Claude B. Loadholt

Plasma lipids and lipoproteins in young insulin-dependent diabetic patients: relationship with control.

SummaryPlasma and lipoprotein cholesterol and triglycerides, glucose and haemoglobin A1c concentrations were measured in 106 patients (56 males) with insulin-dependent diabetes mellitus (age range 2–22 years) and 36 normal volunteers (19 males) with similar age and sex distribution. The diabetic patients were further divided into three subgroups: “good”, fair and poor control, based on 24 h glycosuria and haemoglobin A1c concentrations. Total, low density lipoprotein and very low density lipoprotein cholesterol levels were significantly increased in male patients in poor control when compared with the group in “good” control and with normal subjects. Triglyceride and very low density lipoprotein triglyceride levels were also significantly increased in poorly controlled males. The most significant difference however was a decrease of high density lipoprotein cholesterol in male patients in poor control. There was a significant inverse correlation between haemoglobin A1c and high density lipoprotein cholesterol (r = -0.63) and a direct correlation between haemoglobin A1c and low density lipoprotein cholesterol (r = 0.35) and triglycerides (r = 0.62) in the male diabetics. The findings were similar in females. The most striking change was observed in low density lipoprotein cholesterol levels, which were more markedly increased in poorly controlled females than in poorly controlled males. No statistical singificant differences were found between the groups in good and fair control for any of the plasma and lipoprotein lipids studied. A significant difference however was found between the groups in poor and fair control. There was a significant correlation in females between haemoglobin A1c and low density lipoprotein cholesterol levels (r = 0.43), haemoglobin A1c and triglycerides levels (r = 0.54) and an inverse correlation between haemoglobin A1c and high density lipoprotein cholesterol (r = -0.59).

Prolonged ingestion of commercial DDT and PCB; effects on progesterone levels and reproduction in the mature female rat

A report linking human polycystic ovary with increased exposure to environmental DDT (Heinrichset al. 1971) prompted the present study comparing effects of PCB and DDT or their combination on reproduction in female rats under more realistic conditions with respect to level (75 and 150 ppm), route of administration (dietary contaminant), and period of exposure (8 and 36 weeks). Evaluation of estrous cycle length, mating frequency, number and size of litters; as well as plasma levels of DDT, PCB, progesterone (P), and 17α=hydroxyprogesterone (17α=OH-P), permitted comparison of short and long term reproductive changes from ingestion of two levels of DDT and/or PCB.PCB reduced plasma progesterone (p<.01) while plasma 17α OH-P was unchanged by PCB or DDT. High DDT and PCB abolished reproduction. Histologically, distinct ovarian stromal changes accompanied 150 ppm of PCB, while increased numbers of more prominent follicular cysts were evident with 150 ppm of DDT. Although DDT and PCB generally reduced or abolished litter production, no treatment tested significantly altered litter size. Long term chronic ingestion of more realistic levels of technical DDT (85%p,p′, 15%o,p′-DDT) in these studies did not lead to polycystic ovaries in adult rats comparable to those reported following i.v. administration of pureo,p′-DDT to immature rats. Plasma DDT levels above 800 ppb are clearly detrimental to reproduction, while levels below 500 ppb had little effect. Finally, we present the first evidence reported to our knowledge demonstrating that prolonged ingestion of PCB (150 ppm) markedly reduces reproduction (p<.05) accompanied by significantly reduced progesterone in plasma (p<.01) as well as by histologically characteristic ovarian stromal changes not seen with DDT alone.

Platelet Function During Continuous Insulin Infusion Treatment in Insulin-dependent Diabetic Patients

Patients with diabetes mellitus manifest increased in vitro platelet aggregation andincreased synthesis of the proaggregant and vasoconstrictor, thromboxane A2 (TXA2). We studied the effects of continuous insulin infusion treatment on platelet aggregation and arachidonic acid (AA)-stimulated platelet TXA2 synthesis (15 and 30 s post-AA, 1 mM) in 16 type I diabetic patients. Strict glycemic control was induced with the Biostator for 2 days and maintained for 12–14 days with continuous subcutaneous insulin infusion (CSII). The average premeal plasma glucose level (4/day) fell from 184 ± 15, before treatment, to 107 ± 6 mg/dl on the final day (P < 0.001). After control, platelet synthesis of TXA2, measured by radioimmunoassay of its stable metabolite, immunoreactive TXB2 (iTXB2), decreased in all patients (30 s: 276 ± 31 versus 199 ± 28ng iTXB2/ml/ 5 × 105 platelets; P < 0.05). The reductionin platelet iTXB2 synthesis (15 and 30 s) was greater in poorly controlled patients (HbA1c>12%; N = 8), and for all patients the decrease in iTXB2 (15 and 30 s) was correlated with the prestudy HbA1c level (15 s: r = 0.6; P < 0.01). In contrast, platelet aggregation responses did not improve during intensive insulin treatment. The ED50 for AA (dose producing 50% maximum aggregation at 1 min) was unchanged after 2 wk of treatment and the ED50 for aggregation induced by ADP fell significantly inpatients with HbA1c 12% (2.8 ± 1.3 versus 1.2 ± 0.6 μM; P < 0.01). Other factors that were associated in this study with platelet aggregation responses were plasma lipoprotein levels and microvascular disease. In all patients before treatment, the ED50 for AA was inversely correlated with the LDL-cholesterol level(r = 0.57; P < 0.01). Although platelet aggregation did not improve during the period of intensive treatment, when the relations of microvascular disease and glycemic control to platelet aggregation were analyzed together in all patients, the ED50 for AA was greatest (P < 0.02) in thosepatients without microvascular disease and HbA1c <12%, indicating less platelet aggregability. Thus, a brief period of CSII treatment reduced AA-stimulated platelet iTXB2 generation; however, the effects of this treatment on platelet aggregation appear to be complex and other extraplatelet factors also seem to influence the aggregation response.

Perioperative cephalosporin prophylaxis in cesarean section: Effect on endometritis in the high-risk patient

A total of 120 patients who were to be delivered by cesarean section and who were at high risk of postoperative infection received three doses of either cefamandole, cephalothin or placebo perioperatively. Maternal serum levels for both antibiotics were in the therapeutic range. Although both drugs reduced the incidence of febrile morbidity and endometritis, only cefamandole significantly reduced the fever index. Risk factors for postoperative infections were the presence of ruptured membranes, labor, and internal fetal monitoring. Cefamandole beneficially influenced all risk factors while cephalothin was able to reduce only the risk of ruptured membranes. When a new method for obtaining endometrial tissue was utilized, 50% of cultures were negative. There was no difference in the organisms isolated from patients with and without endometritis.

Increased Platelet Arachidonic Acid Metabolism in Diabetes Mellitus

Platelets obtained from some diabetic patients show enhanced in vitro platelet aggregation. This study sought to determine if platelets obtained from insulindependent diabetic subjects synthesize increased quantities of the labile aggregating substance, thromboxane A2 (TXA2), and if it may play a role in the enhanced platelet aggregation. Arachidonic acid (1 mM)-stimulated TXA2 synthesis, as determined via radioimmunoassay of its stable metabolite TXB2, was significantly greater (P < 0.01, N = 12) in platelet-rich plasma obtained from diabetics compared with matched controls. Arachidonic acid-stimulated TXB2 synthesis in the diabetic platelet-rich plasma was positively correlated with the ambient fasting plasma glucose (r = 0.61, P < 0.02, N = 15). Platelet aggregation induced by arachidonic acid (0.4–0.8 mM) was inhibited significantly less by 13-azaprostanoic acid (P < 0.04, N = 14), a competitive antagonist of the actions of prostaglandin H2 or TXA2 on platelets, compared with matched controls. The results support the notion that platelets obtained from some insulin-dependent diabetic subjects manifest increased synthesis of TXA2, which may contribute to the enhanced platelet aggregation.

Variations in same-size endodontic files.

Variations in same-size endodontic files (K-type, style B, stainless steel) were detected with a three-dimensional gauge. The variation between same-size files was within 3 mm. in most instances; however, variations from the smallest file in one size group to the largest file in the next size group was 5 mm. or more in many instances. Overall, about 74 percent of the variations came from the file itself. Suggestions concerning the use of the files are presented.

Effect of Neonatal Cerebrospinal Fluid on Monocyte Chemotaxis

We have reported in our previous study that macrophages constitute 58% of the total number of white cells in noninfected neonatal cerebrospinal fluid (CSF). CSF macrophages are probably derived from blood monocytes. To explain their predominance, we compared the chemotactic response of monocytes from cord and adult blood to neonatal (NCSF) and non-neonatal spinal fluids (NNCSF). Zymosan-activated serum (ZAS) was used as a positive control. Significance was accepted as p less than or equal to 0.05. We observed that both random migratory (RM) activity and chemotactic responses (CM) of cord monocytes to neonatal CSF and ZAS were greater than those of monocytes obtained from adult blood, resulting in a significant increase in the chemotactic differential (CD). Chemotactic responses of neonatal monocytes were significantly greater in the presence of neonatal CSF as compared to CSF from older children as indicated by CD. The CD of neonatal monocytes to neonatal CSF was greater than that of neonatal neutrophils. These findings are consistent with the presence of specific monocyte chemotaxins in noninfected neonatal CSF.

T LYMPHOCYTE SUBSETS IN CHILDREN WITH GRAM NEGATIVE SEPSIS

We compared T lymphocyte subsets of 14 normal term newborns (cord blood) to those of 8 children with gram negative sepsis. Six patients were<3 months, 2 were 3 yrs., and one 11 months of age. Blood cultures were positive for H. influenzae(3), Serratia m. (1), Klebsiella (2) and E. coli (2). Total T cells (OKT3, OKT11), helper/inducer cells (OKT4), and suppressor/cytotoxic cells (OKT8) were analyzed by flow cytometry (Ortho Diagnostic Systems), and the helper/suppressor ratio calculated. Significance was accepted as P <0.05. Suppressor T cells were significantly lower in infected children with a significant increase in helper/suppressor ratio.