The histopathology of freezing injury to the rat spinal cord. A light microscope study. I. Early degenerative changes

In an effort to develop a method of tissue injury which would provide a model for the study of axonal regrowth in adult mammalian central nervous system (CNS), we have analyzed the effects of freezing in the dorsal columns of more than 200 rat spinal cords. The effects of temperature and time of exposure upon the size, shape, distribution and histologic characteristics of the lesion have been assessed during the first seven days following the injury. The upper threshold for injury occurs at -3 degrees C for 15 minutes. Between -3 degrees C and -12 degrees C the tissue changes vary in extent and characteristics. Selective damage to axons and myelin occurs with sparing of the supportive cells followed by proliferation of a cellular matrix. At seven days, the lesions produced by -8 degrees C for 15 to 60 minutes have neither axons nor myelin sheaths and consist of a dense cellular matrix of macrophages and presumed glial cells. With these tissue characteristics, and the preservation of tissue continuity without obstructive barriers, this model would appear to be potentially suitable for the study of axonal regrowth potential in mammalian CNS.     

Intrafollicular blood flow during human ovulation.

Transvaginal ultrasonography with color flow mapping has been used to study changes in intrafollicular blood flow and morphology during follicular rupture and presumed ovulation in one human volunteer. Detailed monitoring started on day 11 of the menstrual cycle and the follicle began to rupture at 14.30 on day 13. This event was preceded by a defined rise and peak in the level of immunoreactive serum luteinizing hormone (LH) by 42 h and 17 h 20 min, respectively. Blood vessels were clearly visible in the inner ring of the follicle (the granulosa layer) at the time of the LH peak and part of the granulosa (probably containing the oocyte) started to detach before the follicle ruptured. The maximum value for the peak blood velocity in the inner vessels was observed 10 s after the start of follicular rupture and there was a concurrent increase in the impedance to blood flow, as reflected by the resistance index and the pulsatility index. The follicle took 14 min 29 s to empty and the corpus haemorrhagicum started to form about 1 min later. These preliminary data suggest that intrafollicular angiogenesis and changes in blood flow can be monitored by a relatively non-invasive technique. Changes in vascularity might be used to predict imminent ovulation and could possibly be identified or modified biochemically to help achieve or avoid a pregnancy.     

Obstetrician-gynecologists as primary care physicians: The Oregon experience—Early perceptions regarding the effects of legislative action

OBJECTIVE: Our purpose was to assess whether legislative action influenced the role of obstetrician-gynecologists as primary care physicians. STUDY DESIGN: An observational study was performed on the basis of a questionnaire sent to 410 obstetrician-gynecologists and 27 medical directors of managed-care organizations. RESULTS: Of 67% of obstetrician-gynecologists and 96% of medical directors who responded, there was agreement as to the content of primary care, but a minority (38%) of obstetrician-gynecologists identified themselves as primary care providers. A minority of medical directors (35%) felt that obstetrician-gynecologists should serve in that role. Both obstetrician-gynecologists and medical directors felt that legislation had little impact. CONCLUSION: The reticence of obstetrician-gynecologists to assume a major role in primary care appears to be the result of an uneasiness with accepting a more comprehensive role in patient management and gatekeeping. They appear comfortable with the more traditional roles but feel that training and experience has not prepared them well for the management of more complex medical problems. (Am J Obstet Gynecol 1998;178:1222-8.)     

Effects of lactation on pregnancy induced analgesia during the postpartum period in rats

Activation of an endogenous opioid system has been associated with an elevation in pain threshold during late pregnancy and the early postpartum period in rats. It is well established that endogenous opiates are involved in the physiological regulation on prolactin secretion. This study examined the influence of lactation on pregnancy-induced analgesia during the early postpartum period in rats. Three tests (colorectal distension, tail-flick and hot-plate) were used to assess each animal's response to painful stimuli. After determining pregnant baseline values, one group of rats (lactating, n = 21) were mated and retested on Day 7 and 21 of gestation and 1, 3, 5, 7 and 14 days after parturition. A non-lactating group of animals (n = 14) whose pups were removed immediately after delivery was tested in the same manner. On Day 21 of gestation significantly higher thresholds and longer latencies were observed. On Day 1 and 3 in both lactating and non-lactating rats, the values were still elevated. No significant difference was observed during the early postpartum period between the two groups. This study confirms the existence, in rats, of pregnancy-induced analgesia late in pregnancy and the early postpartum period. The analgesia during the early postpartum period is not influenced by lactation.     

Evidence for a Type 1 diabetes‐specific mechanism for the insulin gene‐associated IDDM2 locus rather than a general influence on autoimmunity

Aims The Type 1 diabetes susceptibility locus, IDDM2, has been mapped to a variable number of tandem repeats (VNTR) region 5′ upstream of the insulin (INS) and insulin‐like growth factor (IGF2) genes on chromosome 11p15. The function of the VNTR is uncertain; however, it may influence the thymic expression of the insulin gene and affect the development of immune self‐tolerance. The aim of this study was to investigate whether the INS VNTR region is a Type 1 diabetes‐specific locus or acting as a general autoimmunity gene. Methods We genotyped the INS‐IGF2 VNTR [using the surrogate INS?23 HphI single nucleotide polymorphism (SNP)] in 823 Graves’ disease (GD)/multiple sclerosis (MS) families, 1433 GD/MS patients and 837 healthy control subjects. Results We found no evidence of excess transmission of the allele associated with Type 1 diabetes to individuals affected by GD or MS within the families. Analysis of the case–control dataset showed no genotypic or allelic difference between the two populations. Conclusions These data suggest that the INS‐IGF2 VNTR is acting as a Type 1 diabetes‐specific susceptibility gene rather than as an influence on general autoimmunity.     

Indicated and non-indicated preterm delivery in twin gestations: impact on neonatal outcome and cost.

OBJECTIVE: To identify the etiology and impact of preterm delivery in twin gestations. STUDY DESIGN: Twin gestations delivered at 33.0 to 36.9 weeks were identified in a perinatal database, and categorized by indication for delivery. Deliveries were identified as indicated, or non-indicated (discretionary). Neonatal outcomes were measured by birth weight, length of stay, NICU admission, and ventilator utilization. Data were divided and analyzed by indicated or discretionary delivery, and gestational age at delivery. RESULTS: Analyzed were 3252 twin gestations (6504 infants), with 78% having indicated delivery. Of the 22% with discretionary delivery, nearly 40% required NICU admission. With each advancing week of gestation, there was a significant decrease in incidence of NICU admission and nursery days. CONCLUSION: The majority of preterm deliveries were indicated, though 22% were discretionary. It is vital to consider neonatal morbidity and costs related to gestational age when choosing discretionary delivery.     

CNS 7056: A Novel Ultra-short-acting Benzodiazepine

Background: A new benzodiazepine derivative, CNS 7056, has been developed to permit a superior sedative profile to current agents, i.e., more predictable fast onset, short duration of sedative action, and rapid recovery profile. This goal has been achieved by rendering the compound susceptible to metabolism via esterases. The authors now report on the profile of CNS 7056 in vitro and in vivo.

Methods: The affinity of CNS 7056 and its carboxylic acid metabolite, CNS 7054, for benzodiazepine receptors and their selectivity profiles were evaluated using radioligand binding. The activity of CNS 7056 and midazolam at subtypes ([alpha]1[beta]2[gamma]2, [alpha]2[beta]2[gamma]2, [alpha]3[beta]2[gamma]2, [alpha]5[beta]2[gamma]2) of the [gamma]-aminobutyric acid type A (GABAA) receptor was evaluated using the whole cell patch clamp technique. The activity of CNS 7056 at brain benzodiazepine receptors in vivo was measured in rats using extracellular electrophysiology in the substantia nigra pars reticulata. The sedative profile was measured in rodents using the loss of righting reflex test.

Results: CNS 7056 bound to brain benzodiazepine sites with high affinity. The carboxylic acid metabolite, CNS 7054, showed around 300 times lower affinity. CNS 7056 and CNS 7054 (10 [mu]m) showed no affinity for a range of other receptors. CNS 7056 enhanced GABA currents in cells stably transfected with subtypes of the GABAA receptor. CNS 7056, like midazolam and other classic benzodiazepines, did not show clear selectivity between subtypes of the GABAA receptor. CNS 7056 (intravenous) caused a dose-dependent inhibition of substantia nigra pars reticulata neuronal firing and recovery to baseline firing rates was reached rapidly. CNS 7056 (intravenous) induced loss of the righting reflex in rodents. The duration of loss of righting reflex was short (< 10 min) and was inhibited by pretreatment with flumazenil.