Selective attenuation of neuropeptide-Y-mediated contractile responses in blood vessels from patients with diabetes mellitus

Vascular smooth muscle contractile responses to neuropeptide Y, ,ß-methyleneATP and noradrenaline were studied in circular segments of isolated vessels with intact endotheliumin vitro from 12 patients with diabetes mellitus type 2 (NIDDM) and 12 control subjects. The dilatory effect of acetylcholine was used to test the function of the endothelium. Subcutaneous arteries and veins (diameter 0.1–1.1 mm) were obtained during surgery. There was no difference in contractile responses to noradrenaline or ,ß-methyleneATP between diabetic and control vessels. The contractile response to neuropeptide Y, however, was markedly reduced in the diabetic group. The maximal contractile effect (46.0 ± 14.0%,p < 0.05) but not the sensitivity to neuropeptide Y was significantly less in diabetic veins compared to control (107.5 ± 19.6%). Thus, the attenuation of neuropeptide Y responses was present in humans as previously observed in alloxan-induced diabetes mellitus in rabbits. There was no difference in the dilator effect of acetylcholine between the diabetic and the control group in any of the vessel types, indicating that the difference in vascular reactivity to neuropeptide Y was not endothelium-dependent. In conclusion, the present study has shown that the postjunctional effects of neuropeptide Y, a co-transmitter of the peripheral sympathetic nervous system, is selectively attenuated in diabetes mellitus.     

Comparison of autonomic function using Valsalva ratio and 30:15 postural ratio prior to and after haemodialysis treatment

In published studies of chronic haemodialysis patients, the frequency of autonomic dysfunction varies widely. One reason for the variation may be the time of testing with respect to time of dialysis. The current study tests the hypothesis that autonomic function — as measured by heart rate responses to the Valsalva manoeuvre (Valsalva ratio) and 30:15 electrocardiogram (ECG) R—R interval to upright posture (postural ratio) — is different when patients are above dry weight (predialysis) than when they are at or below dry weight (postdialysis). The study also reviews available literature to analyze other factors that may affect the results of autonomic testing in this population. A total of 25 chronic haemodialysis patients underwent standard Valsalva and 30:15 R—R interval postural autonomic testing prior to and after haemodialysis. In addition, pre- and postdialysis orthostatic responses were measured and compared with a control population. The 30:15 ratio increased after dialysis (p = 0.001). The Valsalva ratio did not change with dialysis. Out of 25 subjects, seven had an abnormal 30:15 ratio prior to dialysis decreasing to two out of 25 patients postdialysis (p < 0.03). Orthostatic responses predialysis did not differ from those in the control group. Review of the literature shows great variability in definition of normal Valsalva and postural (30:15 R—R interval) ratios. Diabetic patients in the current and prior studies were more likely to have abnormal responses. In conclusion, the prevalence of autonomic dysfunction in chronic dialysis patients as determined by Valsalva and 30:15 ECG postural ratios may be influenced by the following factors: when subjects are studied with respect to their dialysis treatment; the number of subjects with diabetes; and the cut-off point used to define abnormal test results. Abnormal Valsalva ratios are less frequent when measured postdialysis.     

Hyposensitivity of peripheral α-adrenoceptors in respiratordependent amyotrophic lateral sclerosis assessed by intravenous norepinephrine infusion

Intravenous norepinephrine infusion test was performed in eight patients with amyotrophic lateral sclerosis (ALS) supported by respirators and nine control subjects, to examine -adrenoceptor function of peripheral resistant blood vessels. Baseline plasma norepinephrine concentrations in ALS patients were significantly higher than those in control subjects, indicating basal sympathetic hyperactivity (normal 218.2 ± 59.7 pg/ml; ALS 450.0 ± 288.4 pg/ml). The stimulus-response curves in the patients were similar to those in control subjects, and there were no significant differences between mean gains of the stimulus—response curves in both groups (normal 18.7 ± 5.5; ALS 15.2 ± 11.2). However, three ALS patients, two of whom had circulatory fluctuation and sympathetic hyperactivity, revealed lower gain levels than the mean minus 2 SD in control subjects (4.7, 1.1 and 3.7). This indicates hyposensitivity or down-regulation of the -adrenoceptor function of peripheral blood vessels in these ALS patients. For early detection of sympathetic hyperactivity and prediction of circulatory collapse, it would be useful to measure the plasma norepinephrine concentration and the gain of the norepinephrine infusion curve in respirator-dependent ALS patients.     

Molecular genetic studies of early breast cancer evolution

Summary In the past few years there has been an explosion in the number of patients diagnosed with hyperplastic breast disease andin situ breast cancer. Based on epidemiological data, these morphologically defined lesions may be categorized as those with little malignant potential (e.g. typical hyperplasia or proliferative disease without atypia [PDWA]), those with significant malignant potential which may already be initiated (e.g. atypical ductal hyperplasia [ADH]), and early transformed lesions which are malignant but not yet invasive (e.g. ductal carcinomain situ [DCIS]). They may represent sequential evolutionary stages in the ontogeny of invasive breast cancer, with each morphologically defined stage resulting from accumulating genetic changes culminating in a transformed clonal lineage capable of invasion and metastasis. Using loss-of-heterozygosity (LOH) analysis, we are studying the genetic changes associated with these lesions in archival tissue samples. 50% (6/12) of the proliferative lesions (PDWA and ADH) and 80% of the DCIS shared their LOH patterns with more advanced lesions from the same breast, strongly supporting a precursor/product relationship between these lesions and the cancers they accompany.     

Measurement of gastric and duodenal mucosal protein turnover in humans

Conventional measurement of mucosal turnover is based on labeling cellular DNA with [³H]thymidine, but because of the risk of genetic damage, this technique is not suitable for studies in normal human subjects. Consequently, we have measured mucosal protein turnover by a primed/continuous intravenous infusion of tracer quantities of [1¹⁴C]leucine and measured its incorporation into mucosal protein at 4 hr in nine healthy adult volunteers. Mucosal samples were obtained by standard endoscopic techniques from the distal duodenum and gastric antrum. In addition, duodenal villous height and width were measured by microscopic micrometric techniques in order to calculate villous growth rate. Results demonstrated a mucosal protein turnover of 57±5%/day in gastric antrum and 39±2%/day in duodenum, suggesting a mucosal replacement rate of 1.8 and 2.6 days, respectively. Average duodenal villous height was 433±77 m, suggesting a villous growth rate of approximately 160 m/day. As our mucosal protein turnover rates are similar to epithelial turnover rates measured by cellular labeling techniques, our results support the intestinal proliferon theory that suggests all mucosal elements follow similar turnover characteristics. In conclusion, the technique should provide a practical alternative method of studying the effect of disease upon mucosal regeneration and repair.     

Medical Devices Made Into Weapons by Prisoners: An Unrecognized Risk

Study objective: The alteration of a knee immobilizer into a sharp weapon by a prisoner prompted us to survey neighboring penal institutions to determine the frequency of such events. Design: We mailed a nine-item survey to all detention facilities in Tennessee, Arkansas, and Mississippi. A second survey was sent to nonresponding institutions 6 weeks after the initial mailing. Setting: The Regional Medical Center at Memphis, the designated facility for evaluation and treatment of prisoners from the county jail and state penitentiary. Participants: Survey respondents included 25 state penitentiaries, 31 county jails, 1 state minimum-security facility, 1 state maximum-security facility, 1 work-release center, 1 county detention center for drunken-driving offenders, and 1 federal penitentiary. Results: Of the 81 institutions surveyed, 77% responded to one of the two mailings. Forty percent responded in the affirmative when asked whether stolen or unauthorized medical equipment from outside their institutions had been discovered among inmates. When respondents were questioned as to whether medical equipment, prescribed or not, had been used or altered in a criminal manner, 34% responded "yes." Medications and medical appliances were listed in the responses. Conclusion: A survey of 81 local and neighboring penal institutions in a three-state area revealed that the illicit use of medicine and medical devices by prisoners is a legitimate safety concern of prison personnel and health care workers when medical care for inmates must be sought outside the security of their institutions. The modification of medical equipment into weapons by incarcerated patients, although clearly recognized as a security and safety problem by police authorities, appears to be unappreciated by health care workers providing episodic care to inmates. [Hayden JW, Laney C, Kellermann AL: Medical devices made into weapons by prisoners: An unrecognized risk. Ann Emerg Med December 1995;26:739-742.]     

Primary and preventive care in a university obstetrics and gynecology group practice

Objective: Our purpose was to determine whether primary and preventive care is practiced by a university obstetrician-gynecologist group practice.Study design: A retrospective chart review spanning 2 years of four academic physicians' private practices was performed. A total of 335 patients were reviewed with 739 patient encounters and 1032 patient problems identified. The definition of a primary care physician according to The American College of Obstetricians and Gynecologists was used to standardize data collection and evaluation.Results: Obstetric complaints accounted for 27.7% of all visits, whereas 65.4% were for gynecologic problems. Almost 7% of all complaints were neither obstetric nor gynecologic, and of those 74.6% were primary care problems completely managed by the obstetrician-gynecologist. Only 19.7% of these were referred for management. More than 89% of all encounters () involved some element of primary care.Conclusion: This study provides evidence that the majority of health care provided by the obstetrician-gynecologists is primary care.     

An expert system to teach troubleshooting of common problems associated with the automated anesthesia recordkeeper

Automated anesthesia recordkeepers have been used to monitor patients during surgery in up to 90% of cases at The Ohio State University. The record-keeping devices are complex and can be difficult to troubleshoot. The 1st-CLASS Fusion Program, an expert system shell-program, has been programmed to allow the resident or nurse anesthetist to solve the two most common types of problems associated with the recordkeeper: printer problems and patient monitor problems. Use of this program allows the resident or nurse anesthetist to troubleshoot the recordkeeper quickly and accurately and promotes in the user a sense of competence and control over the technology.     

Is the IV obstructed or infiltrated? A simple clinical test

Objective. The objective of our study was to determine if clinical observation of pressure-flow relationships (PFR) can differentiate between partial external obstruction (obstruction) and infiltration as a cause of poor performance of gravity-fed infusions.Methods. A total of 24 patients with functional intravenous cannulae in situ had obstruction simulated by the application of a tourniquet proximal to the cannula. The change in flow (F) for a discrete change in pressure (P) was determined in each case by counting drop rates at two different elevations of the fluid reservoir level, 10 cm apart. The same process was repeated in 15 patients in whom the cannula was in an extra vascular location (infiltration). Three sizes of cannula—16-gauge, 18-gauge, and 20-gauge—were examined, with equal distribution of sizes in each group. The effect on flow rates of inflating a blood pressure (BP) cuff proximally on the cannulated limb was assessed. The ratio P/F is the total resistance of the infusion system, and by subtracting known values for resistance of infusion tubing and cannula, the venous or tissue resistance was calculated.Results. There was a statistically significant difference between the change in flow for obstructed compared with infiltrated cannulae for the same change in pressure for each cannula size. The mean venous resistance was 23 mm Hg/L/hr, while that of tissue was 280 mm Hg/L/hr, with no overlap between groups. There was no effect on flow rate with blood pressure cuff inflation in the infiltrated group whereas flow progressively fell in the obstructed group.Conclusions. Clinical observation of PFRs in poorly functioning gravity-fed IV infusions can assist in detecting infiltration as a cause. Inflation of a blood pressure cuff will further impair flow where the cannula is intravascular, but will have no effect in an extravascular location.     

Traumatic rupture of the thoracic aorta: Should one always operate immediately?

Although the traditional therapy for blunt traumatic rupture of the thoracic aorta (TRA) is immediate operative repair, there may be a selective role for delayed repair, particularly in patients with head trauma, respiratory failure, or cardiac dysfunction. The present study examines the hypothesis that TRA can be managed by selective delayed operative repair. Clinical data were collected from 59 consecutive patients with TRA at a regional trauma unit. All TRAs were at the aortic isthmus. Patients were retrospectively classified into three groups: group I (n=12) included patients who either arrived in extremis or rapidly became unstable during triage; group II (n=3) included patients who had no contraindications to early repair and underwent repair at the time of diagnosis; and group III (n=44) consisted of patients who because of concomitant injuries or sepsis required initial admission and management in the intensive care unit until their clinical status had improved sufficiently to allow for deliberate delayed operative repair of the TRA. The delay ranged from 1 day to 7 months. Eight patients have yet to undergo repair and remain well at follow-up from 1 to 4 years. Overall survival rates in groups I, II, and III were 17%, 100%, and 82%, respectively. The surgery-related mortality rate in group III was 10% (three patients). Only two (4.5%) patients in group III died as a result of a ruptured aorta within 72 hours of admission. In conclusion, contrary to surgical doctrine, TRA may not require immediate operative repair in all cases, but may instead be managed selectively depending on the patient's clinical status.