A compensatory mirror cortical mechanism for facial affect processing in schizophrenia.

When primates passively observe other subjects perform specific gestures or actions, premotor and motor cortical areas involved in the internal representation and actual execution of those actions exhibit neuronal activation. This mirror mechanism matches observation, representation, and execution, facilitating internal motor rehearsal, imitation, recognition of actions by others and their meanings, and social learning. Schizophrenic patients have deficits in processing affect displayed by other people's faces, which likely relates to the poor social adaptation and functioning seen in the condition. We hypothesized that, when correctly performing working-memory tasks requiring facial affect processing, schizophrenic patients would show relative increased activity in brain areas involved in social learning and in the internal representation of facial expressions when compared to controls. We used functional magnetic resonance imaging in schizophrenic patients and normal controls to detect relative changes of blood flow in cortical areas related to the representation of facial expressions while the subjects performed simple working-memory tasks with facial emotion diagrams or color circles as cues. We found that, when the task cues were facial expressions in contrast to color circles, the schizophrenic group exhibited increased activation of the face movement areas in motor and pre-motor cortex.

Gender differences in regional brain response to visceral pressure in IBS patients.

In two experiments including a total of 30 irritable bowel syndrome patients, symptom-mimicking rectal pressure stimuli elicited changes in regional neural activation as measured by positron electron tomography (PET) cerebral blood flow images. Although most stimuli were not rated as painful, rectal pressure increased regional cerebral blood flow (rCBF) in areas commonly associated with somatic pain, including the anterior cingulate, insula, prefrontal cortex, thalamus, and cerebellum. Despite similar stimulus ratings in male and female patients, regional activations were much stronger for males. In both experiments, rectal pressure activated the insula bilaterally in males but not in females. Insula activation was associated most strongly with objective visceral pressure, whereas anterior cingulate activation was associated more with correlated ratings of subjective discomfort. The insula is discussed as a visceral sensory cortex. Several possible reasons for the insula gender effect are proposed.

The effects of an alpha-2 adrenergic agonist, guanfacine, on rCBF in human cortex in normal controls and subjects with focal epilepsy.

Alpha-2 noradrenergic agonists may have wide applicability in the treatment of pre-frontal cortex deficits in primates and behavioral dysfunction in man. We have undertaken this study to determine the effect of an alpha-2 agonist, guanfacine, on regional cerebral blood flow (rCBF) in humans. Three subject groups were evaluated: normal controls, subjects with frontal lobe epilepsy (FLE), and subjects with temporal lobe epilepsy (TLE). All underwent a number of PET scans using 15O-water, with half before and half after a single dose of guanfacine. A wide area of increased rCBF was seen in the frontal lobe, maximal at the central region, following guanfacine in controls and subjects with TLE. Smaller areas of decrease in rCBF were seen in the posterior temporal-occipital cortex. In the FLE group a decrease in rCBF was seen in the dorsal prefrontal cortex on the epileptogenic side with only small increases seen in the mid- to anterior temporal perisylvian areas. The ability of alpha-2 agonists to enhance performance of tasks reliant on prefrontal cortex, without improving tasks believed to rely on intact temporal-hippocampal function, may be explained by these results. Epileptogenic zones appear to create both direct and indirect changes in patterns of drug response. Further studies on the cognitive properties of these agents in humans should be encouraged.

Normalization of hematocrit in hemodialysis patients with cardiac disease does not increase blood pressure.

UNLABELLED: Since the earliest reports of the use of Epoetin alfa in hemodialysis patients, it has been described that Epoetin alfa may exacerbate preexisting hypertension or induce hypertension in End Stage Renal Disease (ESRD) patients not previously hypertensive. We undertook this study to determine if the correction of anemia in ESRD patients with cardiac disease from a hematocrit of 30+/-3% to 42+/-3% with the use of Epoetin alfa would result in increased blood pressure. This study was a substudy of the "Normal hematocrit Study". METHODS: Thirty-one patients were randomized into one of two arms. Patients in Group A had their hematocrit increased with the use of slowly escalating doses of Epoetin alfa to 42+/-3% and patients in Group B were maintained with a hematocrit of 30+/-3% throughout the course of the study. All patients had their blood pressure recorded with a 24 hour ambulatory BP device at study entry and at 28 weeks following randomization when they had achieved their target hematocrit. Pre-dialysis systolic and diastolic BP was also recorded. RESULTS: The mean hematocrit increased in Group A from 29.1+/-2.4% to 40.8+/-5.2% after 30 weeks. The hematocrit in Group B remained stable at 30+/-3% throughout the course of the study. There was no difference in mean daytime, mean nighttime or 24 hour systolic or diastolic blood pressure between Groups A and B at either baseline or follow-up. Neither was there a difference in mean pre-dialysis systolic or diastolic BP between Groups A or B at baseline or Follow-up. Four patients in Group A and 4 patients in Group B required an increase in their antihypertensive medication during the course of the study. CONCLUSION: It is possible to increase hematocrit to normal levels in hemodialysis with the administration of Epoetin alfa. The increase in hematocrit from 30+/-3% to 42+/-3% is not associated with increased blood pressure.

Normalization of hematocrit in hemodialysis patients does not affect silent ischemia.

UNLABELLED: Transient ST-segment depression measured on ambulatory ECG monitors has been described as representing silent ischemia. Patients who demonstrate silent ischemia have been reported to show increased mortality compared to patients without silent ischemia. We undertook this study to determine if the correction of anemia in End Stage Renal Disease (ESRD) patients from (+/- = standard deviation) 30 +/- 3 to 42 +/- 3 with the use of Epoietin alfa would result in decreased silent ischemia in patients with clinically evident ischemic heart disease or congestive heart failure. METHODS: Thirty one ESRD patients with congestive heart failure or patients with clinically-evident ischemic heart disease were randomized into one of two arms. Patients in Group A had their hematocrit increased with the use of slowly escalating doses of Epoietin alfa to 42 +/- 3% and patients in Group B were maintained with a hematocrit of 30 +/- 3% throughout the course of the study. All patients had a 24 hour Holter monitor recording at baseline and at 28 weeks after randomization (when they had reached their target hematocrit). Significant silent ischemia was considered to be present if patients demonstrated at least 60 seconds of > or = 1 mm ST segment depression. RESULTS: Fifteen patients were randomized to Group A and 16 patients were randomized to Group B. The mean hematocrit increased in group A from 29.1 +/- 2.4% to 40.8 +/- 5.2% after 30 weeks. The mean hematocrit in Group B remained stable at 30 +/- 3% throughout the course of the study. Ten patients demonstrated silent ischemia at baseline. At follow up patients in group A demonstrated a mean of 1.7 +/- 4.9 minutes of ischemia compared to 1.1 +/- 3.4 minutes in group B. These were not significantly different. A similar number of patients in group A and Group B required adjustments in their anti-anginal medication during the course of the study. CONCLUSION: It is possible to increase hematocrit to near normal levels in hemodialysis with the administration of exogenous Epoietin alfa. The increase in hematocrit form 30 +/- 3% to 42 +/- 3% is not associated with a change in the level of silent ischemia these patients demonstrate.

Role of urine and serum protein electrophoresis in evaluation of nephrotic-range proteinuria.

The usefulness of routine serum protein electrophoresis (SPEP) and urine protein electrophoresis (UPEP) screening in the evaluation of proteinuria is not known. The data on the clinical utility of these tests in 165 male patients with proteinuria greater than 3 g/d of protein who were screened for the presence of an M-spike are presented. Two hundred fifty-four studies were performed (SPEP, 155; UPEP 99) in these 165 patients. Twenty-four studies (9.8%) were positive for an M-spike (15 serum; 9 urine samples) in 19 patients (11.5%). Fourteen patients (8.5%) had an M-spike in either serum or urine, five patients (3%) in both studies. Two of these 19 patients were diagnosed with myeloma and 1 patient was diagnosed with primary amyloidosis. The other 16 patients were diagnosed with monoclonal gammopathy of unknown significance (MGUS). The group with a positive M-spike was significantly older (mean +/- SEM, 65 +/- 2 years; range, 39 to 78 years v 58 +/- 1 years; range, 25 to 84 years; P = 0.03), had a lower incidence of coexistent diabetes (21.1% v 61.6%; P = 0. 01), and a lower serum albumin level (3.2 v 3.6 g/dL; P = 0.05). Using a multivariable logistic regression model, the presence of an M band was positively correlated with age (odds ratio [OR], 1.056; 95% confidence interval [CI], 1.006 to 1.108) and negatively correlated for serum albumin level (OR, 0.386; 95% CI, 0.184 to 0. 810), hematocrit (OR, 0.923; 95% CI, 0.852 to 1.001), and the presence of diabetes mellitus (OR, 0.128; 95% CI, 0.038 to 0.434). In summary, routine SPEP and UPEP screening in patients with proteinuria greater than 3 g/d of protein detected an M-spike in 11. 5% and myeloma in 1.2% of the patients. The cost per case of myeloma or MGUS discovered was $1,192.

Implementation of the Dialysis Outcomes Quality Initiative Vascular Access Guidelines.

To better care for patients with chronic renal failure and end-stage renal disease, the National Kidney Foundation has published a set of Clinical Guidelines, the Dialysis Outcomes Quality Initiative, based on current available evidence and, where such evidence is lacking, the expert opinions of current leaders in vascular access research. These Guidelines were developed to standardize the care of chronic renal failure and end-stage renal disease patients. This report describes some of the more important aspects of these recommendations and the authors' implementation strategies.

Survival in renal vascular disease.

Renal artery stenosis (RAS) is a relatively uncommon but important potentially reversible cause of renal failure. Little is known about the natural history of ischemic renal disease secondary to RAS. In previous reports, these researchers examined the incidence and risk factors associated with RAS. The study presented here investigates the long-term follow-up of these patients, specifically the effect of RAS on 4-yr, all-cause mortality in a group of 1235 patients undergoing diagnostic cardiac catheterization and abdominal aortography. A total of 1235 consecutive patients undergoing cardiac catheterization also underwent an abdominal flush aortogram. Significant RAS was considered present if one or more renal artery had 50% or greater narrowing in luminal diameter. Four-year unadjusted survival for patients with RAS was 65% compared with 86% for patients undergoing catheterization without significant RAS. Factors associated with decreased 4-yr survival included increased age, increased serum creatinine, presence of RAS, peripheral vascular disease, congestive heart failure, diabetes, hypertension, and reduced ejection fraction. Using the Cox proportional hazards model, the factors associated with decreased 4-yr survival were the presence of significant RAS, reduced ejection fraction, elevated serum creatinine, and symptoms of congestive heart failure. These observations indicate that the presence of significant RAS is a strong independent predictor of 4-yr survival in this patient population.

A clustering of epidural abscesses in chronic hemodialysis patients: risks of salvaging access catheters in cases of infection.

The objective of this study was to investigate factors that might increase the risk of epidural abscesses in hemodialysis patients. The charts of all hemodialysis patients presenting with an epidural abscess over a period of 5 yr at Duke University Hospital and the Durham Veterans Administration Medical Center were reviewed for patient demographics, months on dialysis, vascular access, recently treated infections, signs and symptoms at presentation, and results of any surgical intervention. Ten patients developed an epidural abscess during a 5-yr period. Severe, debilitating back pain was the only consistent initial complaint. Eight patients had dual-lumen intravenous catheters for hemodialysis access, and five patients had or were receiving parenteral antibiotics for catheter salvage. There were no consistent physical, clinical, or laboratory findings. Surgical drainage of the abscess with removal of the hemodialysis catheters and parenteral antibiotics were required for cure in six patients. It was concluded that attempts at catheter salvage with parenteral antibiotics has significant risks for complications. Hemodialysis patients with recently treated or ongoing bacteremia who complain about severe and debilitating back pain with or without neurologic findings should raise the suspicion of an occult epidural abscess.

No change in complication rate using spring-loaded gun compared to traditional percutaneous renal allograft biopsy techniques.

The previous methods to biopsy renal allografts at our institution involved the use of the Franklin-Silverman or Tru-Cut needles. Unfortunately they had a significant rate of post biopsy bleeding secondary to deep penetration when excess force was used to penetrate a tough transplant capsule. Although spring loaded biopsy devices have been widely used for native kidney biopsies over the past three years, the complication rate for renal allograft biopsies has not been sufficiently evaluated. We describe our experience using a disposable spring loaded biopsy device on transplanted renal grafts. Fifty-four biopsies were performed with the device, all under ultrasound guidance. The ASAP automatic biopsy system by Medi-tech was used comprising of a spring loaded gun with a 15 cm long 15 GA needle echogenic tip and 17 mm specimen notch. All patients were ultrasounded immediately post biopsy to look for hematomas. Compared to 55 previous biopsies performed using Tru-Cut needles, we conclude that the ASAP automated biopsy system proved equally effective in obtaining adequate tissue for diagnosis with fewer post-biopsy hematomas compared to traditional biopsy methods.

Percutaneous renal biopsy of ventilated intensive care unit patients.

The etiology of acute renal failure in ventilated intensive care unit patients can be determined non-invasively in more than 80% of cases. When a pulmonary renal syndrome is suspected however it is important to obtain histological confirmation of the diagnosis prior to initiating therapy. Most text books and review articles have advocated the use of open surgical biopsy in this situation. Seven years ago we began to perform percutaneous renal biopsies on medical intensive care unit ventilated patients when a pulmonary renal syndrome was suspected as an alternative to an open surgical procedure. During this period we performed the technique on 7 patients. Adequate renal tissue was obtained in all cases. We compare the complication rate with that achieved using open surgical biopsy during the same time period. The complication rate using a percutaneous technique was similar to open renal biopsy. We believe that the previously held recommendation that percutaneous renal biopsy should not be performed on ventilated patients should be re-examined.

The renal manifestations and outcome of thrombotic thrombocytopenic purpura/hemolytic uremic syndrome in adults.

Thrombotic thrombocytopenic purpura/Hemolytic uremic syndrome (TTP/HUS) is generally regarded to be a rare disease. The present study was undertaken to identify presenting features, prognostic variables, pathological features and outcome associated with TTP/HUS. The present study is a retrospective chart review of 68 patients treated with plasmapheresis for TTP/HUS at a single tertiary referral medical institution from 1980-1992. The annual number of patients with TTP/HUS treated with plasmapheresis increased from an average of one case per year in 1980 to nine cases per a year in 1992. The in-hospital mortality for patients presenting with TTP/HUS was 25%. Forty four percent of patients presented with an elevated serum creatinine, and 16% required hemodialysis support. Of the seven patients who survived and required hemodialysis support only two patients continued on dialysis. None of the patients presenting with a normal serum creatinine required dialysis at any time in their course. Patient age, sex, presenting platelet count, white blood cell count, hemoglobin level and presence of neurological disease were not significantly associated with death or need for dialysis. The histopathological features of TTP/HUS (fibrin/platelet thrombi in renal vessels and glomeruli, fibrinoid necrosis of vessel walls) were found in all five cases autopsied. The incidence of TTP/HUS may be increasing. Alternative possibilities for the increased frequency of cases seen include greater diagnostic suspicion and referral bias. Despite the use of plasmapheresis, mortality during the initial hospital admission was almost 25%. In retrospect prognosis could not be predicted based on admission biochemical or clinical variables. The majority of patients who developed acute renal failure and survived to hospital discharge recovered renal function and became independent of dialysis.

Correction of central venous stenoses: use of angioplasty and vascular Wallstents.

Central venous stenoses are a frequent complication in hemodialysis patients. These lesions lead to fistula thromboses, arm swelling, and limit future vascular access. Stenoses are characterized by excellent initial response to transluminal angioplasty but rapid recurrence. Response to angioplasty allows classification of stenoses as elastic or nonelastic. The success of angioplasty alone in 30 patients with central venous stenoses was compared to angioplasty and Wallstent placement in 11 patients with recurrent stenoses. In those who had angioplasty alone, 7%+ failed angioplasty, 70% had > or = 50% improvement in the luminal diameter while 23% showed no improvement due to elastic lesions. Subsequently, 81% of those with a successful result restenosed at an average of 7.6 months while 100% of elastic lesions occluded in an average of 2.9 months. In the 10 patients who underwent angioplasty and Wallstent placement, 5 were due to elastic lesions with four recurrences at a mean of 8.6 months. Four of five patients (80%) stented with nonelastic lesions had reappearance of symptoms at a mean of 4.2 months. We conclude that vascular stents should be reserved for those lesions that show elastic recoil after standard angioplasty.

Double antibody radioimmunoassay for monitoring metastatic breast cancer.

We previously reported the production of a panel of murine monoclonal antibodies which recognize glycoproteins abnormally expressed in human breast tumours. Using two of these antibodies, a double antibody radioimmunoassay was designed to quantify levels of these breast tumour marker glycoproteins in serum. Marker levels greater than 28 units were considered abnormal. Using this criterion, 63% and 75% of patients with breast cancer stages I and II, respectively, and 88% of those with metastatic disease were found to have elevated marker levels. Thirteen percent of patients with non-malignant breast disease also had elevated marker levels. Elevated marker levels were also detected in patients with non breast neoplasms. One hundred and eleven women with metastatic disease were followed. Eighty-two percent of those with progressive disease and 73% of those where disease regressed had 20% changes in marker levels. These changes in marker levels preceded by up to 6 months changes in disease state. From these results we conclude that this assay may be useful for monitoring the course of disease in breast cancer patients.

Monoclonal antibodies to antigens abnormally expressed in breast cancer.

We report the production, screening, and characterization of ten murine monoclonal antibodies directed at antigens that are expressed abnormally in human breast tumors. Immunoperoxidase staining of frozen and fixed tissues shows the antigens to be present at low levels on the luminal membrane of normal breast cells and at high levels in the cytoplasm and surface membrane of breast tumor cells. The ten antibodies appear to recognize six different epitopes on the basis of their quantitative differences in reactivity against four antigen preparations, as measured by ELISA. Immunoblots show that eight of the ten antibodies recognize a 300,000 MW molecule from breast tumor preparations; six of these antibodies also react with a second molecule from the same tumor preparations of 280,000 MW. Seven antibodies react with an antigen from milk fat globule membrane of 330,000 MW. It therefore appears that the two molecules from tumor tissue and the one molecule from normal tissue share common epitopes. Selected antibodies were tested for reactivity against 25 primary breast tumors and 14 pairs of primary and metastatic breast tumors. Three antibodies have broad reactivity and stain more than 80% of primary tumors; the three other antibodies identify subsets of those tumors. Results of staining pairs of primary and metastatic lesions show that metastases continue to express antigens of the primary lesion in a high percentage of cells.