Charge transfer doping of silicon.

We demonstrate a novel doping mechanism of silicon, namely n-type transfer doping by adsorbed organic cobaltocene (CoCp2*) molecules. The amount of transferred charge as a function of coverage is monitored by following the ensuing band bending via surface sensitive core-level photoelectron spectroscopy. The concomitant loss of electrons in the CoCp2* adlayer is quantified by the relative intensities of chemically shifted Co2p components in core-level photoelectron spectroscopy which correspond to charged and neutral molecules. Using a previously developed model for transfer doping, the evolution in relative intensities of the two components as a function of coverage has been reproduced successfully. A single, molecule-specific parameter, the negative donor energy of -(0.50±0.15) eV suffices to describe the self-limiting doping process with a maximum areal density of transferred electrons of 2×1013 cm-2 in agreement with the measured downward band bending. The advantage of this doping mechanism over conventional doping for nanostructures is addressed.

Charge-induced distortion and stabilization of surface transfer doped porphyrin films.

The interaction between zinc-tetraphenylporphyrin (ZnTPP) and fullerenes (C60 and C60F48) are studied using ultraviolet photoelectron spectroscopy (UPS) and scanning tunneling microscopy (STM). Low temperature STM reveals highly ordered ZnTPP monolayers on Au(111). In contrast to C60, a submonolayer coverage of C60F48 results in long-range disorder of the underlying single ZnTPP layer and distortion of individual ZnTPP molecules. This is induced by substantial charge transfer at the organic-organic interface, revealed by the interface energetics from UPS. However, a second layer of ZnTPP prevents C60F48 guests from breaking the self-assembled porphyrin template. This finding is important for understanding the growth behaviour of "bottom-up" functional nanostructures involving strong donor-acceptor heterojunctions in molecular electronics.

Surface transfer doping of hydrogen-terminated diamond by C60F48: energy level scheme and doping efficiency.

Surface sensitive C1s core level photoelectron spectroscopy was used to examine the electronic properties of C(60)F(48) molecules on the C(100):H surface. An upward band bending of 0.74 eV in response to surface transfer doping by fluorofullerene molecules is measured. Two distinct molecular charge states of C(60)F(48) are identified and their relative concentration determined as a function of coverage. One corresponds to ionized molecules that participate in surface charge transfer and the other to neutral molecules that do not. The position of the lowest unoccupied molecular orbital of neutral C(60)F(48) which is the relevant acceptor level for transfer doping lies initially 0.6 eV below the valence band maximum and shifts upwards in the course of transfer doping by up to 0.43 eV due to a doping induced surface dipole. This upward shift in conjunction with the band bending determines the occupation of the acceptor level and limits the ultimately achievable hole concentration with C(60)F(48) as a surface acceptor to values close to 10(13) cm(-2) as reported in the literature.

Peritoneal dialysis underscores its merits in portal hypertensionrelated and nephrogenic ascites.

In the Western world, peritoneal dialysis (PD) is less frequently applied as substitute therapy in end-stage renal disease (ESRD). In the Netherlands the use of PD has decreased from 30.3 to 13.5% due to several factors, but not due to lower PD-related outcome. The lower penetrance of PD diminishes experience with and exposure of young professionals to this treatment modality. This does not enhance a free and motivated choice among renal replacement therapies for patients who cannot be transplanted pre-emptively. To rejuvenate interest in PD and to underscore its merits, we would like to share the use of PD on two extraordinary occasions, where PD was the only way out. Ascites due to portal hypertension with profound gastrointestinal haemorrhage and nephrogenic ascites poses major management challenges in ESRD patients. In conclusion, PD came to the rescue and tremendously increased quality of life in the patients presented. To be readily available, a certain penetrance of and expertise in PD as renal replacement therapy is warranted.

Pancreas transplantation restores epinephrine response and symptom recognition during hypoglycemia in patients with long-standing type I diabetes and autonomic neuropathy.

Impaired epinephrine secretion and symptom unawareness are characteristic of severe hypoglycemia in individuals with long-standing type I diabetes. Recently, the avoidance of clinical hypoglycemia has been reported to improve epinephrine and symptom responses to hypoglycemia in type I patients. However, the extent to which these defects can be restored in individuals with long-standing type I diabetes and autonomic neuropathy has not been assessed, nor has it been determined whether pancreas transplantation, which not only obviates hypoglycemia but also prevents hyperglycemia, results in the complete recovery of either epinephrine response or symptom awareness during insulin-induced hypoglycemia. We performed stepped hypoglycemic clamp studies in successful pancreas transplantation recipients to assess epinephrine and other counterregulatory hormone responses during hypoglycemia and to determine the degree to which hypoglycemic symptom recognition could be restored. Thirteen pancreas transplant recipients and matched control subjects were studied utilizing stepped hypoglycemic clamp protocol to achieve target glucose levels of 3.9, 3.3, 2.8, and 2.2 mmol/l (70, 60, 50, and 40 mg/dl, respectively). Plasma epinephrine response was significantly greater in healthy control subjects and pancreas transplant patients compared with type I subjects at the glucose plateaus of 3.9, 3.3, and 2.8 mmol/l. However, epinephrine response in pancreas transplant recipients was significantly less than that seen in either healthy control subjects or nondiabetic kidney transplant recipients at each of these glucose plateaus. The magnitude of the epinephrine response in pancreas transplant type I patients did not correlate with either the duration of diabetes, the duration of transplantation, or the measures of autonomic nerve function. Hypoglycemic symptom recognition was significantly greater in pancreas transplant subjects than type I patients and did not differ between pancreas transplant and control groups. No improvement in norepinephrine response was observed after pancreas transplantation, while glucagon responses to hypoglycemia were normalized in pancreas transplant patients. In conclusion, these studies uniquely demonstrate that successful pancreas transplantation improves epinephrine response and normalizes hypoglycemia symptom recognition in patients with long-standing diabetes and established autonomic neuropathy. No correlation was observed between the severity of autonomic neuropathy or the duration of diabetes and the recovery of either the epinephrine or symptom responses to hypoglycemia.

Successful islet autotransplantation in humans: functional insulin secretory reserve as an estimate of surviving islet cell mass.

Islet autotransplantation for treatment of chronic painful pancreatitis in nondiabetic patients reliably establishes normoglycemia and phasic insulin secretion and can achieve prolonged insulin independence. Whether functional transplanted beta-cell reserve is normal after intrahepatic islet transplantation is not known, nor is it known whether conventional measures of insulin secretion accurately reflect the functional beta-cell mass. To determine insulin secretory reserve after islet transplant, we performed studies of glucose potentiation of arginine-induced insulin secretion (GPAIS) in eight recipients of intrahepatic islet autotransplants. All eight subjects (and matched, healthy controls) were studied cross-sectionally 49 +/- 12 months posttransplant, and four subjects were studied pre- and posttransplant. Subjects had received a mean +/- SE of 479,000 +/- 79,000 islets, and all were insulin independent and normoglycemic at the time of study. Acute insulin responses to arginine, glucose, and GPAIS were significantly reduced after islet transplantation in both study groups. Importantly, the magnitudes of these three responses were highly correlated to the mass of islets transplanted (response to glucose: r = 0.84, P < 0.01; response to arginine: r = 0.69, P < 0.05; response to GPAIS = 0.81, P < 0.01). Data from hemipancreatectomized and normal control subjects generally agreed with the regression lines. These findings demonstrate that despite normoglycemia and insulin independence, recipients of intrahepatic islet transplantation have significantly reduced functional beta-secretory reserve and that after islet transplantation, functional beta-cell mass can be estimated by measurements of glucose and arginine-induced insulin responses. Thus, these measurements can be used to estimate the mass and functional capacity of islets surviving intrahepatic transplantation in humans.

Insulin secretion and sensitivity after simultaneous pancreas-kidney transplantation estimated by continuous infusion of glucose with model assessment.

BACKGROUND: Monitoring of insulin secretion and sensitivity after pancreas transplantation remains a practical problem. METHODS: We introduced the simple structural model, continuous infusion of glucose with model assessment (CIGMA), to obtain insulin secretion and insulin sensitivity estimations after 35 successful simultaneous pancreas-kidney transplantations. Eighteen non-diabetic kidney transplant recipients were used as control group. RESULTS: The baseline characteristics were equal between the two groups except for higher fasting insulin levels in the pancreas transplant group. After the 1-hr CIGMA glucose load, the pancreas transplant group reached a mean +/- SD blood glucose of 8.2+/-1.7 mmol/L compared with 7.3+/-1.0 mmol/L in the control group (P = 0.05). Concurrent stimulated insulin and C-peptide levels were 48+/-28 mU/L and 2.3+/-0.9 nmol/L in the pancreas transplant group compared with 36+/-21 mU/L and 2.9+/-1.1 nmol/L in the control group (P = 0.1 and P = 0.03, respectively). Both the CIGMA estimation for secretion as well as the CIGMA estimation for sensitivity were lower in pancreas transplant group (P = 0.003 and P = 0.01, respectively). Mean +/- SE coefficients of variation for the model estimations were 15+/-4% for secretion and 17+/-6% for sensitivity. CONCLUSIONS: We conclude that CIGMA can be used clinically to evaluate carbohydrate metabolism in pancreas-kidney transplant recipients. These patients have a reduction in insulin secretory capacity and evidence of more insulin resistance than non-diabetic kidney transplant recipients.

Pancreatitis-associated protein: a putative marker for pancreas graft rejection.

BACKGROUND: Graft rejection is one of the major causes of graft loss after pancreas transplantation. Pancreatitis-associated protein (PAP) is synthesized by the pancreas due to pancreatic inflammation and has shown to be a good serum marker for injury of the pancreas. It may also be potentially useful in the early recognition of rejection and may thus improve pancreas survival. METHODS: We retrospectively evaluated PAP as an early serum marker of pancreas graft rejection in a cross-sectional study in which immunohistochemical analysis of pancreas biopsies was undertaken using antibodies against PAP. PAP concentrations were also measured in sera of blood donors and in patients with renal failure, renal replacement therapy, kidney transplantation alone, and simultaneous pancreas-kidney transplantation. RESULTS: All patients had elevated PAP serum levels compared with blood donors (median PAP: 22 ng/ml, range: 5-75 ng/ml; P<0.0001). Patients on renal replacement therapy had higher values than patients with renal failure (median: 420 ng/ml and 150 ng/ml, respectively). There was a strong inverse correlation between PAP levels and creatinine clearance (P<0.001). PAP values in simultaneous pancreas-kidney transplantation patients with histological rejection were significantly higher than values in those who were clinically stable (median: 925 ng/ml and 322 ng/ml, respectively; P=0.006). Rejection was significantly associated with PAP staining of acinar cell surface. There was also a significant correlation between surface positivity of staining and serum PAP levels (P=0.008). No positive PAP staining was observed in concurrently collected biopsies of renal allografts undergoing rejection. CONCLUSIONS: Serum PAP levels appear to strongly correlate with creatinine clearance measurements. In patients with a pancreas-kidney transplantation, PAP may prove to be a useful biological and histological marker of pancreatic graft rejection.

[Tetany due to excessive use of alcohol: a possible magnesium deficiency]. / Tetanie bij overmatig alcoholgebruik: mogelijk een magnesiumtekort.

Two alcoholic patients, a woman aged 64 and a man aged 69 years, were admitted with tetany. Both had severe electrolyte disorders, with low plasma levels of calcium, magnesium and potassium. Following mineral supplementation both patients recovered. Hypomagnesaemia plays a central role in the pathophysiology of this syndrome. Chronic alcohol abuse results in hypomagnesaemia in 30% of patients by decreasing renal tubular reabsorption. Hypomagnesaemia leads to suppression of parathyroid-hormone secretion, parathyroid-hormone resistance and vitamin-D suppression, resulting in hypocalcaemia. Hypomagnesaemia also causes kaliuresis leading to hypokalaemia. Supplementation with magnesium is crucial in the treatment of this combined electrolyte disorder.

Infectious disease complications of simultaneous pancreas kidney transplantation.

BACKGROUND: Although technical success rate of simultaneous pancreas kidney (SPK) transplantation in insulin-dependent diabetes mellitus (IDDM) patients with diabetic nephropathy has improved, morbidity remains high due to infection and rejection. The purpose of this study was to analyse infections encountered in our series of SPK transplants, using a restrictive antibiotic prophylaxis policy. METHODS: We reviewed all infectious diseases after 66 consecutive bladder-drained SPK transplantations in 64 IDDM patients with end-stage renal disease due to diabetic nephropathy. During follow-up, the perioperative antibiotic regimen was altered (from 5 days preemptive therapy with multiple drugs to 1 day prophylaxis with cefamandole), and long-term viral prophylaxis (high-dose aciclovir) was introduced. For post-operative urinary tract or opportunistic infection, no prophylaxis was given. RESULTS: Overall mean infection rate was 2.9 infections/ patient/year after a mean follow-up of 2.3 years. Surgical site infections (SSI) were seen in 30% of the patients, with Enterococci present in 47%. Logistic regression showed one day cefamandole prophylaxis to be associated with SSI, but there was no significant influence of SSI on either graft or patient survival. Forty-eight percent of all infections were lower urinary tract infections (UTI). There were 59 first UTIs (89%), probably related to long-term Foley catheter use, and 47 second UTIs (71%). Subsequent UTIs were not microbiologically related to first UTIs. Cytomegalovirus (10 patients) and other opportunistic agents did not cause mortality or graft loss. Five grafts were lost due to infection (SSI three times, post-transplant lymphoproliferative disease twice). Only one patient died because of infection (2%). CONCLUSIONS: Infectious diseases after SPK transplantation caused significant morbidity but did not influence either patient or graft survival. A change in prophylactic policy for both SSI as well as recurrent UTI, combined with earlier Foley removal, may lower incidences of these infections.

Low bone mass and high incidence of fractures after successful simultaneous pancreas-kidney transplantation.

BACKGROUND: Simultaneous pancreas-kidney transplantation successfully restores normoglycaemia and corrects uraemia in insulin-dependent diabetes mellitus patients with end-stage renal failure due to diabetic nephropathy. Low bone turnover and cortical osteopenia are often associated with the diabetic state and corticosteroid-induced bone loss, predominantly trabecular, is expected post-transplantation. Little is known, however, about the resultant long-term effects of successful simultaneous pancreas-kidney transplantation on bone mass and consequent fracture rate. METHODS: We studied bone and mineral metabolism, bone densitometry (using dual X-ray absorptiometry), and fracture prevalence in a cross-sectional design in 31 IDDM patients at least 12 months (mean 40+/-23 months) after successful simultaneous pancreas-kidney transplantation. RESULTS: All patients were insulin-independent and mean creatinine clearance was 64 +/- 21 ml/min. Secondary hyperparathyroidism, probably multifactorial, was found in 55% of the patients. Increased bone turnover as suggested by elevated osteocalcin concentrations was present in 45% of the patients. Twenty-three per cent of patients had a significant decrease in bone mass (T score < -2.5 SD) at the predominantly trabecular lumbar spine sites. In contrast, 58% demonstrated a similarly low bone mass at the femoral neck, where cortical bone is prevalent. Forty-five per cent of patients had documented vertebral (mostly asymptomatic) and non-vertebral fractures. CONCLUSION: Our findings suggest that low bone mass is prevalent after successful simultaneous pancreas-kidney transplantation, and that this is associated with a high incidence of fractures, representing a cause for concern with regard to long-term morbidity. Contrary to the predominant trabecular bone loss expected with corticosteroid excess, cortical bone loss was prevalent in our patients, possibly due to pre-existing diabetic state and persistent hyperparathyroidism.

Effect of simultaneous pancreas-kidney transplantation on mortality of patients with type-1 diabetes mellitus and end-stage renal failure.

BACKGROUND: Long-term prognosis of patients with type-1 diabetes mellitus and end-stage renal failure appears to be better after kidney transplantation compared with dialysis. Controversy exists about the additional benefit of a simultaneously transplanted pancreatic graft. We studied the effect on mortality of simultaneous pancreas-kidney transplantation compared with kidney transplantation alone from regional differences in transplantation protocols. METHODS: All 415 patients with type-1 diabetes (aged 18-52 years) who started renal-replacement therapy in the Netherlands between 1985 and 1996 were included in the analysis. Patients were allocated to a centre based on their place of residence at onset of renal failure. In the Leiden area, the primary intention to treat was with a simultaneous pancreas-kidney transplantation, whereas in the non-Leiden area, kidney transplantation alone was the predominant type of treatment. All patients were followed up to July, 1997. Analyses, mortality, and graft failure were by Cox proportional-hazard model adjusted for age and sex. FINDINGS: Simultaneous pancreas-kidney transplantation was done in 41 (73%) of 56 transplanted patients in the Leiden area compared with 59 (37%) of 158 transplanted patients in the non-Leiden area (p<0.001). The hazard ratio for mortality after the start of renal-replacement therapy was 0.53 (95% CI, 0.36-0.77, p<0.001) in the Leiden area compared with the non-Leiden area. When just the transplanted patients were analysed the mortality ratio was 0.4 (95% CI 0.20-0.77, p=0.008) and was independent of duration of dialysis and early transplant-related deaths. Equal survival was found for patients on dialysis only. INTERPRETATION: These data support the hypothesis that simultaneous pancreas-kidney transplantation prolongs survival in patients with diabetes and end-stage renal failure.

Interstitial and vascular pancreas rejection in relation to graft survival.

To examine the incidence of interstitial and vascular rejection in pancreas allografts and its impact on graft survival, we studied 36 percutaneous pancreas biopsies and 10 pancreas transplantectomy specimens from 32 patients who had undergone simultaneous pancreas-kidney transplantation. Interstitial rejection (IR) was predominantly found in the biopsies, while vascular rejection (VR) was most prominent in the transplantectomies. Pancreas graft survival was significantly decreased for pancreas graft that had suffered from vascular rejection when compared to those with only interstitial rejection. Potential rejection markers, i.e., serum amylase, glucose, creatinine, and urinary amylase, did not correlate with histological signs of rejection, although increased levels of serum amylase were, in all but one case, associated with rejection. We conclude that a percutaneous pancreas biopsy remains the most reliable method to determine pancreas rejection, and that by distinguishing between IR and VR, a pancreas biopsy may provide important diagnostic as well as prognostic information.