Postural instability in patients with diabetic sensory neuropathy.

OBJECTIVE: Recent survey evidence suggests that sensory ataxia due to diabetic neuropathy may be a more frequent and serious problem than is commonly recognized. This view is further supported by research that confirms the major contribution of the somatosensory system to the control of posture. We therefore sought to determine the effects of significant diabetic distal symmetrical polyneuropathy on the control of posture. RESEARCH DESIGN AND METHODS: Fifty-one subjects, divided into three groups, participated in this study. Seventeen had diabetes and significant sensory neuropathy, 17 had diabetes and no neuropathy, and 17 had neither diabetes nor neuropathy. The subjects were matched across groups, and stringent exclusion criteria were applied. Postural stability during quiet standing was measured using a force platform. In addition to electrophysiological and quantitative sensory tests of neuropathy, a number of physical and functional characteristics were measured for all subjects. RESULTS: Postural instability was found to be significantly associated with sensory neuropathy, but not with diabetes per se. Patients with sensory neuropathy demonstrated between 66 and 117% more instability than did control subjects (depending on the testing condition). Based on multiple linear regression analyses, the most significant correlates of instability were the quantitative sensory measures of neuropathy and age. CONCLUSIONS: The loss of sensory perception secondary to diabetic distal symmetrical sensory neuropathy has a markedly detrimental effect on postural stability. The deficit is greatest when visual or vestibular cues are absent or degraded. Patients with neuropathy need to be informed of the postural consequences of this condition to limit the potential morbidity caused by falls.

Prolactin variants in ram adenohypophyses vary with season.

Secretion of PRL in sheep is affected by photoperiod being highest during the spring and summer, lowest in fall and winter. The objectives of this study were to determine if 1) the production of variant forms of PRL, and 2) immuno- and bioactivities of PRL (iPRL and bPRL) differ during times of the year selected to represent periods of low, transitional and high PRL secretion. Twelve mature rams were maintained on pasture and killed in October, December, and April (n = 4/month). Individual pituitary glands were dispersed, cells obtained, and fixed for immunocytochemical flow cytometry, extracted with 0.01 N NaHCO3 or cultured in serum-free, defined media. The Mr of PRL extracted from cells immediately following dispersion ranged from 14-140K, with significantly more bands greater than 40K being detected from rams sacrificed in December than from those killed in October and April (P less than 0.01). No bands of PRL greater than 25K were observed when samples were reduced with beta-mercaptoethanol prior to electrophoresis, indicating that the high Mr forms were disulfide-linked aggregates. Culture media from October and April contained variants of PRL that ranged from 22-40K but those greater than 25K were generally not observed from cells harvested during December. Extracts of cells after 24 h in culture contained fewer high Mr species during December than had been present in initial extracts from that month. In contrast, during April more high Mr intracellular forms were present after culture than had been detected prior to culture during that month. The percentage of lactotrophs averaged 50.0 +/- 2.5, 47.4 +/- 5.7, and 59.4 +/- 5.5 for October, December, and April, respectively. Initial lactotroph content (pg/lactotroph) of iPRL was higher (P = 0.06) in April (46.0 +/- 17.0) when compared to October and December (8.0 +/- 2.0 and 20.0 +/- 10.0, respectively). In contrast, the bPRL content of initial extracts was higher (P = 0.05) in December (267.0 +/- 68.0) than in October (101.0 +/- 35.0), but not than in April (190.0 +/- 70.0). Although iPRL and bPRL concentrations in culture media were similar for the 3 months, the intracellular iPRL (P less than 0.001) and bPRL (P less than 0.0001) content after culture was greatest during April. In summary, in addition to the well-documented seasonal changes in blood concentrations of PRL, different molecular forms of PRL were found within the pituitary at different times of the year and seasonal variations in iPRL and bPRL did not occur in parallel.

The multi-site tumour transplantation model for human endometrial carcinoma: a statistical evaluation.

We studied the effect of multi-site tumour transplantation on tumour growth by implanting varying numbers of EnCa 101 human endometrial tumours in athymic mice. One treatment group received a single tumour per mouse, another group received two tumours per mouse and a third group received four tumours per mouse. Tumour growth was sustained in all animals by implantation of oestradiol-17 beta pellets. We observed positive correlation between tumours within the same mouse, which implies that individual tumours are not statistically independent. The correlation is sufficiently large that failure to account for it in statistical design and analysis could result in studies with insufficient power and in spurious assertions of significance. Regression modelling of tumour growth curves showed that mean tumour volume per animal is not affected by the number of tumours growing on the animal; that is, the data are consistent with the null hypothesis that mean tumour volume is the same regardless of the number of tumours present. Our results therefore suggest that the use of multiple tumours per animal can increase the precision of experiments without loss of validity and at relatively little cost. However, correct and efficient analysis of the data so obtained requires more sophisticated techniques than those--such as fixed-effects analysis of variance and the two sample t-test--that assume independence of tumours.

Effects of a milk chocolate bar per day substituted for a high-carbohydrate snack in young men on an NCEP/AHA Step 1 Diet.

This study compares the plasma cholesterol response with the isoenergetic substitution of a milk chocolate bar (46 g) given daily for a high-carbohydrate snack in healthy young men on a Step 1 Diet. Normocholesterolemic men (n = 42) were fed a Step 1 Diet for 21 d (run-in diet) followed by a 27-d experimental period during which they consumed the same diet plus either a milk chocolate bar or a high-carbohydrate snack; after this they consumed the run-in diet for 21 d followed by the other snack for 27 d. When subjects consumed a milk chocolate bar instead of the high-carbohydrate snack, high-density-lipoprotein (HDL) cholesterol was 0.08 +/- 0.03 mmol/L higher (P < 0.01) and plasma triglycerides were 0.06 +/- 0.03 mmol/L lower (P < 0.05). Substitution of a milk chocolate bar for a high-carbohydrate snack did not adversely affect the low-density-lipoprotein-(LDL) cholesterol response to a Step 1 Diet despite an increase in total fat and saturated fatty acid content of the diet. This response may be due to stearic acid.

Mass spectrometry for monitoring respiratory and anesthetic gas waveforms in rats.

A method is presented for real-time monitoring of airway gas concentration waveforms in rats and other small animals. Gas is drawn from the tracheal tube, analyzed by a mass spectrometer, and presented as concentration vs. time waveforms simultaneously for CO2, halothane, and other respiratory gases and anesthetics. By use of a respiratory simulation device, the accuracy of mass spectrometric end-tidal CO2 analysis was compared with both the actual gas composition and infrared spectrophotometry. The effects of various ventilator rates and inspiration-to-expiration ratios on sampling accuracy were also examined. The technique was validated in male Sprague-Dawley rats being ventilated mechanically. The difference between the arterial PCO2 (PaCO2) and the end-tidal PCO2 (PETCO2) was not significantly different from zero, and the correlation between PETCO2 and PaCO2 was strong (r = 0.97, P less than 0.0001). Continuous gas sampling for periods up to 5 min did not affect PaCO2, PETCO2, or airway pressures. By use of this new method for measuring end-tidal halothane concentrations in rats approximately 6.5 mo of age, the minimum alveolar concentration of halothane that prevented reflex movement in response to tail clamping was 0.97 +/- 0.04% atmospheric (n = 14). This mass spectrometric technique can be used in small laboratory animals, such as rats, weighing as little as 250 g. Gas monitoring did not distort either PETCO2 or PaCO2. Under the defined conditions of this study, accurate and simultaneous measurements of phasic respiratory concentrations of anesthetic and respiratory gases can be achieved.

Chronic hormone replacement therapy alters thermoregulatory and vasomotor function in postmenopausal women.

This investigation examined effects of chronic (>/=2 yr) hormone replacement therapy (HRT), both estrogen replacement therapy (ERT) and estrogen plus progesterone therapy (E+P), on core temperature and skin blood flow responses of postmenopausal women. Twenty-five postmenopausal women [9 not on HRT (NO), 8 on ERT, 8 on E+P] exercised on a cycle ergometer for 1 h at an ambient temperature of 36 degrees C. Cutaneous vascular conductance (CVC) was monitored by laser-Doppler flowmetry, and forearm vascular conductance (FVC) was measured by using venous occlusion plethysmography. Iontophoresis of bretylium tosylate was performed before exercise to block local vasoconstrictor (VC) activity at one skin site on the forearm. Rectal temperature (Tre) was approximately 0.5 degrees C lower for the ERT group (P < 0.01) compared with E+P and NO groups at rest and throughout exercise. FVC: mean body temperature (Tb) and CVC: Tb curves were shifted approximately 0.5 degrees C leftward for the ERT group (P < 0.0001). Baseline CVC was significantly higher in the ERT group (P < 0.05), but there was no interaction between bretylium treatment and groups once exercise was initiated. These results suggest that 1) chronic ERT likely acts centrally to decrease Tre, 2) ERT lowers the Tre at which heat-loss effector mechanisms are initiated, primarily by actions on active cutaneous vasodilation, and 3) addition of exogenous progestins in HRT effectively blocks these effects.

The use of running shoes to reduce plantar pressures in patients who have diabetes.

We compared the plantar pressures generated by walking in leather-soled Oxford-style shoes and by walking in inexpensive running shoes with those generated by walking in thin socks on a hard surface for thirty-nine individuals (thirteen who had diabetes and neuropathy, and thirteen who had diabetes without neuropathy, and thirteen who had neither diabetes nor neuropathy [controls]). Except for two anatomical regions, the plantar pressure associated with the Oxford-style shoes were not different from those associated with walking without shoes. In comparison, the inexpensive running shoes relieved plantar pressure in the forefoot and heel by a mean (and standard deviation) of 31 +/- 9.1 per cent, with the most relief occurring in the feet that had the highest pressures when they were unshod. There were significant reductions in pressure in all regions of the foot except for the midfoot (p < 0.01), and there were no significant differences between the groups. Individuals who have insensate feet should be discouraged from wearing leather-soled Oxford-style shoes because of the risk of ulceration due to elevated plantar pressures. Inexpensive running shoes should be viewed as the very minimally acceptable choice for footwear for these individuals if the feet are free of deformity.

Day-to-day energy expenditure variability in low birth weight neonates.

We estimated the metabolic rate of 13 low birth weight infants over a 9-day period, using indirect calorimetry in conjunction with serial measurements of oxygen consumption, carbon dioxide production, and total urinary nitrogen excretion. The mean percent error for oxygen consumption and carbon dioxide production measurements (determined by alcohol combustion experiments) assignable to the open-circuit system was 0.4 and 3.8%, respectively. Error in the total urinary nitrogen excretion measurement was less than 1% by the Kjeldahl technique. In the clinical setting, however, the range of deviation of measured oxygen consumption, carbon dioxide production and total urinary nitrogen excretion was +/- 12, 12, and 15% of the mean value respectively for an individual patient under standardized controlled conditions. The variability of metabolic rate between infants may be as much as 76%. Factors that had a small effect on metabolic rate were difficult to detect because of the variability inherent in the short-term measurement of metabolic rate. It was virtually impossible to control the sources of variation in the resting metabolism of low birth weight neonates over extended experimental periods. Day-to-day variations in resting energy expenditure may explain, in part, the widely different growth rates of premature infants receiving similar caloric intakes.

The accuracy of Finapres noninvasive mean arterial pressure measurements in anesthetized patients.

The Finapres (FIN) is a new noninvasive blood pressure monitor that provides continuous arterial waveform display with the use of a finger cuff. The authors assessed the accuracy of FIN mean arterial pressure (MAP) measurements relative to simultaneous direct radial arterial pressures in 20 patients undergoing general anesthesia for major elective surgery. Data were collected digitally with the use of RS-232 communications over a total of 16.2 h. The data were processed into 6012 interference-free time samples, each spanning 6 s. The authors determined the difference between FIN and direct MAPs during each time sample. The authors calculated not only the bias of FIN measurements, but also the frequency, magnitude, and duration of discrepancies between simultaneous FIN and direct MAPs. The overall bias of the FIN MAP was -0.5 +/- 1.0 mmHg, which was not significantly different from zero. However, 32.3 +/- 6.2% of all MAP comparisons differed by greater than +/- 10 mmHg, and 5.0 +/- 1.1% differed by greater than +/- 20 mmHg. Moreover, there was an average of one episode every 2 patient-hours when the FIN MAP differed by greater than +/- 20 mmHg for more than 1 min. Although the MAP measured by FIN accurately reflected direct MAPs most of the time, there were occasional discrepancies of different magnitude such that clinical usefulness may be limited in patients in whom continuous accurate blood pressure measurements are essential.

Problems with gait and posture in neuropathic patients with insulin-dependent diabetes mellitus.

Peripheral neuropathy secondary to diabetes mellitus is believed to cause postural instability and uncoordinated gait, although this is not well documented. Two groups of patients from the Pittsburgh Epidemiology of Diabetes Complications Study, matched for age and duration of Type 1 diabetes, but with significantly different vibratory sensation thresholds as determined by Vibratron II testing, were therefore surveyed. The mean ages were 32.9 and 31.9 years and durations of diabetes were 22.0 and 18.8 years for the neuropathic and control groups, respectively. Patients provided details of fall injuries, and perception of safety during standing and walking. Multiple linear and logistic regression models were used to account for potentially associated variables such as gender, retinopathy, and duration of diabetes. The neuropathic group had adjusted odds ratios for reported injuries during gait of 15.0 relative to the control group (95% confidence intervals 1.04-216.59). The neuropathic group also reported significantly lower scores (less safe, p = 0.004) than the control group on perceived safety in unusual conditions. It is concluded that peripheral neuropathy has an effect on gait and posture which is clinically significant and that this effect merits further biomechanical study in neuropathic patients.

Time and cost analysis of a computer-assisted telephone interview system to collect dietary recalls.

This study, conducted in 1991, examined the time requirements and costs of obtaining 24-hour dietary recalls via telephone interviews using the University of Minnesota's microcomputer Nutrient Data System to conduct the interviews and compute the nutrient composition of the diets. The subjects were 156 hypercholesterolemic children (aged 4-10 years) and 102 hypercholesterolemic adults (aged 21-65 years), who were participating in ongoing cholesterol education programs. A total of 391 recalls were completed with the children and 278 with the adults. For each completed interview, 3.5 and 2.8 attempts were required, respectively. Evenings were the most productive time for completing interviews. All tasks associated with completing the interviews (attempts to call, interviews per se, and postinterview procedures) required an average of 39.7 and 35.5 minutes per completed interview with the children and adults, respectively. About half of these total times were actually devoted to conducting the interview. The costs per completed interview were $9.22 for the children versus $6.99 for the adults. This difference reflects the greater number of attempts required to reach the children, the longer duration of their interviews, and the higher intrastate toll rates for calls to them as compared with the interstate rates for calls to the adults.

Decreased active vasodilator sensitivity in aged skin.

Older men and women respond to local and reflex-mediated heat stress with an attenuated increase in cutaneous vascular conductance (CVC). This study was performed to test the hypothesis that an augmented or sustained noradrenergic vasoconstriction (VC) may play a role in this age-related difference. Fifteen young (22 +/- 1 yr) and 15 older (66 +/- 1 yr) men exercised at 50% peak oxygen uptake in a 36 degrees C environment. Skin perfusion was monitored at two sites on the right forearm by laser-Doppler flowmetry: one site pretreated with bretylium tosylate (BT) to block the local release of norepinephrine and thus VC and an adjacent control site. Blockade of reflex VC was verified during whole body cooling using a water-perfused suit. CVC (perfusion divided by mean arterial pressure) at each site was reported as a percentage of the maximal CVC (%CVCmax) induced at the end of each experiment by prolonged local heating at 42 degrees C. Neither age nor BT affected the %CVCmax (75-86%) attained at high core temperatures. During the early rise phase of CVC, the %CVCmax-change in esophageal temperature (delta T(es)) curve was shifted to the right in the older men (effective delta T(es) associated with 50% CVC response for young, 0.22 +/- 0.04 and 0.39 +/- 0.04 degrees C and for older, 0.73 +/- 0.04 and 0.85 +/- 0.04 degrees C at control and BT sites, respectively). BT had no interactive effect on this age difference, suggesting a lack of involvement of the VC system in the attenuated CVC response of individuals over the age of 60 yr. Additionally, increases in skin vascular conductance were quantitatively compared by measuring increases in total forearm vascular conductance (FVC, restricted to the forearm skin under these conditions). After the initial approximately 0.2 degrees C increase in T(es), FVC was 40-50% lower in the older men (P < 0.01) for the remainder of the exercise. Decreased active vasodilator sensitivity to increasing core temperature, coupled with structural limitations to vasodilation, appears to limit the cutaneous vascular response to exertional heat stress in older subjects.

Halothane selectively attenuates alpha 2-adrenoceptor mediated vasoconstriction, in vivo and in vitro.

The mechanism by which halothane interferes with catecholamine-induced vasoconstriction was examined, utilizing specific agonists at postjunctional alpha 1- and alpha 2-adrenoceptors on vascular smooth muscle. Stimulation of either adrenoceptor subtype normally produces vasoconstriction. Two experimental models of drug-induced vasoconstriction were used: in vivo blood pressure response in pithed rats, and in vitro isometric tension development in canine saphenous vein rings. These models were then utilized to examine the anti-vasoconstriction properties of halothane. In vivo, halothane (1 MAC) produced a significant depression in the vascular response to azepexole (an alpha 2-adrenoceptor agonist), but halothane did not alter vasoconstriction by phenylephrine (an alpha 1-adrenoceptor agonist). Halothane caused a 24% reduction of maximal response (P less than 0.0001) to azepexole in pithed rats, and a 3.2-fold rightward shift of the log dose-response curve (P less than 0.0001). Similarly, in vitro, halothane significantly attenuated alpha 2- but not alpha 1-adrenoceptor responsiveness. Halothane (4%) depressed maximal vein contraction to azepexole by 26% (P less than 0.0001), and shifted the log concentration-response curve 2.4-fold to the right (P less than 0.0001). The observed selective interference with alpha 2-mediated vasoconstriction by halothane is unlikely to represent drug antagonism at the receptor level. Our observations may suggest, indirectly, that halothane interferes with Ca+2 entry into vascular smooth muscle. The phenomenon of selective anti-vasoconstriction at alpha 2-adrenoceptors by halothane may explain why alpha 1-adrenergic agonists often appear to retain their vasopressor activity during halothane anesthesia. The mechanism of halothane-induced vasodilation thus includes attenuation of alpha 2- but not alpha 1-adrenergic vasoconstriction; this further demonstrates the multifactorial nature of halothane-induced vasodilation.

Diabetic sensory neuropathy effect on ankle joint movement perception.

OBJECTIVE: To determine if diabetic subjects with lower extremity cutaneous sensory neuropathy also have a loss of ankle joint movement perception. The strength of association between measurements of ankle joint movement perception and measures of cutaneous sensory function was also investigated. DESIGN: Diabetic subjects with and without sensory neuropathy and individuals without diabetes participated in this study. SETTING: All subjects were community-living individuals. PARTICIPANTS: Fifty-one subjects, ages 40 to 68. Seventeen of the 34 subjects with diabetes had significant distal sensory neuropathy as determined by cutaneous perception of mechanical vibration. All individuals without diabetes were volunteers from the community. Most subjects with diabetes were recruited through direct referral from their physicians. INTERVENTIONS: Ankle joint movement perception threshold (JMPT) was assessed using a device designed for this study. Cutaneous sensory function under both halluces was measured for vibration perception using a vibrometer and for touch-pressure perception using Semmes-Weinstein monofilaments. MAIN OUTCOME MEASURES: Ankle JMPTs (degrees) were compared to measurements of cutaneous vibration perception (volts) and touch-pressure perception (monofilaments force ratings). RESULTS: Diabetic subjects with cutaneous sensory neuropathy demonstrated a significant loss of ankle movement perception (p < .01). Correlation between JMPT and cutaneous sensory tests ranged from Spearman's rank r = .43 to .67. CONCLUSIONS: Although individuals with cutaneous sensory loss secondary to diabetic neuropathy also demonstrated loss of movement perception at the ankle, the relatively low explained variance between the two types of assessment (18% to 45%) indicates that the severity of ankle joint movement perception deficits cannot be directly implied from cutaneous sensory tests.

Diltiazem withdrawal before coronary artery bypass surgery.

The authors studied the effects of withdrawing oral diltiazem therapy on the subsequent course of coronary artery bypass graft surgery. Patients with severe coronary artery disease were divided into three groups using a prospective, controlled, randomized protocol. In group D (diltiazem-continuation) patients, diltiazem was administered 2.1 +/- 0.1 hours (mean +/- SEM) before anesthetic induction (n = 10). Group DW (diltiazem-withdrawal) patients received their final diltiazem dose 17.3 +/- 2.9 hours before anesthesia (n = 10). Group R was a reference group of patients not receiving diltiazem (n = 11; not randomized). Anesthesia was induced and maintained with fentanyl and pancuronium without use of halogenated anesthetics. No clinically important differences were detected in measured hemodynamics or drug requirements. Group D patients did not have a lower systemic vascular resistance (SVR) index (P greater than 0.31) or mean arterial pressure (P greater than 0.08) compared with group DW. Also, no evidence for a diltiazem withdrawal response was found, because group DW did not have either a higher SVR index (P = 0.99) or a higher pulmonary vascular resistance index (P = 0.99) compared with group R, and no severe myocardial ischemia, coronary artery spasm, or postoperative heart block were seen. Plasma diltiazem concentrations decreased significantly during CPB (P less than 0.0001), but showed overlap between groups D and DW. Plasma diltiazem concentration did not correlate significantly with simultaneous SVR. These data show the benign effects of both diltiazem administration and its acute withdrawal before coronary artery bypass surgery with high-dose fentanyl anesthesia.

Carbon dioxide elimination during total cardiopulmonary bypass in infants and children.

The authors measured the rate of carbon dioxide elimination (VCO2) in 25 pediatric patients (age 2 days to 9 yr) during total cardiopulmonary bypass at average venous blood temperatures ranging from 19.5 to 35.9 degrees C. A multiplexed mass spectrometer was connected to the gas inlet and exhaust ports of the bubble oxygenator, and the gas-phase Fick principle was used to determine VCO2. A curvilinear relationship was found between log VCO2 and venous blood temperature, and a quadratic regression equation (r2 = 0.74) was fit to the data. Q10 (the ratio of VCO2 before and after a 10 degree C temperature change) was estimated to be 2.7 or 3.0, depending on the analytic method used. Venous blood temperature as a predictor variable explained a greater proportion of the variability of log VCO2 than did nasopharyngeal or rectal temperatures. Analysis of covariance revealed that total circulatory arrest during bypass (utilized in 10 patients for 34 +/- 4 min, mean +/- SEM) affected the relationship of venous blood temperature with log VCO2, by increasing the y-intercept (P = .008) but not the slope. These data, with associated 95% prediction intervals, define the expected CO2 elimination rates at various temperatures during standard bypass conditions in our patients. Real-time measurement of VCO2 using mass spectrometry can be a useful routine monitor during CPB that may help to assess patient metabolic function, adequacy of perfusion, and oxygenator performance.

Vibration perception threshold testing in patients with diabetic neuropathy: ceiling effects and reliability.

AIMS: To test the reliability of a new vibrometer (Maxivibrometer) which was constructed so that vibration perception threshold (VPT) could be determined without the disadvantage of the off-scale measurements frequently experienced with the Biothesiometer. METHODS: The two devices were compared and tested on a group of diabetic neuropathic subjects and a group of healthy, matched control subjects. VPT was tested on the plantar surface of the feet. RESULTS: The Maxivibrometer gave an actual measurement in all cases even if subjects were severely neuropathic. The replication-to-replication and day-to-day intraclass correlation coefficients for the Maxivibrometer VPT were, except in one case, above 0.94, indicating excellent reliability. The Biothesiometer VPT could also be measured with excellent reliability but only within a limited range of mild to moderate neuropathy, so it appears to be an appropriate screening tool. The replication-to-replication intraclass correlation coefficient was 0.93. CONCLUSIONS: Because VPT could be measured over a wide range with the Maxivibrometer, it was demonstrated that loss of sensation in diabetic neuropathy can progress far beyond the maximum VPT value of the Biothesiometer. The wide measurement range and the excellent reliability make the Maxivibrometer a valuable research tool to quantify loss of sensation, particularly in the presence of severe neuropathy and to record changes over time. Diabet. Med. 18, 469-475 (2001)