Neuropsychiatric manifestations in a patient with prolonged COVID-19 encephalopathy: case report and literature review.

While the respiratory complications of COVID-19 infection are now well known, psychiatric manifestations are an emerging issue. We report a case of prolonged encephalopathy secondary to COVID-19 which was associated with prominent neuropsychiatric features. The patient went on to develop sub-clinical seizures, a rare but recognised complication of SARS-CoV-2.

Restrictive interventions on a psychiatric admission ward before and after COVID-19.

OBJECTIVES: Restrictive interventions (seclusion, restraint and special observations) are used on psychiatric wards when there are no other means available to keep a patient or others safe. These measures can be traumatic, and the Mental Health Commission and the Health Service Executive are focused on minimising their use. We set out to determine whether, following a COVID related reduction in bed numbers on a high dependency psychiatric ward in St John of God Hospital in Dublin, there was a change in their incidence. METHODS: Data on restrictive interventions and challenging behaviours were gathered for 9-month periods before and after March 2020 when COVID related ward changes took place. Figures were also collected on seclusion and restraint for the previous 18 months for a longer-term view. Ward and hospital occupancy levels were also recorded. RESULTS: Between the two time periods, episodes of seclusion fell by 53% and episodes of restraint by 56%. The hours devoted to special observation declined by 30% and incidents of challenging behaviours fell by 26%. Ward occupancy levels fell by only 5%. The longer-term comparison of figures for seclusion and restraint point towards a downward trend from mid-2019 that was accentuated in the post-COVID period. CONCLUSIONS: The changes found may relate to reduced crowding on the ward or other COVID related factors such as the emphasis on social distancing and a shared sense of purpose on the ward. The longer-term trend points towards an emerging cultural shift. The challenge now is to sustain and build upon these changes.

A magnetically shielded room with ultra low residual field and gradient.

A versatile and portable magnetically shielded room with a field of (700 ± 200) pT within a central volume of 1 m × 1 m × 1 m and a field gradient less than 300 pT/m, achieved without any external field stabilization or compensation, is described. This performance represents more than a hundredfold improvement of the state of the art for a two-layer magnetic shield and provides an environment suitable for a next generation of precision experiments in fundamental physics at low energies; in particular, searches for electric dipole moments of fundamental systems and tests of Lorentz-invariance based on spin-precession experiments. Studies of the residual fields and their sources enable improved design of future ultra-low gradient environments and experimental apparatus. This has implications for developments of magnetometry beyond the femto-Tesla scale in, for example, biomagnetism, geosciences, and security applications and in general low-field nuclear magnetic resonance (NMR) measurements.

Through the looking glass; bioactive glass S53P4 (BonAlive®) in the treatment of chronic osteomyelitis.

BACKGROUND: In terms of eradication, osteomyelitis represents one of the most challenging infective conditions in medicine and surgery. In recent years, the use of bioactive glass in conjunction with antimicrobial therapy has emerged as a viable new treatment. AIM: We present a short study, from a regional orthopaedic unit, demonstrating its successful use in three patients with chronic osteomyelitis. METHODS: Between September 2010 and May 2011, bioactive glass S53P4 was used in conjunction with intravenous and oral antibiotics to treat chronic osteomyelitis in three patients (two male, one female). All patients underwent debridement and sequestrectomy procedures with the insertion of bioactive glass followed by antimicrobial regimens tailored to isolated pathogen sensitivities. Patient age ranged from 28 to 68 years, with a mean age of 44.7 years. The presentation period, from time of initial diagnosis to treatment, varied from 16 months to 16 years and all three patients had underwent multiple previous debridements and antimicrobial regimens to no avail. RESULTS: A follow-up of 14-21 months has been achieved with a mean follow-up of 17.3 months. We have seen excellent results in all three patients. All haematological and biochemical parameters have returned to normal, pain has ceased and function has returned in the affected limbs. All antibiotics have stopped and there is no radiological evidence of osteomyelitis. The bioactive glass has integrated with the surrounding bone. CONCLUSIONS: Though a relatively recent development, bioactive glass used in concurrence with antibiotic therapy has significant potential in the treatment of chronic osteomyelitis.

Effects of pyrrolidine dithiocarbamate on endothelial cells: protection against oxidative stress.

The dithiocarbamates are well known for their antioxidant properties and effects on cellular transcriptional events. For example, pyrrolidine dithiocarbamate (PDTC) is widely used as an inhibitor of nuclear factor kappa B (NFkappaB) and this, or related compounds may have therapeutic potential in inhibiting atherosclerosis. However, the precise molecular mechanisms through which PDTC could elicit antioxidant or cell signaling effects in a cellular setting remain unclear. Furthermore, the mechanisms for the effects of PDTC on NFkappaB are likely to involve inhibition of binding of the transcription factor to DNA rather than an effect on the activation process as first proposed. In relation to pharmacological applications of such compounds, little is known of their interaction with endothelial cells, the anticipated site of action for inhibition of vascular related diseases. Until recently, PDTC was generally classified as an antioxidant but evidence for pro-oxidant effects have been reported. In this study, we have addressed this issue in bovine aortic endothelial cells and identified two mechanisms through which PDTC can exert antioxidant effects. At low concentrations (0-25 microM), PDTC induces a concentration dependent increase in cellular GSH levels through the increased activity of gamma-glutamylcysteine synthetase. At higher concentrations, GSH oxidation and apoptotic cell death occur. Using 2,3 dimethoxy-1,4-napthoquinone (DMNQ) as an intracellular generator of superoxide radicals, we find PDTC (10 microM) protects against the cytotoxicity of this agent through a GSH-independent mechanism.

Biological aspects of reactive nitrogen species.

Nitric oxide (NO) plays an important role as a cell-signalling molecule, anti-infective agent and, as most recently recognised, an antioxidant. The metabolic fate of NO gives rise to a further series of compounds, collectively known as the reactive nitrogen species (RNS), which possess their own unique characteristics. In this review we discuss this emerging aspect of the NO field in the context of the formation of the RNS and what is known about their effects on biological systems. While much of the insight into the RNS has been gained from the extensive chemical characterisation of these species, to reveal biological consequences this approach must be complemented by direct measures of physiological function. Although we do not know the consequences of many of the dominant chemical reactions of RNS an intriguing aspect is now emerging. This review will illustrate how, when specificity and amplification through cell signalling mechanisms are taken into account, the less significant reactions, in terms of yield or rates, can explain many of the biological responses of exposure of cells or physiological systems to RNS.

Nitric oxide-dependent induction of glutathione synthesis through increased expression of gamma-glutamylcysteine synthetase.

The nitric oxide (NO) donors S-nitrosopenicillamine or DetaNONOate, which release NO at a rate of 0-15 nM sec-1, were exposed to rat aortic vascular smooth muscle cells for a period of 0-24 h. This treatment resulted in an increase in total glutathione levels of two- to threefold under conditions where no cytotoxicity was detected. The signaling pathways do not involve activation of protein kinase G Ialpha nor are they cGMP dependent. Oxidation of reduced glutathione (GSH) was found after exposure to NO for 3-4 h at rates of formation at or above 8 nM sec-1. Increased intracellular GSH was due to enhanced expression of the rate-limiting enzyme for GSH synthesis, gamma-glutamylcysteine synthetase. Since NO has been shown previously to protect cells against oxidative stress, we propose that the increase in GSH by NO is a potential mechanism for enhancing the antioxidant defenses of the cell. This result also has important implications for identifying redox-sensitive cell signaling pathways that can be activated by NO.

The interplay of nitric oxide and peroxynitrite with signal transduction pathways: implications for disease.

Since the discovery that at least one form of endothelium derived relaxing factor is nitric oxide (NO), numerous studies have uncovered diverse roles for this free radical in a variety of physiological and pathophysiological processes. NO production, a process mediated by a family of enzymes termed NO synthases, has been detected in most cell types. Many of the effects of NO are thought to be mediated through its direct interaction with specific and defined cell signaling pathways. The nature of such interactions are highly dependent on the concentration of NO and cell type. Furthermore, specific NO derived reaction products, such as peroxynitrite, also have the potential to effect cell signal transduction events. As with NO, this can occur through diverse mechanisms and depends on concentration and cell type. It is perhaps not surprising that the reported effects of NO in different disease states are often conflicting. In this brief overview, a framework for placing these apparently disparate properties of NO will be described and will focus on the effects of NO and peroxynitrite on signaling pathways.

Targeting of transforming growth factor-alpha expression to pituitary lactotrophs in transgenic mice results in selective lactotroph proliferation and adenomas.

The PRL-secreting cells of the pituitary gland normally express transforming growth factor-alpha (TGF alpha). To determine the effect of increasing TGF alpha expression in the pituitary, a transgenic mouse model was created in which overexpression of human TGF alpha was directed to the pituitary lactotrophs using the rat PRL promoter. Of the four gene-positive mouse lines, two expressed the messenger RNA corresponding to the transgenic in the pituitary glands. However, in both these lines, expression could only be detected in the female animals. Expression of the transgenic could be detected as early as 1 month of age, but no pathology or developmental abnormalities were detected until the animals reached 6 months, at which time, hyperplasia of the lactotrophs. By the age of 12 months, all of the homozygous transgenic females had developed pituitary adenomas that were immunopositive for PRL. The other hormone-producing cells of the pituitary showed no obvious pathology. The male transgenics developed neither hyperplasia nor adenomas, nor did the gene-positive transgenic lines that did not express the transgene. In no case was an aggressive pituitary tumor seen. This transgenic mouse model indicates that TGF alpha overexpression by lactotrophs stimulates the growth of these pituitary cells. Furthermore, TGF alpha has a highly localized action in the pituitary gland, resulting only in lactotroph hyperplasia and prolactinomas. These observations suggest that TGF alpha might play a role in the development of prolactinomas.

Immunolocalization of alpha-transforming growth factor in the developing rat mammary gland in vivo, rat mammary cells in vitro and in human breast diseases.

Immunoreactive alpha-transforming growth factor (alpha-TGF) was shown by immunocytochemistry to be present in the rat mammary gland at various stages of development, the staining being most intense in mature myoepithelial cells. Alpha-TGF was also detected in the secretions of the mammary glands of pregnant and lactating rats. alpha-TGF in the extracts of rat mammary glands at each stage of development, and in several rat mammary cell lines and in culture medium in which they had been grown, was shown by Western blotting to consist primarily of a protein of molecular weight 50 kDa. The amount of this protein was greater in the mammary gland of the lactating rat than in resting or involuting glands. alpha-TGF was also found in some, but not all, human breast carcinomas, and in benign hyperplastic breast diseases.

Radiographic evaluation of renal trauma: evaluation of 1103 consecutive patients.

OBJECTIVE: To review the records of patients with suspected urinary tract trauma to determine whether eliminating imaging studies would have missed any significant injuries. PATIENTS AND METHODS: The records of 1103 consecutive patients who underwent radiographic evaluation of the urinary tract because of suspected renal trauma were evaluated retrospectively. A comprehensive review was made of the group of patients who were normotensive and had only microscopic haematuria. RESULTS: Abnormal intravenous pyelograms (IVP) were found in 10% of patients with normotension and microscopic haematuria. In patients with injuries due to penetrating trauma, five of 16 with an abnormal IVP required operative intervention, while in patients with injuries due to blunt trauma, only one of 60 had a significant renal injury. None of the 605 patients with a blunt injury, microscopic haematuria, no history of hypotension, and no significant associated injuries required operative intervention solely for the renal injury. CONCLUSION: Radiographic evaluation of the urinary tract is recommended for all patients with penetrating trauma and any degree of haematuria, but only for patients with blunt trauma if associated with gross haematuria, microscopic haematuria and hypotension, or microscopic haematuria and significant associated injuries.

Secretion of transforming growth factor alpha and expression of its receptor in human mammary cell lines.

The secretion of transforming growth factor alpha (TGF alpha) and the expression of cell-surface receptors for epidermal growth factor (EGF) were measured in a series of human mammary cell lines. The amount of TGF alpha secreted by the cells did not correlate with the phenotype of the cells (epithelial or myoepithelial), the mechanism of immortalization of the cells (SV40 or spontaneous) or the source of the cells (normal mammary gland, benign hyperplastic lesion, malignant tumour). The level of expression of cell-surface receptors for EGF was markedly increased as a consequence of SV40-immortalization of mammary cells, but otherwise did not correlate with the phenotype of the cells or the source of the cells. Much of the increase was accounted for by the appearance of a large number of low-affinity receptors for EGF in the SV40-immortalized cells. It is suggested that one of the mechanisms whereby SV40-immortalization suppresses the senescence of primary cultures of human mammary epithelial cells involves increasing the level of expression of receptors for EGF. In contrast the level of secretion of TGF alpha by cells in culture is probably a consequence of the mechanisms of adaptation of each cell line to culture conditions, and does not reflect the level of secretion of TGF alpha by cells in vivo.

Recurring bilateral renal agenesis diagnosed by ultrasound with the aid of amnioinfusion at 18 weeks' gestation.

Recurrent bilateral renal agenesis in siblings is very rare. Presented is a case diagnosed with sonographically aided amnioinfusion at 18 weeks in a woman with an infant affected with the same condition in a previous pregnancy.

alpha-Chloralose alters autonomic reflex function of the lower urinary tract.

The effects of alpha-chloralose on the micturition reflex were evaluated using an efficiently voiding decerebrate cat model. At laparotomy cannulas were introduced into the urethra and/or bladder for measurement of urethral perfusion pressure and/or bladder pressure during bladder filling and voiding. After establishment of efficient voiding in the anesthetic-free decerebrate cat, chloralose, 50 mg/kg iv, was administered. Parameters assessed before and after anesthetic included bladder pressure at peak of contraction (voiding pressure), intravesical pressure at onset of bladder contraction (threshold pressure), contraction amplitude, duration of bladder contraction, bladder volume at onset of bladder contraction (volume threshold), and residual bladder volume after voiding (postvoid residual). In addition to these parameters, preparations with intact bladder-urethra and with divided bladder-urethra were used to assess effects of chloralose on voiding efficiency and coordination between bladder and urethra, respectively. Chloralose significantly reduced voiding pressure, contraction amplitude, and voiding efficiency. Neither vehicle for the chloralose nor sympathetic denervation of the lower urinary tract affected these reductions. Chloralose had no effect on direct contraction of the bladder and urethra produced by intra-arterial acetylcholine (25-100 micrograms). Chloralose converted the synergic bladder and urethral responses during voiding to dyssynergic responses. Neuromuscular blockade with gallamine, 10 mg/kg iv, improved voiding efficiency.(ABSTRACT TRUNCATED AT 250 WORDS)

Intraoperative decision-making in renal trauma surgery.

Surgery for renal trauma requires three intraoperative decisions: Should the kidney be explored? Is pedicle control necessary? What procedure should be performed? In 85 explorations for penetrating (66) and blunt (19) trauma, we found that penetrating injuries, active hemorrhage, or major tissue destruction are reasons for mandatory renal exploration. This resulted in 26 nephrectomies, 9 partial nephrectomies, and 4 major renorrhaphies. Forty-six patients underwent minor renorrhaphy or needless exploration without complications. Formal pedicle control was carried out 33 times (39%), but it was never necessary to control parenchymal hemorrhage. Unless a wound overlies the great vessels, perirenal hematomas can be safely entered laterally without prior pedicle control using manual pedicle or parenchymal control if needed.

Invited case transcript. Obsessive-compulsive disorder: a behavioral case formulation.

The interviewing skills of many behavior therapists are inadequate and several possible reasons are discussed. The present manuscript focuses on construction of initial clinical hypotheses. A strategy for developing and testing initial hypotheses is presented and illustrated by transcripts from a complex case. The transcript is taken from the initial interviews with a 26 year old woman presenting the problems of emotional distress related to thoughts of harming others, and anxiety concerning her difficulty in controlling physical aggression. A behavioral analysis of the origins and maintaining factors indicated that while the patient's compulsions were a vehicle to manage anxiety, the wellspring of her attempts to exert control over her thoughts was a fear of anger, loss of control, negative evaluation, criticism, and rejection. Distal and proximal predisposing events were examined in order to help explain the development of this maladaptive behavioral pattern, and to plan therapeutic strategy.

Effect of exogenous ANP on initial renal function following 24-hour cold preservation.

The impact of synthetic atrial natriuretic peptide (sANP) on renal function following cold ischemic injury was studied in a canine autotransplant model. Following a prenephrectomy inulin clearance determination (CIn), the left kidney was excised, flushed with Eurocollins solution, and cold-stored for 24 hours. Immediately following reperfusion and a 10 minute equilibration period, baseline CIn was measured over a 20-minute time interval (Collection Period I). Experimental animals (N = 11) then received 1 mcg/kg sANP by intravenous bolus followed by a continuous infusion at 0.3 mcg/kg/min for 30 minutes. CIn was measured throughout the infusion (Collection Period II). Normal saline was substituted for sANP in control animals (N = 11). CIn was also measured 24 hours following reimplantation in seven control and seven sANP-treated animals. Autograft inulin clearance increased from 0.32 +/- 0.11 ml/min during Period I to 2.5 +/- 0.6 ml/min during sANP infusion (P less than 0.01). This increase in CIn associated with ANP infusion was accompanied by increases in urine flow rate (V) (0.15 +/- 0.05 ml/min to 0.98 +/- 0.21 ml/min, P less than 0.01) and renal blood flow (RBF) measured by electromagnetic flow probe (85 +/- 17 ml/min to 171 +/- 13 ml/min, P less than 0.05). No significant changes in CIn, V, or RBF occurred in control animals between periods I and II. Although systemic blood pressure declined during sANP infusion, it did not decrease to an extent that compromised peripheral perfusion. CIn determined 24 hours after autograft reimplantation in the ANP-treated animals approximated or exceeded values determined during ANP infusion (Period II).(ABSTRACT TRUNCATED AT 250 WORDS)

Blood flow to acutely ischaemic myocardium during pericardial tamponade: dominant influence of aortic blood pressure.

The effect of increased pericardial pressure on blood flow to acutely ischaemic and normal myocardium was investigated and the mechanisms responsible for this effect evaluated in eight open chest anaesthetised dogs. After coronary artery occlusion regional myocardial blood flows were estimated from the tissue content of radioactive microspheres administered systemically during control conditions, mild tamponade (pericardial pressure 8.4(1.0) mmHg), severe tamponade (pericardial pressure 13.3(1.4) mmHg), and severe tamponade (pericardial pressure 13.5(1.6) mmHg) with aortic blood pressure held constant by blood volume expansion. Mild tamponade decreased aortic blood flow by 20% and aortic pressure by 90%. Right and left atrial blood pressures were moderately increased. Blood flow to ischaemic and normal myocardium was not significantly altered. Severe tamponade decreased aortic blood flow by 50% and aortic pressure by 35%. Heart rate increased by 18%, and right and left atrial pressures were appreciably increased. Blood flow to ischaemic and normal myocardium decreased in proportion to the decrease in aortic pressure, but the transmural distribution of flow in ischaemic myocardium was not altered. During severe tamponade with constant aortic pressure, right and left atrial blood pressures were further increased, but blood flow to ischaemic and normal myocardium was similar to that observed under pre-tamponade control conditions. These results show that blood flow to acutely ischaemic myocardium during tamponade is determined primarily by aortic pressure.