Wound healing after laser surgery

Compared with scalpel wounds, CO2 laser wounds show delays in inflammation, collagen production, reepithelialization, and tensile strength in the early stages of healing. Some of these delays are similar to those seen with electrocautery and burn wounds. Later stages compensate for these early deficiencies, because scalpel and laser wounds become more similar in epithelialization and wound strength over time. Healed CO2 laser wounds tend to have less scar contraction than scalpel wounds. Débridement of initial laser wound char, tissue cooling techniques during lasering, and pulsed modes of laser delivery all seem to result in more rapid, favorable healing. Similar wound healing trends have been seen with the CO2 laser in bone, with other lasers, and with laser vascular and neural anastomosis. Biostimulation with low-level laser energy is a complex subject of ongoing investigations.     

Treatment of advanced hemorrhoidal disease: a prospective, randomized comparison of cold scalpel vs. contact Nd:YAG laser

PURPOSE: Recently, laser technology has been advocated for the treatment of hemorrhoids. However, there has been little scientific evaluation of the use of the Nd:YAG laser for excisional treatment of hemorrhoidal disease. The purpose of this study was to perform a prospective randomized study of the Nd:YAG laser vs. scalpel excision, when performing a standard Ferguson-closed hemorrhoidectomy. METHODS: Patients presenting for internal-external hemorrhoidectomy were eligible for study. Hemorrhoidectomies were performed under epidural or caudal blocks. The standard Ferguson closed hemorrhoidectomy technique was used. Data evaluated included: age, sex, estimated blood loss, operative time, postoperative pain scores, postoperative analgesic use, wound healing, and time for return to work. Eighty-six patients were eligible for study (laser, N = 51; scalpel, N = 35). RESULTS: There were no significant differences between the groups, except for a greater degree of wound inflammation and dehiscence at the 10 day postoperative visit for the laser group (laser, 1.7 +/- .2; scalpel, 0.8 +/- .2; P < 0.05, t-test). The use of the Nd:YAG laser added $480 per case; as a result, the treatment cost for the laser group was $15,360 higher than that of the conventional group. CONCLUSION: The results indicate that there are no patient care advantages associated with the use of the Nd:YAG laser for excisional hemorrhoidectomy compared with scalpel excision. As new technology becomes available, surgeons must rigorously assess therapeutic efficacy and cost-benefit ratio before deciding to employ this technology for patient care.     

Comparison of the effectiveness of various comprehensive treatments for locally advanced breast cancer

OBJECTIVE: Auditory testing is not routinely performed within 4-6 weeks after stapedotomy, because hearing acuity is thought to be transiently depressed. In rare circumstances, postsurgical auditory and vestibular complaints may lead one to test hearing soon after stapedotomy. The early postoperative effects of carbon dioxide (CO2) and potassium titanyl phosphate (KTP) lasers, which now are routinely used to perform stapedotomies, have not been reported. The purpose of this report is to present normative data for auditory thresholds measured within 2 weeks of laser stapedotomy. STUDY DESIGN: The study design was a prospective, unblinded study. SETTING: The study was conducted at three academic medical centers. PATIENTS: Thirty-six subjects undergoing 38 stapedotomies for otosclerosis by 5 surgeons participated. MAIN OUTCOME MEASURES: Behavioral audiometry was performed using standard techniques beginning before surgery and continuing through > 1 year after surgery. RESULTS: The CO2 laser was used in 26 stapedotomies and the KTP laser was used in 12. Nine cases were revision procedures. Bone conduction pure-tone averages and speech discrimination scores did not worsen during the early postoperative period. Bone conduction at 250 and 4,000 Hz dropped slightly within the first 2 weeks (-4.3 and -6.7 dB) but recovered thereafter. Bone conduction at 1,000 Hz actually improved within the first week after surgery (+6.2 dB, p = 0.021). Significant improvements in air conduction thresholds (and air-bone gap) were seen at the second week and late audiometry. The results for CO2 and KTP laser-treated groups were not significantly different. CONCLUSIONS: Cochlear function is not significantly depressed in the early postoperative period after laser (CO2 or KTP) stapedotomy.     

Coronary angioplasty, bypass surgery, and retransplantation in cardiac transplant patients with graft coronary disease

BACKGROUND AND OBJECTIVE: Prior studies of laser tissue soldering (LTS) of epithelial skin have shown poor wound strength in the short-term; however, we hypothesize that greater tensile strength and healing properties will result from directing laser energy to the dermal aspect of the skin. The current study compares wound strength and histology in a rat skin flap model of epithelial and dermally applied LTS. STUDY DESIGN/MATERIALS AND METHODS: Skin flaps (2.5 x 4 cm) were raised and bisected on the dorsum of Sprague-Dawley rats. The center line of bisection was closed from a dermal approach by LTS (LTS-D, diode laser 15.9 W/cm2 + Columbia solder), the upper incision by epithelial LTS (LTS-E), and the lower incision by suturing (7-0 Vicryl). Wound skin strips (1-2 mm x 10 mm) were studied immediately (N = 14) and at 3 (N = 57), 7 (N = 31), and 10 (N = 28) days postoperatively and were subjected to tensiometric analysis. Histologic staining with hematoxylin and eosin and Mallory's trichrome methods were used to define wound architecture. RESULTS: No wound dehiscences were noted in any group. Greater immediate tensile strength was noted in wounds closed by LTS-D (521 +/- 61 g/cm2) versus LTS-E (342 +/- 65 g/cm2); however, this difference was not statistically significant (P = .08). By 3 days, both LTS-D (476 +/- 55 g/cm2) and LTS-E (205 +/- 37 g/cm2) maintained their initial strength; however, LTS-D and sutured (436 +/- 49 g/cm2) wounds were stronger (P < .05) than LTS-E. At 7 and 10 days, LTS-D (2,433 +/- 346 g/cm2 and 3,100 +/- 390 g/cm2) showed superior tensile strength (P < .05) compared to both LTS-E (1,542 +/- 128 g/cm2 and 2,081 +/- 219 g/cm2) and suturing (1,342 +/- 119 g/cm2 and 1,661 +/- 115 g/cm2). Histologic analysis of LTS-D wounds at 3 days showed full-thickness tissue apposition, complete epithelialization, and minimal inflammation or thermal injury. At 7 days, solder was present in the wounds. In contrast, LTS-E wounds at 3 days displayed lack of epithelialization secondary to thermal injury and partial-thickness tissue apposition. However by 7 days, epithelialization was complete with moderate scarring, and no solder was seen. Sutured samples appeared similar to LTS-D, except for poorer tissue apposition at the hypodermis. CONCLUSION: Our results show that skin flap wound healing after dermal LTS is superior to epithelial LTS and emphasizes the importance of site specificity in the utilization of this operative technique in reconstructive surgery.     

A simple breathing circuit minimizing changes in alveolar ventilation during hyperpnoea

Many clinical and research situations require maintenance of isocapnia, which occurs when alveolar ventilation (V'A) is matched to CO2 production. A simple, passive circuit that minimizes changes in V'A during hyperpnoea was devised. It is comprised of a manifold, with two gas inlets, attached to the intake port of a nonrebreathing circuit or ventilator. The first inlet receives a flow of fresh gas (CO2=0%) equal to the subject's minute ventilation (V'E). During hyperpnoea, the balance of V'E is drawn (inlet 2) from a reservoir containing gas, the carbon dioxide tension (PCO2) approximates that of mixed venous blood and therefore contributes minimally to V'A. Nine normal subjects breathed through the circuit for 4 min at 15-31 times resting levels. End-tidal PCO2 (Pet,CO2) at rest, 0, 1.5 and 3.0 min were (mean+/-SE) 5.1+/-0.1 kPa (38.1+/-1.1 mmHg), 4.9+/-0.1 kPa (36.4+/-1.1 mmHg), 5.0+/-0.2 kPa (37.8+/-1.6 mmHg) and 5.0+/-0.2 kPa (37.6+/-1.4 mmHg) (p=0.53, analysis of variance (ANOVA)), respectively; without the circuit, Pet,CO2 would be expected to have decreased by at least 2.7 kPa (20 mmHg). Six anaesthetized, intubated dogs were first ventilated at control levels and then hyperventilated by stepwise increases in either respiratory frequency (fR) from 10 to 24 min(-1) or tidal volume (VT) from 400 to 1,200 mL. Increases in fR did not significantly affect arterial CO2 tension (Pa,CO2) (p=0.28, ANOVA). Only the highest VT decreased Pa,CO2 from control (-0.5 +/- 0.3 kPa (-3.4 +/- 2.3 mmHg), p<0.05). In conclusion, this circuit effectively minimizes changes in alveolar ventilation and therefore arterial carbon dioxide tension during hyperpnoea.     

Tendon repair by laser welding: a histologic and biomechanical comparison and suture repair with CO2 and argon lasers

BACKGROUND AND OBJECTIVE: The purpose of this study was to determine whether welding of tendinous tissue is possible with the application of thermal lasers. STUDY DESIGN MATERIALS AND METHODS: After sharp transection of a unilateral achilles tendon, 40 male outbred Spraque Dawley rats were divided equally between four treatment groups. Ten animals underwent repair using the modified Kessler suture technique. The remaining animals underwent application of laser after the tendon edges were reapproximated and held in place with a vascular clamp. CO2 and Nd:YAG lasers were applied using 25% human albumin as a solder. Fluorescein dye was added to albumin and used as solder for the Argon laser. Biomechanical and histologic testing were performed immediately and 14 days postoperatively. RESULTS: Argon and CO2 lasers successfully fused the tendon ends together. However, immediately postoperative, the resultant tissue weld was tenuous and conventional tensile strength testing was not possible. At 14 days postoperatively, all modes of tendon repair resulted in tensile failure at consistently lower levels of tension than those required for the normal uninjured tendons. The ultimate tensile strength for the suture-repaired, CO2 laser welded, and Argon laser welded tendons were 74%, 59%, and 64% of the strength of the control tendons respectively. No statistically significant difference was found in the tensile strength among the three repair groups. Histologic evaluation at 14 days revealed the greatest degree of inflammatory response in those tendons repaired with the Argon laser. Those tendons repaired with suture demonstrated the least amount of inflammatory change. CONCLUSION: Our study demonstrates that welding of a tendon is possible with the application of laser energy. However, we were unable to produce a weld sufficient to withstand significant tensile loads in the immediate postoperative period.     

Noninvasive capnometry monitoring for respiratory status during pediatric seizures

OBJECTIVE: To determine the reliability and clinical value of end-tidal CO2 by oral/nasal capnometry for monitoring pediatric patients presenting post ictal or with active seizures. DESIGN: Clinical, prospective, observational study. SETTING: University affiliated children's hospital. INTERVENTIONS: One hundred sixty-six patients (105 patients with active seizures, 61 post ictal patients) had end-tidal CO2 obtained by oral/nasal sidestream capnometry, and respiratory rates, oxygen saturation, and pulse rates recorded every 5 mins until 60 mins had elapsed. End-tidal CO2 values were compared with a capillary PCO2 and clinical observation. MEASUREMENTS AND MAIN RESULTS: The mean end-tidal CO2 reading was 43.0 +/- 11.8 torr [5.7 +/- 1.6 kPa] and the mean capillary PCO2 reading was 43.4 +/- 11.7 torr [5.7 +/- 1.6 kPa]. The correlation between end-tidal CO2 and capillary PCO2 was significant (r2 = .97; p < .0001). A relative average bias of 0.33 torr (0.04 kPa) with end-tidal CO2 lower than capillary PCO2 was established with 95% limits of agreement +/-4.2 torr (+/-0.6 kPa). Variability of difference scores was not related to range of mean scores (r2 = .00003), age (r2 = .0004), or respiratory rates (r2 = .0009). End-tidal CO2 (r2 = .22; p < .001) correlated better with respiratory rate changes when compared with oxygen saturation (r2 = .02; p = .01). CONCLUSIONS: Dependable end-tidal CO2 values can be obtained in pediatric seizure patients using an oral/nasal cannula capnometry circuit. Continuous end-tidal CO2 monitoring provides the clinician with a reliable assessment of pulmonary status that can assist with decisions to provide ventilatory support.     

Effects of hypothermia in hypercapnia and hypercapnic hypoxemia

Anesthetized, paralyzed and mechanically ventilated pigs were hypoventilated to extreme hypercapnia (PaCO2 approximately 20 kPa) at FiO2 0.5, and allotted to a hypothermic group (31.5 +/- 0.1 degrees C, n = 6) or a control group (39.6 +/- 0.2 degrees C, n = 6). Compared with the controls, the hypothermic animals had higher PaO2 (19.2 vs 15.6 kPa, P < 0.05), SaO2 (97.2 vs 89.3%), SvO2 (78.7 vs 68.2%), end-tidal O2 (34.5 vs 24.8 kPa) and arterial pH (7.01 vs 6.91), (P < 0.01), but lower PvO2 (7.0 vs 10.2 kPa) and PaCO2 (13.2 vs 23.5 kPa), (P < 0.01). Hypothermia reduced O2 delivery (DO2), O2 consumption (VO2) and CO2 production by 40-45% (P < 0.05), but O2 extraction ratio, i.e. VO2.DO(2)-1 x 100(%), did not differ between groups. Hypothermic animals had lower heart rate (127 vs 223 beats.min-1, P < 0.05) and cardiac output (2.5 vs 3.9 l.min-1, P < 0.01). Subsequently, the inspired oxygen fraction (FiO2) was decreased stepwise (0.3, 0.25, 0.21, 0.15, 0.10) at 30-min intervals. At FiO2 0.3, the hypothermic group had higher PaO2 (10.0 vs 5.7 kPa), SaO2 (91.3 vs 28.5%), PvO2 (5.8 vs 3.4 kPa), SvO2 (70.7 vs 10.3%), end-tidal O2 (16.7 vs 8.5 kPa), O2 delivery (344 vs 155 ml.min-1), arterial pH (7.02 vs 6.94) and systemic vascular resistance (3850 vs 1652 dyn.s.cm-5 (38,500 vs 16,520 microN.s.cm-5)) compared with the controls (P < 0.01), while PaCO2 was lower (12.4 vs 22.7 kPa), as well as O2 extraction ratio (23 vs 63%) and O2 half saturation tension (4.3 vs 8.0 kPa) (P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)     

Keratinocyte growth factor-2 accelerates wound healing in incisional wounds

BACKGROUND: Keratinocyte growth factor-2 (KGF-2) also described as fibroblast growth factor-10 (FGF-10) is a newly identified member of the fibroblast growth factor family. KGF-2 is 96% identical to the recently identified rat FGF-10 and specifically stimulates growth of normal human epidermal keratinocytes. The present study was undertaken to examine the effects of topically applied KGF-2 in an incisional wound healing model. KGF-2 treatment resulted in an improvement in incisional wound healing as characterized by an increase in breaking strength, collagen content, and epidermal thickness. METHODS: KGF-2 was topically applied to linear incisions made in the dorsal skin of Sprague-Dawley rats. Biomechanical testing was done using an Instron tensiometer for breaking and tensile strength determinations. Wound collagen content was determined using the Sircol collagen assay. Epidermal thickness measurements were conducted using Masson's trichrome-stained sections of the wound. RESULTS: A single topical application of KGF-2 at the time of wounding resulted in an increase in wound breaking and tensile strength at Day 5 after wounding. Breaking strength of KGF-2-treated wounds was significantly higher compared with the buffer control (1 microgram, 222.1 +/- 13.5 g, P = 0.0007; 4 microgram, 248.7 +/- 15.4 g, P = 0.0001; 10 microgram, 247.2 +/- 21.9 g, P = 0.001; buffer, 141.0 +/- 9.7 g). Epidermal thickness and wound collagen content were significantly increased following treatment with KGF-2. CONCLUSIONS: Based on our findings, KGF-2 is a potent stimulator of wound healing as demonstrated by increased mechanical strength accompanied by an increase in wound collagen content. KGF-2 could be an important cellular mediator responsible for the initiation and acceleration of wound healing and may enhance the healing of surgical wounds.     

The phylogenetic position of alpha- and beta-tubulins from the Chlorarachnion host and Cercomonas (Cercozoa)

The purpose of this study was to investigate the effect of acid conditioning of root surfaces during recombinant human bone morphogenetic protein-2 (rhBMP-2) induced periodontal regeneration in vivo. The buccal aspect of molar roots were denuded of their periodontal ligament through a bony window created in the mandible of 34 Wistar rats under general anesthesia. Three groups of 11 or 12 animals received either 10 microL of 50 g/mL rhBMP-2 in a collagen gel over the surgical defect (BMP) or 10 microL of collagen gel only (COL) or were left untreated (UN). Each of the 3 groups were further subdivided into those that received prior root acid conditioning with 35% phosphoric acid gel and those without acid conditioning. Animals were sacrificed 10 days after surgery and the tissues processed for histological examination. The BMP groups with and without acid conditioning developed significantly more bone over the second molar (3.89+/-0.86% and 7.62+/-0.93%, respectively; mean+/-SE), compared with the respective COL (1.24+/-0.26% and 2.77+/-0.52%) and UN groups (1.34+/-0.35% and 3.69+/-0.37%) (P <0.05). Furthermore, significantly more bone was found in the BMP non-acid conditioned group compared with all other groups (P <0.05). Acid conditioning promoted significantly more ankylosis (50%) compared with non-acid conditioning (6.3%) (P=0.007). New cementum formation was greatest in the BMP acid conditioned group (628.4+/-253.8 microm2) and lowest in the non-acid conditioned UN group (207.6+/-36.4 microm2) (P <0.05). This is the first known report evaluating the effects of root acid conditioning after a single application of rhBMP-2 in vivo. Results suggest that root conditioning agents operating at low pH administered into the periodontal wound impairs early BMP-induced osteogenesis while simultaneously promoting BMP-induced cementogenesis.     

Induced astigmatism and its decay with a frown incision

Forty consecutive patients selected for cataract extraction by phacoemulsification were studied to evaluate prospectively the amount of and changes in surgically induced astigmatism from a 5 mm to 6 mm pocket incision with the external opening made convex against the limbus (frown incision). All incisions had an internal corneal valve and were closed by a single X-stitch to counteract the relaxing effect of the pocket in the 90-degree meridian. Surgically induced astigmatism calculated by simple subtraction was 0.64 +/- 0.90 diopters (D) (P < .0001) on the first postoperative day, 0.03 +/- 0.58 D (P = .75) six weeks after surgery, and -0.18 +/- 0.44 D (P = .01) six months after surgery. Calculated from polar equivalents, the induced astigmatism on the first postoperative day was 0.98 D +/- 1.03 D (P = .0001), after six weeks -0.11 D +/- 0.64 D (P = .30), and after six months -0.28 D +/- 0.49 D (P = .0009). On the first postoperative day 42% of eyes had less than 0.5 D of induced astigmatism, 68% had less than 1.0 D, and 79% had less than 1.5 D. After six weeks the respective percentages increased to 61%, 97%, and 97% and after six months to 84%, 100%, and 100%. The distribution of patients with against-the-rule, oblique, and with-the-rule astigmatism preoperatively was nine, 20, and 11, respectively, and 11, 19, and nine after six months. The amount of astigmatism induced from the 5 mm to 6 mm frown incision did not differ from that found in previously published studies of smaller incisions (to about 4 mm).(ABSTRACT TRUNCATED AT 250 WORDS)     

Area and depth of surfactant-induced corneal injury correlates with cell death

PURPOSE: In previous studies in which in vivo confocal microscopy (CM) was used, quantifiable differences were identified in the corneal epithelium and stroma for surfactants producing different degrees of ocular irritation. In the present study, in vivo confocal microscopy was used to determine area and depth of the initial corneal changes, and the correlation of the data to cell death was characterized by ex vivo live-dead assay. METHODS: In four groups of rabbits (12 animals each), 10 microl surfactants known to produce slight, mild, moderate, or severe irritation was applied to the central cornea of one eye; 4 untreated rabbits served as controls. Measurements of group total mean epithelial thickness, epithelial cell area, and depth of keratocyte loss in four corneal regions were made by in vivo CM in 6 rabbits of each group and in 4 control animals at 3 hours and in the remaining rabbits at 3 hours and 1 day. Corneas were then removed and fixed for conventional histologic examination (two eyes/treatment/group), or regions were excised and placed in culture media containing 2 microM calcein-acetoxymethyl ester (calcein-AM) and 4 microM ethidium homodimer. Using laser scanning CM, the number of dead epithelial or stromal cells in a 300 x 300 x 170 microm (in the x, y, and z axes, respectively) volume of the cornea was determined. RESULTS: Confocal microscopy showed that application of the slight irritant resulted in decreased epithelial thickness at 3 hours (41.2+/-2.6 microm in treated eyes versus 43.6+/-3 microm in control eyes; n=6 and 4, respectively) and a significant decrease (P < 0.001) in epithelial cell size (630+/-203 microm2 versus 1427.2+/-90.7 microm2). On day 1, mild, moderate, and severe irritants caused complete loss of epithelium and disappearance of keratocytes to a depth of 30.8+/-10.7 microm, 47.2+/-10.4 microm, and 764.6+/-159.6 microm (n=6, 5, and 6), respectively. At 3 hours, live-dead assay detected more dead epithelial cells as a percentage of total surface cells (49.2+/-4.5% in slightly irritated eyes versus 20.9+/-3.2% in control eyes), significantly correlating with the measurement by in vivo CM of average epithelial cell size in each eye (r=-0.96; P < 0.005). On day 1, mild and moderate irritants showed increasing stromal cell death from 9.8+/-16.2 cells to 36.4+/-17.7 cells, which significantly correlated with the depth of stromal injury determined by in vivo CM (r=0.79; P < 0.00001). No surviving keratocytes were detected in severely irritated eyes. CONCLUSIONS: The data support the hypothesis that differences in surfactant-induced ocular irritation are directly related to area and depth of acute corneal injury.     

Effects of partial liquid ventilation on lung injury in a model of acute respiratory failure: a histologic and morphometric analysis

OBJECTIVE: To compare the histopathologic changes observed in a sheep model of oleic acid-induced acute respiratory failure during partial liquid ventilation with perflubron with gas ventilation. DESIGN: Randomized, controlled study. SETTING: Animal laboratory and pathology laboratories of a university hospital. SUBJECTS: Fourteen healthy adult sheep, weighing 64.9 +/- 6.4 kg. INTERVENTIONS: Lung injury was induced with oleic acid (0.15 mL/kg). A tracheostomy tube was inserted, along with systemic and pulmonary artery monitoring catheters. Animals were randomized to undergo either partial liquid ventilation (n = 7) or gas ventilation (n = 7). Animals underwent euthanasia at the end of the 90-min study period, after which the endotracheal tube was clamped with the lungs in expiratory hold at a positive end-expiratory pressure of 5 cm H2O. En bloc excision of the heart and lungs was performed by thoracotomy. Perfusion of the isolated lung vasculature with 2.5% paraformaldehyde and 0.25% glutaraldehyde in a 0.1-M phosphate buffer was performed. Histologic analysis followed. MEASUREMENTS AND MAIN RESULTS: Gas exchange increased markedly in the animals that underwent partial liquid ventilation compared with the gas-ventilated animals (PaO2 at 90 mins: gas ventilation-treatment group, 40 +/- 8 torr [5.3 +/- 1.1 kPa]; partial liquid ventilation-treatment group, 108 +/- 60 torr [14.4 +/- 8.0 kPa]; p = .004). Lung histologic analysis demonstrated a better overall diffuse alveolar damage score (partial liquid ventilation-treatment group, 12.4 +/- 1.4; gas ventilation-treatment group, 15.0 +/- 1.7; p = .01). In the partial liquid ventilation-treatment group, we observed an increase in mean alveolar diameter (partial liquid ventilation-treatment group, 82.4 +/- 2.9 microm; gas ventilation-treatment group, 67.7 x 3.9 microm; p = .0022) and a decrease in the number of alveoli per high-power field (partial liquid ventilation-treatment group, 25.7 +/- 0.9, gas ventilation-treatment group, 31.4 +/- 2.5; p = .0022), in septal wall thickness (partial liquid ventilation-treatment group, 6.0 +/- 0.6 microm; gas ventilation-treatment group, 8.3 +/- 1.0 microm; p = .0033), and in mean capillary diameter (partial liquid ventilation-treatment group, 13.0 +/- 0.8 microm; gas ventilation-treatment group, 19.9 +/- 1.4 microm; p = .0022). CONCLUSIONS: Partial liquid ventilation is associated with notable improvement in gas exchange and with a reduction in the histologic and morphologic changes observed in an oleic acid model of acute lung injury.     

Laser-assisted microvascular anastomosis of human adult and placental arteries with expanded polytetrafluoroethylene microconduit

Laser-assisted microvascular anastomoses can be performed more quickly than sutured anastomoses, yet manifest similar patency rates and tensile strength. This study was undertaken to determine if in vitro laser-assisted microvascular anastomoses could be created between human adult arteries (anterior tibial arteries), human placental arteries, and expanded polytetrafluoroethylene microconduits. A CO2 laser was applied in single or continuous bursts with a matrix of variables encompassing power P = 80 to 160 mW, spot size SS = 150 to 500 microns, and exposure time EXP = 1.0-second continuous exposure (n = 2 each composite setting). The endpoints measured to assess the ability to laser-weld vessels were morphologic appearance by scanning electron microscopy and bursting strength. Scanning electron microscopy revealed apparent fusion of human placental arteries and human adult arteries to expanded polytetrafluoroethylene microconduits at settings of P = 130 mW, SS = 300 microns, and EXP = 1.0 second, though bursting pressure at all settings was less than 10 mmHg. Laser-assisted microvascular anastomoses of human placental artery to human placental artery and human adult artery to human adult artery were successful at this setting, though bursting pressures of anastomoses incorporating placental vessels were significantly weaker than those created with adult tissue. The relative weakness of laser-assisted microvascular anastomoses incorporating placental arteries might be explained by qualitative or quantitative differences in vessel wall collagen, as seen in fetal tissue, and deserves further characterization.     

Effect of low-dose acetazolamide on the ventilatory CO2 response during hypoxia in the anaesthetized cat

Acetazolamide, a carbonic anhydrase inhibitor, is used in patients with chronic obstructive pulmonary diseases and central sleep apnoea syndrome and in the prevention and treatment of the symptoms of acute mountain sickness. In these patients, the drug increases minute ventilation (V'E), resulting in an improvement in arterial oxygen saturation. However, the mechanism by which it stimulates ventilation is still under debate. Since hypoxaemia is a frequently observed phenomenon in these patients, the effect of 4 mg x kg(-1) acetazolamide (i.v.) on the ventilatory response to hypercapnia during hypoxaemia (arterial oxygen tension (Pa,O2)=6.8+/-0.8 kPa, mean+/-SD) was investigated in seven anaesthetized cats. The dynamic end-tidal forcing (DEF) technique was used, enabling the relative contributions of the peripheral and central chemoreflex loops to the ventilatory response to a step change in end-tidal carbon dioxide tension, (PET,CO2) to be separated. Acetazolamide reduced the CO2 sensitivities of the peripheral (Sp) and central (Sc) chemoreflex loops from 0.22+/-0.08 to 0.11+/-0.03 L x min(-1) x kPa(-1) (mean+/-SD) (p<0.01) and from 0.74+/-0.32 to 0.40+/-0.10 L x min(-1) x kPa(-1) (p<0.01), respectively. The apnoeic threshold B (x-intercept of the ventilatory CO2 response curve) decreased from 2.88+/-0.97 to 0.95+/-0.92 kPa (p<0.01). The net result was a stimulation of ventilation at PET,CO2 <5 kPa. The effect of acetazolamide is possibly due to a direct effect on the peripheral chemoreceptors as well as to an effect on the cerebral blood flow regulation. Possible clinical implications of these results are discussed.     

Value of single oral loading dose of propafenone in converting recent-onset atrial fibrillation. Results of a randomized, double-blind, controlled study

OBJECTIVE: To assess the effects of dobutamine at a rate of 5 micrograms/kg/min on hemodynamics and gastric intramucosal acidosis in patients with hyperdynamic septic shock treated with epinephrine. DESIGN: A prospective, interventional, clinical trial. SETTING: An adult, 16-bed medical/surgical intensive care unit of a university hospital. PATIENTS: Twenty septic shock patients with a mean arterial pressure of > 75 mm Hg and a cardiac index of > 3.5 L/min/m2. INTERVENTIONS: After baseline measurements (H0), each patient received dobutamine at a rate of 5 micrograms/kg/min. Baseline measurements included: hemodynamic parameters, tonometric parameters, arterial and mixed venous gases, and arterial lactate concentrations. These measurements were repeated after 1 (H1), 2 (H2), and 3 (H3) hrs. After H2 measurements, dobutamine was stopped. The patients were separated into two groups according to their PCO2 gap (tonometer PCO2-PaCO2). The increased PCO2 gap group was defined by a PCO2 gap > 8 torr (> 1.1 kPa) (n = 13), and the normal PCO2 gap group by a PCO2 gap < or = 8 torr (< or = 1.1 kPa)(n = 7). MEASUREMENTS AND MAIN RESULTS: Dobutamine at 5 micrograms/kg/min had no significant effects on mean arterial pressure, heart rate, cardiac index, systemic vascular resistance, oxygen delivery, and oxygen consumption in epinephrine-treated septic shock. No patients developed arrhythmia or electrocardiographic signs of myocardial ischemia. During dobutamine infusion, arterial lactate concentration decreased from 5.1 +/- 0.4 in the increased PCO2 gap group and 4.2 +/- 0.4 in the normal PCO2 gap group to 3.9 +/- 0.3 and 3.5 +/- 0.3 mmol/L, respectively (p < .01). The PCO2 gap decreased and gastric intramucosal pH increased in the increased PCO2 gap group from 12 +/- 0.8 (1.6 +/- 0.1 kPa) to 3.5 +/- 0.8 torr (0.5 +/- 0.1 kPa) (p < .01) and from 7.11 +/- 0.03 to 7.18 +/- 0.02 (p < .01), respectively, and did not change in the normal PCO2 gap group. After stopping dobutamine infusion, the PCO2 gap and intramucosal pH returned to baseline values in the increased PCO2 gap group. CONCLUSION: The addition of 5 micrograms/kg/min of dobutamine added to epinephrine in hyperdynamic septic shock selectively improved the adequacy of gastric mucosal perfusion without modification in systemic hemodynamics.     

Functional outcome of patients with chronic obstructive pulmonary disease and exercise hypercapnia

Chronic hypercapnia is associated with a poor prognosis in chronic obstructive pulmonary disease (COPD). Some patients are normocapnic at rest but retain CO2 during exercise. The significance of this abnormality on the course of the disease is unknown. Sixteen stable COPD patients (13 males and 3 females, aged 60 +/- 5 yrs, mean +/- SD) who had previously undergone pulmonary function tests and progressive exercise testing with arterial blood sampling at rest and maximal capacity, entered the study. At first evaluation (E1), subjects were normocapnic at rest (arterial carbon dioxide tension (Pa,CO2): 4.9-5.7 kPa, (37-43 mmHg)) and all presented exercise-induced hypercapnia (end-exercise Pa,CO2 > 5.7 kPa (43 mmHg) with a minimal 0.5 kPa (4 mmHg) increase from resting value). The subjects were re-evaluated 24-54 months later (34 +/- 8 months) (second evaluation (E2)). At E2, forced expiratory volume in one second (FEV1) had decreased from 42 +/- 13 to 38 +/- 15% of predicted values, and mean resting Pa,CO2 had increased from 5.2 +/- 0.3 to 5.7 + 0.4 kPa. Maximal exercise capacity (Wmax) decreased between E1 and E2 from 76 +/- 30 to 56 +/- 22 W. Even if Wmax was lower at E2, end-exercise, Pa,CO2 was higher than at E1 (6.6 +/- 0.8 vs 6.4 +/- 0.5 kPa). At E2, eight subjects presented resting hypercapnia (group H), whilst the others remained normocapnic (Group N). Group H subjects had higher Pa,CO2, at Wmax than Group N and lower Wmax than Group N at E2.(ABSTRACT TRUNCATED AT 250 WORDS)     

Induction of early atherosclerosis in LDL-receptor-deficient mice immunized with beta2-glycoprotein I

BACKGROUND: Immunization with beta2-glycoprotein I (beta2GPI), the probable target of autoimmune anticardiolipin antibodies, results in experimental antiphospholipid syndrome in different mouse strains. The present study was undertaken to evaluate the effect of beta2GPI immunization on the progression of atherosclerosis. METHODS AND RESULTS: In the first experiment, 3 groups of LDL receptor-deficient (LDL-RD) mice (n=15 per group) were immunized with either beta2GPI or ovalbumin or were not immunized and were fed a chow diet for 12 weeks. In a second experiment, 3 groups of LDL-RD mice (n=10 per group) were immunized similarly and fed an atherogenic diet for 6 weeks. All beta2GPI-immunized mice developed high titers of anti-beta2GPI antibodies as well as a specific lymph node proliferation to beta2GPI. The average cholesterol levels did not differ between the mice fed similar diets, regardless of the immunization protocol. Atherosclerosis was enhanced in the beta2GPI-immunized mice (mean aortic lesion, 26 000+/-5700 microm2) in comparison with their ovalbumin-immunized (mean, 3000+/-1099 microm2; P<0.01) and nonimmunized (mean, 2250+/-700 microm2; P<0.01) littermates. The average lesion size in the beta2GPI-immunized mice fed an atherogenic diet (mean, 98 000+/-8305 microm2) was larger than the ovalbumin-immunized mice (mean, 81 250+/-12 933 microm2; P=NS) or the nonimmunized controls (mean, 75 625+/-7281 microm2; P=NS). The atherosclerotic plaques in the beta2GPI-immunized mice appeared to be more mature, and denser infiltration of CD4 lymphocytes was present in the subendothelium of the aortic sinuses from this group of mice. CONCLUSIONS: The results of the present study provide the first direct evidence for the proatherogenic effect of ss2GPI immunization and establish a new model for immune-mediated atherosclerosis.     

A novel parameterization scheme for energy equations and its use to calculate the structure of protein molecules

A generalized, weighted, nonlinear least squares procedure is developed, based on pH titration data, for the refinement of octanol-water partition coefficients (log P) and ionization constants (pKa) of multiprotic substances. Ion-pair partition reactions, self-association reactions forming oligomers, and formations of mixed-substance complexes can be treated with this procedure. The procedure allows for CO2 corrections in instances where the base titrant may have CO2 as an impurity. Optionally, the substance purity and the titrant strength may be treated as adjustable parameters. The partial differentiation in the Gauss-Newton refinement procedure is based on newly derived analytical expressions. The new procedure was experimentally demonstrated with benzoic acid, 1-benzylimidazole, (+/-)-propranolol, and mellitic acid (benzenehexacarboxylic acid, AH6). Ionic strength (l) was adjusted with KNO3. Benzoic acid (20 degrees C; l 0.1 M): pKa = 3.99 +/- 0.02, log P = 1.96 +/- 0.02, log P (anion) = -1.2; 1-benzylimidazole (25 degrees C; l 0.1 M): pKa = 6.70 +/- 0.03, log P = 1.60 +/- 0.04; propranolol (25 degrees C; l 0.1 M): pKa = 9.53 +/- 0.06, log P = 3.35 +/- 0.03, log P (cation) = 0.62 +/- 0.08; mellitic acid (26 degrees C; l 0.2 M): pKas 1.10 +/- 0.46, 1.69 +/- 0.03, 2.75 +/- 0.02, 4.00 +/- 0.02, 5.05 +/- 0.01, and 6.04 +/- 0.02; in the presence of 0.01 M n-Bu4NBr, log P (AH6) = 1.5, log P (AH5-) = 1.1, log P (AH4(2-)) = 0.8, log P (AH3(3-)) = 0.3, log P (AH2(4-)) = -0.1, and log P (AH5-) = -0.5 (all +/- 0.1).(ABSTRACT TRUNCATED AT 250 WORDS)     

In vitro effects of holmium. YAG laser on caprine stifle retinacular restraints

This study was designed to evaluate the efficacy of the Holmium:YAG laser for performing lateral release and medial joint capsular tightening intracapsularly and to compare the efficacy of the laser versus a scalpel blade for performing a lateral release by performing arthroscopic surgery on 29 caprine patellofemoral joints. Specimens were divided into six treatment groups and treatments consisted of lateral release alone, medial capsular tightening alone, or both treatments, and the effect of each treatment on patellar tracking was evaluated using video analysis of optical markers. Each treatment caused significantly different magnitudes of medial patellar displacement throughout a 75 degrees range of motion: medial tightening followed by lateral release (1.5 +/- 0.10 mm, mean +/- standard error of the mean); lateral release followed by medial tightening (1.1 +/- 0.11 mm); medial tightening alone (0.73 +/- 0.10 mm); lateral release alone (0.36 +/- 0.09 mm); and sham (-0.15 +/- 0.05 mm). There were no significant differences between performing the lateral release using the laser (1.5 +/- 0.10 mm) versus a scalpel (1.4 +/- 0.11 mm). This study shows that lateral release can be performed as effectively with the laser as with a scalpel and that the laser is an effective tool for performing lateral release and medial joint capsular tightening procedures intracapsularly in this caprine model.