Anxiety spectrum disorders are common in patients with orthostatic tremor.

BACKGROUND: Orthostatic Tremor (OT) is a rare movement disorder characterized by a sensation of unsteadiness while standing and associated with high frequency tremors. Patients with OT commonly report a fear of falling and significant limitations in everyday activities. The prevalence of psychiatric comorbidities in OT patients has not been well-studied. METHODS: Subjects were evaluated by trained psychiatry researchers using the Mini International Neuropsychiatric Interview (M.I.N.I.). The M.I.N.I is a validated screening tool for psychiatric disorders. A standardized history covering previous psychiatric symptoms and illnesses was also obtained. RESULTS: 29 OT subjects were evaluated. The mean age was 67.7 years with female preponderance (89.3%). The average disease symptom duration was 18.2 years. 58.6% of the subjects had seen a mental health professional during the course of their OT illness. 24.1% of the subjects had a past history of depression, and 10.3% reported a family history of any psychiatric condition. 37.9% of the subjects screened positive for agoraphobia. Two of 29 subjects (6.9%) were classified as having a current major depressive episode and one subject (3.4%) was at risk for suicide. CONCLUSIONS: Psychiatric comorbidities are highly prevalent in OT patients, especially anxiety-spectrum disorders. Further studies are needed to understand if psychiatric disorders appear as a secondary response to the patient's symptoms, or are a primary non-motor manifestation of OT.

Novel amidine derivatives of benzanthrone: Effect of bromine atom on the spectral parameters.

Several new substituted amidine derivatives of benzanthrone were synthesized by condensation reaction from 2-bromo-3-aminobenzo[de]anthracen-7-one and appropriate aromatic or aliphatic amides. The novel benzanthrone derivatives were characterized by TLC analysis, NMR, IR, MS, UV/Vis, and fluorescence spectroscopy. The obtained derivatives have yellow or orange fluorescence in organic solvents. The solvent effect on photophysical behaviors of these dyes was investigated, and the results showed that the introduction of a bromine atom causes a blue-shift of the absorption and emission bands and decrease in the fluorescent quantum yield in comparison with unbromated analogues. The difference in the excited state and the ground state dipole moments was estimated by using the variation of Stokes shift and by semiempirical molecular calculations. The crystal structure and packing of four novel dyes has been revealed by the X-ray single crystal structure analysis.

No iron fertilization in the equatorial Pacific Ocean during the last ice age.

The equatorial Pacific Ocean is one of the major high-nutrient, low-chlorophyll regions in the global ocean. In such regions, the consumption of the available macro-nutrients such as nitrate and phosphate is thought to be limited in part by the low abundance of the critical micro-nutrient iron. Greater atmospheric dust deposition could have fertilized the equatorial Pacific with iron during the last ice age--the Last Glacial Period (LGP)--but the effect of increased ice-age dust fluxes on primary productivity in the equatorial Pacific remains uncertain. Here we present meridional transects of dust (derived from the (232)Th proxy), phytoplankton productivity (using opal, (231)Pa/(230)Th and excess Ba), and the degree of nitrate consumption (using foraminifera-bound δ(15)N) from six cores in the central equatorial Pacific for the Holocene (0-10,000 years ago) and the LGP (17,000-27,000 years ago). We find that, although dust deposition in the central equatorial Pacific was two to three times greater in the LGP than in the Holocene, productivity was the same or lower, and the degree of nitrate consumption was the same. These biogeochemical findings suggest that the relatively greater ice-age dust fluxes were not large enough to provide substantial iron fertilization to the central equatorial Pacific. This may have been because the absolute rate of dust deposition in the LGP (although greater than the Holocene rate) was very low. The lower productivity coupled with unchanged nitrate consumption suggests that the subsurface major nutrient concentrations were lower in the central equatorial Pacific during the LGP. As these nutrients are today dominantly sourced from the Subantarctic Zone of the Southern Ocean, we propose that the central equatorial Pacific data are consistent with more nutrient consumption in the Subantarctic Zone, possibly owing to iron fertilization as a result of higher absolute dust fluxes in this region. Thus, ice-age iron fertilization in the Subantarctic Zone would have ultimately worked to lower, not raise, equatorial Pacific productivity.

How well can we quantify dust deposition to the ocean?

Deposition of continental mineral aerosols (dust) in the Eastern Tropical North Atlantic Ocean, between the coast of Africa and the Mid-Atlantic Ridge, was estimated using several strategies based on the measurement of aerosols, trace metals dissolved in seawater, particulate material filtered from the water column, particles collected by sediment traps and sediments. Most of the data used in this synthesis involve samples collected during US GEOTRACES expeditions in 2010 and 2011, although some results from the literature are also used. Dust deposition generated by a global model serves as a reference against which the results from each observational strategy are compared. Observation-based dust fluxes disagree with one another by as much as two orders of magnitude, although most of the methods produce results that are consistent with the reference model to within a factor of 5. The large range of estimates indicates that further work is needed to reduce uncertainties associated with each method before it can be applied routinely to map dust deposition to the ocean. Calculated dust deposition using observational strategies thought to have the smallest uncertainties is lower than the reference model by a factor of 2-5, suggesting that the model may overestimate dust deposition in our study area.This article is part of the themed issue 'Biological and climatic impacts of ocean trace element chemistry'.

A population pharmacokinetic and pharmacodynamic evaluation of pralatrexate in patients with relapsed or refractory non-Hodgkin's or Hodgkin's lymphoma.

In a pralatrexate phase I study, patients displayed a high incidence of mucositis of grades 3 and 4. Preliminary evaluations of the pharmacokinetics of the drug and its association with mucositis suggested that pralatrexate exposure (area under the concentration-time curve (AUC)) could be controlled with body size (e.g., weight or body surface area)-based dosing and that pretreatment with folic acid and vitamin B(12) might diminish the incidence and severity of mucositis. The study was amended, with revised dosing and vitamin B(12) administration. Data from 47 patients were evaluated using NONMEM. Weight and methylmalonic acid (MMA) level were predictive of pharmacokinetic (PK) variability. AUC and MMA level were positively correlated with the risk of developing mucositis. A lower AUC schedule with vitamin B(12) pretreatment may control mucositis without compromising efficacy. The covariates identified in this study are comparable with other antifolate analogs. The application of modeling was a critical step in the development of pralatrexate, yielding important suggestions for dose, scheduling, and pretreatment modifications.

Wind-driven upwelling in the Southern Ocean and the deglacial rise in atmospheric CO2.

Wind-driven upwelling in the ocean around Antarctica helps regulate the exchange of carbon dioxide (CO2) between the deep sea and the atmosphere, as well as the supply of dissolved silicon to the euphotic zone of the Southern Ocean. Diatom productivity south of the Antarctic Polar Front and the subsequent burial of biogenic opal in underlying sediments are limited by this silicon supply. We show that opal burial rates, and thus upwelling, were enhanced during the termination of the last ice age in each sector of the Southern Ocean. In the record with the greatest temporal resolution, we find evidence for two intervals of enhanced upwelling concurrent with the two intervals of rising atmospheric CO2 during deglaciation. These results directly link increased ventilation of deep water to the deglacial rise in atmospheric CO2.

Detection of circulating tumor cells in patients with urothelial cancer.

BACKGROUND: Approximately 50% of patients with metastatic urothelial cancer (UC) respond to chemotherapy and several months of therapy is required to assess for radiographic response. Blood-based biomarkers may identify patients in whom a specific therapy provides clinical benefit, and this study sought to characterize circulating tumor cells (CTCs) in patients with metastatic UC. PATIENTS AND METHODS: Peripheral blood from patients with metastatic UC was evaluated for CTCs using the CellSearch system. We assessed for associations between CTC counts and the number and sites of metastatic disease. RESULTS: CTC evaluations were carried out in 33 patients with metastatic UC. Fourteen of 33 patients (44%; 95% confidence interval 27% to 59%) had a positive assay (range 0-87 cells/7.5 ml of blood) with 10 patients (31%) having five or more CTCs. A significantly higher number of CTCs was seen in patients with two or more sites of metastases compared with those with less than one or one site of metastases (3.5 versus 0, P = 0.04). CONCLUSIONS: CTCs, detected by antibody capture technology, are present in 44% of patients with metastatic UC. Higher numbers of CTCs are seen in patients with a greater number of metastatic sites. One-third of patients have five or more CTCs providing a potential early marker to monitor response to chemotherapy.

Results of a phase I/II trial adding carmustine (300 mg/m2) to melphalan (200 mg/m2) in multiple myeloma patients undergoing autologous stem cell transplantation.

Autologous stem cell transplantation (SCT) with high-dose melphalan (HDM, 200 mg/m2) is the most effective therapy for multiple myeloma. To determine the feasibility of combining carmustine (300 mg/m2) with HDM, we enrolled 49 patients with previously treated Durie-Salmon stage II/III myeloma (32M/17W, median age 53) on a phase I/II trial involving escalating doses of melphalan (160, 180, 200 mg/m2). The median beta2-microglobulin was 2.5 (0-9.3); marrow karyotypes were normal in 88%. The phase I dose-limiting toxicity was > or =grade 2 pulmonary toxicity 2 months post-SCT. Other endpoints were response rate and progression-free survival (PFS). HDM was safely escalated to 200 mg/m2; treatment-related mortality was 2% and > or =grade 2 pulmonary toxicity 10%. The complete (CR) and near complete (nCR) response rate was 49%. With a median post-SCT follow-up of 2.9 years, the PFS and overall survival (OS) post-SCT were 2.3 and 4.7 years. PFS for those with CR or nCR was 3.1 years while for those with stable disease (SD) it was 1.3 years (P=0.06). We conclude that carmustine can be combined with HDM for myeloma with minimal pulmonary toxicity and a high response rate.

Hematopoietic stem cell mobilization with intravenous melphalan and G-CSF in patients with chemoresponsive multiple myeloma: report of a phase II trial.

Multiple myeloma (MM) is an incurable hematologic malignancy for which autologous hematopoietic stem cell transplantation (HCT) is a standard therapy. The optimal method of stem cell mobilization is not defined. We evaluated intravenous melphalan (60 mg/m2), the most effective agent for MM, and G-CSF (10 microg/kg/day) for mobilization. End points were safety, adequacy of CD34+ collections, MM response, and contamination of stem cell components (SCC). In total, 32 patients were mobilized. There were no deaths or significant bleeding episodes; 14 patients (44%) required hospitalization for neutropenic fever. Median days of grade 3 or 4 neutropenia or thrombocytopenia were 7 (2-20) and 8 (3-17). Median mobilization days, CD34+ cells/kg and total leukaphereses were 16 (12-30), 12.1 million (2.6-52.8), and 2 (1-5) respectively. Four patients (12.5 %) failed to achieve the target of 4 million CD34+ cells/kg in five leukaphereses. Reduction in myeloma was seen in 11 patients (34%) with 3 (9%) achieving complete response; 15 (47%) maintained prior responses. Estimated MM contamination per SCC (N=48) was 0.0009% (range 0-0.1) and 0.21 x 10(4) cells per kg (range 0-41.2). Increased contamination was associated with increased patient age. This strategy for mobilization is feasible, frequently requires hospitalization and transfusion, and controls disease in most patients.

Systemic AL amyloidosis due to non-Hodgkin's lymphoma: an unusual clinicopathologic association.

Systemic AL amyloidosis (AL) is a disorder in which light chains form fibrillar deposits, leading to organ dysfunction and death. Rarely, AL has been associated with non-Hodgkin's lymphoma (NHL), although this association has not been well characterized. We report a series of six patients with AL associated with NHL, primarily lymphoplasmacytic lymphoma. Organ involvement was variable, with frequent bulky lymphadenopathy and visceral cavity deposits, but no cardiac involvement. Positron emission tomography scans were negative. Bone marrow and lymph node biopsies showed a mixed population of CD20+ lymphoid and CD138+ plasma cells. Serum free light chains were elevated, and correlated with response to therapy. Immunoglobulin light chain variable region (Ig VL) germline gene use was typical for AL, reflecting previously observed correlations between germline gene use and organ tropism. Five patients received rituximab-based therapies with two responses. Two patients underwent autologous stem cell transplantation with one complete haematological response. Four patients survive at 10-132 months from diagnosis. AL with NHL has distinctive clinical features but employs the same Ig VL gene repertoire as AL with clonal plasma cell dyscrasias. Serial serum free light chain levels are useful for tracking response to therapy. Treatments aimed at both lymphoid and plasma cell components appear warranted.

Radioiodine ablation of thyroid remnants after preparation with recombinant human thyrotropin.

Radioiodine ablation (RA) of normal thyroid remnants after thyroidectomy for differentiated thyroid carcinoma improves the sensitivity of subsequent radioiodine scans and serum thyroglobulin measurements for detection of residual thyroid carcinoma. Local cancer recurrences are also lower after RA. One standard preparation for RA involves rendering the patient hypothyroid in order to stimulate endogenous thyrotropin (TSH) secretion and sodium iodide symporter (NIS) activity. An alternative approach is to prescribe thyroxine after thyroidectomy and to stimulate NIS with exogenous recombinant human thyrotropin (rhTSH). This latter approach was used in 10 patients at our medical center. Complete resolution of all visible 131I thyroid bed uptake was achieved in all when follow-up scans were performed 5 to 13 months later. This approach has the potential to successfully ablate thyroid remnants without the need to induce hypothyroidism.

Diltiazem treatment does not alter renal function after thoracic surgery.

BACKGROUND: There are conflicting reports on the effects of diltiazem treatment on renal function in surgical patients. We sought to determine whether diltiazem treatment alters renal function in patients undergoing major thoracic surgery. METHODS: In a prospective study, 330 patients scheduled for elective thoracic surgery received either IV diltiazem (n = 167) or placebo (n = 163) immediately after the operation and orally thereafter for 14 days in an effort to prevent postoperative atrial arrhythmias. Serum creatinine and BUN levels were compared before and during the first postoperative week. RESULTS: Patients treated with diltiazem were similar to control subjects in terms of age (mean +/-SD, 66 +/- 10 years vs 67 +/- 10 years, respectively), baseline serum creatinine or BUN levels, prevalence of comorbid conditions, and surgical characteristics. During the first 5 postoperative days, the two groups did not differ in terms of serum creatinine or BUN levels. The incidence of renal failure was 0.6% in the diltiazem group and 1.2% in the placebo group (difference was not significant). There was no difference in the length of hospitalization or mortality rate. CONCLUSIONS: In patients without renal disease who are undergoing elective thoracic surgery, prophylactic diltiazem treatment did not alter postoperative renal function.

Insight and symptom change in schizophrenia and other disorders.

OBJECTIVE: This study sought to evaluate levels of insight and change in insight in subjects with schizophrenia and other major psychiatric disorders. This study also evaluated the relationship of insight to acute psychopathology. METHOD: One-hundred and eighty-seven subjects consecutively admitted to an acute care psychiatric unit and who met DSM-III-R criteria were evaluated by the Insight and Treatment Attitudes Questionnaire and Brief Psychiatric Rating Scale on admission and discharge. Relationships of insight to diagnosis, involuntary commitment status and change in insight were evaluated with analysis of variance and post hoc Tukey's Standardized Range test. Relationships of change in insight and symptoms were evaluated with analysis of covariance (ANCOVA) and correlation. RESULTS: Insight deficits were more prevalent in schizophrenia, a mixed group of other psychosis and bipolar disorder as compared with major depressive and schizoaffective disorder. Committed patients had lower insight. Insight improved across diagnoses during hospital care in both voluntary and committed patients. Significant relationships between improved symptoms and improved insight were obtained in the bipolar, schizophrenia and major depressive groups. CONCLUSION: Insight deficits are prevalent in schizophrenia and bipolar disorder. Many patients show improved insight as their acute symptoms improve. Some aspects of insight are state related during exacerbation of illness in patients with schizophrenia and bipolar disorder.

Multicenter study of whole-blood creatinine, total carbon dioxide content, and chemistry profiling for laboratory and point-of-care testing in critical care in the United States.

OBJECTIVES: To introduce a creatinine biosensor and a total carbon dioxide content (TCO2) method for whole-blood measurements, to evaluate the clinical performance of a new transportable analyzer that simultaneously performs these two and six other tests (Na+, K+, Cl-, glucose, urea nitrogen, and hematocrit), and to assess the potential of the new analyzer for point-of-care testing in critical care by comparing results obtained by nonlaboratory personnel and by medical technologists. DESIGN: Multicenter sites compared whole-blood measurements with the transportable analyzer to plasma measurements from the same specimens with local reference instruments. One site compared whole-blood results produced by nonlaboratory personnel vs. medical technologists and evaluated day-to-day and within-day precision at the point of care. SETTINGS AND PATIENTS: Four medical centers in the United States. Venous and arterial specimens from 710 critically ill patients with a variety of diagnoses. Point-of-care testing in the emergency room and operating room. RESULTS: The linear regression analyses at the four medical centers showed the following: creatinine (a) slope, 0.91 to 1.22, (b) y intercept, -0.07 to 0.15 mg/dL, and (c) r2, 0.77 to 1.00; and TCO2: (a) slope, 0.64 to 1.00, (b) y intercept, 1.36 to 9.6 mmol/L, and (c) r2, 0.52 to 0.72 (yi, whole-blood analyses; xi, plasma reference measurements). Bland-Altman plots also were used to assess multicenter creatinine and TCO2 results. Of the other analytes, K+, glucose, and urea nitrogen had the highest r2-values. For the eight chemistry profile tests performed at the point of care (yi, nonlaboratory personnel results; xi, medical technologist results), the average value of r2 was 0.96 (SD 0.08) in the operating room and 0.96 (SD 0.06) in the emergency room, and mean paired differences (yi - xi) were not statistically or clinically significant. Precision was acceptable. CONCLUSIONS: The performance of the creatinine biosensor and the TCO2 method was acceptable for whole-blood samples. Comparisons of whole-blood results from the transportable analyzer and plasma results from the local reference instruments revealed analyte biases that may be attributed to differences between direct whole-blood analyses and indirect-diluted plasma measurements and other factors. Performance of nonlaboratory personnel and medical technologists was equivalent for point-of-care testing in critical care settings. The whole-blood analyzer should be useful when patient care demands immediate results.

Genotype/phenotype relationships in HNF-4alpha/MODY1: haploinsufficiency is associated with reduced apolipoprotein (AII), apolipoprotein (CIII), lipoprotein(a), and triglyceride levels.

Hepatocyte nuclear factor (HNF)-4alpha is a transcription factor that plays an important role in regulation of gene expression in pancreatic beta-cells and in the liver. Heterozygous mutations in the HNF-4alpha gene are responsible for maturity-onset diabetes of the young 1 (MODY1), which is characterized by pancreatic beta-cell-deficient insulin secretion. HNF-4alpha is a major transcriptional regulator of many genes expressed in the liver. However, no liver defect has been identified in individuals with HNF-4alpha mutations. In this study, we have identified HNF-4alpha target genes that are mainly expressed in the liver, including alpha1-antitrypsin, alpha1-antichymotrypsin, alpha-fetal protein, ceruloplasmin, IGF binding protein 1, transferrin, apolipoprotein(AI) [apo(AI)], apo(AII), apo(B), and apo(CIII). Serum levels of these proteins and Lp(a) and triglycerides were measured in 24 members of the HNF-4alpha/MODY1 RW pedigree (Q268X mutation), including 12 diabetic patients with HNF-4alpha mutations (D-HNF4+/-), 6 nondiabetic subjects with HNF-4alpha mutations (N-HNF4+/-), 6 normal relatives (N-HNF4+/+), 6 unrelated normal matched control subjects (N-HNF4+/+), and 12 matched diabetic (non-MODY1-5) patients (D-HNF4+/+). Serum levels of apo(AII), apo(CIII), lipoprotein(a) [Lp(a)], and triglyceride were significantly reduced in HNF4+/- subjects (26.9, 19.8, 12.1, and 72.1 mg/dl, respectively) compared with HNF4+/+ subjects (37.4, 26.5, 45.2, and 124.2 mg/dl, respectively) (P = 0.00001, P = 0.01, P = 0.00006, and P = 0.000003, respectively). This reduction was not found when apo(AII), apo(CIII), Lp(a), and triglyceride levels were compared in D-HNF4+/- versus N-HNF4+/- or in D-HNF4+/+ versus N-HNF4+/+ subjects, which indicates that HNF-4alpha haploinsufficiency rather than hyperglycemia is the primary cause of decreased serum protein and triglyceride concentrations. Furthermore, we determined that genetic or environmental modifiers other than HNF-4alpha do not appear to contribute to the observed decrease of HNF-4alpha-regulated serum proteins. This study demonstrates that a heterozygous HNF-4alpha mutation leads to an HNF-4alpha-dependent hepatocyte secretory defect of liver-specific proteins.

Perioperative alterations in plasma endothelin-1 and echocardiographic correlates of right heart function.

OBJECTIVE: To determine whether greater changes in plasma endothelin-1 (ET-1) concentrations and right ventricular systolic pressure occur after major thoracic surgery than after major abdominal operations. DESIGN: Prospective study. SETTING: University hospital. PARTICIPANTS: Patients undergoing elective thoracotomies (n = 12) or laparotomies (n = 10). INTERVENTIONS: ET-1 was measured from blood obtained before anesthesia and again on postoperative days 1, 2, 3, and 5 (or 6). Transthoracic echocardiography was performed before surgery and on postoperative day 2 to evaluate right-sided heart function. MEASUREMENTS AND MAIN RESULTS: After abdominal and thoracic surgery, systemic and estimated pulmonary vascular pressures were normal in both groups and unaffected by surgery. Plasma ET-1 concentrations decreased from baseline values during the first postoperative week with no differences between the groups. CONCLUSIONS: In patients without organic heart disease, plasma ET-1 levels do not increase in response to major abdominal or thoracic surgery. Whether or not plasma ET-1 concentrations are elevated in patients developing clinically significant postoperative pulmonary hypertension requires further study.

Malignant neoplasms subsequent to treatment of inflammatory bowel disease with 6-mercaptopurine.

OBJECTIVE: Most complications of 6-mercaptopurine (6MP) used in the treatment of inflammatory bowel disease (IBD) occur early, whereas neoplasms occur late in the course. Concern persists that the risk is increased when 6MP is used. We report our experience with malignant tumors developing over 27 yr of treating IBD patients with 6MP. METHODS: A total of 591 patients with IBD treated with 6MP between 1969 and 1997 were followed or traced until present to identify all malignant tumors and blood dyscrasias that had developed to determine the type, distribution, and duration of the IBD, the dose and duration of 6MP therapy, the concurrent versus previous use of 6MP, the incidence and probable relationship of 6MP to specific neoplasms, and whether the 6MP had been effective in treatment. RESULTS: A total of 550 patients (93%) fulfilled the criteria for follow-up; these included 380 with Crohn's disease (CD) and 170 with ulcerative colitis (UC). Twenty-five patients had developed neoplasms (16 of 380 CD and nine of 170 UC) (p = 0.66). In half of the cases, the goal of therapy had been achieved with 6MP. In 10 patients, the neoplasm was diagnosed while the patients were taking 6MP (40%) and in 15, many years after the 6MP had been terminated (60%). The incidence of neoplasms (25 of 550) was 2.7/1000 patient-years of follow-up. The most common neoplasms were found in the bowel (eight of 550, 1.6%; five CD, and three UC), and breast (three, 0.5%; two CD, and one UC). Non-Hodgkins lymphomas occurred in two patients with CD; one was cerebral and the other abdominal. One patient with CD developed leukemia. The duration of 6MP therapy ranged from 5 months to 22 yr, with a mean of 5 yr. The dose of 6MP ranged from a quarter of a tablet/day (12.5 mg) to 100 mg/day, with the majority in a range from 50 to 75 mg/day. CONCLUSION: In no instance could a neoplasm be attributed to the use of 6MP. The incidence of colon cancer is not greater than that with long standing colitis. Suspicion of a relationship between 6MP and leukemia/lymphoma persists, but the incidence is low. This must be weighed against the improved quality of life due to 6MP for patients with IBD.

Complications of voiding cystourethrography in the evaluation of infants with prenatally detected hydronephrosis.

PURPOSE: We determined complications in infants undergoing voiding cystourethrography as part of the evaluation for prenatally detected hydronephrosis. MATERIALS AND METHODS: We retrospectively reviewed the records of infants referred to our institution for the evaluation of prenatal hydronephrosis from 1992 to 1997. Infants with a prenatal history of bilateral hydronephrosis, bladder distention and oligohydramnios, oligohydramnios only or a prenatal abnormality involving any other organ system were excluded from study. Of 206 patients 129 male and 49 female infants underwent postnatal voiding cystourethrography at our institution. Chart review and a telephone interview with the parents were done to assess lower urinary tract infection, pyelonephritis, hospital admission for urosepsis, gross hematuria, urinary retention or skin rash. RESULTS: Postnatal voiding cystourethrography was normal in 138 patients but it diagnosed bilateral vesicoureteral reflux in 15, unilateral vesicoureteral reflux in 20, ureterocele in 4 and refluxing megaureter in 1. Of the 129 male infants evaluated 101 had undergone circumcision as a newborn, 14 were uncircumcised and the circumcision status of 14 was unknown. At voiding cystourethrography suppressive antibiotics were administered to 166 infants, 7 were not on suppressive antibiotics and antibiotic status was unknown in 5. No patient had a lower urinary tract infection, pyelonephritis or urosepsis. In addition, there were no episodes of urinary retention, gross hematuria or skin rash. CONCLUSIONS: While the reported rate of new or recurrent infection associated with voiding cystourethrography is as high as 6%, we did not identify any infectious or other complications in infants undergoing voiding cystourethrography for prenatal hydronephrosis. When properly performed, we believe that voiding cystourethrography is safe and presents little risk in these patients.

Differential diagnosis of gammopathies by capillary electrophoresis and immunosubtraction: analysis of serum samples problematic by agarose gel electrophoresis.

The capabilities of capillary electrophoresis (CE) for serum protein electrophoresis and immunotyping have been demonstrated. CE-based systems specifically designed for serum protein electrophoresis and immunotyping via immunosubtraction (IS) are now available and are being evaluated for efficiency, specificity and sensitivity by several groups. The use of CE for serum protein electrophoresis and immunotyping (IS) in the clinical laboratory compares well with agarose gel electrophoresis (AGE) and immunofixation (IF) for the detection and characterization of monoclonal proteins. In addition to routine use, this technology is useful for a subset of serum samples that are difficult to interpret with conventional technology. In this study, sera abnormalities difficult to detect/interpret by AGE-IF are subdivided into four categories: (i) patients with polyclonal increases in immunoglobulin, (ii) point of application artifacts, (iii) abnormalities in the beta region, and (iv) patients with free light chains. CE is superior to AGE for evaluating samples characterized by the above abnormalities. Sera containing monoclonal proteins within a polyclonal increase are easier to detect by CE as well as being easier to type by IS than by IF. Point-of-application artifacts, periodically observed with AGE, do not exist on CE since the point of detection is remote from the point of application. Enhanced resolution in the beta region allows for increased detection of monoclonal proteins migrating in this region. Some free light chains are undetected by CE as a result of no apparent abnormalities on the CE serum protein profile and, thus, still require IF for detection. CE detects more serum electrophoretic abnormalities than AGE in this clinically important group of patients with Bence Jones proteinemia.

Persistent alterations of the autonomic nervous system after noncardiac surgery.

UNLABELLED: BACKGROUND. Changes in the sympathetic nervous system may be a cause of postoperative cardiovascular complications. The authors hypothesized that changes in both beta-adrenergic receptor (betaAR) function (as assessed in lymphocytes) and in sympathetic activity (assessed by plasma catecholamines and by heart rate variability [HRV] measurements obtained from Holter recordings) occur after operation. METHODS: The HRV parameters were measured in 28 patients having thoracotomy (n = 14) or laparotomy (n = 14) before and for as long as 6 days after operation. Transthoracic echocardiography was performed before and on postoperative day 2. Lymphocytes were also isolated from blood obtained before anesthesia and again on postoperative days 1, 2, 3, and 5 (or 6). They were used to examine betaAR number (Bmax) and cyclic adenosine monophosphate (cAMP) production after stimulation with isoproterenol and prostaglandin E1. In addition, plasma epinephrine, norepinephrine, and cortisol concentrations were determined at similar intervals. RESULTS: After abdominal and thoracic surgery, most time and all frequency indices of HRV decreased significantly, as did Bmax and basal and isoproterenol-stimulated cAMP production. The decrements in HRV correlated with those of Bmax and isoproterenol-stimulated cAMP throughout the first postoperative week and inversely correlated with the increase in heart rate. Plasma catecholamine concentrations did not change significantly from baseline values, but plasma cortisol levels did increase after operation in both groups. Left ventricular ejection fraction was normal in both groups and unaffected by surgery. CONCLUSIONS: Persistent downregulation and desensitization of the lymphocyte betaAR/adenylyl cyclase system correlated with decrements in time and frequency domain indices of HRV throughout the first week after major abdominal or thoracic surgery. These physiologic alterations suggest the continued presence of adaptive autonomic regulatory mechanisms and may explain why the at-risk period after major surgery appears to be about 1 week or more.