Intestinal antilectin immunoglobulin A antibody response and immunity to Entamoeba dispar infection following cure of amebic liver abscess

We followed 93 subjects with amebic liver abscess (ALA) and 963 close associate controls at 3-month intervals for 36 months to characterize intestinal and humoral antibody responses to the amebic galactose-inhibitable lectin and to determine whether immunity developed to Entamoeba histolytica or Entamoeba dispar infection following cure of ALA. We found that ALA subjects had a higher prevalence and level of intestinal antilectin immunoglobulin A (IgA) and serum anti-LC3 (cysteine-rich recombinant lectin protein) IgA and IgG antibodies, P < 0.01 and P < 0.05, respectively, compared to controls. The intestinal antilectin IgA antibody response was sustained over a longer time period in ALA subjects (71.8% remained positive at 18 months and 52.6% at 36 months, P < 0.001 compared to 17.6% and 10.3% of controls, respectively). ALA subjects were highly immune to E. dispar infection throughout the study (0% infected at 6 and 36 months, compared to 6.5% and 4.9% of control subjects, respectively, P < 0.05). Upon entry into the study, 6.3% of ALA subjects were infected with E. histolytica; the incidence of new E. histolytica infections in controls (as determined by culture) was too low (1.4%) to determine whether ALA subjects exhibited immunity to new infections. We found that stool cultures every 3 months markedly underestimated the occurrence of new E. histolytica infections, as 15.3% of controls seroconverted after 12 months of follow-up. Unfortunately, under the field conditions present in Durban, South Africa, enzyme-linked immunosorbent assay for detection of lectin antigen in stool yielded unreliable results. In summary, subjects cured of ALA exhibited sustained mucosal IgA antibody responses to the amebic galactose-inhibitable lectin and a high level of immunity to E. dispar infection. Determination of immunity to E. histolytica following cure of ALA will require the use of more sensitive and reliable diagnostic methods.     

Aggressive preoperative use of intraaortic balloon pump in elderly patients undergoing coronary artery bypass grafting

BACKGROUND: The use of the intraaortic balloon pump (IABP) in patients undergoing coronary artery bypass grafting has been traditionally associated with a high complication rate and adverse outcomes. However, recent reports show that many of these catastrophic outcomes can be avoided by preoperatively placing the IABP in high-risk patients. To further validate these reports, we defined a set of liberal criteria for preoperative IABP insertion and applied them to a series of elderly patients (70 years or older) undergoing isolated coronary artery bypass grafting. METHODS: Two hundred six consecutive patients who underwent isolated coronary artery bypass grafting with cardiopulmonary bypass were retrospectively reviewed. A rapid recovery protocol emphasizing reduced cardiopulmonary bypass time, an anesthetic protocol for early extubation, perioperative administration of corticosteroids and thyroid hormone, and aggressive diuresis was applied to all patients. Patients who required an urgent operation because of failed percutaneous transluminal coronary angioplasty, a critical left main stenosis (70% or greater), pronounced left ventricular dysfunction (left ventricular ejection fraction 40% or less), or unstable angina refractory to medical therapy or who required an emergency reoperation received preoperative IABP support. RESULTS: The 30-day mortality rate for the entire group was 4.4%. There were 97 patients (47%) who received a preoperative IABP (group II) in comparison with 109 patients (53%) who did not fulfill the preoperative insertion criteria (group I). Patients in group II had a lower left ventricular ejection fraction (mean, 46% versus 59%, p<0.001) and a higher incidence of congestive heart failure (35% versus 17%, p<0.01) and acute myocardial infarction (37% versus 17%, p<0.01) than patients in group I. The average postoperative hospital length of stay for patients in group II was slightly longer than for those in group I (9.0+/-10.5 versus 6.0+/-3.7 days, p<0.01). However, there were no statistically significant differences in complication or mortality rates between the two groups. Only 2 patients (2.2%) had complications related to IABP insertion. Lower extremity ischemia occurred in both patients, and both were treated successfully with thromboembolectomy. CONCLUSIONS: Liberal preoperative insertion of the IABP can be performed safely in high-risk elderly patients undergoing coronary artery bypass grafting, with results comparable to those in lower risk patients.     

Reduced postoperative atrial fibrillation using multidrug prophylaxis

BACKGROUND: Atrial fibrillation (AFIB) is the most common complication following coronary artery bypass grafting (CABG). Despite three decades of recognition, efforts to reduce the high incidence reported (15%-30%) have been largely unsuccessful. Reasons for postoperative AFIB are likely multifactorial. As a result, we defined a multidrug prophylaxis based on agents known to be individually effective. This method was applied prospectively to a series of consecutive CABG patients with the goal of reducing the incidence of new-onset postoperative AFIB. METHODS: Isolated CABG with cardiopulmonary bypass was performed on 517 consecutive patients. A rapid recovery protocol emphasizing AFIB multidrug prophylaxis was applied to all patients. All patients received 10 microg of triiodothyronine intraoperatively when the clamp on the aorta was released. Immediately following CABG, parenteral magnesium was administered to assure a serum magnesium > 2.2 mEq/dL. Thyroxine 200 microg was administered parenterally to all patients on postoperative days 1 and 2. Metoprolol (25 mg to 100 mg/day) was begun on all patients after extubation provided: heart rate > 85 beats/min and systolic blood pressure > 130 mmHg. Parenteral procainamide (12 mg/kg) loading dose, followed by a maintenance dose (2 mg/min), was used for patients who developed premature atrial contractions (> 1/min), nonsustained supraventricular tachycardia, or any episodes of atrial fibrillation. All patients also received postoperative digitalization, steroids, and aggressive diuresis. RESULTS: The 30-day operative mortality was 3.7%. The overall incidence of new-onset postoperative AFIB was 10.3% (53 patients). There was no major difference in operative mortality (7.5% vs 3.2%, p = 0.23), Parsonnet risk score, or intraoperative variables between AFIB patients and the non-AFIB patients. Patients presenting with a preoperative acute myocardial infarction (p < 0.05), left main stenosis > or = 70% (p < 0.01), and advanced age > or = 70 years (p < 0.05) were at increased risk of developing AFIB. The length of stay for patients with AFIB was 9.9 +/- 9.6 days versus 5.9 +/- 5.2 days (p < 0.001). CONCLUSION: Application of a multidrug prophylaxis can reduce postoperative AFIB to a low incidence. Identification of associated clinical features can help predict patients at risk for postoperative AFIB. Additional strategies to target postoperative AFIB may include treatment at the earliest recognition of atrial rhythm instability.     

p53 mutations in human aggressive and nonaggressive basal and squamous cell carcinomas.

PURPOSE: The purpose is to investigate whether aggressive basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) differ from nonaggressive BCC and SCC with respect to the p53 mutation spectrum and whether specific mutations can serve as prognostic indicators of tumor aggressiveness. EXPERIMENTAL DESIGN: We analyzed 342 tissues from patients with aggressive and nonaggressive BCCs and SCCs for p53 mutations by single-strand conformation polymorphism and nucleotide sequencing. RESULTS: p53 mutations were detected in 33 of 50 aggressive BCCs (66%), 37 of 98 nonaggressive BCCs (38%), 28 of 80 aggressive SCCs (35%), 28 of 56 nonaggressive SCCs (50%), and 3 of 29 samples of sun-exposed skin (10%). About 71% of the p53 mutations detected in aggressive and nonaggressive BCCs and SCCs were UV signature mutations. The frequency of CC to TT mutations in aggressive (36%) and nonaggressive SCCs (39%) was 2-fold higher than in aggressive (18%) and nonaggressive (14%) BCCs. In contrast, aggressive BCCs had a higher frequency (24%) of transversions than nonaggressive BCCs (8%) and aggressive (14%) and nonaggressive (11%) SCCs did. CONCLUSIONS: Our results indicate that UV radiation is responsible for the induction of p53 mutations and perhaps for the initiation of both aggressive and nonaggressive BCCs and SCCs. Although some differences in p53 mutation frequency, types of mutation, and hot spots were seen between aggressive and nonaggressive BCCs and SCCs, these factors do not constitute as clear-cut diagnostic or prognostic indicators of tumor aggressiveness. Tumor aggressiveness may be attributable to other genetic changes or events that occur during tumor progression.     

Intralenticular changes in eyes with mature senile cataract on modified posterior segment optical coherence tomography

Purpose:To study the morphological changes within mature senile cataracts on modified posterior segment optical coherence tomography (OCT).Methods:A cross-sectional observational study recruiting patients of mature cataracts admitted for elective cataract surgery in tertiary eye care. A modified OCT imaging of the lens was done and lenticular findings were noted by a single observer. Corresponding slit-lamp biomicroscopic findings and intraoperative experiences were also noted by a second observer and respective surgeons.Results:Forty-four eyes of 44 patients were included. The mean age of patients was 65 ± 5.7 years. The intralenticular findings were uniform in groups of eyes, and they were characterized into three stages. First was a stage of early lamellar separation where small intralenticular clefts were noted superficially. Second was the stage of established lamellar separation where crescentic fluid clefts appeared interspersed between the lens fibers, and the depth increased as a function of severity. Both these stages did not show any distinct slit-lamp or intraoperative findings. A third stage of liquefaction identified as extensive lamellar separation with subcapsular fluid pockets. This was also reflected in slit-lamp biomicroscopy, showing the hydrated cortex with intraoperative challenges. Two cases showed peculiar changes, one of a hyperreflective subcapsular sheath and another of superficial nuclear lamellar separation.Conclusion:Mature cataracts may also show graded progression, which could be delineated on lenticular OCT. This could be of immense help in pre-operative planning and optimal management of these high-risk cases.     

Glyburide metabolism by placentas of healthy and gestational diabetics

The aim of this investigation was to determine the metabolism of glyburide (GL) by microsomes prepared from placentas obtained from uncomplicated pregnancies (UP), women with gestational diabetics (GD) on a diabetic diet, and those on a diet and GL. Term placentas were obtained from UP and GD. Crude microsomal fractions were prepared by differential centrifugation and stored at -80 degrees C. The activity of the microsomes in metabolizing glyburide to the trans-4-hydroxycyclohexyl glyburide (THCGL) and cis-3-hydroxycyclohexyl glyburide (CHCGL) was determined and quantified using high-performance liquid chromatography-mass spectrometer (HPLC-MS). The activity of the placental microsomes varied widely between individual placentas in each group. The median values (pmol.mg (-1) P.min (-1)) for the rates of THCGL formation were 0.34, 0.3, and 0.23 for placentas of UP, GD on diet, and GD on GL and a diet, respectively. The median values for CHCGL formation were 0.13 for UP, 0.11 for GD on a diet, and 0.10 (pmol.mg (-1) P.min (-1)) for GD on GL and a diet. A pool of individual microsomal fractions from each group was prepared and its activity revealed the following: greater formation of THCGL in the UP (0.36 +/- 0.10) than GD (0.22 +/- 0.03) ( P = 0.058 for GD on a diet, 0.04 for GD on GL). There was greater formation of CHCGL in UP (0.26 +/- 0.04) than GD (0.12 +/- 0.003) ( P < 0.006). There was no difference in GD on a diet and GD on GL plus diet. We concluded that the apparent differences in the formation of metabolites may be statistically significant, but it is unlikely to be of physiological importance, given the sample size and other experimental factors. Therefore, a more comprehensive investigation is underway.     

Cancer vaccine potency: is there a dose/response relationship for patient-specific vaccines and clinical outcomes?

PURPOSE: Determination of potency is a challenging problem for patient-specific products derived from autologous cells. For several years, we have been investigating the safety and therapeutic potential of patient- specific vaccines derived from short-term autologous cell lines. We investigated whether clinical potency of these vaccines could be determined by retrospective correlation between the numbers of cells injected (quantity of tumor antigens) and clinical outcome. METHODS: The averages and standard deviations of irradiated tumor cells were determined for those patients who received the first 3 weekly injections, and for the subset that had a recording of results from tumor delayed-type hypersensitivity testing (DTH). Correlations were made between the numbers of cells injected and DTH conversion and survival. RESULTS: One hundred fifty-six patients received the vaccine product, 136 of whom received the first 3 weekly vaccinations. The most common reason for not receiving 3 injections or having a repeat tumor DTH test was rapidly progressive disease. Ninety-nine patients had cell count data for all 3 injections; 73 had a tumor DTH test at baseline and at week 4. The average number of cells injected over 3 weeks, in millions per patient, by quartile were: 6.0 +/- 1.8, 10.2 +/- 1.4, 15.1 +/- 1.4, and 31.2 +/- 9.8, with respective median survivals of 24.7, 25.5, 24.0, and 21.0 months, with the respective number of DTH conversions being 4, 8, 4, and 6. There were no statistical differences in survival or in the number of patients who had a positive tumor DTH test at week 4. CONCLUSIONS: We were unable to define potency--based on a relationship between the number of tumor cells injected as part of vaccination and survival or the reactivity to pure autologous tumor--in a tumor DTH test, over the range of 2-30 million injected cells over 3 weeks.