Laser treatment of medical skin disease in women.

Laser treatment is a relatively new and increasingly popular modality for the treatment of many dermatologic conditions. A number of conditions that predominantly occur in women and that have a paucity of effective treatments include rosacea, connective tissue disease, melasma, nevus of Ota, lichen sclerosus (LS), notalgia paresthetica and macular amyloidosis, and syringomas. Laser therapy is an important option for the treatment of patients with these conditions. This article will review the body of literature that exists for the laser treatment of women with these medical conditions.

Effect of primary coronary intervention on heart rate variability and left ventricular function in patients with acute myocardial infarction.

AIM: Several studies showed that primary percutaneous coronary interventions (PCI) have a favourable impact on left ventricular remodeling and heart rate variability (HRV) both at short- and long-term follow-up in patients suffering an acute myocardial infarction (AMI). However, no previous study investigated the relationship between left ventricular remodeling and changes in HRV during follow-up in AMI patients treated by primary PCI. METHODS: We studied 28 patients with AMI (57+/-8 years, 27 men), treated by PCI within 12 hours of symptom onset. Patients underwent a 24-hour ECG Holter recording and left ventricular ejection fraction (LVEF) echocardiographic assessment before discharge, and at 1-month and 6-month follow-up. HRV was measured in the time- and frequency-domain. RESULTS: A significant improvement of both time- and frequency-domain HRV variables was observed at 1-month and at 6-month follow-up with the most significant changes being found for standard deviation of normal-normal beat intervals (SDNN) in the time-domain (95.5+/-26.1 ms vs 125.5+/-29.8 ms vs 142.8+/-28.8 ms, respectively; P<0.001) and for very low frequency (VLF) amplitude in the frequency-domain (36.7+/-9.8 ms vs 44.1+/-11.1 vs 48.9+/-12.2 ms, respectively; P<0.001). In contrast, compared to basal values, LVEF was substantially unchanged at 1-month and 6-month follow-up (48.8+/-8.5% vs 50.8+/-10% vs 49.6+/-9%, respectively; P=0.25). At 6-month follow-up 11 patients showed an improvement of >or= 5% of LVEF, whereas 17 patients did not show any improvement of LVEF. HRV variables significantly improved in a similar way in these two subgroups both at 1-month and at 6-month follow-up. CONCLUSION: Our data demonstrate that, in AMI patients treated by primary PCI, HRV improves over time, independent of changes in LVEF. The clinical implications of these findings deserve to be addressed in future studies.

Electromyographic reliability and analysis of selected lower extremity muscles during lateral step-up conditions.

OBJECTIVE: To determine 1) the electromyographic (EMG) reliability within and between testing sessions; 2) the effect of sex on the EMG activity of the vastus medialis oblique (VMO), vastus lateralis (VL), hamstring (HS), and gluteus maximus (GM) and VMO:VL ratios during maximal voluntary isometric contraction (MVIC) and lateral step-up (LSU) conditions; and 3) the muscle recruitment and VMO:VL ratios during MVIC and LSU conditions. DESIGN AND SETTING: Subjects participated in a familiarization session and two testing sessions in which they performed a 20.32-cm (8-in) LSU with and without resistance while the EMG activity was monitored for the VMO, VL, HS, and GM muscles. SUBJECTS: Nineteen subjects performed LSUs holding 25% body weight (Group 25%), and 13 subjects performed LSUs holding 10% body weight (Group 10%). There were 32 subjects total: 19 males and 13 females. MEASUREMENTS: Statistical analyses included a two-way analysis of variance (ANOVA) to compare sex and testing conditions for percentage of MVIC and VMO:VL ratios; three-way repeated-measures ANOVA to compare muscle, resistance, and session factors for percentage of MVIC; and a two-way repeated-measures ANOVA to compare conditions and session factors for VMO:VL ratios. These analyses were performed for both groups. RESULTS: Reliability results revealed good intrasession and poor intersession intraclass correlation coefficients. No difference existed in muscle recruitment or VMO:VL ratios between males and females for either group. The three-way ANOVA revealed a significant two-way interaction (muscle x resistance) for both groups. Post hoc testing revealed the following EMG recruitment patterns: VMO > HS, GM, VL;VL > HS, GM; HS = GM for both groups. For Group 25%, the two-way ANOVA revealed greater VMO:VL ratios during MVIC for session one than for LSU. CONCLUSIONS: Intrasession reliability was higher than intersession reliability, but similar conclusions were reached concerning muscle recruitment in both testing situations. No sex differences existed in recruitment patterns. The LSU requires greater VMO and VL recruitment than HS and GM recruitment. In addition, VMO:VL ratios varied tremendously in a group of asymptomatic subjects, which challenges the theory of a "normal" VMO:VL ratio of 1:1 in asymptomatic subjects.

Ultrasound-guided compression of iatrogenic femoral pseudoaneurysm failure, recurrence, and long-term results.

PURPOSE: Iatrogenic femoral pseudoaneurysms (IFP) have traditionally been treated surgically. Recently, this common problem has been successfully treated without operation by use of ultrasound-guided compression (UGC) to induce thrombosis of the false aneurysm cavity, but the risk factors for failure and the long-term outcome have not been defined. METHODS: All patients referred to the vascular laboratory from June 1992 to November 1994 whose femoral pseudoaneurysms were treated by UGC were included in the study. Data were collected prospectively during the last 18 months of the study. Data regarding the location and morphologic characteristics of the pseudoaneurysms and anticoagulation status were documented. Patients who had successful UGC underwent follow-up duplex scanning and ankle-brachial arterial pressure evaluations. RESULTS: Fifty-seven patients with IFP were treated with UGC over a 30-month period; the last 34 were evaluated prospectively. UGC was successful at obliterating the false aneurysm cavity with the initial attempt in 47 (83%). Thrombosis of seven additional pseudoaneurysms was achieved on subsequent UGC attempts for an overall success rate of 95%. Recurrent false aneurysms were noted in two patients 2 and 10 days after initially successful UGC. Both were treated successfully with repeat UGC. Multivariate analysis of 14 variables revealed heparin anticoagulation (chi-square 9.025, p = 0.001) as the only significant risk factor for failure of UGC. There were no episodes of arterial thrombosis, embolization, or femoral nerve injury associated with UGC. Temporary occlusion of femoral artery during UGC and compression intervals of 20 minutes were well tolerated. Long-term follow-up from 30 to 400 days after UGC was available in 36 patients. There was no late recurrence or significant change in ankle-brachial pressures (p > 0.05). CONCLUSION: UGC is a safe and effective treatment for most catheter-induced femoral pseudoaneurysms with a low complication rate and excellent long-term results at a cost substantially lower than operative treatment. Because the natural history of IFP is unpredictable, UGC appears to be the preferred treatment for all IFPs persisting after cessation of heparin anticoagulation.

Neutrophil cathepsin G modulates the platelet surface expression of the glycoprotein (GP) Ib-IX complex by proteolysis of the von Willebrand factor binding site on GPIb alpha and by a cytoskeletal-mediated redistribution of the remainder of the complex.

The effects of neutrophil cathepsin G on the glycoprotein (GP) Ib-IX complex of washed platelets were examined. Cathepsin G resulted in a concentration- and time-dependent decrease in the platelet surface GPIb-IX complex, as determined by flow cytometry, binding of exogenous von Willebrand factor (vWF) in the presence of ristocetin, and ristocetin-induced platelet agglutination. Cathepsin G resulted in proteolysis of the vWF binding site on GPIb alpha (defined by monoclonal antibody [MoAb] 6D1), as determined by increased supernatant glycocalicin fragment (a proteolytic product of GPIb alpha); decreased total platelet content of GPIb; and lack of effect of either cytochalasin B (an inhibitor of actin polymerization), prostaglandin I2 (an inhibitor of platelet activation), or prior fixation of the platelets. However, cathepsin G resulted in minimal decreases in the binding to fixed platelets of MoAbs TM60 (directed against the thrombin binding site on GPIb alpha) and WM23 (directed against the macroglycopeptide portion of GPIb alpha). In contrast to its proteolytic effect on GPIb alpha, the cathepsin G-induced decrease in platelet surface GPIX and the remnant of the GPIb-IX complex (defined by MoAbs FMC25 and AK1) was via a cytoskeletal-mediated redistribution, as determined by lack of change in the total platelet content of GPIX and the GPIb-IX complex; complete inhibition by cytochalasin B, prostaglandin I2, and prior fixation of platelets. Experiments with Serratia protease-treated and Bernard-Soulier platelets showed that neither platelet surface GPIb nor cathepsin G-induced proteolysis of GPIb were required for the cathepsin G-induced redistribution of the remnant of the GPIb-IX complex or the cathepsin G-induced increase in platelet surface P-selectin. In summary, neutrophil cathepsin G modulates the platelet surface expression of the GPIb-IX complex both by proteolysis of the vWF binding site on GPIb alpha and by a cytoskeletal-mediated redistribution of the remainder of the complex. Prior studies show that, although thrombospondin 1, antiserine proteases, and plasma are all inhibitors of cathepsin G, the effects of cathepsin G on platelets, including an increase in surface GPIIb-IIIa, occur during close contact between neutrophils and platelets in a protective microenvironment (eg, thrombosis and local inflammation).(ABSTRACT TRUNCATED AT 400 WORDS)

Human neutrophil cathepsin G is a potent platelet activator.

PURPOSE: Neutrophil activation has been implicated in the pathophysiologic condition of ischemia-reperfusion injury, the formation of arterial aneurysms, the progression of myocardial ischemia, and the initiation of deep venous thrombosis. Activated neutrophils release cathepsin G, a serine protease, from their granules, which may cause platelet activation that leads to intravascular thrombosis, tissue infarction, and systemic release of the thrombogenic products of platelet granules. This study used flow cytometry to quantify the extent of cathepsin G-induced platelet activation and degranulation through changes in the expression of platelet surface glycoproteins. METHODS: Increasing concentrations of human neutrophil-derived cathepsin G were incubated with washed platelets or whole blood from healthy human donors. The platelet surface expression of glycoproteins, including P-selectin, a platelet membrane glycoprotein only expressed after platelet alpha granule release, were determined by quantifying the platelet binding of a panel of fluorescently labeled monoclonal antibodies. Results were compared with the effect of a maximal dose of thrombin, the most potent known platelet activator. RESULTS: In a washed platelet system, cathepsin G increased platelet surface expression of P-selectin (an activation-dependent neutrophil binding site), the glycoprotein IIb/IIIa complex (fibrinogen receptor), and glycoprotein IV (thrombospondin receptor), and decreased surface expression of glycoprotein Ib (von Willebrand factor receptor) to an extent comparable to maximal thrombin. However, these effects were not observed in a whole blood system. Further experiments revealed that preexposure to plasma completely inhibited cathepsin G-induced washed platelet activation and degranulation. Prostacyclin treatment of washed platelets markedly inhibited cathepsin G-induced platelet activation. CONCLUSIONS: Cathepsin G is a very potent platelet agonist and degranulator, comparable to maximal thrombin, which alters platelet surface glycoprotein expression for enhanced neutrophil binding and effective platelet aggregation. This study helps to elucidate a possible pathway through which neutrophils may directly activate platelets, leading to intravascular thrombosis, irreversible ischemia, and tissue death in cardiovascular disease states. Patients with diseased endothelium that is deficient in prostacyclin production may be particularly prone to the detrimental effects of neutrophil-derived cathepsin G platelet activation.

Parathyroid localization prior to primary exploration.

The success of parathyroid surgery is based on accurate localization of normal and abnormal parathyroid glands, knowledge of the pathologic conditions, and meticulous dissection during removal of the abnormal glands. Although parathyroid localization is essential in cases requiring re-exploration, there is considerable controversy regarding the indications for localization studies prior to primary exploration, since the success rate for surgery exceeds 90% to 95%. However, in specific circumstances, including diagnostic problems, technical considerations, and high-risk patient factors, preoperative parathyroid localization assists the operating surgeon even during the primary cervical exploration. The purpose of this paper is to define these specific circumstances and discuss the appropriate studies.

The adaptive ability of transplanted rat small intestine.

This study was performed to determine the extent to which intestinal transplants undergo functional and morphologic compensation. Animals were studied after 25 days to document how rapidly the changes occurred and after 150 days to establish whether the effects were maintained long term. Lewis isografts and Lewis Brown Norway F1 allograft recipient rats had comparable degrees of morphologic (increased bowel diameter, crypt depth, and villus height) and functional (absorption of 3H-glucose, 14C-maltose, and cyclosporine) compensation. These changes were already present by day 25 and persisted until at least day 150. The results were independent of the loss of extrinsic innervation or the intramuscular administration of cyclosporine (5 mg/kg/day). These observations support the usefulness of segmental intestinal transplantation in the treatment of surgically induced short bowel syndrome.

Successful segmental intestinal transplantation in enterectomized pigs.

The aim of this study was to determine whether short-segment jejunal allografts maintained the viability and nutritional status of outbred recipient pigs treated with low-dose cyclosporine. The animals were subjected to total small bowel resection (from the ligament of Treitz to the ileocecal valve, approximately 15 m). Short-gut control animals (n = 8) who had no transplant died of malabsorption on day 62.5 +/- 4.1 (mean +/- SEM). Without cyclosporine immunosuppression, recipients (n = 5) of 3 m to 4 m jejunal allografts died of rejection on day 8.8 +/- 0.7. However enterectomized pigs (n = 11) who had segmental jejunal allograft transplants and were treated with cyclosporine (10 mg/kg/day) demonstrated significantly prolonged survival (to day 80.9 +/- 22.3; p less than 0.05). By 180 days after transplant, surviving animals increased their weight by almost 40%. In conclusion short-segment jejunal allografts significantly improved the mortality and morbidity rates from surgically created short bowel syndrome in pigs.

Effect of transplantation on tissue levels of substance P, vasoactive intestinal polypeptide, and serotonin in rat small intestine.

Denervation of the gut, resulting in altered bowel function, has been viewed as an impediment to the clinical success of small intestinal transplantation. This study examined the effect of complete extrinsic denervation of the jejunum and ileum on tissue levels of VIP, SP, and 5-HT in a rat model of small intestinal transplantation. Orthotopic total small bowel isograft transplants were performed in 18 Lewis inbred rats. Sham operations consisted of occluding the superior mesenteric artery of 18 Lewis rats for 10 minutes to provide comparable degrees of ischemia. Six rats from each group were sacrificed 1, 2, and 4 weeks following transplantation or sham operation. The jejunum and ileum were removed and extracted in acid for measurement of VIP, SP, and 5-HT by radioimmunoassay. There were no statistically significant differences in the jejunal or ileal content of VIP or 5-HT or the jejunal content of SP between the transplant and sham groups. An initial decrease in ileal SP content at 1 week following transplantation was no longer evident by the fourth week. We conclude that the extrinsic denervation of small intestinal transplantation has minimal effects on the intestinal content of VIP, SP, and 5-HT and should not significantly affect physiologic function controlled by these gastrointestinal hormones.

The role of serotonin in the canine secretory response to cholera toxin in vivo.

This study was initiated to evaluate the role of serotonin in cholera toxin-induced jejunal secretion of water and electrolytes. Chronic Thiry-Vella loops, constructed in six dogs, were perfused with an isosmotic neutral perfusate containing [14C]polyethylene glycol as the recovery marker. Fluxes of water, sodium, chloride and potassium were calculated and immunoreactive serotonin levels were measured in blood and effluent perfusates. Intraluminal application of 20 micrograms of cholera toxin induced secretion; fluxes of water (basal, 32.3 +/- 11.1; 6 hr, -541 +/- 35 microliter/min), sodium (basal, 9.0 +/- 2.8; 6 hr, -78.3 +/- 5.6 microEq/min), chloride (basal, 3.8 +/- 1.5; 6 hr, -65.7 +/- 4.0 muEq/min) and potassium (basal, 0.10 +/- 0.08; 6 hr, -2.80 +/- 0.18 muEq/min) were all significantly different from basal. Serum electrolytes remained normal, except that potassium fell from 4.9 +/- 0.5 to 3.9 +/- 0.2 mEq/l. Although circulating serotonin levels did not change from base line (180.9 +/- 29.3 ng/ml), effluent concentrations increased significantly from 68.2 +/- 4.6 to 81.1 +/- 5.0 ng/ml (at 3 hr) and jejunal outputs increased from 136.6 +/- 10.2 to 205.1 +/- 10.1 ng/min (at 6 hr). In a separate set of experiments, verapamil was infused i.v. (12.5 micrograms/kg/min) during the 4th hr in four dogs exposed to cholera toxin. The lower dose of toxin (5 micrograms) induced secretion which was unaffected by the calcium channel blocker. In another series of studies, ketanserin (a 5-HT2 receptor blocker) was infused i.v. at 33 micrograms/kg/min during the 4th hr in four additional dogs exposed to the lower dose of cholera toxin. This potent serotonin antagonist failed to inhibit cholera toxin-induced jejunal secretion.(ABSTRACT TRUNCATED AT 250 WORDS)

The effect of small intestinal transplantation on intraluminal levels of serotonin and substance P.

This study was performed to examine the effect of transplantation, and thus extrinsic denervation, of the small intestine on intraluminal release of serotonin and substance P. Heterotopic 40-cm-long proximal (jejunal) small intestinal isografts were performed in six 200- to 250-g adult male Lewis rats under general anesthesia. Bowel ends were exteriorized as ostomies. Six Lewis rats with neurovascularly intact 40-cm proximal small bowel Thiry-Vella loops exteriorized as ostomies served as the control animals. On the seventh postoperative day, the intestinal loops were perfused at 0.5 ml/min for three 10-min periods with normal saline followed by an equilibrium period and then for three 10-min periods with 20% dextrose. Perfusates were collected for each period and levels of serotonin and substance P were determined by radioimmunoassay. Intraluminal serotonin levels rose from 29 +/- 9 ng/ml during saline perfusion to 115 +/- 28 ng/ml during intestinal perfusion with 20% dextrose in the innervated loops and from 21 +/- 7 ng/ml to 94 +/- 26 ng/ml in the transplanted loops. While there was a statistically significant increase in mean intraluminal serotonin levels following perfusion with 20% dextrose in both the control and transplant groups, there was no difference in the intraluminal serotonin response between controls and transplant recipients. In contrast, 20% dextrose had no effect on luminal release of substance P in either group. These results indicate that extrinsic denervation of the small intestine has no effect on the intraluminal serotonin response to stimulation and suggest that serotonin and substance P are not released into the intestinal lumen by the same regulatory mechanisms.

Prostaglandins and surgical diseases: Part II.

Prostaglandins are important in the allograft response. Allograft antigenic stimulation causes release of prostaglandins both in vivo and in vitro. Macrophages and monocytes are the cells that produce the prostaglandins from arachidonic acid via the cyclooxygenase pathway. Prostaglandins exert immunosuppressive effects at several steps on both afferent and efferent phases in the cell-mediated immune system: reduction of Ia expression in antigen-presenting cells, inhibition of IL-1 and IL-2 production, and activation of suppressor cells. The immunosuppressive effects of blood transfusions and essential fatty acids appear to be mediated by PGE.

Segmental intestinal transplantation in rats with resected entire small bowel, ileocecal valve, and cecum.

Segmental intestinal transplantation was studied in a rat model of severe short gut syndrome across major histoincompatibility barriers. Lewis (RT1l) recipient rats whose entire small bowel (approximately 80 cm), ileocecal valve, and cecum were resected and who had no transplant, uniformly died of malabsorption on Day 9.8 +/- 0.4 (n = 11). Without cyclosporine, allograft recipients (n = 2), died of rejection on Days 8 and 10. Recipient animals with 20-cm jejunum and 40-cm jejunal transplants from Buffalo (RT1b) rats and treated daily with cyclosporine (5 mg/kg/day) intramuscularly (Days 0-28) and vitamin B12 (every other week) enjoyed significantly prolonged survival to Day 58.2 +/- 13.7, P less than 0.003, n = 10, and Day 129.1 +/- 7.4, P less than 0.001, n = 10, respectively. While 7 of 10 rats in the 20-cm jejunal transplant group died of malabsorption between Days 14 and 58, none of 10 animals in the 40-cm jejunal transplant group died of this complication. Four of 10 rats in the 40-cm jejunal transplant group thrived at 150 days after the operation, at which time they were sacrificed. Morphologically, the grafts demonstrated hypertrophic changes. The data from this study suggest that intestinal allografts have pronounced intestinal adaptative characteristics. Using segmental jejunal grafts, intestinal transplantation is an effective surgical modality for the short gut syndrome in the rat.

Mouse brain contains a high molecular weight nonfunctional protein with antigenic homology to dihydrofolate reductase.

The cytosol of brain tissue from mature BDF1 mice contains very little dihydrofolate reductase activity but it does contain a high molecular weight nonfunctional protein which cross-reacts in a radioimmunoassay for the active enzyme. Liver cytosol contains less of this high molecular weight cross-reacting protein and more of the functional dihydrofolate reductase. The cytosol from kidney contains very little of the high molecular weight cross-reacting protein, 95% of the immunoreactive proteins being the functional form of dihydrofolate reductase. The modification of dihydrofolate reductase into a nonfunctional form may be an intrinsic property of some cells and this finding could explain the variability in measuring the activity of this enzyme in brain tissue of mature animals.

Immunologic heterogeneity of dihydrofolate reductase from methotrexate sensitive and resistant L1210 leukemia cells.

Dihydrofolate reductase from L1210 leukemia cells which are sensitive and resistant to methotrexate has the same physical and kinetic properties and immunoreactivity with a guinea pig antiserum raised to the enzyme purified from the methotrexate resistant strain. However, a chicken antiserum to dihydrofolate reductase from methotrexate sensitive L1210 cells has greater affinity for the homologous enzyme than for the enzyme from the MTX resistant cells indicating that there is some antigenic difference in these molecules.