Diabetic ketoacidosis: low-dose insulin therapy by various routes.

Since in normal persons the hypoglycemic effect of low-dose intramuscular exceeds that of subcutaneous insulin we studied the effect of routes of insulin therapy in diabetic ketoacidosis. Forty-five patients with diabetic ketoacidosis entered a randomized prospective protocol with insulin administered either intravenously, subcutaneously or intramuscularly. Initial priming dose of insulin had to be repeated in two of 15, three of 15 and six of 15 of the intravenous, subcutaneous and intramuscular groups respectively. The intravenous group had a more rapid fall in plasma glucose (P less than 0.01) and ketone bodies (P less than 0.05) during the first two hours. Thereafter, there were no significant differences in the rate of decline of plasma glucose or ketones nor in the time required for glucose to reach 250 mg per deciliter or for complete recovery from diabetic ketoacidosis. The data confirm the efficacy of low-dose insulin therapy for diabetic ketoacidosis and indicate that the optimal route of insulin administration is by initial intravenous combined with subcutaneous or intramuscular.     

Taxonomic and diagnostic markers for identification of Coccidioides immitis and Coccidioides posadasii.

The ribosomal Internal Transcribed Spacer (ITS) regions of the two recognized species of Coccidioides were studied using a reference set of strains that had been previously identified with species defining microsatellite polymorphisms. Unambiguous identification of the two species proved to be possible by amplifying and sequencing the ITS region. PCR-reactions are sensitive to amplification conditions requiring their careful optimization. Stable amplification and sequencing was achieved with primers ITS3 and 4, enabling species diagnosis. Alternatively, Restriction Fragment Length Polymorphism (RFLP) of the entire ITS region using an annealing temperature of 52 degrees C with the restriction enzymes BsrI and XcmI can also distinguish the species. Three strains typifying the species, Glenospora meteuropaea, G. metamericana and Geotrichum louisianoideum, were analyzed and found to be conspecific with C. posadasii. Although these species have nomenclatural priority over C. posadasii, the latter will be proposed for conservation as it has been included in the US select agent list. In addition, Coccidioides immitis is neotypified in this report. Results of antifungal susceptibility testing did not reveal differences between the two species.     

Psychophysiological correlates of induced headaches

The psychophysiological correlates of induced headaches were examined. Subjects with frequent muscle-contraction headaches, frequent migraine headaches, or infrequent headaches were exposed to a 1-h cognitive stressor while multiple electromyographic and cardiovascular measures were monitored. The stressor was associated with significant changes in all psychophysiological measures. Eleven of 16 headache subjects and 2 of 8 control subjects developed headaches. Significant associations between several psychophysiological variables and headache occurrence were found and individual differences in the association between psychophysiological variables and headaches intensity were examined. The results were consistent with the hypothesized role of cardiovascular factors in the pathophysiology of muscle-contraction headache. This was the first controlled demonstration of headaches occurring as a function of environmental stressors.This research was supported by Grant 5-R01-NS-1875 from the National Institute of Health.     

Degree of light damage to the retina varies with time of day of bright light exposure

After adaptation to cyclic illumination (14:10 light-dark cycle; intensity = 1.4 log ftc) male albino rats were exposed to brighter light (2.15 log ftc) seven hours daily for 25 days. The extent of retinal damage was determined histologically. Daily exposure to bright light in the morning produced greater photoreceptor loss than daily afternoon exposure. Severe retinal damage was partially prevented by brief light adaptation (20 minutes duration, at 1.4 log ftc intensity) before the onset of morning exposure. However, light adaptation did not remove the differential effect of time of day. The authors conclude that increased light exposure during the period of rod outer segment phagocytosis enhances photoreceptor damage.     

Vagal control of the breathing pattern and respiratory mechanics in the adult and newborn rabbit

In an attempt to define the role of SARs on the breathing pattern and respiratory mechanics, we have studied adult rabbits anaesthetised, supine and tracheostomised during air breathing (A), after SO₂ breathing (200 ppm for a period long enough to abolish the apnea following lung inflation, 10–30 min) (S), and after bilateral vagotomy (V). Tidal volume and inspiratory time increased, while breathing frequency decreased from A to V. The effects of S depended upon the type of anaesthesia used, with a definite increase in volume and a drop in frequency in the urethane anaesthetized animals and a trend toward opposite changes with barbiturate anaesthesia. Total and lung compliance increased and total pulmonary resistance decreased from A to S; no further changes were observed with V. The combined changes in breathing pattern and mechanics decreased the respiratory work per minute from A to V, suggesting that the primary concern of the vagal afferent information is to regulation even with SO₂ concentration up to 330 ppm for 30 min. From A to V the changes in breathing pattern and compliance were similar to those observed in the adult.     

Significance of depression and cognitive impairment in patients undergoing programed stimulation of cardiac arrhythmias

Although depression and cognitive impairment have been associated with excess mortality following heart surgery, the relationship of these factors to death following treatment for cardiac arrhythmias is unknown. We prospectively examined the associations between biobehavioral factors, mortality, and arrhythmia manageability in 88 patients undergoing programed electrical stimulation for the diagnosis and treatment of supraventricular and ventricular tachyarrhythmias or syncope of unknown origin. Statistically significant relationships were identified between depression and mortality, and between cognitive impairment and mortality. No relationships were observed between cognitive impairment or psychologic profile and arrhythmia severity or treatment efficacy. Our data suggest that arrhythmia morbidity and mortality may in part be a function of cognitive and emotional impairments that lessen the individual's capacity to comply with lifesaving therapy, maintain a stable physiologic milieu, and continue an adaptive emotional life. Failure to recognize the clinical significance of these impairments in patients at risk for sudden cardiac death will contribute to the current difficulty reducing the death and disability associated with cardiac arrhythmias.     

Identification, characterization and biological activity of oxytocin receptor in the developing human penis

Although abnormalities of the male external genitalia (MEG) are a relatively common problem, little is known concerning the molecular mechanisms that finely regulate penile development. We report here the expression of the oxytocin receptor (OTR) gene by real-time RT-PCR in human fetal tissues (11th-12th week of gestation), including the MEG. The developing penis expressed a very high level of OTR mRNA, only a half log(10) unit lower than fetal central nervous system, used as a positive control. The OTR protein is also highly expressed (western, immunohistochemistry and binding studies) and immunolocalized both in the mesenchymal body and in the surrounding blood capillaries, which will later constitute penile trabeculae and sinusoids. Binding studies using [125I]oxytocin antagonist ([125I]OTA) in cultured human fetal penile smooth muscle cells (hfPSMC) revealed the presence of specific OTR with a high capacity and affinity for oxytocin (OT) and for OTA. Increasing concentrations of OT dose-dependently induced intracellular Ca2+ mobilization. Furthermore, OTR mediated an increase in the proliferation and the migration of hfPSMC. In conclusion, we demonstrate that in the developing human MEG, OTR is highly expressed and might be involved in coordinating timely and appropriate proliferation and migration of the penile cells. Thus, OTR might represent an additional target for investigating human fetal MEG organogenesis.     

Eight-year results of a randomized clinical trial comparing total mastectomy and lumpectomy with or without irradiation in the treatment of breast cancer

In 1985 we presented results of a randomized trial involving 1843 women followed for five years that indicated that segmental breast resection (lumpectomy) followed by breast irradiation is appropriate therapy for patients with Stage I or II breast cancer (tumor size, less than or equal to 4 cm), provided that the margins of the resected specimens are free of tumor. Women with positive axillary nodes received adjuvant chemotherapy. Lumpectomy followed by irradiation resulted in a five-year survival rate of 85 percent, as compared with 76 percent for total mastectomy, a rate of survival free of distant disease of 76 percent, as compared with 72 percent, and a disease-free survival rate of 72 percent, as compared with 66 percent. In the current study, we have extended our observations through eight years of follow-up. Ninety percent of the women treated with breast irradiation after lumpectomy remained free of ipsilateral breast tumor, as compared with 61 percent of those not treated with irradiation after lumpectomy (P less than 0.001). Among patients with positive axillary nodes, only 6 percent of those treated with radiation and adjuvant chemotherapy had a recurrence of tumor in the ipsilateral breast. Lumpectomy with or without irradiation of the breast resulted in rates of disease-free survival (58 +/- 2.6 percent), distant-disease-free survival (65 +/- 2.6 percent), and overall survival (71 +/- 2.6 percent) that were not significantly different from those observed after total mastectomy (54 +/- 2.4 percent, 62 +/- 2.3 percent, and 71 +/- 2.4 percent, respectively). There was no significant difference in the rates of distant-disease-free survival (P = 0.2) or survival (P = 0.3) among the women who underwent lumpectomy (with or without irradiation), despite the greater incidence of recurrence of tumor in the ipsilateral breast in those who received no radiation. We conclude that our observations through eight years are consistent with the findings at five years and that these new findings continue to support the use of lumpectomy in patients with Stage I or II breast cancer. We also conclude that irradiation reduces the probability of local recurrence of tumor in patients treated with lumpectomy.