The influence of different gases on acoustic properties of a spherosome-based ultrasound contrast agent (BY963). A transcranial Dopplersonography study.

Ultrasound contrast agents improve the signal-to-noise ratio of reflected ultrasound, enhancing the diagnostic value of transcranial Doppler (TCD). In dog studies, we investigated the time course of TCD signal amplitude after application of a phospholipid-containing ultrasound contrast agent (BY963) filled with different gases. The median time of Doppler amplitude enhancement exceeding 5 dB was determined using isoflurane-, isopentane-, trichlortrifluoroethane-, air-, argon-, and perfluoropentane-filled BY963 (69, 72, 75, 78, 88, and 245 seconds respectively). The decrease of time-intensity curve and the duration of signal enhancement showed significant differences comparing the different gases (p = 0.04 and 0.03, respectively). The time course of in vitro stability of BY963 agitated with the different gases measured by absorbance of light (500 nm) showed a retarded decay for perfluoropentane, a rapid decrease for air, isopentane, trichlortrifluoroethane, and argon, and a very rapid decrease using isoflurane. The time course of the different gases depended on the physiochemical properties (lipophilicity and the solubility in water) of the gas encoated in the phospholipid shell. Perfluoropentane-filled BY963 showed the highest in vitro stability and the longest duration of TCD enhancement compared with the other gases used.

The role of computed tomographic scanning in the management of facial trauma.

OBJECTIVE: To determine how often the management of patients with blunt facial trauma was altered by plain roentgenograms or facial computed tomographic (CT) scans compared with findings from physical examination. METHOD: This is a retrospective review of consecutive patients admitted with blunt facial trauma and evaluated by the Division of Plastic Surgery from 1988 to 1994. Physical findings were correlated with fractures detected by plain roentgenograms or facial CT reports. Treatment plans were reviewed to determine how management was altered by radiographic studies. Hospital charges were determined for the various studies. RESULTS: One hundred thirty-seven records were reviewed. Thirty patients had only lacerations and no fractures. Two hundred forty-three fractures were detected on physical examination among 98 patients (91.5%). One hundred two patients (95.3%) had facial CT scans and 85 patients (79.4%) had facial plain films obtained. Radiographic findings identified a total of 255 fractures among 107 patients (78%). Ninety-four patients (87.9%) required operative interventions for these facial fractures. Only 19 patients (17.8%) had management altered by radiographic findings: CT scan (7 patients) and plain films (12 patients). The management of 88 facial fractures (34.5%) in this series did not appear to be altered by x-ray findings. Computed tomography was most beneficial in the management of orbital fractures (N = 7). Plain films affected mostly the evaluation of mandibular injuries (N = 7). Selective use of CT scan could lead to hospital savings estimated at $11,864 for the diagnosis of facial fractures after blunt trauma. CONCLUSION: Physical examination reliably assessed the facial skeleton for clinically significant fractures in the majority of patients. In an alert and cooperative patient, CT scan is not required before operative repair in all cases. CT scans are expensive, time-consuming, and labor-intensive and in selected cases add little clinical information to that obtained by physical examination and plain films.

Chiral resolution of pantoprazole sodium and related sulfoxides by complex formation with bovine serum albumin in capillary electrophoresis.

The separation of enantiomers of pantoprazole sodium, omeprazole and lansoprazole by capillary zone electrophoresis using bovine serum albumin (BSA) as the chiral selector is described. Baseline separation of the three structurally related drugs was obtained after optimization of the most important experimental parameters. For this purpose, influences such as BSA concentration, pH and concentration of 1-propanol as organic modifier on the separation were investigated. Increasing concentrations of BSA improved the chiral resolution but lowered the sensitivity of the detection system. Discrimination of the enantiomers was observed only in a narrow pH range of 7-8. An optimum of pH 7.4 was a good compromise in terms of enantio-resolution and peak shape. 1-Propanol when added to the buffer system, improved the peak shape of the analytes and the resolution. The optimized method has been validated for pantoprazole sodium and is useful for routine analysis.

Breast biopsy with needle localization: accuracy of specimen x-ray and management of missed lesions.

BACKGROUND: One of the more frustrating complications after breast biopsy with needle localization is a missed lesion. To reduce the number of missed lesions, radiographs of the surgical specimen are usually obtained. In this study we determined the accuracy of specimen x-ray, the incidence of missed lesions, and the management of patients with this complication. METHODS: The result of specimen x-ray was compared with that of a postoperative mammogram in 192 patients who underwent breast biopsy with needle localization. The incidence of missed lesions was also determined from postoperative mammogram, and the management of patients with this complication was analyzed. RESULTS: The incidence of false-positive specimen x-ray was 7.8% and that of false-negative 55%. The sensitivity, specificity, and accuracy of specimen x-ray were 96%, 28%, and 89%, respectively. The incidence of missed lesions was 3.2% and of incompletely excised lesions 6.4%. Eighteen of 24 patients with a missed or incompletely excised lesion were treated expectantly because postoperative mammogram showed the lesion to be stable. None of these patients has required a subsequent biopsy. CONCLUSIONS: Specimen x-ray can be false positive or false negative. An important implication of this finding is that a postoperative mammography should always be performed after biopsy with needle localization, regardless of the result of the specimen x-ray, to make certain the lesion has not been missed.

PDGF and FGF reverse the healing impairment in protein-malnourished diabetic mice.

BACKGROUND: Growth factors have been shown to improve healing in impaired models but not after malnutrition. The effects of growth factors on altered tissue repair caused by malnutrition were examined. METHODS: Nondiabetic and diabetic mice fed a 1% protein diet received full-thickness skin wounds. Wounds were treated topically with vehicle, platelet-derived growth factor (PDGF, 10 micrograms) or basic fibroblast growth factor (bFGF, 1 microgram), for 5 days. RESULTS: Malnourished animals developed significantly impaired wound closure. PDGF or bFGF did not enhance closure in nondiabetic C57BL/KsJ-db/m mice, whether fed normal or restricted diets. The same treatment regimen was effective in reversing the delayed wound closure in their genetically diabetic C57BL/KsJ-db/db littermates. The growth factors significantly enhanced tissue repair in diabetic mice fed a 1% protein diet starting as early as day 15 and continuing until day 21. Protein-depleted diabetic wounds had significantly decreased cellularity and granulation tissue formation. These deficiencies were reversed with growth factor treatment. CONCLUSIONS: Despite the lack of effects in nondiabetic animals, growth factors improve healing in diabetic mice with restricted protein intake. The differential effects may result from different healing mechanisms: nondiabetic animals heal mainly by contraction; diabetic animals require granulation tissue formation and reepithelialization.

Comparison of postoperative wound complications and early cancer recurrence between patients undergoing mastectomy with or without immediate breast reconstruction.

The incidence of postoperative wound complications and early cancer recurrence was studied in 289 patients who had mastectomy alone and in 113 patients who underwent immediate reconstruction following mastectomy. Patients undergoing immediate reconstruction were younger and had less advanced disease than patients who had mastectomy alone. The postoperative hospital stay was 3.8 days and 4.4 days (p < 0.05) in patients with and without reconstruction, respectively. The overall incidence of postoperative complications was similar in the two groups of patients: 31% and 28% in patients with and without reconstruction, respectively. The incidence of postoperative seroma was higher among patients with mastectomy alone (19% versus 3%, p < 0.05), whereas the incidence of other wound complications was similar in the two groups of patients. Prosthesis-specific complications occurred in 17%. Eight prostheses were removed because of complications. During the relatively short follow-up period (approximately 20 months), local recurrence was noted in 16 patients (6%) who had mastectomy alone and in 1 patient (1%) who had immediate reconstruction after mastectomy (p < 0.05). There was no significant difference in the incidence of distant metastases between the two groups of patients. The results suggest that immediate breast reconstruction can be performed following mastectomy for cancer without increased risk for overall postoperative complications, prolonged hospital stay, or local recurrence. However, patients who choose to have immediate reconstruction need to be informed about risks for specific complications associated with the procedure, especially if an implant is used.

Germicidin, an autoregulative germination inhibitor of Streptomyces viridochromogenes NRRL B-1551.

During germination spores of Streptomyces viridochromogenes NRRL B-1551 excrete a compound, germicidin, which has an inhibitory effect on the germination of its own arthrospores at a concentration as low as 200 pM (40 pg/ml). At higher concentrations germicidin inhibits porcine Na+/K(+)-activated ATPase and retards the germination of the cress Lepidium sativum. Germicidin is the first known autoregulative inhibitor of spore germination in the genus Streptomyces and was isolated from the supernatant of germinated spores, but also from the supernatant of the submerged culture. Spectroscopic analysis and derivatization reactions revealed germicidin to be 6-(2-butyl)-3-ethyl-4-hydroxy-2-pyrone (C11H16O3). Crude isolates of germicidin from the supernatant of submerged culture, but not from the spores, contained a second, structurally very similar compound (C10H14O3), in which in contrast to germicidin a 2-propyl instead of the 2-butyl chain was bound to C-6 and which did not show any activity in the germination and ATPase assay. The germination assay was evaluated as a new screening model for specifically active compounds.

Synergistic actions of platelet-derived growth factor and the insulin-like growth factors in vivo.

Topical application of growth factors has been shown to benefit both normal and impaired wound healing. In normal tissue repair, resident cells produce a "cocktail" of various types of growth factors that overlap in function. In vitro studies have proved that growth factor combinations can act synergistically to enhance cellular function beyond that achieved with individual growth factors. To determine whether similar combinations have a synergistic effect in vivo, we applied growth factor combinations topically to full-thickness skin wounds created in genetically diabetic mice. The C57BL/KsJ-db/db mouse is obese and has insulin-resistant diabetes, and it has been proved that this mouse has markedly impaired wound healing. Topical application of platelet-derived growth factor, insulin-like growth factor-I, or insulin-like growth factor-II enhances healing in this model. Marked synergism was found when platelet-derived growth factor and insulin-like growth factor-II were combined to produce augmentation in wound closure beyond that achieved by application of the individual growth factors. The synergistic effect allowed for improved tissue repair at doses of platelet-derived growth factor and insulin-like growth factor-II that were ineffective when applied individually. The addition of insulin-like growth factor-I or insulin to platelet-derived growth factor produced no significant synergism. Because multiple growth factors are released in the wound during the healing process, it is not surprising that their combination further enhances healing. Growth factor combinations should become an important addition to the armamentarium for the treatment of chronic, nonhealing wounds.

Outcome and socioeconomic aspects of suspected child abuse scald burns.

Fifty-two children suffering from abuse-related scald burns were admitted between January 1, 1986, and June 30, 1991. Their clinical and socioeconomic aspects were compared with those of 50 nonabused scalded children. Patients were matched for age, total body surface area burn, and percentage of full-thickness burn. Patient characteristics and initial nutritional parameters were similar except for race; a higher percentage of black children were in the abused group. A significantly longer length of hospital stay was found in the abused children after using analyses of covariance to control for percentages of total and full-thickness body surface area burn. The number of operations and frequency of complications were increased in the abused group, but not significantly so. Several significant differences were found in the socioeconomic characteristics of the two groups. Children suspected of being scalded intentionally were more likely to be part of a broken home, belong to a single parent, and have a younger mother than were children in the control group. The majority of the parents of abused children were unemployed, and all but two earned less than $20,000/year. All but one of the abused children were discharged with a person other than their parents, and compliance with rehabilitation follow-up was significantly worse than with the control group. The person suspected of performing the abuse was always a family member, except in cases where the baby-sitter was the suspected abuser. Child abuse hurts not only the child but also society by increasing the need for resources to pay for extended hospital admissions.(ABSTRACT TRUNCATED AT 250 WORDS)

Samuel Preston Moore: Surgeon-General of the Confederacy.

Samuel Preston Moore was trained as a military surgeon in the US Army but resigned his commission and was appointed Surgeon-General of the Confederate States Army Medical Department at the beginning of the American Civil War. He reformed the mediocre medical corps by raising recruiting standards and improving treatment protocols and by placing the most capable surgeons in positions of authority. He improved the ambulance corps and directed the construction of many new hospitals for Confederate casualties. He was directly responsible for the barracks hospital design, which is still used today. He established the Confederate States Medical and Surgical Journal and directed a successful effort to develop substitutes for scarce pharmaceuticals from the indigenous flora of the South. He founded the Association of Army and Navy Surgeons of the Confederate States of America. With skill and dedication, Dr. Moore transformed the medical corps into one of the most effective departments of the Confederate military and was responsible for saving thousands of lives on the battlefield.

Breast biopsy with needle localization: influence of age and mammographic feature on the rate of malignancy in 350 nonpalpable breast lesions.

The purpose of this study was to determine the influence of mammographic feature and patient age on the rate of malignancy in nonpalpable breast lesions. During a 3-year period, 305 patients underwent biopsy after needle localization of 350 nonpalpable breast lesions. A total of 66 malignant breast tumors were found (biopsy yield rate, 19%): 23 carcinoma in situ, 43 infiltrating cancer. The biopsy yield rate in women younger than 50 years was 8% (12 of 153) and in women 50 years or older 27% (54 of 197; p less than 0.001). The biopsy yield rate varied with the mammographic feature in both groups of patients and was highest for spicular masses (61%), followed by strongly suspicious calcifications (29%). No cancers were found among well-defined masses or asymmetric densities. Other factors that were associated with high biopsy yield rate were personal or family history of breast cancer and diagnostic, rather than screening, mammography. The results suggest that the rate of malignancy in nonpalpable breast lesions is influenced by several factors, including age of patient and mammographic feature of the lesion. By taking all these factors into account, biopsies can possibly be performed more selectively thereby increasing the cost effectiveness of biopsy for occult breast cancer.

Histopathological studies on the local reactions induced by complete Freund's adjuvant (CFA), bacterial lipopolysaccharide (LPS), and synthetic lipopeptide (P3C) conjugates.

The inflammatory reactions following subcutaneous application of adjuvants revealed characteristic pathological patterns. The injection of complete Freund's adjuvant (CFA) resulted in the formation of large lipid deposits encircled by an inflammatory reaction and concentrically arranged collagen bundles. Bacterial lipopolysaccharide (LPS) caused granulomatous aggregations of mononuclear cells with thrombotic vessel occlusions. Inoculation of the lipopeptide adjuvants induced accumulation of mononuclear cells with only minimal fibrotic changes which were resolved after day 28. Lipopeptide conjugates based on the head group tripalmitoyl-S-glyceryl-cysteinyl-serin (P3CS) can thus be used as effective immunogens and adjuvants without long-term tissue damage.

Effect of sepsis on amino acid transport system A and its response to insulin in incubated rat skeletal muscle.

The effect of sepsis on neutral amino acid transport systems A, ASC, and L, was studied in incubated rat soleus (SOL) muscles. We also examined the effects of plasma from septic rats and of varying concentrations of insulin (10 to 10(5) microU/mL), added in vitro to incubated muscles, on system A amino acid transport. Sepsis was induced by cecal ligation and puncture (CLP) in rats weighing 40 to 60 g. Control rats were sham-operated. System A activity was assessed by determining uptake of 2-(methylamino)isobutyrate (MeAIB) 16 hours after CLP or sham-operation. System ASC was studied by measuring uptake of alpha-aminoisobutyric acid (AIB) in the presence of 25 mmol/L MeAIB and 25 mmol/L 2-amino-2-norbornane carboxylic acid (BCH) to inhibit uptake by systems A and L. System L activity was defined as sodium-independent uptake of cycloleucine. MeAIB uptake was reduced by 28% in muscles of septic rats, while amino acid transport by systems ASC and L was almost identical in muscles from control and septic rats. Addition of plasma from septic rats to incubated normal SOL muscles inhibited MeAIB uptake by 31%. Addition of insulin to the incubation medium resulted in increased uptake of MeAIB, both in nonseptic and septic muscle. The lowest hormone concentration tested that significantly enhanced MeAIB uptake in nonseptic muscle was 10(2) microU/mL and in septic muscle 10 microU/mL. The results suggest that sepsis in rats specifically inhibits amino acid transport system A and that reduced muscle amino acid uptake may be caused by a circulating factor in sepsis.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of catabolic hormone infusion on protein turnover and amino acid uptake in skeletal muscle.

Increased plasma levels of the catabolic hormones glucagon, epinephrine, and cortisol have been implicated in mediating various metabolic alterations in trauma and sepsis. Their role in altered protein turnover and amino acid transport in skeletal muscle during sepsis, however, is not known. In the current study, rats were infused with a mixture of the catabolic hormones for 16 hours. Control animals were infused with vehicle solution. Protein synthesis and degradation rates were measured in incubated, intact soleus muscles as incorporation of 14C-phenylalanine into protein and release of tyrosine into incubation medium, respectively. Muscle amino acid uptake was determined by measuring the intracellular to extracellular ratio of [3H]-alpha-aminoisobutyric acid after incubation for 2 hours. Infusion of catabolic hormones for 16 hours resulted in elevated plasma glucose and lactate levels, reduced plasma concentrations of most amino acids, and accelerated muscle protein breakdown, similar to previous findings in septic rats. Protein synthesis rates and amino acid uptake in incubated muscles were not significantly different in control and hormone-infused rats. The current study suggests that increased muscle proteolysis in sepsis and severe injury may be mediated in part by catabolic hormones. In contrast, reduced muscle protein synthesis and amino acid uptake are probably signaled by other substances or mechanisms.

Reduced amino acid transport in skeletal muscle caused by a circulating factor during endotoxemia.

The present study was designed to determine whether reduced amino acid uptake in skeletal muscle during endotoxemia is due to associated hypotension or is caused by a factor present in plasma. Three series of experiments were performed. In the first series of experiments, mean arterial pressure (MAP), heart rate, and amino acid uptake in incubated soleus muscles were measured after intravenous injection of endotoxin (1 mg/kg) in male Sprague-Dawley rats (40 to 60 g). Amino acid transport was measured by determining intracellular uptake of [3H]-alpha-amino-isobutyric acid (AIB) during 2 hours of incubation. In the second series of experiments, hypotension was induced by bleeding and muscle amino acid uptake was measured. In the third series of experiments, whole plasma or a low molecular weight fraction (less than 10,000 d) of plasma from endotoxin-injected rats was added in vitro to incubated muscles and amino acid uptake was determined. One hour after injection of endotoxin, MAP was reduced from 80 +/- 2 mmHg to 54 +/- 4 mmHg (p less than 0.05). AIB uptake was reduced by 20% (p less than 0.05) 2 hours after endotoxin injection. When MAP was maintained at 50 mmHg for 1 hour by bleeding, no changes in muscle AIB uptake were noted. When plasma obtained from rats 2 hours after endotoxin injection was added to incubated soleus muscles, AIB uptake was reduced by 22%. This effect was duplicated by a fraction of endotoxic plasma containing substances with a molecular weight less than 10,000 d. The present results suggest that reduced muscle amino acid uptake during endotoxemia is not due to associated hypotension, but may be caused by a circulating factor(s) with a molecular weight less than 10,000 d.

Inhibited amino acid uptake in skeletal muscle during starvation.

Amino acid uptake in skeletal muscle is reduced during different catabolic conditions such as sepsis, endotoxic shock, and uremia. The present study was designed to determine the effect of another catabolic condition, starvation, on amino acid transport in skeletal muscle. Male Sprague-Dawley rats (40-60 g) were starved for 24, 48, or 72 hr and soleus (SOL) muscles were removed intact and incubated for 2 hr in a medium consisting of Krebs-Henseleit bicarbonate buffer (pH 7.4) with glucose (5 mM), [14C]-inulin, and [3H]-alpha-aminoisobutyric acid (AIB). Amino acid uptake was determined from intracellular to extracellular ratio of AIB following incubation. AIB uptake was significantly reduced after 24 hr of starvation and remained low with further fasting. After 72 hr the AIB distribution ratio was approximately 50% of initial value. Amino acid uptake returned to normal within 24 hr after refeeding of animals that had been starved for 72 hr. Plasma (0.25 ml) from starved rats, added to the incubation medium (2.75 ml) of muscles from nonfasted rats, significantly inhibited AIB uptake. The present results suggest that amino acid uptake in skeletal muscle is progressively reduced during starvation, an effect that may be mediated by a circulating factor(s) present in blood.

Distinction between HIV-1 and HIV-2 infection using novel synthetic lipopeptide conjugates as antigens in enzyme immunoassays.

A novel immunoassay technique using synthetic lipopeptide (Pam3Cys-Ser) linked to immunodominant peptide domains of HIV-1 and HIV-2 envelope proteins as an antigen adsorbent has been developed. Attachment of peptides to microtiter plates can be considerably improved with this method by employing the hydrophobic properties of lipopeptide. From the sera of 121 HIV-1 infected patients 117 reacted with Pam3Cys-Ser-[HIV-1(598-609)cyclic disulfide]. Five of 5 HIV-2 positive sera were positive with Pam3Cys-Ser-[HIV-2(593-603)cyclic disulfide]. Control sera failed to react with these conjugates.

The effect of sepsis in rats on skeletal muscle protein synthesis in vivo and in periphery and central core of incubated muscle preparations in vitro.

Recent studies demonstrated the development of a central, hypoxic core in incubated rat skeletal muscles. The influence of a central core on changes in protein synthesis rate, observed in incubated muscles from septic rats, is not known. In the present study, intact soleus muscles from 40 to 60-g sham-operated control rats and from septic rats (16 hours after cecal ligation and puncture) were incubated in vitro in a flaccid or stretched state. Protein synthesis rate was determined in whole muscle and in the central core and periphery of the muscle by measuring incorporation of 14C-phenylalanine into protein. Protein synthesis rate in vivo was measured with a flooding-dose technique using 3H-phenylalanine. The development of a central, hypoxic core in incubated muscles was assessed histochemically by staining the muscles for alpha-glucan phosphorylase activity. A central core with loss of alpha-glucan phosphorylase activity was noted after incubation for 30 minutes in both control and septic muscles. The protein synthesis rate was lower in the central core than in the periphery of incubated flaccid control muscles. In all other in vitro muscle preparations, however, there were no significant differences in protein synthesis rate among whole muscles, central core and periphery. Protein synthesis rate in septic muscles was reduced to a similar extent, approximately 20%, in vivo and in the different in vitro preparations, both when measured in whole muscle and in the central core or periphery.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of indomethacin and leupeptin on muscle cathepsin B activity and protein degradation during sepsis.

The roles of prostaglandins and lysosomal proteases in accelerated skeletal muscle proteolysis during sepsis are not yet fully understood. In this study rats received intraperitoneal injections of the prostaglandin synthesis inhibitor indomethacin (IND, 5.0 mg/kg), the lysosomal cathepsin B inhibitor leupeptin (LEU, 2.5 mg/kg), or normal saline 2 hr before cecal ligation and puncture (a model of intraabdominal sepsis) or sham-operation. The injections were repeated every 6 hr for a total of four doses. Sixteen hours after operation, intact extensor digitorum longus (EDL) muscles were harvested and cathepsin B activity was measured in one muscle. The contralateral muscle was incubated in oxygenated Krebs-Henseleit bicarbonate buffer containing glucose (10 mM) and cycloheximide (0.5 mM), and protein degradation rate was determined as the release of tyrosine into the incubation medium. Both muscle cathepsin B activity and protein degradation rate were higher in septic than in sham-operated rats. Treatment with IND or LEU significantly reduced the elevated cathepsin B activity in septic muscles, but failed to significantly alter muscle proteolysis. In nonseptic muscle, both cathepsin B activity and protein degradation rate were unaffected by the different types of treatment. The results suggest that although prostaglandins may influence muscle lysosomal protease activity, neither prostaglandins nor the lysosomal protease cathepsin B appear to be major regulators of accelerated muscle protein breakdown during sepsis.