Aerosolisation during tracheal intubation and extubation in an operating theatre setting.

Aerosol-generating procedures such as tracheal intubation and extubation pose a potential risk to healthcare workers because of the possibility of airborne transmission of infection. Detailed characterisation of aerosol quantities, particle size and generating activities has been undertaken in a number of simulations but not in actual clinical practice. The aim of this study was to determine whether the processes of facemask ventilation, tracheal intubation and extubation generate aerosols in clinical practice, and to characterise any aerosols produced. In this observational study, patients scheduled to undergo elective endonasal pituitary surgery without symptoms of COVID-19 were recruited. Airway management including tracheal intubation and extubation was performed in a standard positive pressure operating room with aerosols detected using laser-based particle image velocimetry to detect larger particles, and spectrometry with continuous air sampling to detect smaller particles. A total of 482,960 data points were assessed for complete procedures in three patients. Facemask ventilation, tracheal tube insertion and cuff inflation generated small particles 30-300 times above background noise that remained suspended in airflows and spread from the patient's facial region throughout the confines of the operating theatre. Safe clinical practice of these procedures should reflect these particle profiles. This adds to data that inform decisions regarding the appropriate precautions to take in a real-world setting.

The clinical impact of maternal COVID-19 on mothers, their infants, and placentas with an analysis of vertical transfer of maternal SARS-CoV-2-specific IgG antibodies.

INTRODUCTION: The effect of SARS-CoV-2 severity or the trimester of infection in pregnant mothers, placentas, and infants is not fully understood. METHODS: A retrospective, observational cohort study in Chapel Hill, NC of 115 mothers with SARS-CoV-2 and singleton pregnancies from December 1, 2019 to May 31, 2021 via chart review to document the infants' weight, length, head circumference, survival, congenital abnormalities, hearing loss, maternal complications, and placental pathology classified by the Amsterdam criteria. RESULTS: Of the 115 mothers, 85.2% were asymptomatic (n = 37) or had mild (n = 61) symptoms, 13.0% had moderate (n = 9) or severe (n = 6) COVID-19, and 1.74% (n = 2) did not have symptoms recorded. Moderate and severe maternal infections were associated with increased C-section, premature delivery, infant NICU admission, and were more likely to occur in Type 1 (p = 0.0055) and Type 2 (p = 0.0285) diabetic mothers. Only one infant (0.870%) became infected with SARS-CoV-2, which was not via the placenta. Most placentas (n = 63, 54.8%) did not show specific histologic findings; however, a subset showed mild maternal vascular malperfusion (n = 26, 22.6%) and/or mild microscopic ascending intrauterine infection (n = 28, 24.3%). The infants had no identifiable congenital abnormalities, and all infants and mothers survived. DISCUSSION: Most mothers and their infants had a routine clinical course; however, moderate and severe COVID-19 maternal infections were associated with pregnancy complications and premature delivery. Mothers with pre-existing, non-gestational diabetes were at greatest risk of developing moderate or severe COVID-19. The placental injury patterns of maternal vascular malperfusion and/or microscopic ascending intrauterine infection were not associated with maternal COVID-19 severity.

An engineered, orthogonal auxin analog/AtTIR1(F79G) pairing improves both specificity and efficacy of the auxin degradation system in Caenorhabditis elegans.

The auxin-inducible degradation system in C. elegans allows for spatial and temporal control of protein degradation via heterologous expression of a single Arabidopsis thaliana F-box protein, transport inhibitor response 1 (AtTIR1). In this system, exogenous auxin (Indole-3-acetic acid; IAA) enhances the ability of AtTIR1 to function as a substrate recognition component that adapts engineered degron-tagged proteins to the endogenous C. elegans E3 ubiquitin ligases complex [SKR-1/2-CUL-1-F-box (SCF)], targeting them for degradation by the proteosome. While this system has been employed to dissect the developmental functions of many C. elegans proteins, we have found that several auxin-inducible degron (AID)-tagged proteins are constitutively degraded by AtTIR1 in the absence of auxin, leading to undesired loss-of-function phenotypes. In this manuscript, we adapt an orthogonal auxin derivative/mutant AtTIR1 pair [C. elegans AID version 2 (C.e.AIDv2)] that transforms the specificity of allosteric regulation of TIR1 from IAA to one that is dependent on an auxin derivative harboring a bulky aryl group (5-Ph-IAA). We find that a mutant AtTIR1(F79G) allele that alters the ligand-binding interface of TIR1 dramatically reduces ligand-independent degradation of multiple AID*-tagged proteins. In addition to solving the ectopic degradation problem for some AID-targets, the addition of 5-Ph-IAA to culture media of animals expressing AtTIR1(F79G) leads to more penetrant loss-of-function phenotypes for AID*-tagged proteins than those elicited by the AtTIR1-IAA pairing at similar auxin analog concentrations. The improved specificity and efficacy afforded by the mutant AtTIR1(F79G) allele expand the utility of the AID system and broaden the number of proteins that can be effectively targeted with it.

Effects of methionine and lysine on fermentation in vitro and in vivo, nutrient flow to the intestine, and milk production.

Three experiments were conducted to investigate the feasibility of using crystalline methionine and lysine as protein supplements for lactating Holstein cows. In the first experiment, Met (dl-methionine) and Lys (l-lysine-HCl) were added to diets used in continuous culture bioreactors to estimate optimal concentrations for use in subsequent in vivo experiments. The second experiment measured ruminal fermentation and nutrient flow to the small intestine when Met and Lys were top-dressed on diets fed to nonlactating cows. The third experiment measured lactation performance when Met and Lys were added to diets fed to late-lactation cows. Providing 0.29 and 2.27% of dry matter as Met and Lys, respectively, provided the largest improvement in fermentation in vitro and these concentrations were used in subsequent experiments. When Met and Lys were top-dressed on diets fed to nonlactating cows, no changes in total tract N digestion were observed. No changes in microbial protein production or ruminal fermentation were observed. Adding Met and Lys did not change production or efficiency of production of milk or milk components by late lactation cows. These data indicate that providing supplemental Met and Lys during late lactation does not significantly improve the protein status of the cow and therefore may not improve milk production.

Improving prognosis in type 2 diabetes. Diabetic neuropathy is in trouble.

Painful sensory syndromes and the anesthetic foot result in much clinical morbidity and patient unhappiness in diabetes. As yet, a satisfactory and fundamental therapy is not available to us to help patients. Effective blood glucose control and vigilant screening programs for foot problems are all we have to offer. Clinical observation of neuropathic syndromes and measures of nerve function have not led to significant understanding of pathogenesis. The primary source of understanding of pathways to nerve damage come from animal studies, despite the fears that the model in diabetes in no way reflects the human situation. Therapeutic hope at the moment from such animal work must focus on the interference of pathways known to lead to neural blood-flow abnormalities and a variety of metabolic abnormalities, as well as the possibility that addition of nerve growth factor will assist repair and regeneration. The understanding of these multiple pathways in the animal model underlines the likely enormous complexity in the final picture of understanding in diabetic neuropathy. Modern imaging techniques such as magnetic resonance imaging should, in the future, allow more significant investigation of the human subject.

The prevalence of symptomatic, diabetic neuropathy in an insulin-treated population.

The prevalence of symptomatic sensorimotor polyneuropathy has been determined in a population of 382 insulin-treated diabetic subjects aged 15-59 yr. Forty-one subjects (10.7%) were found to have diabetic neuropathy, according to strict diagnostic criteria that required the presence of symptoms and signs of nerve dysfunction in the absence of peripheral vascular disease. There was a significant correlation between glycosylated hemoglobin levels and motor conduction velocity in the median and peroneal nerves in all subjects. This finding further emphasizes the importance of metabolic factors related to hyperglycemia in the impaired nerve function seen in diabetic patients.

Symptomatic hypoglycemia in NIDDM patients treated with oral hypoglycemic agents.

We assessed the prevalence of hypoglycemic symptoms in patients (aged 40-65 yr) treated with oral hypoglycemic agents (OHAs) attending routine diabetes clinics at our hospital. Symptoms were experienced during the previous 6 mo in 41 of 203 (20.2%) patients treated with sulfonylureas but in none of the 16 patients treated with metformin alone. Hypoglycemic symptoms were experienced at least monthly in 5.9% and less frequently in 14.3% of patients. The prevalence of symptoms decreased with increasing duration of sulfonylurea administration (P less than .01). Mean glycosylated hemoglobin and postprandial plasma glucose were significantly lower in patients reporting hypoglycemic symptoms than in those without symptoms (P less than .001). The prevalence of hypoglycemic symptoms was significantly higher in patients treated with glyburide than in patients treated with gliclazide (P less than .01) or chlorpropamide (P less than .05). The prevalence of symptoms was higher in patients taking medications in addition to OHAs (P less than .01). Ten (24%) of the patients who experienced hypoglycemic symptoms were taking drugs that may potentiate sulfonylureas.

Early identification of diabetic foot ulcers that may require intervention using the micro lightguide spectrophotometer.

OBJECTIVE: Adequate tissue oxygenation is known to be essential for the healing of diabetic foot ulcers, but hypoxia has also been shown to be a potent stimulus for growth. There are no studies looking specifically at ulcer oxygen levels during the healing process. We measured the serial microvascular oxygen saturation (SaO2) of the foot ulcer, the ulcer margin, and a control site using the Erlangen micro lightguide spectrophotometer (EMPHO II; Bodenseewerk Geratetechnik, Erlangen, Germany) to study serial changes during healing. RESEARCH AND DESIGN METHODS: Studied over 9 months were 14 patients with neuropathy with a total of 24 foot ulcer sites. Of these patients, four (seven ulcers) had significant ischemia as determined by the ankle-brachial pressure index (ABPI) and transcutaneous oxygen tension. RESULTS: Of 21 ulcer sites with serial measurements, only 13 ulcers healed. In those ulcers, a significant reduction (P<0.05) in SaO2 occurred with healing. SaO2 dropped from 58% at initial presentation (mean area 2.6 cm2) to 47% at midsize (mean area 1.2 cm2 at 5.2 weeks) and finally reduced to 45% just before it healed. Similar trends were also seen around the margin of the ulcers (initial 49%, midsize 45%, and final 41%; P = 0.1). However, there were no such changes on the control sites (43, 40, and 40%; P = 0.5) or within the eight ulcers that did not heal (46, 42, and 53%; P = 0.2). CONCLUSIONS: Serial microvascular oxygen measurements may be used to identify at an early stage those ulcers that are unlikely to heal and, therefore, need surgical intervention.

Continuous subcutaneous insulin infusion in the management of painful diabetic neuropathy.

Nine patients with diabetic neuropathy were treated as outpatients with continuous subcutaneous insulin infusion (CSII). Painful symptoms were scored on a 10-cm horizontal graphic rating scale; motor conduction velocity (MCV) was measured in the median and peroneal nerves; and vibration perception threshold (VPT) was recorded in the great toes. All investigations were repeated after 6 wk and at the completion of 4 mo of CSII. Improved diabetic control was confirmed by significantly lower mean blood glucose levels, M-values, and glycosylated hemoglobin. Symptomatic relief was noted by all patients and was accompanied by a significant improvement in pain scores. There was also significant improvement in VPT and MCV after 6 wk of CSII, which was maintained throughout the 4-mo period. However, sensory studies in the median nerve showed no significant changes during the study. It is concluded that strict glucoregulation is indicated in all cases of symptomatic diabetic neuropathy. It remains to be seen whether strict diabetic control from diagnosis will lead to a reduction in the incidence of this complication.

Randomized trial comparing continuous subcutaneous insulin infusion and conventional insulin therapy in type II diabetic patients poorly controlled with sulfonylureas.

OBJECTIVE: To compare the effects of continuous subcutaneous insulin infusion (CSII) and conventional insulin therapy (CIT) in patients with poorly controlled sulfonylurea-treated diabetes mellitus. RESEARCH DESIGN AND METHODS: Twenty-five patients aged 40-65 yr and poorly controlled with sulfonylureas and without severe diabetic complications comprised the study group. Five patients left the study (3 achieved satisfactory glycemic control without insulin, 1 defaulted, 1 developed ketonuria). Ten patients were treated with CSII and 10 with CIT. Outpatient treatment consisted of CIT (twice-daily injections of regular and NPH insulin) or CSII (basal infusion and prandial boluses of regular insulin). RESULTS: Glycosylated hemoglobin improved with both methods of insulin delivery (P less than 0.01), but 8 of 10 CSII-treated patients achieved satisfactory glycemic control (HbA1 less than 50 mmol hydroxymethylfurfural/mol Hb), whereas only 3 of 10 CIT-treated patients achieved this (P less than 0.05). Weight gain, insulin dosage, and prevalence of hypoglycemia were similar in the two groups. Retinal deterioration occurred in one CSII-treated patient and three CIT-treated patients, but there were no episodes of infusion site infection or metabolic decompensation. Patients' satisfaction with treatment improved during insulin therapy (P less than 0.02), and significant changes in beliefs about diabetes and its treatment were observed in CSII-treated patients (P less than 0.05). CONCLUSIONS: Glycemic control improved with both methods of insulin treated patients achieved satisfactory glycemic control (HbA1 less than 50 mmol hydroxymethylfurfural/mol Hb), whereas only 3 of 10 CIT-treated patients achieved this CSII. Patients' satisfaction with treatment improved during insulin therapy.

Asymptomatic myocardial ischemia in diabetes and its relationship to diabetic neuropathy: an exercise electrocardiography study in middle-aged diabetic men.

The incidence of painless ischemic heart disease is increased in diabetic patients, and it has been suggested that this may be partly due to diabetic neuropathy involving cardiac afferent nerves. We have performed exercise electrocardiography in middle-aged diabetic men without cardiac symptoms to see if silent myocardial ischemia is more common in patients with neuropathy. Thirty patients had diabetic neuropathy (group 1), and 30 did not (group 2). The groups were matched for age and duration of diabetes. The exercise test was abnormal in 14 patients. A positive test was no more common in patients with diabetic neuropathy. During a mean follow-up period of 50 mo, five patients developed clinical heart disease, four of whom had a positive exercise test. An abnormal exercise ECG is common in diabetic men without cardiac symptoms, but our study does not suggest that the high incidence of silent myocardial ischemia in diabetic patients is related to the presence of diabetic neuropathy. In patients with diabetes a positive exercise test is associated with a high risk of developing clinical heart disease in subsequent years.

Reduction of abnormal foot pressures in diabetic neuropathy using a new polymer insole material.

The precise pressures and loads under 69 neuropathic feet have been measured during walking using a modified microprocessor-controlled optical system. Abnormally high pressures were demonstrated in 94% of feet with a history of foot ulceration, with pressures as high as 20-30 kg X cm-2 under the forefoot. All subjects were also studied using a new visco-elastic polymer material recently used for insole manufacture. A reduction in pressure was demonstrated that was proportional to peak pressure (linear regression line correlation coefficient of 0.91; P less than 0.001). We conclude that this material causes a significant reduction in the abnormally high pressures recorded under neuropathic feet, and should provide a useful insole for the management of patients at risk of neuropathic foot ulceration.

Dynamic foot pressure and other studies as diagnostic and management aids in diabetic neuropathy.

The pressures and loads under the feet during walking have been compared in three groups of 41 patients each, using a microprocessor-controlled optical system. Group A consisted of patients with diabetic neuropathy, group B of non-neuropathic diabetic patients, and group C of nondiabetic controls. Thirteen patients in group A had a history of neuropathic foot ulceration. Other investigations in the diabetic patients included motor conduction velocity (MCV) in the median and peroneal nerves, vibration perception threshold (VPT) in the great toes, the valsalva response (VR), skin resistance (SR), and the ankle pressure index (API). Fifty-one percent of neuropathic feet had abnormally high pressures underneath the metatarsal heads compared with 17% of the diabetic controls and 7% of nondiabetic subjects. All those feet with previous ulceration had abnormally high pressures at the ulcer sites. Of the other investigations, the VPT correlated most significantly with the presence of foot ulceration. In addition, a low median and peroneal nerve MCV, an abnormal VR, a high API, and the absence of sweating all correlated with the presence of foot ulceration. We therefore conclude that simple bedside investigations, such as measurement of the VPT alone, may be useful in identifying those patients at risk of foot ulceration. Foot pressure studies may then be used in such patients as a predictive and management aid by determining specific areas under the foot that are prone to ulceration.

A double-blind crossover trial comparing human insulin (recombinant DNA) with animal insulins in the treatment of previously insulin-treated diabetic patients.

Ninety-four diabetic patients established on treatment with pork (N = 47) or beef insulin (N = 47) took part in a double-blind crossover trial in which 6-wk treatment periods of their animal insulin were compared with similar periods on human insulin (recombinant DNA). Six patients withdrew during the trial--in three cases for hypoglycemia while taking human insulin. In patients initially treated with beef insulin there was no significant change in the mean blood glucose, the 'M' index, the total daily insulin dose, or the frequency of hypoglycemic attacks after the change to human insulin. Home blood glucose sample values were greater before the morning and evening insulin injection on human insulin (morning: 12.8 mmol/L [beef] versus 14.2 mmol/L [human insulin] [P less than 0.05]; evening: 10.0 mmol/L versus 11.6 mmol/L [P = 0.05]). In pork insulin-treated patients greater values while on human insulin were found for mean glucose (9.0 mmol/L [pork] versus 9.7 mmol/L [human insulin], P = 0.05), 'M' index (65.0 [pork] versus 79.6 [human insulin], P less than 0.025), and total daily insulin dose (50.9 U/day [pork] versus 52.5 U/day [human insulin], P less than 0.001). The early morning glucose sample was also greater on human insulin (9.6 mmol/L [pork] versus 12.1 mmol/L [human insulin], P less than 0.001). No significant differences in either insulin antibody levels or E. coli protein antibody levels were found between either of the animal-insulin treatment periods and human insulin treatment periods.(ABSTRACT TRUNCATED AT 250 WORDS)

Diabetic neuropathic pain in a leg amputated 44 years previously.

The mechanism of neuropathic pain in the diabetic limb is far from clear. Phantom limb pain likewise is of obscure aetiology. The development of typical pain in an absent leg in a patient with diabetes many years after the amputation stimulates thought as to the mechanism, not only of neuropathic pain, but also of phantom limb pain. A 58-year-old man was diagnosed with type 2 diabetes 44 years after having undergone left below knee amputation for congenital AV malformation, at the age of 13. Eight months before the diagnosis of diabetes he began to complain of pain in the leg on the amputated side-pain very similar to that described in typical diabetic neuropathy. This was followed by similar pain in the right leg. MR scan of the spine revealed a small syringohydromyelia of the thoracic cord in addition to a prolapse of disc at L(5)/S(1) level on the left side, which was first noted 5 years previously. There were no other features of S(1) compression. The typical neuropathic character of the pain involving both the amputated and the intact limbs that developed with the diagnosis of type 2 diabetes suggest that the neuropathic pain may originate from centres higher than peripheral nerves.

Relationships between haemostatic factors and capillary morphology in human diabetic neuropathy.

We have examined haemostatic factors in 15 diabetic patients with peripheral neuropathy and 10 diabetic patients without clinical complications. Plasma and blood viscosity, fibrinogen, factor VIIIc, von Willebrand factor activity, spontaneous platelet aggregation and fibrinolytic activity were not significantly different between diabetic patients without clinical complications and diabetic patients with peripheral neuropathy. Platelet aggregation was enhanced in diabetic patients with neuropathy compared with those without complications. In the 15 patients with neuropathy and 3 without complications, who underwent biopsy of sural nerve, skin and muscle, associations were found between haemostatic variables and measures of nerve capillary pathology, notably: plasma fibrinogen and nerve capillary basement membrane thickness (r = 0.70, p < 0.001); thromboxane B2 production and nerve capillary basement membrane thickness (r = -0.61, p < 0.01); plasma fibrinolytic activity and endoneurial capillary lumen size (r = 0.60, p < 0.01) and endothelial cell outer perimeter (r = 0.65, p < 0.01). The main associations of skin and muscle capillary abnormalities were with measures of in vitro platelet aggregation, and the correlations found with nerve capillary measurements were not echoed in the overlying muscle and skin. The results are supportive of the involvement of haemostatic abnormalities in the pathogenesis of diabetic neuropathy.

Diabetic neuropathies. Current concepts in prevention and treatment.

Diabetic nerve damage leads to a wide variety of unpleasant problems: painful sensations, muscle weakness, numb feet predisposing to ulcers, impotence, and a series of distressing effects due to autonomic dysfunction. At present, there is no single effective treatment for the many clinical syndromes--each of which may well have a different cause. Improved blood glucose control must remain the first line of treatment, hopefully to improve nerve structure and function but also to raise the pain threshold. A variety of sedatives and analgesics may also help some patients. Inhibition of the enzyme aldose reductase with resultant interference with neural sorbitol and myo-inositol metabolism would seem to have a good theoretical basis in therapy, and detailed results of long term clinical trials of aldose reductase inhibitors such as sorbinil and tolrestat are awaited with interest. Their role in the future could be more important in prevention of nerve damage than in attempting to reverse gross end-stage nerve destruction. In diabetic subjects with loss of pain sensation in the foot due to neuropathy or in the more advanced state of foot ulceration, intensive educational and clinical efforts should be exerted to prevent this distressing and common problem. In the future, a more detailed understanding of the biochemical abnormalities occurring in nerves and their effect on nerve function, structure and vasculature may lead to more satisfactory and logical treatments for this the commonest single complication of diabetes.

Gram-negative septicaemia during haemorrhage from an anastomotic ulcer.

Gram-negative septicaemia (Klebsiella) occurred on two occasions in a patient bleeding from an anastomotic ulcer. It is postulated that the presence of this organism in the gut of such a patient provided the portal of entry for this infection.

Electron microscopical studies of vessels in diabetic peripheral neuropathy.

the results of an electron microscopical study of sural nerve biopsies from 11 patients with diabetic neuropathy are presented. Thrombi were seen in six cases in at least one intraneural vessel; nine cases showed hyperplasia of endothelial cells, and in seven out of these nine the hyperplasia was sufficient to occlude completely the lumen of small vessels; six cases showed degenerate pericytes and endothelial cells, and in some cases endothelial cells had been shed from the vessel wall, exposing the blood within the vessel to the underlying basement membrane; in five cases large lipid droplets were seen within endothelial cells. Abnormalities of the vessel wall would result in decreased fibrinolytic activity and a reduction of the antiplatelet aggregating proprties of the vessel. Desquamation of endothelial cells from the vessel wall, with exposure of platelets to underlying collagen, may act as a trigger for thrombus formation, particularly as the blood of diabetic patients is often in a hypercoagulable state. The significance of hyperplasia of endothelial cells is at present unknown but, once established, this too would result in profound alterations of loal blood flow and ischaemia of nerve. Damage to endothelial cells may also allow seepage of haematological constituents into the vessel wall, resulting in its progressive thickening.

Small vessel disease in progressive diabetic neuropathy associated with good metabolic control.

Clinical, electrophysiological, and electron microscopical data are presented on 10 diabetic patients with severe progressive neuropathy, predominantly motor in type, in the presence of good blood glucose control, and for one patient with painful neuropathy and third cranial nerve palsy. Endothelial cell hyperplasia was seen in small vessels in all cases, and seven patients showed plugging of the vascular lumen by degenerate cellular material and electron dense protein. It is suggested that these cells desquamate and occlude smaller peripheral vessels at a point of narrowing. In one case the lumen of a vessel was occluded by thrombus. Electron microscopical examination showed a vessel occluded by degranulated platelets. Electrophysiological studies showed a pattern of denervation that was asymmetrical and distally predominant in some patients, suggesting that the neuropathy, at least in part, relates to multiple small infarcts.