Increased erythropoiesis and elevated erythropoietin in infants born to diabetic mothers and in hyperinsulinemic rhesus fetuses.

The pathogenesis of the increased erythrocytosis and extramedullary erythropoiesis observed in infants of diabetic mothers (IDM) has been obscure. In the present studies, IDM were found to have elevated umbilical plasma erythropoietin (Ep) concentrations by radioimmunoassay. 22 of 61 IDM (36%) had levels above the range of 28 nonasphyxiated, appropriately grown normal infants. In 16 controls and 20 IDM, plasma Ep correlated directly with plasma insulin (P less than 0.001, r = 0.73). To investigate this relationship further, a chronic rhesus model was studied with continuous fetal hyperinsulinemia for 21 d in utero in the last third of pregnancy. In five experimental fetuses, plasma insulin levels averaged 4,210 microU/ml at delivery, whereas plasma Ep was above the range of six controls. In addition, the experimental fetuses had elevated reticulocyte counts in umbilical cord blood. The mechanism for the increased plasma Ep associated with hyperinsulinemia in the fetus is unexplained but may be mediated by fetal hypoxia.

Functional nature of glomerular injury in progressive diabetic glomerulopathy.

We describe in physiological terms the increasing glomerular capillary wall (GCW) dysfunction of 20 patients with diabetic glomerulopathy and heavy proteinuria. The clearances of uncharged polysaccharide markers of graded size were used to probe the glomerular filter on three occasions over a 24-mo period. The findings were analyzed with a theoretical model of solute transport that depicts most of the GCW as an isoporous membrane and the minor portion as a nondiscriminatory shunt pathway. Initially, the mean glomerular ultrafiltration coefficient Kf is computed to have been 3-5 times lower and mean pore radius of the major membrane component (r0) 2 A smaller than normal control values. In contrast, the model computes the fraction of filtrate volume permeating the nondiscriminatory shunt pathway (omega 2) to have been sixfold elevated above control values and to have correlated strongly in individual patients with the fractional clearances of albumin (r = .72) and of IgG (r = .73). Sequential studies after 12 and 24 mo revealed an invariable decline in glomerular filtration rate (GFR). Fractional clearances of albumin and IgG increased with time in most patients but declined in a few instances (20-25%). Change in omega 2 tended to occur in parallel with fractional protein clearance, regardless of its direction. We conclude that in progressive diabetic glomerulopathy GFR declines because of a loss by glomerular capillaries of ultrafiltration capacity, proteinuria is largely a consequence of increasingly impaired barrier-size selectivity, and the foregoing injuries reflect damage to different parts of the GCW and may become dissociated from one another with the passage of time.

Effects of pregnancy on hemoglobin AIc in normal, gestational diabetic, and diabetic women.

Hemoglobin AIc, a normal minor hemoglobin, has glucose linked by a Schiff base to the N-terminal end of the beta chain. The glucose interferes with the binding of 2,3 diphosphoglycerate, probably resulting in an increased affinity of that hemoglobin for oxygen. Hb AIc is increased to twice normal levels in juvenile-onset (insulin-dependent) diabetes. In the present studies, the Hb AIc, when expressed as per cent of total hemoglobin, was found to be elevated slightly in pregnany normal (m = 6.97 per cent), pregnant nondiabetic obese (m = 6.89 per cent), and gestationally diabetic subjects (m = 8.77 per cent) above that of normal females (m = 5.68 per cent). A remarkable difference was observed between the nonpregnant diabetics (m = 12.77 per cent) and the pregnant diabetics (m = 8.46 per cent). This decrease in the level of Hb AIc in diabetics who are pregnant more than 30 weeks may reflect either a better state of diabetic control and/or a compensatory mechanism to protect the fetus by facilitating oxygen exchange from mother to fetus.

Acarbose treatment of non-insulin-dependent diabetes mellitus.

Acarbose is a newly developed inhibitor of intestinal alpha-glucosidase, and in the current study its ability to lower plasma glucose levels was studied in 12 patients with non-insulin-dependent diabetes mellitus, poorly controlled on diet plus sulfonylurea drugs. Patients were studied before and three months after the addition of acarbose to their treatment program, and there was a notable fall in postprandial plasma glucose concentrations that approximated 60 mg/dL. When acarbose therapy was discontinued in five patients, plasma glucose levels rapidly returned toward pretreatment levels. In addition to the improvement in glycemia, acarbose treatment also led to a notable reduction in Hb A1c and triglyceride concentrations. Finally, considerable individual variation was noted in the response to acarbose, and the results in four patients were quite dramatic, with striking reductions in both fasting and postprandial glucose concentrations. These data suggest that acarbose may be a useful addition in the treatment of patients with non-insulin-dependent diabetes mellitus.

Effect of acarbose on carbohydrate and lipid metabolism in NIDDM patients poorly controlled by sulfonylureas.

The ability of acarbose to lower plasma glucose concentration was studied in 12 patients with non-insulin-dependent diabetes mellitus (NIDDM) who were poorly controlled by diet plus sulfonylurea drugs. Patients were studied before and 3 mo after the addition of acarbose to their treatment program, and a significant improvement in glycemic control was noted. Although the decrease in fasting plasma glucose concentration was modest (12.0 +/- 0.8 to 10.8 +/- 0.3 mM), average postprandial plasma glucose concentration decreased by 3.4 mM. When acarbose therapy was discontinued in 5 patients, plasma glucose levels rapidly returned toward pretreatment levels. In addition to the improvement in glycemia, acarbose treatment also led to a significant reduction in HbA1c (7.4 +/- 0.2 to 6.4 +/- 0.2%, P less than 0.01) and triglyceride (2.4 +/- 0.1 to 2.1 +/- 0.1 mM, P less than 0.01) concentrations. Neither the plasma insulin response to meals nor insulin-stimulated glucose uptake improved with acarbose therapy, consistent with the view that acarbose improves glycemic control by delaying glucose absorption. Considerable individual variation was noted in the response to acarbose, and the results in 4 patients were dramatic, with striking reductions in both fasting and postprandial glucose concentrations. The addition of acarbose to patients with NIDDM not well controlled by sulfonylureas appears to have significant clinical benefit.

The modification of hemoglobin affinity for oxygen and tumor radiosensitivity by antilipidemic drugs.

It has been recognized for some time that alterations in the affinity of Hb for oxygen could offer a means of improving oxygen delivery to tumors and achieving radiosensitization. Three antilipidemic drugs, clofibrate, bezafibrate, and gemfibrozil, two of which had previously been shown to reduce Hb/O2 affinity in vitro, were tested in mice for their ability to affect Hb/O2 affinity and to alter the radiosensitivity of the RIF-1 sarcoma. Each of the drugs produced a significant increase in the P50 of the blood, from a mean control value of 45 mm Hg to 55, 74, and 51 mm Hg after a dose of 1 g/kg of clofibrate, bezafibrate, and gemfibrozil, respectively. However, they had very different effects on the radiosensitivity of the RIF-1 tumor. When the mice breathed air at the time of irradiation, clofibrate produced a marked sensitization equivalent at the optimum time to a 20-fold reduction in hypoxic fraction; bezafibrate gave a lower sensitization equivalent to a 4-fold reduction, while gemfibrozil caused dramatic radioresistance equivalent to a 10-fold increase in hypoxic fraction. When the mice were given 95% O2/5% CO2 to breathe at the time of irradiation to ensure complete Hb saturation in the lungs, a large increase in the sensitization by bezafibrate was seen, but there was only a small change with clofibrate. We conclude that drugs which reduce Hb/O2 affinity could have a role in sensitizing tumors to radiation.

Glycohemoglobin in postpartum women.

As women giving birth to large for gestational age (LGA) infants are at risk for glucose intolerance during pregnancy, fasting plasma glucose (FPG) and glycohemoglobin levels (Hb AIc) were studied in the immediate postpartum period (less than 10 days). These laboratory tests, in addition to infant birth weights and perinatal histories in a group of 146 women whose infants were above the 95th percentile for gestational age, were compared with those of a group of women whose infants were appropriate for gestational age (AGA: above the 25th percentile but below the mothers 75th percentile) as well as with those of a group of control mothers without diabetic risk factors. Mean Hb AIc and FPG were elevated in the mothers of the LGA infants. When either the LGA group alone or all 3 groups together were analyzed by linear regression, significant relationships were observed for maternal Hb AIc versus FPG (P less than .001); maternal Hb AIc versus birth weight corrected for gestational age (P less than .001); and maternal FPG versus birth weight corrected for gestational age (P less than .001). In addition, infant weight correlated with maternal prepregnancy weight (r = .36), maternal weight gain in pregnancy (r = .23), and maternal height (r = .17), but not with any of the paternal anthropometric features studied. Twenty-six women with LGA infants underwent postpartum oral glucose tolerance tests before discharge. Four had abnormal results and all had Hb AIc values above SD of the nonrisk control values (5.8% total Hb). Of the 16 mothers of LGA infants with FPG levels greater than 85 mg/dl (above SD of the nonrisk control values), 7 (44%) also had Hb AIc levels of more than 5.8%. Moreover, on retrospective analysis, the LGA infants manifested increased perinatal morbidity (P less than .05) compared to the combined control groups.

Increased immunoreactive erythropoietin in cord plasma and neonatal bilirubin production in normal term infants after labor.

The purpose of this investigation was to compare immunoreactive erythropoietin levels in umbilical cord plasma and neonatal bilirubin production in infants born of normal women who delivered with or without labor. Two groups of term (38 to 42 weeks) singleton pregnancies were compared: 1) those delivered by repeat elective cesarean section without prior labor (N = 17), and 2) those delivered vaginally or by cesarean section after labor (N = 24). None of the infants was asphyxiated, and there was no difference in Apgar scores between the no-labor and labor groups. The cord plasma erythropoietin levels were lower in the infants of women who had repeat elective cesarean section without labor than in those whose mothers had labor before delivery (Wilcoxon rank sum test, P less than .025). The median erythropoietin for the no-labor group was 22.9 mU/mL compared with 38.8 mU/mL for the labor group. The pulmonary excretion rate of carbon monoxide (VeCO), an index of bilirubin production, for the no-labor group was 14.3 +/- 6.2 SD microL/kg per hour compared with 18.0 +/- 4.9 SD microL/kg per hour for the labor group (P less than .05). The hemoglobin concentration for the no-labor group was 16.0 +/- 1.5 SD g/dL compared with 17.7 +/- 2.2 SD g/dL for the labor group (P less than .05). The VeCO correlated with the hemoglobin concentration (N = 32, r = 0.37, P less than .05). The results of the present study suggest that labor is normally associated with increases in the cord plasma erythropoietin level.(ABSTRACT TRUNCATED AT 250 WORDS)

Osteonecrosis of the jaws: a complication of cancer chemotherapy.

Two unusual cases of osteonecrosis of the jaws in edentulous patients are described. One case involved the maxilla and the other the mandible. Both patients were compromised hosts who were undergoing cancer chemotherapy. Both developed local mucosal infections beneath their dentures before the bone became involved. The role of dentures in producing local irritation and in masking the problem is discussed.

The semantic side of decision making.

The research reported in this paper follows the perspective that decision making is a meaningful act that conveys information. Furthermore, the potential meanings associated with decision options may affect the decisions themselves. This idea is examined in the contexts of compensation, donation, and exchange. In general, judgments were relation dependent and meaning dependent. Furthermore, the results show nonmonotonicities and limited substitutability in a pattern that challenges straightforward ways of mapping decisions onto a common currency of utility.

Mandibular reconstruction using the Dacron-urethane prosthesis and autogenic cancellous bone: review of 32 cases.

The prosthesis and cancellous bone graft technique has proven to be versatile, reliable, and highly successful when applied to mandibular reconstruction. The type of prosthesis used appears to be of some importance. Analysis of 32 cases in which the Dacron-urethane mandibular prosthesis was used is presented. Among these cases there were one failure (3 percent) and three minor complications (9 percent). These results are superior to those reported in the series in which metallic prostheses were used.

The mandibular body bone (MBB) graft: an alternative source of membranous bone.

The use of mandibular body bone (MBB) as an alternative source of membranous bone graft is described. The MBB technique is a simple, safe and rapid method of obtaining cortical bone for grafting. Furthermore MBB is membranous bone, which has been reported to be more dimensionally stable after grafting than is endochondral bone. The donor site is more readily accessible than is that for cranial bone, the other source of membranous bone. Two 1.5 x 3 cm rectangular grafts are generally available. We recommend the use of MBB in situations where the technique provides sufficient bone.

Postoperative irradiation of fresh autogenic cancellous bone grafts.

Discontinuity defects were created in the mandibles of dogs and then reconstructed immediately with fresh autogenic cancellous bone grafts and Dacron-urethane prostheses. The grafts were irradiated to a total dose of 5000 rads after waiting intervals of between 3 and 12 weeks. Nonirradiated grafts served as controls. The grafts were evaluated clinically, radiographically, and histologically. There was complete incorporation of all grafts, regardless of the interval between surgery and radiotherapy. There were no soft-tissue complications. The controls were distinguishable from the irradiated grafts only by the presence of hematopoietic bone marrow. Fibrofatty marrow was observed in the irradiated grafts. Theoretical support for this technique is found in the biology of cancellous bone grafting and the pathology of radiation injury. In view of the difficulties associated with mandibular bone grafting in preoperatively irradiated patients, a new method of reconstructing selected cancer patients who require both mandibular resection and radiotherapy is suggested.

Rhinolithiasis: a disorder not to be approached transorally.

Rhinolithiasis is a disorder that results from the calcification of intranasal foreign bodies. An unusual case is presented in which a rhinolith was discovered on a maxillary occlusal radiograph. The rhinolith was initially confused with a lesion of the palate. Precise localization of lesions is mandatory before transoral exploration is attempted.

Unusual presentation of Paget's disease of the maxilla.

Paget's disease is a disorder of bone metabolism that is relatively common in the elderly population. The jaw bones are affected in 17% of cases. A case of maxillary involvement with unusual clinical and radiographic findings is presented.

Postanginal septicaemia with external jugular venous thrombosis: case report.

Postanginal septicaemia is a syndrome of anaerobic septicaemia, septic thrombophlebitis of the internal jugular vein, and metastatic infections, that follows a localized infection in the area drained by the large cervical veins. The syndrome was well-known and often fatal in the preantibiotic era. It is now rather rare, presumably as a result of the almost routine use of prophylactic antibiotics. The symptoms are classic, and it should be suspected in any case where septicaemia and metastatic lesions are preceded by a head and neck infection. We report a case that is typical, except that branches of the external jugular vein were thrombosed. To our knowledge this has not been reported previously.

Does computer-aided surgical simulation improve efficiency in bimaxillary orthognathic surgery?

The purpose of this study was to compare the efficiency of bimaxillary orthognathic surgery using computer-aided surgical simulation (CASS), with cases planned using traditional methods. Total doctor time was used to measure efficiency. While costs vary widely in different localities and in different health schemes, time is a valuable and limited resource everywhere. For this reason, total doctor time is a more useful measure of efficiency than is cost. Even though we use CASS primarily for planning more complex cases at the present time, this study showed an average saving of 60min for each case. In the context of a department that performs 200 bimaxillary cases each year, this would represent a saving of 25 days of doctor time, if applied to every case. It is concluded that CASS offers great potential for improving efficiency when used in the planning of bimaxillary orthognathic surgery. It saves significant doctor time that can be applied to additional surgical work.