Vessel density in endometrium of women with and without intrauterine contraceptive devices: a morphometric evaluation.

Increased vascularity was found in the endometrial functionalis in uteri of women wearing intrauterine contraceptive devices (IUDs) as compared to uteri of women without IUDs (control subjects). Vessel concentration was highest in endometrial tissue adjacent to that tissue which was depressed by the IUD. In control tissues there was a significant variation in vascularity according to geographic location in the following order of magnitude: fundus greater than corpus greater than cornua greater than isthmus. No significant variation was found, however, among different phases of the ovarian cycle in either control or IUD cases. Increased endometrial vascularity could be a reaction to vessel damage caused by the IUD and for several reasons may contribute to IUD-induced endometrial bleeding.     

Stimulation of pyruvate dehydrogenase activity in intact rat adipocytes by insulin mediator from rat skeletal muscle

This study compared the effects of insulin and insulin mediator from skeletal muscle of control and insulin-treated rats on intact adipocyte pyruvate dehydrogenase. Increasing insulin concentrations stimulated pyruvate dehydrogenase activity in a biphasic manner with a maximal stimulation at 100 microU/ml which was 2-fold and sustained for up to 1 h. The mediators from control or insulin-treated rats also stimulated pyruvate dehydrogenase of intact adipocytes with the effect increasing in a linear manner up to a 1:10 final dilution. The latter mediator had twice the stimulatory activity as the former. Peak stimulation of pyruvate dehydrogenase by the mediators was attained within 10 min of incubation. The enzyme activity rapidly declined thereafter, with the stimulation by mediator from control rats decreasing at a faster rate than that due to mediator from insulin-treated rats. The stimulatory effect of the mediators on adipocyte pyruvate dehydrogenase was found to be additive to that of insulin. This study demonstrates: 1) that insulin mediator can act on mitochondrial pyruvate dehydrogenase of intact, functional adipocytes as it does on isolated intact or broken mitochondria; 2) that the mediator is degraded by the adipocyte; and 3) that the amount of mediator generated by insulin probably limits the stimulation of pyruvate dehydrogenase by insulin. These findings further substantiate the physiological relevance of this putative insulin second messenger.     

Inhibition of platelet function by contrast media: iopamidol and ioxaglate versus iothalamate. Work in progress

The effects of an ionic contrast agent, meglumine iothalamate (Conray-60), and two newer low-osmolality radiographic contrast media, sodium meglumine ioxaglate (Hexabrix) and iopamidol (B-15,000), on platelet aggregation and secretion responses were studied. All three agents inhibited platelet responses during stimulation with adenosine diphosphate (ADP), epinephrine, and collagen. Platelet function was inhibited by iothalamate at concentrations of 11 mg iodine/ml and above, and by the newer agents at concentrations above 30 mg iodine/ml. Addition of exogenous calcium decreased the iothalamate-induced inhibition of aggregation but did not improve dense granule secretion. There was no consistent effect of exogenous calcium on platelet inhibition by iopamidol and ioxaglate. These studies indicate that the newer agents inhibit platelet function less than iothalamate does, and that chelation of Ca2+ may not be the major mechanism of platelet inhibition by contrast agents.     

Physical characterization and molecular cloning of the Shope fibroma virus DNA genome

DNA from several independent strains of Shope fibroma virus, a tumorogenic leporipoxvirus of rabbits, was isolated and analyzed by restriction endonuclease digestion and Southern blotting. The restriction profiles indicated a high degree of sequence conservation among the isolates but blotting under standard stringencies revealed no detectable cross homology with a member of the orthopoxvirus group, vaccinia. The genome of the fibroma virus was calculated to be in excess of 160 kilobases and shown to possess two features analogous to the orthopoxvirus group: (1) the terminal restriction fragments possess covalently closed hairpin structures; and (2) the terminal sequences are present as inverted repeats of greater than 10 kilobases. The terminal 3.6 kilobase BamHI restriction fragment was cloned in pBR322 after removal of the hairpin structure with mung bean single strand-specific endonuclease and addition of BamHI linkers. SFV sequences within this terminal region were shown, using 32P SFV cloned terminal probe, to have none of the sequence heterogeneity characteristic of vaccinia DNA termini. The remaining 20 internal SFV BamHI restriction fragments were propagated in bacterial plasmids either as intact fragments, or after secondary digestion with HindIII, and together constitute the complete cloned SFV sequence library.     

Management of a complex diving accident

After the accidental ascent of a diving bell from 80 m, one diver died from pulmonary barotrauma and the other-though grossly ill-survived. After recompression therapy, this diver was tetraplegic with evidence of patchy microcirculatory damage of brain, cord, liver, kidneys, and gut. All systems eventually returned to normal, except the spinal cord, mainly because of the post-recompression phase of management, in which pharmacological doses of steroids, hyperbaric oxygen, and dextran were used. Although function returned in the upper limbs, the diver remained paraplegic.     

Continuous monitoring of fetal temperature by noninvasive probe and its relationship to maternal temperature, fetal heart rate, and cord arterial oxygen and pH.

The human fetus is normally warmer than its mother. The principal route of fetal heat dissipation is through the placental circulation. We developed a technique that is noninvasive to the fetus to record the fetal skin and maternal uterine wall temperatures, from which we derived the temperature difference. We have established a range of normal values (mean temperature difference 0.24C) and present some preliminary data. The results show a correlation between changing temperature and baseline fetal heart rate (r = 0.628, P less than .001) and the influence of contractions and epidural analgesia on these measurements. Measurement of the fetal-maternal temperature difference during labor may help detect abnormal umbilical-placental blood flow, resulting in fetal distress, and may help distinguish sinister from iatrogenic fetal tachycardias. Our technique provides the first simple means of recording this basic fetal variable.     

Staple Line Reinforcement Reduces Postoperative Pancreatic Stump Leak After Distal Pancreatectomy

Pancreatic stump leak is the major source of morbidity after stapled distal pancreatectomy. We hypothesized that reinforcement of the stapler system with a buttress mat can improve leak rates when compared to standard stapling alone. We performed 13 consecutive distal pancreatectomies using our reinforced stapler system, forming our experimental group. A historical control group was composed of 18 patients undergoing stapled pancreatic closure without reinforcement. The main outcome measure was pancreatic leak in the postoperative period. Pancreatic leaks included fistulas and fluid collections (sterile or infected). Hospital length of stay was recorded as a secondary measure. Postoperative pancreatic leak rate was zero in the experimental group, but 39% in the control group (P = 0.025). Development of a pancreatic leak resulted in prolonged hospital stays: 13.6 vs 8.3 days (P < 0.03). We conclude that staple line reinforcement is a simple and effective method of reducing pancreatic stump leakage after distal pancreatectomy. The economic impact of lower leak rates is reflected in significantly shorter hospital stays. The results of our study should be validated in a randomized controlled trial.     

Characteristics of elderly patients admitted to an urban tertiary care hospital with osteoporotic fractures: correlations with risk factors, fracture type, gender and ethnicity

Osteoporosis is a major public health problem in the United States of America and around the world, largely due to the morbidity and mortality associated with osteoporotic fractures. In the past decade, large epidemiologic studies have contributed greatly to our understanding of patients who fracture. However, most studies are limited to postmenopausal white women. In this retrospective review, we analyze data from 185 men and women with acute fragility fractures who received osteoporosis consultations during admission to a single urban hospital between 2001 and 2003. Men and women differed in terms of risk factors for falls and osteoporosis but had areal bone mineral density (BMD) measurements remarkably similar, except at the total hip. Black and Hispanic subjects with fractures were significantly younger than whites yet were much more likely to have serious co-morbidities, such as diabetes mellitus and hypertension. In spite of significantly higher BMD measurements, black patients had the highest rates of vitamin D deficiency and secondary hyperparathyroidism. Patients admitted with hip fractures differed from those with non-hip fractures on a number of important variables. Based on these data, we conclude that elderly subjects admitted to an urban hospital with osteoporotic fractures are a heterogeneous group, with features that vary according to fracture type, gender and ethnicity. Future studies of patients with clinical fragility fractures should include ample numbers of men and ethnic minorities, since differences in underlying risk factors may suggest alternative strategies for fracture prevention.     

In vitro effects of substance P analogue [D-Arg1, D-Phe5, D-Trp7,9, Leu11] substance P on human tumour and normal cell growth.

Analogues of the neurotransmitter substance P (SP) can interact with neuropeptide receptors, and are reported to inhibit growth of small cell lung cancer cell lines (SCLC CLs). We found [D-Arg1, D-Phe5, D-Trp7,9, Leu11] substance P (D-Phe5SP) significantly inhibited DNA synthesis by 10/10 human tumour CLs; six SCLC, one N-SCLC (squamous), two ovarian and one squamous cervical carcinoma, with inhibition to 50% control levels (IC50) of 20-50 microM. There was dose dependent inhibition of colony forming efficiency (CFE) in 3/3 SCLC and 1/1 N-SCLC CL, IC50s of 0.5-6.5 microM in 5% serum. Exposure of SCLC CL HC12 to 100 microM D-Phe5SP for 1-4 h caused a progressive fall in viable cell number; surviving cells, grown in the absence of peptide, showed a decreased growth rate. During 1 week's exposure of two SCLC CLs to 20 microM D-Ph5SP, growth was slower than control cultures, while 50-100 microM completely inhibited growth. These inhibitory effects were partially reversed by increasing serum concentration from 5 to 20%, but not by SP, vasopressin, bombesin or insulin-like growth factor 1. There was some inhibition of CFE by 3/3 normal human bone marrows, IC50s of 30-80 microM, compared with 8 microM for HC12 in 20% FCS. Therefore D-Phe5SP appears to have more potent antiproliferative effects in tumour cells than normal cells, suggesting a role for this analogue in tumour treatment.