 had a 0% mortality. Children whose P.T.S. was between 0 and 8 had an increasing mortality related to their decreasing P.T.S. (r2 = 0.86), and children whose P.T.S. was below 0 had 100% mortality. This study documents the direct linear relationship between P.T.S. and injury severity, and confirms the P.T.S. as an effective predictor of both severity of injury and potential for mortality.

Child↗