Initial results of QuantiFERON-TB Gold testing in patients with uveitis.

PURPOSE: To describe the use of the second-generation QuantiFERON-TB Gold (QFT-G) test in a series of patients in an ophthalmic practice. METHODS: The charts of all patients who had QFT-G tests ordered by Mayo Clinic ophthalmologists in the past 3 years were reviewed. RESULTS: A total of 27 QFT-G tests were ordered. Thirteen (48%) tests were negative, six (22%) were indeterminate, two (7%) tests were re-ordered after a lab accident or an improper cancellation, four (15%) were positive and represented infection, and two (7%) were positive but negative when re-tested. Of the four truly positive cases, three were treated for tuberculosis (TB): one had tuberculous iritis, one had retinal vasculitis and haemorrhage, and one had asymptomatic TB but was on immunosuppressive therapy. The fourth patient had previously been treated for latent infection. CONCLUSIONS: In a series of selected patients with uveitis, the QFT-G test was able to detect TB infection in 15% of the patients, though it does not differentiate between active and latent TB infection. QFT-G should be considered in place of purified protein derivative testing in those with uveitis that have had prior BCG vaccination and in immunocompromised patients. Patients with a positive QFT-G, but who have little risk for TB infection and a negative systemic work-up, should be re-tested.

Quantitative analysis of allele imbalance supports atypical ductal hyperplasia lesions as direct breast cancer precursors.

It remains unclear whether hyperplastic breast lesions, especially with atypia, are cancer precursors or markers of increased cancer risk. Quantified comparisons of genomic alterations in coexisting lesions could address this question. Therefore, we examined allele imbalance (AI), also known as loss of heterozygosity (LOH), at 20 microsatellite markers on nine chromosome arms, in DNA from 106 samples microdissected from 17 randomly selected cancer-containing breast specimens: 13 simple (DH) and 45 atypical ductal hyperplastic (ADH) lesions, 30 in situ (DCIS) and 18 invasive ductal carcinomas (IDC). Data were analysed using regression models and generalized estimating equations. We found that AI increased as histology became more aberrant and varied with histology across the chromosome arms (p<0.0001). ADH had more AIs on 1q (p=0.03) and 16q (p=0.02) and fewer AIs on 17p (p=0.06) and 17q (p<0.0001) than on other arms. In cancers, AIs remained high on 1q and 16q, and became frequent on 17p and 17q. Concordance between AIs in ADHs and cancers exceeded the 50% expected if the lesions were separate clones in 16/20 (80%) ADHs (p=0.05), from 9/11 (82%) cases (p=0.03), and involved 41/51 (80%) evaluable markers (p=0.05). The occurrence of any AI in ADH predicted greater AI (p=0.009) and possibly lower grade (p=0.05) in coexisting cancers. Nevertheless, ADHs were not genetically identical to cancers or to each other. We found AIs discordant between ADHs and cancers (always on 1q and 16q), AIs unique to ADH (usually on 11q) and some genetic heterogeneity among coexisting ADHs. We conclude that ADH lesions are genetically advanced, with frequent alterations on 1q and 16q, and are often direct cancer precursors. Their global genetic characteristics predict features of cancers in the same breast. Nevertheless, the genetic heterogeneity detected suggests that hyperplasias and cancers may arise on a field at generalized increased cancer risk.

Is antibiotic prophylaxis ever necessary before transoesophageal echocardiography?

Evidence strongly suggests that antibiotic prophylaxis should not be used routinely for transoesophageal echocardiography for any indication.

Cardiovascular changes with the laryngeal mask airway in cardiac anaesthesia.

BACKGROUND: The laryngeal mask airway (LMA) causes fewer haemodynamic changes, particularly in mean arterial pressure (MAP) and heart rate (HR), than tracheal intubation using either laryngoscopy or the intubating LMA. There are no data for patients with coronary artery disease. METHOD: We studied 27 patients having coronary artery bypass grafting, prospectively randomized to be managed with either the LMA or tracheal intubation using either laryngoscopy or the ILMA. We used invasive monitoring to compare the haemodynamic effects in each group during induction and emergence from anaesthesia. RESULTS: Both methods of intubation caused an increase in MAP compared with the LMA (P<0.05). Mixed venous oxygen saturation increased in the intubated patients but not with the LMA (P<0.05). HR did not change at induction in the LMA group. Changes at extubation were similar in all groups but cardiac index was lower in the LMA group (P<0.05). CONCLUSION: The LMA allows airway management without hypertension and tachycardia and should be considered when anaesthetizing patients with coronary disease.

Angiotensin in cardiac surgery: efficacy in patients on angiotensin converting enzyme inhibitors.

BACKGROUND: Patients presenting for cardiac surgery are often treated with angiotensin converting enzyme inhibitors (ACEIs), either for heart failure or hypertension. Control of systemic vascular resistance (SVR) during surgery can be difficult in such patients. Angiotensin II has been available as an unlicensed vasoconstrictor, but there is concern about renal damage and its use. AIM: This study compared a standard vasoconstrictor with angiotensin II and examined the effect on renal function after cardiac surgery. METHOD: Twenty consecutive, consenting patients scheduled for cardiac surgery that had been taking ACEIs for at least 6 months, were randomly assigned to receive either phenylephrine or angiotensin II for the control of SVR during and for 24 h after cardiac surgery. A pulmonary artery catheter was used to guide therapy. Creatinine clearance was measured before, 24 and 48 h after surgery. RESULTS: Low SVR and blood pressure requiring intervention was seen in all patients, particularly during cardiopulmonary bypass. One patient in the control group failed to respond to P, but responded normally to angiotensin II. Neither drug caused renal impairment. CONCLUSION: Angiotensin II is a safe alternative to phenylephrine in patients on ACEIs and should be considered in patients who fail to respond to conventional vasoconstrictors.

Sevoflurane versus isoflurane in patients undergoing valvular cardiac surgery.

OBJECTIVE: To determine if sevoflurane provides hemodynamic and recovery characteristics comparable to isoflurane in patients undergoing surgery for valvular heart disease. DESIGN: A prospective crossover, dose-response study using sevoflurane and isoflurane before the start of surgery, followed by randomization to sevoflurane or isoflurane for surgery with blinded assessment for recovery. SETTING: Tertiary referral cardiac center. PARTICIPANTS: Twenty-seven patients scheduled for elective valve surgery. Surgery consisted of 18 aortic valve and 12 mitral valve replacements, of which 3 patients had 2 valves replaced; 1, tricuspid repair; and 8, coronary artery bypass procedures. INTERVENTIONS: A pulmonary artery catheter was used to obtain a complete hemodynamic profile during the dose-response study before surgery. Transesophageal echocardiography was used to confirm the diagnosis, and electrocardiography monitored for myocardial ischemia. MEASUREMENTS AND MAIN RESULTS: Both agents showed similar hemodynamic effects at 0.5 and 1.0 minimum alveolar concentration. There was a tendency to decreases in heart rate, blood pressure, and cardiac output, whereas filling pressures remained stable with each volatile agent. Electrocardiography did not detect ischemic changes. Times to eye opening and extubation were similar with both agents, with sevoflurane tending to be earlier than isoflurane. CONCLUSION: Sevoflurane showed a tendency to lower heart rates and cardiac index compared with isoflurane. Eye opening and extubation were slightly earlier. These findings were not statistically significant, however.

Transpupillary thermotherapy as primary treatment for small choroidal melanomas.

OBJECTIVE: To report the short-term follow-up results of eyes containing small choroidal melanomas that were treated with transpupillary thermotherapy. METHODS: Twenty eyes with suspected small choroidal melanomas were treated with transpupillary thermotherapy using infrared light delivered from the diode laser. RESULTS: The age of the patients ranged from 26 to 82 years. In 14 patients, there was documented growth of the melanoma before transpupillary thermotherapy. The tumor thickness ranged from less than 1.0 to 3.2 mm. Seven tumors were treated more than once. Follow-up ranged from 6 months to more than 3 years. Following treatment, the tumor thickness decreased in all cases, usually within 2 months. Progressive atrophy of tumor mass and loss of pigmentation within the tumor continued beyond 1 year of follow-up in some eyes. Complications included field defects, vascular changes, and macular abnormalities. CONCLUSIONS: Transpupillary thermotherapy of small choroidal melanomas is usually followed by early tumor shrinkage but is complicated by dense scotomas, nerve fiber bundle defects, and, occasionally, macular abnormalities. The short-term follow-up results suggest that transpupillary thermotherapy may arrest the growth of selected small melanomas.

Transpupillary thermotherapy as primary treatment for small choroidal melanomas.

PURPOSE: To report short-term follow-up of eyes containing small choroidal melanomas that were treated with transpupillary thermotherapy (TTT). METHODS: Twenty eyes with suspected small choroidal melanomas were treated with TTT using infrared light delivered from the diode laser. RESULTS: The age of patients ranged from 26 to 82 years. In 14, there was documented growth of the melanoma prior to TTT. Tumor thicknesses ranged from less than 1 to 3.2 mm. Seven tumors were treated more than once. Follow-up ranged from 6 months to more than 3 years. Following treatment, tumor thicknesses decreased in all cases, usually within 2 months. Progressive atrophy of tumor mass and loss of pigmentation within the tumor continued beyond 1 year of follow-up in some eyes. Complications included field defects, vascular changes, and macular abnormalities. CONCLUSIONS: Transpupillary thermotherapy of small choroidal melanomas is usually followed by early tumor shrinkage but is complicated by dense scotomas, nerve fiber bundle defects, and occasionally macular abnormalities. Short-term follow-up suggests that TTT may arrest growth of selected small melanomas.

Sevoflurane versus isoflurane in patients undergoing coronary artery bypass grafting: a hemodynamic and recovery study.

OBJECTIVE: To determine if sevoflurane provides comparable hemodynamics and recovery characteristics to isoflurane in cardiac anesthesia. DESIGN: A prospective, crossover, dose-response study using sevoflurane and isoflurane before the start of surgery, followed by randomization to sevoflurane or isoflurane for surgery with blinded assessment for recovery. SETTING: Tertiary referral cardiac clinic and intensive care. PARTICIPANTS: Sixteen elective patients scheduled for coronary artery bypass grafting. INTERVENTIONS: A pulmonary artery catheter was used to obtain a complete hemodynamic profile during the dose response study before surgery. Transesophageal echocardiography (TEE) and an electrocardiogram (ECG) were used to assess myocardial ischemia. MEASUREMENTS AND MAIN RESULTS: Both agents showed similar hemodynamic effects at 0.5 and 1.0 minimum alveolar concentration (MAC). There was a tendency toward decreases in heart rate, blood pressure, vascular resistance, and cardiac output with a rise in central pressures. Ischemic changes were not detected by TEE or ECG. Times to eye opening and extubation were similar for both agents. CONCLUSION: At MAC equivalent doses, sevoflurane showed comparable hemodynamics to isoflurane. Both agents when used as the primary anesthetic showed similar recovery characteristics, with no statistical difference between them at any stage of the study.

B cells directly tolerize CD8(+) T cells.

This report investigates the response of CD8(+) T cells to antigens presented by B cells. When C57BL/6 mice were injected with syngeneic B cells coated with the Kb-restricted ovalbumin (OVA) determinant OVA257-264, OVA-specific cytotoxic T lymphocyte (CTL) tolerance was observed. To investigate the mechanism of tolerance induction, in vitro-activated CD8(+) T cells from the Kb-restricted, OVA-specific T cell receptor transgenic line OT-I (OT-I cells) were cultured for 15 h with antigen-bearing B cells, and their survival was determined. Antigen recognition led to the killing of the B cells and, surprisingly, to the death of a large proportion of the OT-I CTLs. T cell death involved Fas (CD95), since OT-I cells deficient in CD95 molecules showed preferential survival after recognition of antigen on B cells. To investigate the tolerance mechanism in vivo, naive OT-I T cells were adoptively transferred into normal mice, and these mice were coinjected with antigen-bearing B cells. In this case, OT-I cells proliferated transiently and were then lost from the secondary lymphoid compartment. These data provide the first demonstration that B cells can directly tolerize CD8(+) T cells, and suggest that this occurs via CD95-mediated, activation-induced deletion.

Help for cytotoxic-T-cell responses is mediated by CD40 signalling.

Cytotoxic T lymphocytes (CTLs) which carry the CD8 antigen recognize antigens that are presented on target cells by the class I major histocompatibility complex. CTLs are responsible for the killing of antigen-bearing target cells, such as virus-infected cells. Although CTL effectors can act alone when killing target cells, their differentiation from naive CD8-positive T cells is often dependent on 'help' from CD4-positive helper T (TH) cells. Furthermore, for effective CTL priming, this help must be provided in a cognate manner, such that both the TH cell and the CTL recognize antigen on the same antigen-presenting cell. One explanation for this requirement is that TH cells are needed to convert the antigen-presenting cell into a cell that is fully competent to prime CTL. Here we show that signalling through CD40 on the antigen-presenting cells can replace the requirement for TH cells, indicating that T-cell 'help', at least for generation of CTLs by cross-priming, is mediated by signalling through CD40 on the antigen-presenting cell.

Peptide-induced deletion of CD8 T cells in vivo occurs via apoptosis in situ.

The ultimate fate of T cells undergoing antigen-induced cell death in vivo remains controversial. Whereas apoptosis of CD4+ T cells driven by superantigen is readily detectable in lymphoid organs, CD8+ T cells have been reported to disappear from the lymphoid organs and accumulate in the liver where they undergo apoptosis. Using transgenic mice that produce large numbers of ovalbumin-specific CD8+ T cells (OT-I cells), we were able to investigate the events that follow soluble peptide administration in an independent CD8+ T cell system. Here we show that the OT-I cells undergo proliferation and apoptosis in situ in lymphoid organs in response to antigenic stimulation with no evidence for liver involvement. This is similar to the course of events found for CD4+ T cell activation and counters the view that the liver is a general site for CD8+ T cell clearance following antigen-specific activation.

Induction of a CD8+ cytotoxic T lymphocyte response by cross-priming requires cognate CD4+ T cell help.

Class I-restricted presentation is usually associated with cytoplasmic degradation of cellular proteins and is often considered inaccessible to exogenous antigens. Nonetheless, certain exogenous elements can gain entry into this so-called endogenous pathway by a mechanism termed cross-presentation. This is known to be effective for class I-restricted cytotoxic T lymphocyte (CTL) cross-priming directed against a variety of exogenous tumor, viral, and minor transplantation antigens. The related effect of cross-tolerance can also effectively eliminate responses to selected self components. In both cases, this presentation appears to require the active involvement of a bone marrow-derived antigen presenting cell (APC). Here, we show that CTL induction by cross-priming with cell-associated ovalbumin requires the active involvement of CD4+ helper T cells. Importantly, this CD4+ population is only effective when both the helper and CTL determinants are recognized on the same APC. Moreover, we would argue that the cognitive nature of this event suggests that the CD4+ T cell actively modifies the APC, converting it into an effective stimulator for the successful priming of the CTL precursor.

Surgical management of posteriorly dislocated silicone plate haptic intraocular lenses.

PURPOSE: To report a large series of delayed posterior dislocation of silicone plate haptic intraocular lenses after Nd:YAG laser capsulotomy and discuss the surgical management of this complication. METHODS: We reviewed the records of 11 consecutive patients (11 eyes) with delayed onset of posterior dislocation of a plate haptic silicone intraocular lens. The cause of the posterior capsular defect, time to dislocation, surgical management techniques, complications, and visual outcome were recorded. RESULTS: In eight of the 11 eyes, the silicone plate haptic intraocular lens dislocated an average of 1.8 months (range, 0 to 6.5 months) after Nd:YAG posterior capsulotomy. The other three eyes had surgical complications at the time of cataract extraction that compromised posterior capsular or zonular integrity and led to silicone plate haptic intraocular lens dislocation from 9 weeks to 6 months (mean, 3.6 months) postoperatively. Surgical management consisted of pars plana vitrectomy with intraocular lens repositioning (six eyes) or exchange (five eyes). The average follow-up period after intraocular lens repositioning or exchange was 6.5 months (range, 1 to 14 months). Best-corrected visual acuity at the last follow-up examination measured 20/40 or better in all but one eye that had preexisting macular disease. CONCLUSIONS: Cataract surgeons and patients should be aware of the potential for plate haptic silicone intraocular lenses to undergo delayed posterior dislocation through capsular defects. This complication can be managed effectively with vitrectomy and either repositioning or exchange of the implant. Postoperative visual acuity is generally excellent, and complications are minimal.

Reversible loss of light perception after vitreoretinal surgery.

PURPOSE: We studied reversible loss of light perception after vitreoretinal surgery to show that functional vision can return in some patients. METHODS: We reviewed the medical records of seven patients who had postoperative reversible loss of light perception in the eye that underwent vitreoretinal surgery. Differences in the postoperative courses and interventions were studied. RESULTS: Five of the seven patients had diabetes mellitus but none had hypertension. The indications for vitreoretinal surgery were severe proliferative diabetic retinopathy in five patients and retinal detachment with advanced proliferative vitreoretinopathy in two patients. Seven patients had reversible loss of light perception within the first three postoperative days. Six of the seven patients had an intraocular pressure greater than 26 mm Hg at the time the eye had no light perception. Decreasing the intraocular pressure was associated with return of light perception in five of seven patients. Return of useful vision was gradual. Four of seven patients had a visual acuity of 20/400 or better one month after surgery, and all seven had a visual acuity of 20/400 or better three months after surgery. Visual acuity in four eyes improved further to 20/70 or better at six months or more after surgery. CONCLUSION: Reversible loss of light perception after vitreoretinal surgery does occur in some patients. Monitoring vision and intraocular pressure is important because prompt treatment may assist in the recovery of functional vision.

Specificity and properties of propofol as an antioxidant free radical scavenger.

The active component of the anesthetic propofol (2,6-diisopropylphenol), which structurally resembles butylated hydroxy-toluene (BHT), a known free radical scavenger, was examined and compared to BHT with regard to its dose-dependent radical scavenging activity. Studies on the ameliorating effect of propofol in inhibiting radical production revealed that it preferentially scavenges organoradical species. In aqueous suspension it is more efficient than BHT as a free radical scavenger of riboflavin radicals and in blocking formation of malondialdehyde degradation products generated from lipid hydroperoxides of arachidonic acid. Neither propofol nor BHT showed any radical scavenging activities at concentration ranges less than 10 micrograms/ml. Propofol quenched radicals generated by photoillumination of riboflavin by 50% at 30 micrograms/ml. Under the same conditions BHT still showed no radical scavenging activity. At 50 micrograms/ml propofol the formation of malondialdehyde degradation products of arachidonic acid formed by illuminating arachidonic acid in test mixtures containing riboflavin was decreased by 38% compared to a decrease of only 24% with BHT substituted in place of propofol. The concentration of propofol required to ameliorate free radicals is approximately an order of magnitude higher than therapeutic doses of propofol used in anesthesia, suggesting that its scavenging activity during anesthesia is likely very limited.

Perioperative autologous blood transfusion in elective total hip prosthesis operations.

The aim of this study was to determine if acute perioperative normovolaemic haemodilution with retransfusion of the autologous blood at the end of operation would reduce or eliminate the need for homologous (banked) blood. Forty patients scheduled for total hip prosthesis replacement (THPR) were randomly divided into two groups: Group A, 20 patients from whom 900 ml of blood was taken 20 min preoperatively, the volume being replaced with 1000 ml of gelatin solution (Haemaccel). Group B, 20 patients who were undergoing the same operation but from whom no blood was taken. Both groups were allowed a fall in haematocrit (Hct) to 0.25 before transfusion was started. A standard formula to calculate allowable blood loss plus intraoperative Hct measurements were used to achieve the haemodilution. There was no significant difference in blood loss between the two groups. Transfusion requirement was the same in the two groups. In this study, autotransfusion by the withdrawal of 900 ml of blood is inadequate to reduce the transfusion requirement further than that which can be achieved by haemodilution alone.

Retinal folds in Terson syndrome.

BACKGROUND: Perimacular retinal folds have been reported in the shaken baby syndrome, but have not been described in adults with Terson syndrome. METHODS: The authors present two patients with perimacular retinal folds in adults with Terson syndrome. In one patient, electron microscopy was used to examine the membrane spanning the fold. RESULTS: The membrane spanning the perimacular fold was found to be internal limiting membrane. The pathogenesis of these perimacular folds found in adults sustaining direct head trauma is probably different from that previously described for folds seen in infant eyes with shaken baby syndrome. CONCLUSION: Retinal folds occurring in Terson syndrome are clinically similar to those seen in the shaken baby syndrome.