Sex and androgenic steroid receptor expression in hepatic adenomas

Sex hormones and anabolic-androgenic steroids are implicated in the development and progression of hepatic adenomas (HA). We studied the expression of their receptors in HA and adjacent liver. Archival tissue sections of 27 HA (16 resections, four needle biopsies, seven aspirations) from 18 patients, and the adjacent liver, were immunostained with monoclonal antibody to estrogen receptor (ER, 1/80) (Dako, Carpinteria, CA), progesterone receptor (PR, 1/50) (BioGenex, San Ramon, CA), and androgen receptor (AR, 1/80) (BioGenex). An avidin-biotin complex technique was used with microwave antigen retrieval. Nuclear expression was assessed as 1+ to 3+ intensity, with semiquantitation of the percentage of nuclei immunopositive. Five percent or more nuclei immunopositive was regarded as positive. The 18 patients included 16 females of 34 years mean age (range, 16 to 49) with an available history of oral contraceptives in five; the two men were 24 and 30 years, with no history of androgenic steroids. ER, PR, and AR were present in seven (26%) (1+/-2+ intensity, 5% to 10% of nuclei) of HA, seven (26%) (1+/-2+ intensity, 5% to 30% of nuclei) and nine (33%) (1+/-3+ intensity, 5% to 80% of nuclei), respectively. In the adjacent liver in 11 cases, there were one (9%) ER, (2+ intensity, 5% of nuclei), four (36%) PR (1+/-2+ intensity, 5% to 20% of nuclei), and two (18%) AR (2+/-3+ intensity, 10% of nuclei). Receptors are present and may mediate the action of sex hormones or androgenic steroids on HA and adjacent liver, but in less than one third of patients. This may have therapeutic implications.     

Congenital fibrosis of the extraocular muscles type 2, an inherited exotropic strabismus fixus, maps to distal 11q13

The extraocular fibrosis syndromes are congenital ocular-motility disorders that arise from dysfunction of the oculomotor, trochlear, and abducens nerves and/or the muscles that they innervate. Each is marked by a specific form of restrictive paralytic ophthalmoplegia with or without ptosis. Individuals with the classic form of congenital fibrosis of the extraocular muscles (CFEOM1) are born with bilateral ptosis and a restrictive infraductive external ophthalmoplegia. We previously demonstrated that CFEOM1 is caused by an autosomal dominant locus on chromosome 12 and results from a developmental absence of the superior division of the oculomotor nerve. We now have mapped a variant of CFEOM, exotropic strabismus fixus ("CFEOM2"). Affected individuals are born with bilateral ptosis and restrictive ophthalmoplegia with the globes "frozen" in extreme abduction. This autosomal recessive disorder is present in members of three consanguineous Saudi Arabian families. Genetic analysis of 70 individuals (20 affected individuals) reveals linkage to markers on chromosome 11q13, with a combined LOD score of 12.3 at the single nonrecombinant marker, D11S1314. The 2.5-cM CFEOM2 critical region is flanked by D11S4196/D11S4162 and D11S4184/1369. Two of the three families share a common disease-associated haplotype, suggesting a founder effect for CFEOM2. We hypothesize that CFEOM2 results from an analogous developmental defect to CFEOM1, one that affects both the superior and inferior divisions of the oculomotor nerve and their corresponding alpha motoneurons and extraocular muscles.     

Incidence, timing, and causes of cerebral ischemia during carotid endarterectomy with regional anesthesia

PURPOSE: Controversy exists regarding the best technique to identify cerebral ischemia during carotid endarterectomy (CEA). Regional anesthesia allows continuous evaluation of neurologic function and therefore can help determine the incidence, timing, and causes of cerebral ischemia. METHODS: The timing and clinical manifestations of any neurologic event during CEA and as long as 30 days afterward was determined by review of operative reports, hospital charts, and outpatient records of consecutive patients who underwent CEA under regional anesthesia over a 68-month period. RESULTS: Two hundred patients underwent CEA; indications were asymptomatic stenosis > 60% in 25%, transient ischemic attack with stenosis > 50% in 52%, and prior stroke with stenosis > 50% in 23%. Eight patients (4%) were converted to general anesthesia for non-ischemic reasons. Of the remaining 192 patients, 183 (95.5%) underwent the procedure with regional anesthesia and no shunt, 2% had cerebral ischemia and underwent shunt placement, and 2.5% had cerebral ischemia, were converted to general anesthesia, and underwent shunt placement. Cerebral ischemia developed in nine patients after carotid cross-clamping, manifested by loss of consciousness in four, confusion in two, dysarthria and confusion in one, and decreased contralateral motor strength in two. Immediate cerebral ischemia developed in four of the nine patients within 1 minute of cross-damping; all four underwent shunt placement. In five of the nine patients, cerebral ischemia occurred between 20 and 30 minutes after cross-clamping; all occurred during relative intraoperative hypotension (average reduction of 35 mm Hg in the systolic pressure). All awake patients in whom ischemic symptoms developed immediately regained and maintained normal neurologic function with shunt placement. Five of 26 patients (19%) with contralateral occlusion required a shunt; none had postoperative ischemia. The mean carotid cross-clamp time was 27 minutes. Postoperative (30 day) complications included a 0.5% stroke rate, a 0.5% rate of postoperative transient ischemic attack, a 0.5% rate of worsening of preexisting acute stroke, and a 0.5% rate of myocardial infarction (no deaths). Of the nine patients who had intraoperative ischemic changes, none had a postoperative neurologic deficit; the three patients who had postoperative neurologic changes had no intraoperative ischemic symptoms. CONCLUSIONS: CEA with regional anesthesia allows continuous neurologic monitoring and can be performed safely even when contralateral occlusion coexists; intraoperative shunting for ischemia is necessary in 4.5% of all cases and in 19% of patients with contralateral occlusion. Intraoperative ischemia was flow-related in our patients; it occurred early from ipsilateral carotid clamping and late from reduced collateral flow as a result of hypotension. Monitoring should be continued throughout cross-clamping to identify late cerebral ischemia. Postoperative cerebral ischemia is not associated with intraoperative ischemia, if corrected.     

Resection of the metatarsal head for diabetic foot ulcers

Dobutamine-induced hypotension has been disregarded as a marker of more severe functional abnormalities in patients with suspected coronary artery disease. However, its functional significance in patients with myocardial infarction has not been studied. The aim of this study was to define the predictors of systolic blood pressure (SBP) response to dobutamine in patients with previous myocardial infarction. Dobutamine stress (up to 40 microg/kg per minute) echocardiography was performed in 326 patients with prior myocardial infarction referred for evaluation of myocardial ischemia. A 16-segment, four-grade score model was used to assess left ventricular function. Wall motion score index was derived by summation of wall motion score divided by 16. SBP and heart rate increased from rest to peak dobutamine stress (127 +/- 22 vs 134 +/- 27 mm Hg and 72 +/- 14 vs 122 +/- 24 bpm, p < 0.00001 in both). An increase of SBP > or = 30 mm Hg occurred in 50 patients (15%). By multivariate analysis, independent predictors of failure of SBP increase were higher peak wall motion score index (p < 0.001), higher resting SBP (p < 0.01), and medication with calcium channel blockers (p < 0.05). SBP drop > or = 20 mm Hg occurred in 54 patients (17%). Independent predictors of SBP drop were higher resting wall motion score index (p < 0.001), higher resting SBP (p < 0.0001), and older age (p < 0.05). In patients with myocardial infarction, left ventricular function and baseline systolic blood pressure are powerful predictors of SBP response to dobutamine stress testing.     

Distribution of insertion sequence IS200 among different clonal lines of the related Salmonella serotypes Livingstone and Eimsbuettel

The copy number and genetic location of IS200 have provided evidence of strain relatedness in many serotypes of Salmonella. In this study, 100 isolates of the related serotypes Livingstone (6,7:d:l,w) and Eimsbuettel (6,7,14:d:l,w), representing 10 ribotype/biotype (RT/BT) groups isolated from human and non-human sources in seven countries over a 26-year period, were examined for their IS200 profiles. The distribution of IS200 in strains of these serotypes was limited, being present in all 53 isolates of ribotype 1 (RT1) and its variant type RT6, in one of five isolates of RT5 but in none of 42 isolates of RTs 2, 3 or 4. Although the seven IS200 profiles identified in RT1 isolates were of little value for further discrimination within different biotype groups, they were extremely valuable for confirming serotype: isolates of RT1/BT8/IS200 profile A (or its variants) and those of RT1/BT3/IS200 profile B (or its variants) were almost invariably associated with serotypes Livingstone and Eimsbuettel, respectively.     

Tissue reactions to bacteria-challenged implantable leads with enhanced infection resistance

Tissue reactions to implantable pacemaker leads were investigated in an early infection model in rabbits. Both standard leads and surface-modified leads were used. The surface modification technique was applied to achieve controlled release of the antibiotic gentamicin. The insulating polyurethane tubing material of the leads was provided with an acrylic acid/acrylamide copolymer surface graft and then loaded with gentamicin. Implantation periods varied from day 4, to week 3 1/2, to week 10. We investigated tissue reactions in the absence of an infectious challenge and also the efficacy of surface-modified leads in preventing infection after challenge with Staphylococcus aureus was evaluated. It was demonstrated that the applied surface modification did not induce adverse effects although during early postimplantation an increase in infiltration of granulocytes and macrophages and wound fluid and fibrin deposition were observed. After bacterial challenge, standard leads were heavily infected at each explantation period, denoted by abscesses, cellular debris, and bacterial colonies. In contrast, little or no infection was observed, either macroscopically or by bacterial cultures, with the surface-modified leads. Microscopy showed little evidence of the bacterial challenge, and that primarily at day 4. It was concluded that the applied surface modification demonstrated enhanced infection resistance and thus represents a sound approach to the battle against infectious complications with biomaterials.     

Succinate and malate improve development of hamster eight-cell embryos in vitro: confirmation of viability by embryo transfer

The in vitro development of hamster preimplantation embryos is supported by non-glucose energy substrates. To investigate the importance of embryonic metabolism, influence of succinate and malate on the development of hamster 8-cell embryos to blastocysts was examined using a chemically defined protein-free modified hamster embryo culture medium-2 (HECM-2m). There was a dose-dependent influence of succinate on blastocyst development; 0.5 mM succinate was optimal (85.1% +/- 3.9 vs. 54.5% +/- 3.5). In succinate-supplemented HECM-2m, blastocyst development was reduced by omission of lactate (68.5% +/- 7.2), but not pyruvate (85.8% +/- 6.2) or glutamine (84.1% +/- 2.1). Succinate along with either glutamine or lactate or pyruvate poorly supported blastocyst development (28%-58%). Malate also stimulated blastocyst development; 0.01 mM malate was optimal (86.3% +/- 2.8). Supplementation of both succinate and malate to HECM-2m supported maximal (100%) blastocyst development, which was inhibited 4-fold by the addition of glucose/phosphate. The mean cell numbers (MCN) of blastocysts cultured in succinate-supplemented HECM-2m was higher (28.3 +/- 1.1) than it was for those cultured in the absence of glutamine or pyruvate (range 20-24). The MCN was the highest (33.4 +/- 1.6) for blastocysts cultured in succinate-malate-supplemented HECM-2m followed by those in succinate (28.3 +/- 1.1) or malate (24.7 +/- 0.5) supplemented HECM-2m. Embryo transfer experiments showed that 29.8% (+/- 4.5) of transferred blastocysts cultured in succinate-malate-supplemented HECM-2m produced live births, similar (P > 0.1) to the control transfers of freshly recovered 8-cells (33.5% +/- 2.0) or blastocysts (28.9% +/- 3.0). These data show that supplementation of succinate and malate to HECM-2m supports 100% development of hamster 8-cell embryos to high quality viable blastocysts and that non-glucose oxidizable energy substrates are the most preferred components in hamster embryo culture medium.