David Tatman

Successful unrelated umbilical cord blood transplantation in children with Shwachman-Diamond syndrome

Summary:Shwachman-Diamond syndrome (SDS) is an autosomal recessive disorder characterized by pancreatic insufficiency and variable degrees of neutropenia. SDS patients are at risk of developing myelodysplasia, aplastic anemia, and leukemic transformation. The role and timing of allogeneic hematopoietic stem cell transplantation (HSCT) in SDS remain controversial. We report three SDS patients with severe aplasia transplanted using unrelated umbilical cord blood (UCB). Patients received melphalan (180 mg/m2), etoposide (1200 mg/m2), anti-thymocyte globulin (90 mg/kg), and total lymphoid irradiation (500 cGy); graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporine and prednisone. Myeloid engraftment occurred promptly with absolute neutrophil count >500 cells/mm3 on day 15±5 and all patients displayed 100% donor chimerism by 2 months post transplant. The major complication of transplant was GVHD, with all patients developing grade II or III acute GVHD, one progressing to chronic extensive GVHD. Patients are alive 309, 623, and 2029 days post transplant. Factors important in HSCT outcome for SDS may include transplantation at a young age, avoidance of cyclophosphamide, and adequate GVHD prophylaxis. Importantly, these cases also suggest that unrelated UCB, in the absence of a matched family member, is an excellent alternative stem cell source for SDS patients undergoing HSCT.

Reduced Intravascular Catheter-related Infection by Routine Use of Antibiotic-bonded Catheters in a Surgical Intensive Care Unit

We report a comparative analysis of intravascular catheter-related infection before and after routine use of antibiotic-bonded catheters in an intensive care unit. Cefazolin-bonded catheters were placed in patients requiring catheterization for at least 3 days, or with remote infection, standard catheters at other times. One thousand forty-five catheters (259 patients) over 6 months were compared with 801 (236 antibiotic-bonded, 565 standard) catheters (239 patients) the next 6 months. After use of antibiotic-bonded catheters, we found: 1.7% catheters infected versus 3.7% (p = 0.01); catheter-associated bacteremia 0.1% versus 1.3% (p < 0.005); catheter-related infection rate 4.39 versus 10.73 per 1000 patient days (p < 0.005), and 5.06 versus 11.47 per 1000 catheter days (p < 0.01); and cumulative risk of infection decreased (p < 0.005). Antibiotic-bonded catheters were used with more remote infections (52% versus 27%, p < 0.001), had longer indwelling time (4.4 versus 3.1 days, p = 0.0001), and more were inserted over a guide wire (66% vs. 28%, p < 0.001). In conclusion routine use of antibiotic-bonded catheters was associated with a significant reduction in infectious complications.

Swine model of early adult respiratory distress syndrome induced by intravenous ethchlorvynol

Although ethchlorvynol (ECV) has been used to induce pulmonary damage in animals, changes after injection of this drug have not been studied, nor has the stability of the animal been assessed after injection. Continuously monitored hemodynamic and respiratory changes were followed during and after iv injection of 55 mg/kg ECV in ethanol into anesthetized, paralyzed, and ventilated swine (n = 5) and compared to changes in a control group given ethanol alone (n = 5). Arterial and mixed venous saturations were measured by fiberoptic vascular catheters and oxygen exchange by a gas monitor. Twelve direct and derived variables were monitored every 20 sec using a computer data acquisition system. Arterial oxygen saturation was kept at 90 +/- 2% by adjustment of FIO2. Ethanol produced only transitory changes during infusion. Significant elevations in pulmonary vascular resistance (PVR), shunt (Qsp/Qt) and deadspace (VD/VT) were observed during and after ECV. These were unaccompanied by changes in cardiac output or arterial pressure. PVR increased by 137%, Qsp/Qt by 67%, and VD/VT by 28% over 30 min. These changes were then sustained in the postinfusion period, producing a stable model of early adult respiratory distress syndrome for 3.5 h.

Reduced venous admixture in hemorrhagic hypovolemia: maintenance of arterial oxygenation by selective pulmonary vascular collapse

In nine anesthetized and ventilated swine, a microcomputer calculated cardiac output, venous admixture (Qsp/Qt) and physiologic deadspace (VD/VT) every 20 sec, utilizing dual oximetry and a gas exchange analyzer. After lung injury with ethchlorvynol (ECV), animals were bled 40% blood volume over 40 min. Mean cardiac output decreased 7.0 to 2.2 L/min (p < .05) accompanied by a decrease in mean Qsp/Qt from 0.28 to 0.14 (p < .05) and an increase in mean VD/VT from 0.39 to 0.54 (p < .05). Arterial Hgb saturation (Sao2) increased from 88 ± 7% to 90 ± 6%. On regression of all data points for each variable, Qsp/Qt had a positive correlation with cardiac output (r = .90), mean arterial pressure (MAP, r = .87), mean pulmonary artery pressure (MPAP, r = .86), and mixed venous Hgb saturation (Svo2, r = .89, p < .001). VD/VT had an inverse correlation with cardiac output (r = −.90), MAP (r = −.82), Qsp/Qt (r = −.83), MPAP (r = −.77), and Svo2 (r = −.92, p < .001). The decreasing Qsp/Qt and increasing VD/VT, with decreasing pulmonary perfusion pressures, were attributed to selective loss of perfusion to alveoli with low ventilation/perfusion ratios. (Crit Care Med 1990; 18:208)