Graft-versus-host disease after simultaneous pancreas-kidney transplantation: a case report and review of the literature.

Graft-versus-host disease (GVHD) after solid organ transplantation is rare and usually fatal. We present, to our knowledge, the second successfully treated case in a simultaneous pancreas-kidney (SPK) transplant recipient. A 29-year-old female with end-stage renal disease from type 1 diabetes mellitus received an SPK transplant from a male donor, with rabbit-antithymocyte globulin induction. Twelve days posttransplant, she was readmitted with abdominal pain, nausea and vomiting. She developed leukopenia, abnormal liver enzymes, fever and a skin rash. Skin biopsy showed interface dermatitis consistent with allergic reaction versus GVHD. Fluorescence in situ hybridization of the skin biopsy showed 28% of cells had a Y chromosome confirming GVHD. Short tandem repeats (STR) enriched for CD3+ cells from peripheral blood showed a mixed chimerism. She was successfully treated with a single plasmapheresis to remove antithymocyte globulin, high-dose steroids, photopheresis and high tacrolimus levels (12-15 ng/mL). Five months after transplantation, she has normal renal function and white blood cell count, normal hemoglobin A1C and no evidence of peripheral blood donor chimerism. In conclusion, early diagnosis of GVHD after SPK transplantation may allow successful treatment. STR enriched for CD3+ may be useful to evaluate the response to therapy.

Imaging the phase separation in atomically thin buried SrTiO(3) layers by electron channeling.

A phase-separation instability, resulting in the dewetting of thin SrTiO(3) films grown on Si(100) is shown by scanning transmission electron microscopy. Plan-view imaging of 1-nm thick, buried SrTiO(3) films was achieved by exploiting electron channeling through the substrate to focus the incident 0.2 nm beam down to a 0.04 nm diameter, revealing a nonuniform coverage by epitaxial SrTiO(3) islands and 2 x 1 Sr-covered regions. Density-functional calculations predict the ground state is a coexistence of 2 x 1 Sr-reconstructed Si and Sr-deficient SrTiO(3), in correspondence with the observed islanding.

The safety of dipyridamole in patients undergoing myocardial perfusion scintigraphy prior to lung volume reduction surgery.

Patients with end-stage chronic obstructive pulmonary disease (COPD) undergoing lung volume reduction surgery (LVRS) are at high risk of peri-operative cardiac complications, and myocardial perfusion scintigraphy (MPS) is commonly used for risk stratification. This study prospectively assessed the safety of dipyridamole in these patients and compared the incidence of side-effects (particularly dyspnoea) with that in patients undergoing dipyridamole MPS prior to elective non-cardiothoracic surgery. Fifty patients were enrolled: 25 in the LVRS cohort (13 males, 12 females), with a mean age of 65 years and a mean FEV1 of 0.791, and 25 (with no history of asthma or COPD) in the control cohort (14 males, 11 females), with a mean age of 66 years. Fourteen patients (56%) in each group developed side-effects. Dyspnoea was reported by five patients (20%) in the LVRS and two patients (8%) in the control cohort (P=NS). One patient in each cohort developed severe hypotension and bradycardia. Eight (32%) other patients developed minor side-effects in the LVRS cohort compared with 11 (44%) in the control group. All side-effects responded promptly to intravenous aminophylline. In summary, there was a statistically non-significant increase in the incidence of dyspnoea in patients with end-stage COPD and all side-effects responded to aminophylline. Thus, dipyridamole can be used safely in these patients.

Metabolism and disposition of diethylene glycol in rat and dog.

The disposition of carbon-14-labeled diethylene glycol (DEG) was determined in rats after oral, iv, and dermal administration, and in dogs after oral administration. Oral administration of DEG to rats was by gavage of 50 or 5000 mg/kg doses, or by provision of 0.3 1.0, and 3.0% in drinking water. Oral doses were well absorbed and excreted primarily (approximately 80%) in urine within 24 hr of administration. Greater than half of the dose was excreted unchanged, with 10-30% of the dose appearing as a single metabolite. The metabolite was isolated and characterized by 13C-NMR to be 2-(hydroxy) ethoxyacetic acid (HEAA). Confirmation of identity was provided by synthesis of HEAA and comparison of its NMR spectra and chromatographic behavior with those of the metabolite. Intravenous doses (50 mg/kg) were eliminated by the same routes and at the same rates as those administered orally and exhibited the same metabolic profile. The fate of oral doses of DEG administered to dogs (500 mg/kg) was similar to that of DEG in rats, with about 30% of the administered dose being excreted in urine as HEAA. DEG slowly penetrated the skin of rats after application of 50 mg to a 12-cm2 area. Only about 10% of the dose was absorbed in 72 hr of exposure, and the absorbed dose appeared to have the same fate as doses administered iv or orally. In all studies with rats, excretion of radiolabel in feces and persistence in tissues were low. The highest percentage of conversion to 14CO2 was 7%, found for doses of 0.3% DEG in drinking water.

Effect of intravenous calcium infusions on serum chemistries in neonates.

In 36 newborn infants admitted to the Children's Hospital of Oklahoma, we studied the hypotheses that intravenous bolus infusions of Ca as calcium gluconate over 10 min may (a) result in acute metabolic acidosis, (b) increase serum osmolality, (c) increase serum free bilirubin, and (d) decrease serum phosphorus concentrations. All infants received 18 mg/kg of elemental calcium, as either a 5 or 10% solution of calcium gluconate. Blood ionized calcium (iCa) rose significantly with i.v. bolus Ca infusion (p less than 0.005) and blood pH and serum P declined significantly (p less than 0.05) with i.v. bolus Ca infusion in infants. Serum free bilirubin was not significantly altered. Serum osmolality rose significantly from baseline with bolus infusion of Ca as a 10% calcium gluconate solution and did not change significantly with bolus infusion of a diluted 5% solution. In neonates, intravenous bolus calcium infusion (a) decreases blood pH, (b) infusion of 10% but not 5% calcium gluconate increases serum osmolality, (c) serum free bilirubin concentrations were not altered, and (d) serum phosphorus concentrations were decreased.

Hypercalcitoninemia and hypocalcemia in acutely ill children: studies in serum calcium, blood ionized calcium, and calcium-regulating hormones.

We studied the hypotheses that serum calcium and blood ionized calcium would be low in acutely ill children and would rise with clinical improvement. In 15 children admitted to the pediatric intensive care unit, the blood ionized calcium level was 4.45 +/- 0.06 mg/dl (1.11 +/- 0.015 mmol/L) on entry versus 5.17 +/- 0.03 mg/dl (1.29 +/- 0.01 mmol/L) in control subjects (p less than 0.005), rose significantly on days 2 and 3, and was 5.12 +/- 0.04 mg/dl (1.28 +/- 0.01 mmol/L) at discharge (p less than 0.005). Changes in serum calcium level were similar, whereas serum magnesium and phosphorus levels were normal and did not change. Basal serum parathyroid hormone concentrations were elevated, rose further during the study, and were normal at discharge. Serum parathyroid hormone levels correlated inversely with blood ionized calcium levels, indicating that compensatory hyperparathyroidism occurs with low blood ionized calcium concentrations. Basal serum calcitonin values were evaluated on entry and decreased with clinical improvement. Serum calcitonin levels correlated significantly with low blood ionized calcium levels, indicating that hypercalcitoninemia may play a role in the pathogenesis of hypocalcemia in these children. Urine calcium excretion was not increased in the four children studied. We speculate that with clinical improvement, a rise in serum parathyroid hormone levels and a decline in serum calcitonin levels may help restore normocalcemia in these acutely ill children.

Lowered serum Ca, blood ionized Ca, and unresponsive serum parathyroid hormone with oral glucose ingestion in infants of diabetic mothers.

Oral glucose ingestion may lower serum Ca in infants of diabetic mothers (IDMs). Six metabolically stable IDMs were studied following ingestion of 1.7 +/- 0.1 g/kg (mean +/- SE) of glucose over 20 min and serum Ca, Mg, P, blood iCa, serum PTH, and CT were measured at 0, 1/2, 1, and 2 h. Data obtained in IDMs were compared with previously reported findings in 10 normal neonates. In IDMs as in normal neonates, serum Ca, Mg, P declined significantly after oral glucose ingestion. Blood Ca2+ was significantly lower at +1/2 h in IDMs versus normal neonates, and by analysis of covariance, trends in blood Ca2+ were significantly different in IDMs versus normal neonates, (p less than 0.05). Serum PTH concentrations were unaltered in IDMs versus a significant rise in serum PTH noted in normal neonates. The difference between the two groups was significant statistically (p less than 0.05). Baseline serum CT was elevated in both groups and did not change. Thus, in IDMs responses to oral glucose ingestion differs from that seen in normal neonates as follows: blood Ca2+ is lowered in IDMs versus normal neonates, and serum parathyroid hormone (PTH) does not respond to a decline in blood Ca2+ in IDMs, whereas in normal neonates serum PTH rises and blood Ca2+ is maintained. We speculate that relative parathyroid gland unresponsiveness occurs in IDMs, which may result in lowered blood Ca2+ after oral glucose ingestion in these infants.

Decline in serum calcium, magnesium, and phosphorus values with oral glucose in normal neonates: studies of serum parathyroid hormone and calcitonin.

In 10 normal term infants aged 52 +/- 2.5 hours, serum calcium, magnesium, phosphorus, ionized calcium, parathyroid hormone, and calcitonin were studied at 0, 1/2, 1, and 2 hours after administration of 1.77 +/- 0.08 gm/kg glucose orally over 20 minutes. In response to glucose administration, serum glucose concentration rose and serum P, Ca, and Mg concentrations fell. Serum PTH concentration rose significantly, and blood ionized Ca and pH were unaltered. Serum calcitonin was elevated, as compared with adult values, and did not change. We suggest that in neonates, as in adults, oral ingestion of glucose lowers serum Ca, Mg, and P, and a compensatory rise in serum PTH concentration maintains blood ionized Ca concentration.

Effect of hypocalcemia on cardiac function in very-low-birth-weight preterm neonates: studies of blood ionized calcium, echocardiography, and cardiac effect of intravenous calcium therapy.

Traditionally, in infants, a serum calcium value less than 7.0 mg/dL is considered to impair cardiac function. In very-low-birth-weight infants, we studied the hypotheses that decline in serum calcium to 6.0 mg/dL (1) would not impair cardiac function and (2) ionized calcium would remain greater than 3.0 mg/dL. We also evaluated the effect of calcium infusion on cardiac function. We studied 15 normokalemic and normonatremic infants whose birth weights were 822 to 1,450 g and were less than 32 weeks' gestation. When serum calcium declined to less than 6.0 mg/dL, 18 mg/kg of calcium as 5% calcium gluconate was infused for 10 minutes. Serum total calcium concentration, blood ionized calcium concentration, ECG, and M-mode echocardiogram were obtained on entry into the study, when the infants were hypocalcemic, immediately after treatment with calcium, and eight hours after treatment. Ionized calcium values were calculated based on serum total calcium and serum protein, and corrected calcium values were calculated based on serum total calcium, serum albumin, and blood pH. In all infants, serum calcium value declined to less than 7.0 and in eight infants to less than 6.0 mg/dL. Assessment of heart rate, systolic blood pressure, ejection fraction, left ventricular systolic time interval, right ventricular systolic time interval, fiber shortening index, and left ventricular mean velocity of circumferential fiber shortening showed no significant alteration from baseline during hypocalcemia or in association with intravenous slow bolus infusion of 18 mg/kg of calcium.(ABSTRACT TRUNCATED AT 250 WORDS)

Phase I-II study of isotopic immunoglobulin therapy for primary liver cancer.

A phase I-II study of isotopic immunoglobulin therapy was performed in 18 patients with primary liver cancer; 14 were evaluable for toxicity. The patients received a dose of 37-157 millicuries of 131I-labeled antibody. The dose-limiting factor appears to be hematologic toxicity, especially thrombocytopenia. An objective antitumor effect was seen in six of nine patients who were evaluable for response. Present results suggest that further clinical studies with isotopic immunoglobulin are indicated.