Expanded spatial extent of the Medieval Climate Anomaly revealed in lake-sediment records across the boreal region in northwest Ontario.

Multi-decadal to centennial-scale shifts in effective moisture over the past two millennia are inferred from sedimentary records from six lakes spanning a ~250 km region in northwest Ontario. This is the first regional application of a technique developed to reconstruct drought from drainage lakes (open lakes with surface outlets). This regional network of proxy drought records is based on individual within-lake calibration models developed using diatom assemblages collected from surface sediments across a water-depth gradient. Analysis of diatom assemblages from sediment cores collected close to the near-shore ecological boundary between benthic and planktonic diatom taxa indicated this boundary shifted over time in all lakes. These shifts are largely dependent on climate-driven influences, and can provide a sensitive record of past drought. Our lake-sediment records indicate two periods of synchronous signals, suggesting a common large-scale climate forcing. The first is a period of prolonged aridity during the Medieval Climate Anomaly (MCA, c. 900-1400 CE). Documentation of aridity across this region expands the known spatial extent of the MCA megadrought into a region that historically has not experienced extreme droughts such as those in central and western north America. The second synchronous period is the recent signal of the past ~100 years, which indicates a change to higher effective moisture that may be related to anthropogenic forcing on climate. This approach has the potential to fill regional gaps, where many previous paleo-lake depth methods (based on deeper centrally located cores) were relatively insensitive. By filling regional gaps, a better understanding of past spatial patterns in drought can be used to assess the sensitivity and realism of climate model projections of future climate change. This type of data is especially important for validating high spatial resolution, regional climate models.

Inconsistencies between Pangean reconstructions and basic climate controls.

The supercontinent Pangea dominated our planet from the Permian into the Jurassic. Paleomagnetic reconstructions have been used to estimate the latitudinal position of Pangea during this 100-million-year period. Atmospheric circulation, recorded by eolian sandstones in the southwestern United States, shows a broad sweep of northeasterly winds over their northernmost extent, curving to become northwesterly in the south: This evidence is consistent with paleomagnetic reconstructions of the region straddling the equator in the Early Permian but is at odds with its northward movement to about 20 degrees N by the Early Jurassic. At least one of the following scenarios must be true: The latitude based on paleomagnetism is incorrect; the interpretation of how winds shaped the dunes is mistaken; the basic climate controls in the Jurassic were different from those of today; or the paleogeographic reconstructions available are insufficient to adequately reproduce the wind fields responsible for dune formation.

Large wind shift on the great plains during the medieval warm period.

Spring-summer winds from the south move moist air from the Gulf of Mexico to the Great Plains. Rainfall in the growing season sustains prairie grasses that keep large dunes in the Nebraska Sand Hills immobile. Longitudinal dunes built during the Medieval Warm Period (800 to 1000 years before the present) record the last major period of sand mobility. These dunes are oriented NW-SE and are composed of cross-strata with bipolar dip directions. The trend and structure of the dunes record a drought that was initiated and sustained by a historically unprecedented shift of spring-summer atmospheric circulation over the Plains: Moist southerly flow was replaced by dry southwesterly flow.

New-onset gout after kidney transplantation: incidence, risk factors and implications.

BACKGROUND: Although cyclosporine use has been associated with an increased risk of new-onset gout after renal transplantation, the incidence and risk factors for new-onset gout have not been reported in the era of modern immunosuppression. METHODS: We conducted a retrospective cohort study of Medicare primary renal transplant patients reported in the United States Renal Data System (USRDS), using Medicare claims data to determine the incidence of new-onset gout. Cox regression analysis was used to calculate adjusted hazard ratios (AHR) for cyclosporine (including separate analysis of Neoral) compared directly with tacrolimus, for the risk of new-onset gout, adjusted for baseline demographic factors and posttransplant renal function. RESULTS: The cumulative incidence of new-onset gout was 7.6% at 3 years posttransplant. The following factors were independently associated with an increased risk of new-onset gout: use of Neoral (vs. tacrolimus, AHR 1.25, 95% CI 1.07-1.47) at discharge, recipient male sex (AHR 1.44, 95% CI 1.25-1.67), older age, higher body mass index, and more recent year of transplant. No other immunosuppressive medications were associated with new-onset gout. Diabetes was associated with a significantly lower risk of new-onset gout. The development of new-onset gout was independently associated with decreased patient survival (AHR 1.26, 95% CI 1.08-1.47) as well as death-censored graft survival. CONCLUSIONS: Cyclosporine is an independent risk factor for new-onset gout after transplantation. The incidence of new-onset gout appears to be increasing even while the use of cyclosporine is decreasing, and the development of new-onset gout was an independent predictor for death and graft loss in this population.

Maintenance immunosuppression use and the associated risk of avascular necrosis after kidney transplantation in the United States.

BACKGROUND: Avascular necrosis (AVN) after renal transplantation has been largely attributed to the use of corticosteroids. However, other risk factors such as microvascular thrombosis and hyperlipidemia have been well described and may be of increased importance in the era of early steroid cessation and avoidance. We hypothesized that maintenance immunosuppressive medications known to be associated with these risk factors for AVN would also be associated with a higher risk of AVN. METHODS: By using the U.S. Renal Data System database, we studied 27,772 primary patients on Medicare who received a solitary kidney transplant between January 1, 1996, and July 31, 2000. Cox proportional hazards regression models were used to calculate adjusted hazard ratios (AHRs) for patient- and transplant-related factors (including allograft rejection) with Medicare claims for AVN. The intensity and duration of corticosteroid use could not be assessed. RESULTS: Among patients who were prescribed sirolimus at discharge, 3.5% of patients who received the combination of sirolimus-cyclosporine A (CsA) demonstrated AVN, compared with 1.4% of patients who received the combination of sirolimus-tacrolimus (P=0.06 by chi). In Cox regression, CsA use (vs. tacrolimus) (AHR 1.36, 95% confidence interval, 1.09-1.71) was independently associated with an increased risk of AVN. Sirolimus use showed a trend toward significance (AHR 1.59, 95% confidence interval, 0.99-2.56), with no significant interaction with CsA. CONCLUSIONS: Compared with other maintenance immunosuppression, AVN was significantly more common after use of CsA prescribed at the time of discharge for renal transplantation. Whether this increased risk of AVN was directly attributable to hyperlipidemia, microvascular thrombosis, or differences in corticosteroid dosing could not be determined.

A 36-year-old military recruit with recurrent myalgias and weakness.

The objective of this study was to discuss a comprehensive yet cost-effective approach to working up active duty patients with recurrent rhabdomyolysis. A 36-year-old male Army recruit was evaluated at Walter Reed Army Medical Center for recurrent rhabdomyolysis. This case illustrates a practical and cost-effective approach to this goal. Questions along the way are meant to highlight military relevance and expand diagnostic considerations of muscle pain beyond the usual. The case takes an interesting twist and reinforces that, as providers, we must explore every aspect of our patient's history to the fullest to be effective diagnosticians.

Lake sediments record large-scale shifts in moisture regimes across the northern prairies of North America during the past two millennia.

Six high-resolution climatic reconstructions, based on diatom analyses from lake sediment cores from the northern prairies of North America, show that shifts in drought conditions on decadal through multicentennial scales have prevailed in this region for at least the last two millennia. The predominant broad-scale pattern seen at all sites is a major shift in moisture regimes from wet to dry, or vice versa (depending on location), that occurred after a period of relative stability. These large-scale shifts at the different sites exhibit spatial coherence at regional scales. The three Canadian sites record this abrupt shift between anno Domini 500 and 800, and subsequently conditions become increasingly variable. All three U.S. sites underwent a pronounced change, but the timing of this change is between anno Domini 1000 and 1300, thus later than in all of the Canadian sites. The mechanisms behind these patterns are poorly understood, but they are likely related to changes in the shape and location of the jet stream and associated storm tracks. If the patterns seen at these sites are representative of the region, this observed pattern can have huge implications for future water availability in this region.

Hospitalizations for total hip arthroplasty after renal transplantation in the United States.

The national incidence of and factors associated with total hip arthroplasty in renal transplant recipients has not been reported. We conducted an historical cohort study of 42096 renal transplant recipients in the United States between 1 July 1994 and 30 June 1998. Primary outcomes were associations with hospitalizations for a primary discharge code of total hip arthroplasty (ICD9 procedure code 81.51x) within 3 years after renal transplant using Cox regression. Renal transplant recipients had a cumulative incidence of total hip arthroplasty of 5.1 episodes/1000 person-years, which is 5-8 times higher than reported in the general population. Avascular necrosis of the hip was the most frequent primary diagnosis associated with total hip arthroplasty in this population (72% of cases). Repeat surgeries were performed in 27% of patients with avascular necrosis, vs. 15% with other diagnoses. Total hip arthroplasty was more frequent in transplant recipients who were older, African American, or who experienced allograft rejection. Mortality after total hip arthroplasty was 0.21% at 30 days and 15% at 3 years, similar to the mortality of all transplant recipients. The most common indication for total hip arthroplasty after renal transplant is avascular necrosis of the hip, in contrast to the general population. Although repeat surgeries are common, total hip arthroplasty is well tolerated and is not associated with increased mortality in this population.

Hospitalized avascular necrosis after renal transplantation in the United States.

BACKGROUND: The national incidence of and risk factors for hospitalized avascular necrosis (AVN) in renal transplant recipients has not been reported. METHODS: This historical cohort study consisted of 42,096 renal transplant recipients enrolled in the United States Renal Data System (USRDS) between 1 July 1994 and 30 June 1998. The data source was USRDS files through May 2000. Associations with hospitalizations for a primary diagnosis of AVN (ICD-9 codes 733.4x) within three years after renal transplant were assessed in an intention-to-treat design by Cox regression analysis. RESULTS: Recipients had a cumulative incidence of 7.1 episodes/1000 person-years from 1994 to 1998. The two-year incidence of AVN did not change significantly over time. Eighty-nine percent of the cases of AVN were due to AVN of the hip (733.42) and 60.2% of patients with AVN underwent total hip arthroplasty (THA); these percentages did not change significantly over time. In the Cox regression analysis, an earlier year of transplant, African American race [adjusted hazard ratio (AHR), 1.65, 95% confidence interval (CI) 1.33 to 2.03], allograft rejection (AHR 1.67, 95% CI 1.35 to 2.07), peritoneal dialysis (vs. hemodialysis; AHR 1.44, 95% CI 1.15 to 1.81), and diabetes (AHR 0.41, 95% CI 0.27 to 0.64) were the only factors independently associated with hospitalizations for AVN. CONCLUSIONS: The incidence of AVN did not decline significantly over time in the renal transplant population. Patients with allograft rejection, African American race, peritoneal dialysis and earlier date of transplant were at the highest risk of AVN, while diabetic recipients were at a decreased risk.

Abnormal expression of various molecular forms and distribution of T cell receptor zeta chain in patients with systemic lupus erythematosus.

OBJECTIVE: T cells from the majority of patients with systemic lupus erythematosus (SLE) display antigen receptor-mediated signaling aberrations associated with defective T cell receptor (TCR) zeta chain expression. The TCR zeta chain, a critical signaling molecule, exists in multiple molecular forms and membrane fractions with distinct functions in antigen-mediated signaling processes. This study was undertaken to investigate the complete spectrum of expression of the different forms and distribution of the TCR zeta chain in SLE T cells. METHODS: T cells were isolated from 48 SLE patients and 21 healthy subjects. The expression of various forms of the TCR zeta chain was investigated by immunoblotting with specific antibodies. The lipid raft-associated form of the zeta chain was determined by quantitating the solubilized zeta chain after disruption of the lipid rafts by cholesterol depletion using methyl-betacyclodextrin. The distribution of the zeta chain was investigated by fluorescence microscopy. RESULTS: The phosphorylated 21- and 23-kd forms and the detergent-insoluble membrane-associated form of the TCR zeta chain and alternatively spliced zeta chain were significantly decreased in SLE T cells. In contrast, major ubiquitinated forms of the zeta chain were increased in these cells. We also identified up-regulation of a novel 14-kd form of the zeta chain in SLE T cells. Resting SLE T cell membranes had an increased percentage of the residual membrane-bound zeta chain in the lipid rafts. Fluorescence microscopy findings indicated that the residual zeta chain is more clustered on the cell membranes of SLE T cells. CONCLUSION: These results suggest that, in addition to the 16-kd form, expression of other molecular forms and fractions of the TCR zeta chain as well as its membrane distribution are abnormal in SLE T cells. Increased lipid raft association and surface clustering of the zeta chain may explain the molecular mechanisms underlying the signaling abnormalities in these cells.