LD-PACE II: a new cardiomyostimulator for cardiac bioassist.

The LD-PACE II was designed for use in cardiomyoplasty, aortomyoplasty, and skeletal muscle ventricles. All parameters specified as programmable can be changed in a noninvasive manner (using a programming interface wand connected to a computer using the Windows 95/98 environment). Two new functions may be very useful clinically, based on experimental research. 1. Work-rest regimen. The LD-PACE II is able to deliver alternating periods of muscle contractions and rest. Work and rest periods may be programmed independently between 1 and 120 minutes in increments of 1 minute. The work-rest regimen may be useful clinically if muscle contractions are needed for cardiac assist postoperatively. 2. Night/day regimen. This feature allows for a change in the ratio of muscle contractions according to a patient's activity level. During the day the cardiosynchronization ratio may be set from 1:1 to 1:4, and during the night it may be set for 1:8 to 1:16. This allows the muscle to have a long rest period, prevents overuse, and prolongs battery life. These two new features make this cardiomyostimulator very attractive for cardiomyoplasty in particular. The addition of the work-rest and night-day regimens allow the muscle to rest for periods during the day to prevent overuse, subsequent damage, and potential atrophy.

Gestational diabetes mellitus. Levels of glycemia as management goals.

In the United States, glucose tolerance test criteria for the diagnosis of gestational diabetes mellitus are, in plasma glucose after a 100-g challenge, as follows: fasting, greater than 5.8 mM; 1 h, greater than 10.6 mM; 2 h, greater than 9.2 mM; and 3 h, greater than 8.1 mM; any two values must be elevated. The Second International Workshop-Conference on Gestational Diabetes Mellitus recommended in 1985 that, once diagnosed, women should receive dietary therapy. If fasting or 2-h postprandial hyperglycemia later occurs (fasting, greater than 5.8 mM; 2-h, greater than 6.7 mM), insulin therapy should begin. Data from others have suggested both that the criteria for diagnosis may be too liberal and that the thresholds for instituting insulin therapy may be too high. We address these two issues by reviewing several papers with conflicting conclusions. There is controversy over whether women with gestational diabetes diagnosed by glucose tolerance testing, but who have fasting plasma glucose levels less than 5.8 mM and 2-h postprandial values less than 6.7 mM, should also be insulin treated. Finally, the usual clinical criteria for making therapeutic decisions all rely on glycemia. Other fuels (amino acids, lipids, and ketones) are regulated by circulating insulin and have deleterious effects on fetal development. Further study is required to make more sound clinical decisions based not just on glycemia but on the entire metabolic milieu.

Prematurity among insulin-requiring diabetic gravid women.

From Jan. 1, 1983, through Dec. 31, 1987, 420 gravidas with insulin-requiring diabetes antedating pregnancy delivered on the Joslin Clinic service. Among them, 110 pregnancies (26.2% of the total) delivered before 37 completed weeks of gestation compared with a 9.7% incidence (906/9368) for the general population at the Brigham and Women's Hospital during calendar year 1985. Thirty-three percent of all premature deliveries were the result of the development of preeclampsia. The relative risk of prematurity for diabetic patients with any hypertensive complication was 2.0 (95% confidence interval, 1.40 to 2.87) compared with normotensive diabetic subjects. Compared with the general population, most of the excess risk of prematurity was confined to hypertensive diabetics and normotensive patients of more advanced White class. A history of having had a previous premature delivery, increasing duration of diabetes antedating pregnancy, and carrying a male fetus in the index pregnancy were significantly associated with premature delivery. Future efforts to reduce the incidence of prematurity among diabetic gravidas should be directed toward reducing the incidence of preeclampsia.

First-trimester hemoglobin A1 and risk for major malformation and spontaneous abortion in diabetic pregnancy.

The relationship between the level of hemoglobin A1 (Hb A1) in the first trimester and major malformations and spontaneous abortions was examined in 303 insulin-requiring diabetic gravidas. During the study period, all patients with insulin-requiring diabetes mellitus antedating pregnancy who registered for prenatal care prior to 12 weeks' gestation and who had a known outcome were included. Thirty-five percent of the patients entered with a first-trimester Hb A1 of greater than 11.0% of total hemoglobin (9 standard deviations above the mean for a nondiabetic population). A broad spectrum of glycemic control was therefore represented. The risk of spontaneous abortion was 12.4% with first-trimester Hb A1 less than or equal to 9.3% and 37.5% with Hb A1 greater than 14.4% (risk ratio 3.0; 95% confidence interval 1.3-7.0). The risk for major malformation was 3.0% with Hb A1 less than or equal to 9.3% and 40% with Hb A1 greater than 14.4% (risk ratio 13.2; 95% confidence interval 4.3-40.4). Although the risks for both adverse outcomes were markedly elevated following a first trimester in very poor metabolic control, there was a broad range of control over which the risks were not substantially elevated. To keep malformations and spontaneous abortions to a minimum among diabetic women does not require "excellent" control; there seems to be a fairly broad range of "acceptable" control.

Pregnancy following renal transplantation in class T diabetes mellitus.

Nine cases of pregnancy complicated by diabetes and prior renal transplantation are reviewed. Maternal and fetal death occurred in a patient with foot and leg ulcers associated with preexisting peripheral vascular disease. Pregnancy-induced hypertension occurred in six cases. Spontaneous weight-bearing fractures occurred in two patients. No episodes of renal allograft rejection occurred. Evidence of fetal compromise was present in six cases. All fetuses were delivered by cesarean section prior to term, with live births occurring from 31 1/2 to 36 weeks' gestation. A single case of hypospadias was the only congenital defect. Prepregnancy screening for complications of diabetes and renal transplantation is advised and euglycemia should be achieved before and during pregnancy. Advanced diabetic vascular disease puts these gestations at significant risk.

Continuous subcutaneous insulin therapy during early pregnancy.

Intensive metabolic control of diabetes is probably important during formation of the embryo early in pregnancy. The purpose of this study was to determine the efficacy and complications of continuous subcutaneous insulin infusion therapy during the fifth to the tenth week of gestation. Twenty-four insulin-dependent subjects were trained to use blood glucose self-monitoring and the Auto Syringe portable insulin infusion pump (AS6C). Regular insulin was administered as a basal infusion of 18 +/- 8 U/24 hours (+/- SD) (12.2 +/- 3.9 mU . kg-1 . h-1) and as bolus injections of 6 +/- 3 U before meals and 1.2 +/- 1 U before snacks. Reasonable control of fasting (119 +/- 30 mg/dL) and postprandial (133 +/- 34 mg/dL) hyperglycemia was achieved, accompanied by an average of 2.2 +/- 1.5 symptomatic hypoglycemic episodes per week. The frequency of complications with this new therapy declined as the authors gained experience in teaching the system. The persistence of good diabetic control in many of the subjects after they returned to conventional insulin therapy points to the need for a controlled trial of continuous subcutaneous insulin infusion therapy versus intensive conventional therapy in pregnancy.

Diabetic nephropathy and perinatal outcome.

We studied the effect of diabetic nephropathy on the course of pregnancy, perinatal outcome, and infant development and determined the influence of pregnancy on maternal hypertension and renal function. Maternal proteinuria usually increased during pregnancy (greater than 3 gm/24 hours in 69%), and hypertension was present by the third trimester in 73%. The degree of proteinuria correlated with diastolic pressure and creatinine clearance. After pregnancy, proteinuria declined in 65% of the mothers, hypertension was absent in 43.5%, and the expected rate of fall in creatinine clearance was not accelerated. Among 35 patients, abortion occurred spontaneously or was performed electively in 25.7%, and 71% of the remainder underwent delivery before 37 weeks. Birth weight was related to maternal blood pressure and creatinine clearance. Neonatal morbidity was common, but the perinatal survival rate was 89%. Infants seen at follow-up without congenital anomalies had normal development at 8 to 36 months of age. We concluded that perinatal outcome has significantly improved for diabetic women with nephropathy.

Resonance Raman spectra of three-iron centers in ferredoxins from Desulfovibrio gigas.

The resonance Raman spectra of ferredoxins (Fd) I and II from Desulfovibrio gigas are reported using 4579 A Ar+ laser excitation. The (3Fe-3S) center in Fd II has a characteristic resonance Raman spectrum, readily distinguishable from those of (2Fe-2S) or (4Fe-4S) clusters. Reduction of Fd II produces a marked alteration in the resonance Raman spectrum. Fd I is shown to contain both (3Fe-3S) and (4Fe-4S) Fd-type clusters. The results illustrate the potential of resonance Raman spectroscopy in Fe-S cluster identification, even in cases where more than one cluster type is present.

Pancreatic alpha cell response to alanine during and after normal and diabetic pregnancies.

Pancreatic alpha cell response to oral alanine was assessed in the third trimester of pregnancy and in the puerperium in 16 insulin-dependent diabetic and 7 normal pegnant women. Insulin response was also measured in the nondiabetic subjects. The nondiabetic subjects had higher basal glucagon and insulin levels as well as a greater response to oral alanine stimulation at 34 weeks' gestation than at 6 weeks post partum. In addition, basal levels of both hormones remained low at a time remote from pregnancy (9 months post partum), indicating both hyperinsulinemia and hyperglucagonemia in the postabsorptive state in normal human pregnancy. The secretory response of glucagon and insulin or oral alanine was blunted at 6 weeks post partum in the nondiabetic subjects. This suggests that the late puerperium may not be an appropriate "nonpregnant control period" for metabolic studies. During pregnancy, basal and stimulated glucagon levels were not significantly different in diabetic and normal women. Despite higher concentrations of blood glucose in diabetic women, basal and stimulated glucagon secretion was equivalent in the 2 groups. No pegnancy-induced increment in glucagon secretion was evident in insulin-treated diabetic subjects. Thus hyperglucagonemia does not contribute to the increased requirements for insulin during pregnancy in these women.

Diabetes and Graves disease complicating pregnancy.

We report here six pregnancies in 5 women with juvenile diabetes and Graves disease. The diabetes was managed in a standard fashion. The Graves disease was managed with propylthiouracil when required. The course of neither the diabetes nor Graves disease was different than expected. When established guidelines for therapy are followed the two have no interaction with one another. One infant was mildly hypothyroid. None developed neonatal Graves disease. Four of the infants had hyperbilirubinemia.

Diabetes mellitus in pregnancy.

Physiologic changes that occur during pregnancy are diabetogenic. If diabetes does not exist before pregnancy, it may become evident, and if diabetes pre-exists, it becomes aggravated. The changing insulin requirements and propensity for ketoacidosis require weekly visits and careful urine testing on a daily basis by the mother. In addition, microvascular complications of diabetes must be carefully monitored. Delivery is planned progressively early in the pregnancy according to diabetic class. Hospitalization is necessary one week before anticipated delivery. Urinary estriol tests, OCT, amniocentesis, and ultrasound are all helpful in managing the pregnancy. Delivery of the fetus and placenta results in a profound fall in the insulin requirement. The neonate should be carefully observed during the first few days of life because of the increased frequency of complications.